Beischer & MacKay’s Obstetrics, Gynaecology and the Newborn [4th Edition] 9780729583824, 9780729583817, 9780729584050

Table of contents :
Front Cover......Page 1
Inside Front Cover......Page 2
Half title page......Page 3
Dedication......Page 4
Beischer & Mackay's Obsterics, gynaecology and the newborn......Page 5
Copyright Page......Page 6
Table Of Contents......Page 7
Foreword......Page 12
Preface......Page 13
Acknowledgements......Page 14
List of editors......Page 15
List of contributors......Page 16
List of reviewers......Page 18
1 Anatomy and Physiology......Page 19
Mons pubis......Page 20
Vaginal orifice......Page 21
Vagina......Page 22
Uterus......Page 23
Uterine tubes......Page 24
The bony pelvis......Page 25
The pelvic joints......Page 27
Luteal phase......Page 28
Gametogenesis......Page 29
Postmenopause......Page 31
Fertilisation......Page 32
Ectodermal layer......Page 34
Mesodermal layer......Page 36
Endodermal layer......Page 37
Early trophoblast......Page 38
Further changes in the trophoblast and decidua......Page 39
Tissues separating maternal and fetal circulations......Page 40
Fetomaternal haemorrhage......Page 42
The umbilical cord......Page 43
2 Obstetrics......Page 45
2.1 Normal Pregnancy......Page 46
Maternal age considerations in the timing of pregnancy......Page 47
Optimising treatment for pregnancy......Page 48
Pharmacological advice......Page 49
Diagnosing pregnancy......Page 50
Other means of determining the gestational age......Page 51
Blood group and antibody screen......Page 52
Thyroid function......Page 53
Exercise......Page 54
Infections......Page 55
Further reading......Page 56
Health promotion and preventative medicine......Page 57
Maternal weight......Page 58
Palpation......Page 59
First antenatal visit......Page 60
Blood group antibody screen......Page 61
Group B streptococcus (GBS) screening......Page 62
Further reading......Page 63
Dietary guidelines in pregnancy......Page 64
Iron......Page 65
Weight gain in pregnancy......Page 66
Further reading......Page 68
2.2 Problems of Early Pregnancy......Page 69
Clinical features......Page 70
Further reading......Page 71
Miscarriage......Page 73
Aetiology......Page 74
Assessment......Page 75
Complete miscarriage......Page 76
Missed miscarriage......Page 77
Recurrent miscarriage......Page 78
Tubal rupture......Page 79
Management......Page 80
Medical treatment......Page 81
Localised GTD......Page 82
Choriocarcinoma......Page 83
Initial management......Page 84
Follow-up......Page 85
Further reading......Page 86
2.3 Prenatal Diagnosis......Page 87
Introduction......Page 88
Second trimester maternal serum screening......Page 89
Integrated testing: combining first- and second-trimester screening......Page 91
Diagnostic tests......Page 92
Haemoglobinopathies......Page 93
Prevention of structural abnormalities......Page 94
Abnormalities of the central nervous system......Page 95
Abnormalities of the skeletal system......Page 96
Fetal tumours......Page 97
Management of pregnancies complicated by fetal genetic or structural abnormalities......Page 98
The expected short- and long-term outcomes......Page 99
Post-termination care......Page 100
Further reading......Page 101
2.4 Obstetric Complications......Page 102
Determine aetiology......Page 103
Clinical features......Page 104
Treatment......Page 105
Placental bed ischaemia......Page 106
Who and where?......Page 107
Further reading......Page 108
Fetal growth restriction......Page 109
Investigating for causes of FGR......Page 110
Management......Page 111
Management of labour......Page 112
Assessment of fetal wellbeing......Page 113
Ultrasound assessment of fetal Doppler studies......Page 114
Further reading......Page 115
Epidemiology......Page 116
Examination......Page 117
Calcium channel blockers......Page 118
Significance......Page 119
Conservative management of PPROM......Page 120
Pessary......Page 121
References......Page 123
Incidence......Page 124
Placental insufficiency and consequences......Page 125
Ultrasound and cardiotocography......Page 126
Further reading......Page 127
Incidence and aetiology of twins......Page 129
Determination of chorionicity and amnionicity......Page 130
Management in early pregnancy......Page 131
Fetal growth surveillance......Page 132
Twin–twin transfusion syndrome (TTTS)......Page 133
Death of one twin......Page 134
Labour and delivery of twins......Page 135
High-order multiple pregnancy......Page 136
Further reading......Page 137
Incidence......Page 138
Determine aetiology (look for a cause)......Page 139
Planned vaginal birth versus elective caesarean section......Page 140
Management on admission......Page 141
First stage of labour......Page 142
Delivery of the aftercoming head......Page 143
Breech extraction......Page 144
Diagnosis......Page 145
Further reading......Page 146
2.5 Medical and Surgical Disorders in Pregnancy......Page 147
Classification of hypertension in pregnancy......Page 148
Deficient placentation......Page 149
Neurological......Page 150
Placental......Page 151
Differential diagnosis......Page 152
Management of preeclampsia without severe features......Page 153
Intravascular volume status......Page 154
Prophylaxis......Page 155
Convulsion first aid......Page 156
Further reading......Page 157
17 Thromboembolism, cardiac disorders and respiratory disease......Page 158
Physiological changes in pregnancy......Page 159
Antenatal......Page 160
Peripartum cardiomyopathy......Page 161
Further reading......Page 162
Pathology......Page 163
Management......Page 164
Transplacental (haematogenous) infections......Page 165
Chlamydial infection......Page 166
Mycoplasmal and ureasplasmal infection......Page 167
Tuberculosis......Page 168
Further reading......Page 169
Cytomegalovirus......Page 170
Rubella......Page 173
Diagnosis and management of fetal infection......Page 174
Fetal infection......Page 175
Maternal HIV......Page 176
Management of the infant......Page 177
Malaria......Page 178
Further reading......Page 179
Clinical sequelae......Page 181
Alpha-thalassaemia......Page 182
Haemoglobinopathies......Page 183
Pathogenesis......Page 184
Further readings......Page 185
Acute appendicitis......Page 186
Management......Page 187
Female genital mutilation......Page 188
Motor vehicle accident in pregnancy......Page 189
Ovarian cysts and tumours......Page 190
Physiological changes in pregnancy......Page 191
Pregnancy......Page 192
Further reading......Page 193
Background......Page 194
Clinical features......Page 195
Autoimmune hyperthyroidism (Graves’ disease)......Page 196
Antiphospholipid syndrome......Page 197
Blood transfusion......Page 198
Passive administration of anti-D......Page 199
Determining the partner’s antigen status......Page 200
Management of the moderate- or high-risk immunised pregnancy......Page 201
Neonatal alloimmune neutropenia......Page 202
23 Diabetes mellitus......Page 203
Screening for GDM at 26 to 28 weeks’......Page 204
The effect of diabetes on pregnancy......Page 205
Treatment......Page 206
Intrapartum care......Page 207
Further Readings......Page 208
Multiple sclerosis in pregnancy......Page 209
Postpartum care......Page 210
Cerebral venous thrombosis......Page 211
Further reading......Page 212
Emotional wellbeing in pregnancy......Page 214
Maternity blues......Page 215
Management of mental illness in pregnancy......Page 216
Electroconvulsive therapy......Page 217
References......Page 218
Further reading......Page 219
2.6 Common Clinical Scenarios and Presenting Problems in Pregnancy......Page 220
Management......Page 221
Differential diagnosis......Page 222
Pathophysiology......Page 223
Management......Page 224
Management......Page 225
Pathophysiology......Page 226
Management......Page 227
Assessment......Page 228
Management......Page 229
Further reading......Page 230
2.7 Labour and Birth......Page 231
2.7.1 Normal Labour and Birth......Page 233
The upper and lower uterine segments......Page 234
Biochemical changes in the myometrium, cervix and membranes prior to and in early labour......Page 235
The pain of uterine contractions......Page 237
The stages of labour......Page 238
Descent......Page 239
Trunk delivery......Page 241
Damage to the tissues of the pelvic floor......Page 242
Uterine atony in the third stage of labour......Page 243
28 Management of normal labour......Page 244
Examination......Page 245
The admission cardiotocograph......Page 247
Partner, family and friends......Page 248
Vaginal examination......Page 249
Auscultation of the fetal heart......Page 250
Ambulation and position......Page 251
Management of the normal second stage of labour prior to the actual birth......Page 253
Cord around the neck......Page 254
Clamping of the cord......Page 255
Await uterine contraction, placental separation and descent......Page 256
Controlled cord traction......Page 257
Management of an incomplete placenta......Page 258
Further reading......Page 259
2.7.2 Induction of Labour, Instrumental Delivery and Casearean Section......Page 260
Risks of birth occurring earlier than it would have occurred spontaneously......Page 261
Contraindications to vaginal birth......Page 262
Fetal surveillance following cervical ripening or induction of labour......Page 263
Contraindications to prostaglandin administration......Page 264
Excessive uterine muscular activity......Page 265
References......Page 266
Fetal compromise and/or inadequate progress with the head on the perineum; vaginal breech delivery......Page 267
Midline episiotomy......Page 268
Repair of the vaginal epithelium......Page 270
Prevention......Page 271
Clinical features......Page 272
Vulval or vaginal haematoma......Page 273
Further reading......Page 274
Choice between instruments: forceps or vacuum?......Page 275
Aftercoming head of a vaginal breech delivery......Page 276
Station prior to instrumental birth......Page 277
Obstetric forceps......Page 278
Mid-cavity forceps delivery......Page 279
Failed instrumental birth......Page 282
Shoulder dystocia......Page 283
Further reading......Page 284
Incidence......Page 285
Indications......Page 286
Inadequate progress in labour and/or fetal compromise (Ch 33)......Page 287
Preparation for caesarean section......Page 288
Surgical technique......Page 289
Postoperative care......Page 290
Uterine rupture......Page 291
Likelihood of achieving a vaginal birth if attempted after a previous caesarean section......Page 292
Further reading......Page 293
2.7.3 Intrapartum Clinical Problems......Page 294
Fetal compromise after epidural anaesthesia......Page 295
Umbilical cord......Page 296
Management of acute intrapartum fetal compromise......Page 297
Assess and treat the underlying cause......Page 298
Amniotic fluid quantity and meconium-staining......Page 299
Diagnosis......Page 300
Incidence......Page 301
Further reading......Page 302
The powers......Page 303
Obstructed labour, sepsis, fetal death, genital tract fistula......Page 304
Signs of obstructed labour......Page 305
Rationale......Page 306
Fetal complications......Page 307
Shoulder dystocia (impacted shoulders)......Page 308
Management......Page 309
5. Cleidotomy......Page 310
7. Caesarean section......Page 311
What causes flexion of the fetal head?......Page 312
Aetiology......Page 313
Sequelae of a posterior position at the start of labour......Page 314
Aetiology......Page 315
Clinical sequlae......Page 317
Clinical sequelae......Page 318
Intrapartum......Page 319
Incidence......Page 320
4. Contract the uterus......Page 321
Uterine atony......Page 322
Pathology......Page 323
Management......Page 324
Trauma......Page 325
The retained placenta in the absence of bleeding......Page 326
Further reading......Page 327
Aetiology......Page 328
Aetiology......Page 330
Aetiology......Page 331
Management......Page 332
Pathophysiology of labour pain......Page 333
Therapies that provide effective analgesia of moderate degree in some patients......Page 334
Establishing and maintaining block......Page 335
Anaesthesia for caesarean section......Page 337
General anaesthesia for caesarean section......Page 338
References......Page 339
2.7.4 The Puerperium and Lactation......Page 340
Physiological changes in the puerperium......Page 341
Renal system and urinary tract......Page 342
Physiology of lactation and breastfeeding......Page 343
Further reading......Page 346
0 to 6 hours after birth......Page 347
6 hours to 7 days after birth......Page 349
The first week......Page 351
Further reading......Page 352
Thromboembolism......Page 353
Secondary postpartum haemorrhage......Page 354
Urinary and bowel problems during the puerperium......Page 355
Further reading......Page 356
2.7.5 Global Women's Health and Indigenous Women's Health......Page 357
Introduction......Page 358
Maternal mortality......Page 359
Abortion......Page 360
Cervical cancer......Page 361
References......Page 362
Australian Indigenous women’s health in pregnancy......Page 363
Barriers to accessing healthcare......Page 364
Social and emotional wellbeing......Page 365
Infection......Page 366
References......Page 367
3 Gynaecology......Page 369
3.1 Gynaecological Assessment......Page 370
Surgical history......Page 371
Menstrual history......Page 372
The gynaecological examination......Page 373
Further reading......Page 375
Microbiology......Page 376
Obtaining the cervical sample......Page 378
Pelvic ultrasound......Page 379
Pelvic MRI......Page 382
Instrumentation......Page 384
Vaginoscopic approach......Page 385
Technique......Page 386
Applications of laparoscopy......Page 387
References......Page 388
3.2 Menstrual Disorders......Page 389
Imperforate hymen......Page 390
Hypothalamic–pituitary causes......Page 391
Absence of secondary sexual hair......Page 392
Sexual activity......Page 393
Further reading......Page 394
47 The menstrual cycle and menstrual disorders......Page 395
Menstruation: general description and terms......Page 396
The menstrual process......Page 397
Menstrual hygiene......Page 399
Clinical features......Page 401
Treatment......Page 402
Medical: hormonal......Page 403
Clinical features......Page 404
Medical: non-hormonal......Page 405
Other......Page 407
History and examination......Page 408
Biopsy......Page 409
Medical: hormonal......Page 410
Surgical......Page 413
Aetiology......Page 414
Examination......Page 415
References......Page 416
3.3 Reproductive Endocrinology and Infertility......Page 418
Aetiology......Page 419
Evaluation......Page 420
Management......Page 422
Hypothalamic dysfunction......Page 423
Tubal factors......Page 424
Management of tubal disease......Page 425
Coital factors......Page 426
Intrauterine adhesions (Asherman’s syndrome)......Page 427
Unexplained infertility......Page 428
IVF and intracytoplasmic sperm injection (ICSI)......Page 429
Further reading......Page 430
Definitions......Page 432
Secondary amenorrhoea......Page 433
3. Ovarian failure......Page 434
Hypothalamic: hyperandrogenism including PCOS......Page 436
Assessment......Page 437
Medical treatment......Page 438
Ovulation induction......Page 439
Injectable gonadotrophin therapy......Page 440
Further reading......Page 441
50 Androgen excess, including PCOS, hirsutism and acne......Page 443
Non-classical congenital adrenal hyperplasia......Page 444
Diagnosis and investigations......Page 445
Mild or idiopathic hirsutism......Page 446
Pathogenesis......Page 447
Diagnosis......Page 448
Weight loss......Page 449
References......Page 450
3.4 The Menopause......Page 451
Physiology......Page 452
Assessment......Page 453
Lipid profile and cardiovascular disease......Page 454
Testosterone......Page 455
References......Page 456
Further reading......Page 457
3.5 Sexuality......Page 458
Introduction......Page 459
Sexual orientation......Page 461
Assessment of sexual problems......Page 462
Disparate sexual desire......Page 463
Painful coitus (dyspareunia)......Page 464
Medical care......Page 465
References......Page 466
3.6 Contraception, Sterilisation and Abortion......Page 468
53 Contraception, sterilisation and abortion......Page 469
Pregnancy risk......Page 470
Initiation of contraception......Page 471
Intrauterine contraceptive devices......Page 472
Combined hormonal contraception......Page 473
The vaginal ring......Page 474
The male condom......Page 476
The diaphragm......Page 477
Emergency contraception......Page 478
Calendar methods: rhythm method......Page 479
Vasectomy......Page 480
Medical termination of pregnancy......Page 481
Complications......Page 482
References......Page 483
Vaginal pH......Page 484
History......Page 485
Examination......Page 486
Vulval HSV types 1 and 2......Page 487
Prevention......Page 488
Syphilis......Page 489
Lymphogranuloma venereum......Page 490
Treatment......Page 491
Non-albicans Candida......Page 492
Cervicitis......Page 493
Neisseria gonorrhoea......Page 494
Diagnosis......Page 495
Criteria for the diagnosis of PID......Page 496
Management of PID......Page 497
References......Page 498
3.7 Urogynaecology......Page 500
Level 2: paracolpos......Page 501
Level 3: the perineal body and the levator plate......Page 502
Physical examination......Page 503
POP-Q terminology......Page 504
Evaluation/work-up......Page 505
Manchester repair......Page 506
Conclusions......Page 508
References......Page 509
Anatomy of the lower urinary tract......Page 510
Neurophysiology of the lower urinary tract......Page 511
Classification and aetiology of urinary incontinence......Page 512
Urgency urinary incontinence......Page 513
History......Page 514
Investigations......Page 516
Medication......Page 519
Surgery for stress urinary incontinence......Page 520
References......Page 521
3.8 Pelvic Pain and Endometriosis......Page 522
Nerve pathways......Page 523
Pain characteristics......Page 524
History......Page 525
Investigations......Page 528
Further reading......Page 529
Aetiology......Page 531
Surgical findings......Page 532
Clinical features......Page 533
Medical management......Page 534
Prognosis......Page 535
Further reading......Page 537
3.9 The Breast......Page 538
Breast anatomy, including anomalies......Page 539
Breast anomalies......Page 540
Breast physiology......Page 541
Mammography......Page 542
Fibroadenoma......Page 543
Duct ectasia......Page 544
Breast infection......Page 545
Paget’s disease of the breast or mammary Paget disease......Page 546
Lymph node status......Page 547
Radiotherapy......Page 548
Chemotherapy......Page 549
Locally advanced breast cancer......Page 550
References......Page 551
3.10 Neoplasia and Other Lumps......Page 553
Lichen sclerosus......Page 554
Lichen planus......Page 555
Cicatricial pemphigoid......Page 556
Management......Page 557
Candidiasis......Page 558
Desquamative inflammatory vaginitis......Page 559
Vulvar intraepithelial neoplasia (VIN)......Page 560
Cancer of the Bartholin’s gland......Page 561
Further reading......Page 562
Eversion and nabothian cysts......Page 563
Endocervical polyps......Page 564
Leiomyomas......Page 565
Aetiology and pathogenesis......Page 566
Histology......Page 569
Cervical screening......Page 570
Cytology......Page 571
HPV testing......Page 572
Treatment......Page 573
Adenocarcinoma in situ......Page 574
The diethylstilboestrol (DES) syndrome......Page 575
Stages IB1–IIA1......Page 576
Stages IB-IVA......Page 577
References......Page 579
Pathology......Page 581
Investigations......Page 582
Endometrial polyps......Page 583
Type 1 and type 2 endometrial carcinoma......Page 584
Clinical presentation......Page 585
Differential diagnosis......Page 586
Features of malignancy on ultrasound......Page 587
Further reading......Page 589
History......Page 590
Functional cysts of the ovary......Page 591
Pathology......Page 592
Borderline and malignant ovarian tumours......Page 593
Cystadenomas......Page 594
Borderline ovarian tumours......Page 595
Pathology......Page 596
Sex-cord stromal tumours......Page 597
Germ cell tumours......Page 598
Gonadoblastomas......Page 599
Further reading......Page 600
4 Neonatology......Page 601
Fetus......Page 602
The heart and lungs......Page 603
Introduction......Page 604
The birth of a newborn: the first minutes of life......Page 605
The Apgar score......Page 608
References......Page 609
General care......Page 610
Urine and stools......Page 611
Neonatal heel-prick screening......Page 612
Bonding, family and siblings......Page 613
The physical examination......Page 615
General observation......Page 616
Hands......Page 623
Grasp and Moro reflexes......Page 624
Fontanelles and sutures......Page 625
Encephalocele......Page 626
Mouth......Page 627
Sternomastoid tumour......Page 628
Female external genitalia......Page 630
Dislocation......Page 631
Tone and back......Page 633
References......Page 634
an international perspective......Page 635
Physiology of lactation......Page 636
Management of breastfeeding......Page 637
Breastfeeding difficulties......Page 638
Breast abscess......Page 639
A sleepy or lethargic baby......Page 640
Relactation......Page 641
Volume of feed......Page 642
Vomiting......Page 643
References......Page 644
Normal bilirubin metabolism......Page 646
Investigations......Page 647
Other Considerations......Page 648
Phototherapy......Page 649
ABO haemolytic disease......Page 651
Kernicterus......Page 652
References......Page 653
Developmental events......Page 654
Neonatal encephalopathy......Page 655
Outcome......Page 656
The floppy newborn......Page 657
Nerve palsies......Page 658
Drug withdrawal (neonatal abstinence syndrome)......Page 659
References......Page 660
Lung fluid......Page 661
Causes......Page 662
Management......Page 663
Investigation......Page 664
Respiratory distress syndrome......Page 665
Pneumothorax......Page 666
Diaphragmatic hernia......Page 667
Further reading......Page 668
The small for gestational age newborn......Page 669
The large for gestational age newborn......Page 671
References......Page 672
Antenatally acquired congenital infections: the TORCH infections......Page 673
Herpes simplex......Page 674
Conjunctivitis......Page 675
Systemic infection: neonatal sepsis......Page 676
Specific infections......Page 677
Viral hepatitis......Page 678
References......Page 679
Prevalence......Page 680
Congenital heart disease......Page 681
Hypoplastic left heart......Page 683
Other CNS malformations......Page 684
Hirschsprung’s disease......Page 685
Tracheo-oesophageal fistula......Page 686
Undescended testes......Page 687
Ambiguous genitalia......Page 688
Trisomy 18 (Edwards’ syndrome)......Page 689
Communication with the parents and genetic counselling......Page 691
References......Page 692
Red blood cells......Page 693
Pathological......Page 694
Hydrops fetalis......Page 695
Disseminated intravascular coagulation......Page 696
Blood in the stool......Page 697
Prematurity: definitions......Page 698
Neurological features......Page 699
Jaundice......Page 700
Intraventricular haemorrhage and periventricular leucomalacia......Page 701
Necrotising enterocolitis......Page 703
Patent ductus arteriosus......Page 704
Neurodevelopmental outcome......Page 705
Follow-up and post-discharge care......Page 706
Transport and retrieval......Page 707
References......Page 710
A......Page 711
B......Page 713
C......Page 716
D......Page 720
E......Page 721
F......Page 723
G......Page 724
H......Page 726
I......Page 728
L......Page 730
M......Page 732
N......Page 734
O......Page 736
P......Page 738
R......Page 744
S......Page 745
T......Page 747
U......Page 749
V......Page 750
Z......Page 752

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Beischer & MacKay’s

OBSTETRICS, GYNAECOLOGY AND THE NEWBORN

DEDICATION This book is dedicated to the students who have taught us and our families who have supported us.

Beischer & MacKay’s

OBSTETRICS, GYNAECOLOGY AND THE NEWBORN FOURTH EDITION

Michael Permezel, Susan Walker & Kypros Kyprianou

Elsevier Australia. ACN 001 002 357 (a division of Reed International Books Australia Pty Ltd) Tower 1, 475 Victoria Avenue, Chatswood, NSW 2067 Copyright © 2015 Elsevier Australia. 3rd edition © 1997; 2nd edition © 1986 Elsevier Australia. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organisations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of product liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. National Library of Australia Cataloguing-in-Publication Data Permezel, Michael, author. Beischer & MacKay’s obstetrics, gynaecology and the newborn / Michael Permezel, Susan Walker & Kypros Kyprianou. 9780729540742 (paperback) Obstetrics–Textbooks. Gynecology–Textbooks. Newborn infants–Care–Textbooks. Walker, Susan, author. Kyprianou, Kypros, author. 613.0432 Content Strategist: Larissa Norrie Content Development Specialist: Neli Bryant Project Manager: Devendran Kannan Edited by Leanne Poll Proofread by Julie Ganner Design by Georgette Hall Permissions by Karen Forsythe & Anita Mercy Vethakkan Index by Robert Swanson Typeset by Toppan Best-set Premedia Limited Printed in China by China Translation and Printing Services

CONTENTS Foreword.................................................................................................................................................................................................................... X Preface.........................................................................................................................................................................................................................XI Acknowledgements...............................................................................................................................................................................XII List of Editors............................................................................................................................................................................................... XIII List of Contributors..........................................................................................................................................................................XIV List of Reviewers....................................................................................................................................................................................XVI Section 1  Anatomy and Physiology CHAPTER 1

Reproductive Anatomy and Physiology..............................................................................................................................................2 Peter Wein and Michael Permezel

CHAPTER 2

Anatomy and Physiology of Pregnancy............................................................................................................................................ 14 Michael Permezel and Peter Wein

Section 2  Obstetrics

Section 2.1  Normal Pregnancy CHAPTER 3

The Prepregnancy Consultation...........................................................................................................................................................29 Michael Permezel

CHAPTER 4

The First Antenatal Visit........................................................................................................................................................................32 Michael Permezel

CHAPTER 5

Antenatal Care Beyond the First Antenatal Visit.......................................................................................................................... 39 Michael Permezel

CHAPTER 6

Obesity and Nutrition in Pregnancy................................................................................................................................................. 46 Alexis Shub

Section 2.2  Problems of Early Pregnancy CHAPTER 7

Hyperemesis Gravidarum......................................................................................................................................................................52 Neil Israelsohn

CHAPTER 8

Bleeding in Early Pregnancy.................................................................................................................................................................55 Neil Israelsohn

Section 2.3  Prenatal Diagnosis CHAPTER 9

Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus.................................... 70 Susan Walker

Section 2.4  Obstetric Complications CHAPTER 10 Antepartum Haemorrhage.................................................................................................................................................................... 85

Neil Israelsohn

v

Contents

CHAPTER 11

Fetal Growth Restriction and Assessment of Fetal Wellbeing................................................................................................... 91 Alexis Shub

CHAPTER 12

Preterm Labour, Including Cervical Insufficiency........................................................................................................................ 98 Alison Fung

CHAPTER 13

The Postdates Pregnancy and Rupture of the Membranes Before Labour at Term......................................................... 106 Michael Permezel and Megan Di Quinzio

CHAPTER 14

Multiple Pregnancy..................................................................................................................................................................................111 Susan Walker

CHAPTER 15

Malpresentation......................................................................................................................................................................................120 Michael Permezel

Section 2.5  Medical and Surgical Disorders in Pregnancy CHAPTER 16

Hypertensive Disorders of Pregnancy Eclampsia ...................................................................................................................... 130 Michael Permezel

CHAPTER 17

Thromboembolism, Cardiac Disorders and Respiratory Disease........................................................................................... 140 Michael Permezel and Lisa Hui

CHAPTER 18

Bacterial Infections in Pregnancy......................................................................................................................................................145 Peter Wein

CHAPTER 19

Viral and Protozoan Infections in Pregnancy............................................................................................................................... 152 Susan Walker

CHAPTER 20 The Blood: Anaemia, Thrombocytopenia and Coagulopathy...................................................................................................163

Lisa Hui and Michael Permezel CHAPTER 21

Gastrointestinal, Hepatobiliary, Gynaecological and Renal Problems....................................................................................168 Michael Permezel

CHAPTER 22 Autoimmune and Isoimmune Disease in Pregnancy.................................................................................................................. 176

Michael Permezel and Gillian Paulsen CHAPTER 23 Diabetes Mellitus....................................................................................................................................................................................185

Peter Wein CHAPTER 24 Neurological Disease...............................................................................................................................................................................191

Susan Walker CHAPTER 25 Mental Health Disorders during the Perinatal Period.................................................................................................................196

Megan Galbally and Martien Snellen

Section 2.6  Common Clinical Scenarios and Presenting Problems in Pregnancy CHAPTER 26 Common Problems in Pregnancy.....................................................................................................................................................203

Michael Permezel and Megan Di Quinzio

Section 2.7  Labour and Birth

Section 2.7.1  Normal Labour and Birth CHAPTER 27 The Physiology of Parturition.............................................................................................................................................................216

Michael Permezel and Megan Di Quinzio CHAPTER 28 Management of Normal Labour....................................................................................................................................................... 226

Michael Permezel

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Contents

Section 2.7.2  Induction of Labour, Instrumental Delivery and Casearean Section CHAPTER 29 Induction of Labour, Including Cervical Ripening.....................................................................................................................243

Michael Permezel and Gillian Paulsen CHAPTER 30 Episiotomy and Vaginal Outlet Tears.............................................................................................................................................. 249

Michael Permezel and Gillian Paulsen CHAPTER 31

Instrumental Delivery.......................................................................................................................................................................... 257 Michael Permezel and Gillian Paulsen

CHAPTER 32 Caesarean Section and Trial of Labour after Caesarean............................................................................................................ 267

Michael Permezel

Section 2.7.3  Intrapartum Clinical Problems CHAPTER 33 Intrapartum Fetal Compromise........................................................................................................................................................ 277

Michael Permezel and Julia Francis CHAPTER 34 Failure to Progress in Labour............................................................................................................................................................ 285

Michael Permezel and Julia Francis CHAPTER 35 Malpresentation and Malposition.................................................................................................................................................... 294

Julia Francis and Michael Permezel CHAPTER 36 Postpartum Haemorrhage...................................................................................................................................................................302

Michael Permezel CHAPTER 37 Maternal Collapse.................................................................................................................................................................................. 310

Michael Permezel CHAPTER 38 Obstetric Analgesia and Anaesthesia...............................................................................................................................................315

Richard Hiscock

Section 2.7.4  The Puerperium and Lactation CHAPTER 39 The Physiology of the Puerperium and Lactation...................................................................................................................... 323

Elizabeth Anne McCarthy CHAPTER 40 Normal Postpartum Care..................................................................................................................................................................... 329

Elizabeth Anne McCarthy CHAPTER 41

Puerperal Disorders...............................................................................................................................................................................335 Elizabeth Anne McCarthy

Section 2.7.5  Global Women’s Health and Indigenous Women’s Health CHAPTER 42 Maternal and Perinatal Mortality and Morbidity and Global Reproductive Health....................................................... 340

Laurel Bennett CHAPTER 43 Australian Indigenous Women’s Health in Pregnancy..............................................................................................................345

Jacqueline Boyle and Marilyn Clarke

Section 3  Gynaecology

Section 3.1  Gynaecological Assessment CHAPTER 44 Gynaecological History and Examination...................................................................................................................................... 353

Emma Readman and Kate McIlwaine

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Contents

CHAPTER 45 Gynaecological Investigations............................................................................................................................................................358

Kate McIlwaine and Emma Readman

Section 3.2  Menstrual Disorders CHAPTER 46 Paediatric and Adolescent Gynaecology......................................................................................................................................... 372

Sonia Grover CHAPTER 47 The Menstrual Cycle and Menstrual Disorders........................................................................................................................... 377

Carol Vance

Section 3.3  Reproductive Endocrinology and Infertility CHAPTER 48 Infertility.................................................................................................................................................................................................. 401

Sameer Jatkar CHAPTER 49 Amenorrhoea, Hyperprolactinaemia and Ovulation Induction...............................................................................................414

Sameer Jatkar CHAPTER 50 Androgen Excess, Including PCOS, Hirsutism and Acne......................................................................................................... 425

Chris Russell

Section 3.4  The Menopause CHAPTER 51

The Menopause, Climacteric and Hormone Replacement Therapy......................................................................................434 Michael Rasmussen, Samantha Mooney and Michael Permezel

Section 3.5  Sexuality CHAPTER 52 Normal Sexuality, Sexual and Relationship Dysfunction, and Sexual Assault...................................................................441

Patricia Moore

Section 3.6  Contraception, Sterilisation and Abortion CHAPTER 53 Contraception, Sterilisation and Abortion......................................................................................................................................451

Patricia Moore CHAPTER 54 Genital Tract Infections.......................................................................................................................................................................466

Kathryn Anne Cook

Section 3.7  Urogynaecology CHAPTER 55 Pelvic Organ Prolapse...........................................................................................................................................................................483

Julio Alvarez and Peter Dwyer CHAPTER 56 Urinary Incontinence........................................................................................................................................................................... 492

Kristina Cvach and Peter Dwyer

Section 3.8  Pelvic Pain and Endometriosis CHAPTER 57 Pelvic Pain................................................................................................................................................................................................505

Lenore Ellett and Peter Maher CHAPTER 58 Endometriosis..........................................................................................................................................................................................513

Peter Maher and Lenore Ellett

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Contents

Section 3.9  The Breast CHAPTER 59 Breast Disorders...................................................................................................................................................................................... 521

Antonia McLaren Jones

Section 3.10  Neoplasia and Other Lumps CHAPTER 60 Benign and Malignant Disorders of the Vulva and Vagina......................................................................................................536

Ross Pagano CHAPTER 61

Benign and Malignant Disorders of the Cervix...........................................................................................................................545 Jeffrey Tan

CHAPTER 62 Benign and Malignant Disorders of the Uterus, and the Pelvic Mass.................................................................................. 563

Michael Quinn and Adam Pendlebury CHAPTER 63 Benign and Malignant Disorders of the Ovary and the Fallopian Tube...............................................................................572

Vivek Arora

Section 4  Neonatology CHAPTER 64 Neonatal Physiology: Adaptation and Resuscitation..................................................................................................................584

Kypros Kyprianou CHAPTER 65 Routine Neonatal Care......................................................................................................................................................................... 592

Kypros Kyprianou CHAPTER 66 Assessment of the Neonate................................................................................................................................................................ 597

Kypros Kyprianou CHAPTER 67 Neonatal Feeding and Nutrition........................................................................................................................................................ 617

Kypros Kyprianou CHAPTER 68 Neonatal Jaundice.................................................................................................................................................................................. 628

Kypros Kyprianou CHAPTER 69 Neonatal Neurological Presentations...............................................................................................................................................636

Kypros Kyprianou CHAPTER 70 Neonatal Respiratory Distress...........................................................................................................................................................643

Kypros Kyprianou CHAPTER 71

The Small for Gestational Age and Large for Gestational Age Neonate...............................................................................651 Kypros Kyprianou

CHAPTER 72 Neonatal Infection................................................................................................................................................................................. 655

Kypros Kyprianou CHAPTER 73 Congenital Malformations.................................................................................................................................................................. 662

Kypros Kyprianou CHAPTER 74 Neonatal Haematology..........................................................................................................................................................................675

Kypros Kyprianou CHAPTER 75 The Preterm Neonate and Perinatal Transport........................................................................................................................... 680

Kypros Kyprianou

Index.............................................................................................................................................................................................................................. 693

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FOREWORD Since the third edition of Obstetrics and the Newborn was published in 1997, there have been enormous changes in the practice of care before, during and after pregnancy, and in gynaecological management of both pre- and postmenopausal women. Routine investigations are more numerous and sophisticated. Caesarean section rates have doubled, but the image of delivery of a healthy infant remains the greatest experience patients will enjoy in their journey through life. Cooperation between carers, midwives, medical officers, and both clinical and laboratory scientists remains an important requirement. Likewise, in gynaecology the number of subspecialties has increased and marvellous new technology and investigative procedures have altered the techniques of surgical procedures. A new range of drugs have given respite from infertility, and improved chemotherapy has significantly advanced the treatment of gynaecological cancers. Unusually, this volume combines the disciplines of obstetrics, neonatal medicine and gynaecology into a single source that facilitates learning for medical students, midwives and postgraduates. This creates harmony, from adolescent gynaecology through to reproductive life and the management of pregnancy, and finally the gynaecological problems of the postmenopausal woman. This volume contains a unique collection of photographs taken many years before restrictions in teaching hospitals, which have now made collecting clinical photographs more difficult. In my view there are no more appealing medical occupations available than the practice of obstetrics, neonatal care and all aspects of gynaecology. It should not be overlooked that in spite of modern changes in practice, the vast majority of women—with conventional methods of support—continue to have a normal labour with spontaneous delivery of a normal, healthy infant. We practitioners should aim to be the custodians of normality. Norman Beischer AO, MD, MGO, FRCS(Ed), FRCOG, FRACS, FRACOG, DMedSci(Hon)

x

PREFACE A love of face-to-face teaching led the authors into their respective academic careers. There are few experiences more exhilarating than seeing not just knowledge but also clinical reasoning being passed to a subsequent generation of students, residents or registrars. Assessment tasks for both undergraduate and postgraduate courses make much of assessing cognitive skills rather than knowledge. However, knowledge is the key ingredient from which the competent clinician conjures the recipe for expert care. Reasoning without a knowledge base is like building with substandard materials: the product may seem good at first, but will not last a lifetime along the clinical journey. This book is for the student who has a genuine interest in women’s health and neonatal paediatrics. While previous editions have been directed largely to the medical undergraduate, this edition will find a place on the bookshelves of the postgraduate preparing for the diploma of obstetrics and gynaecology, the general practitioner with an interest in women’s health, the nurse-midwifery student, and the pre-vocational doctor or new trainee who is preparing for a career in women’s health. This reminds us that if we are to be any good, we will indeed be medical students our whole lives. This book is an evidence-based textbook in obstetrics, gynaecology and neonatal paediatrics. It is more than just lists of referenced facts; sometimes evidence does come from a randomised controlled trial, and the various landmark trials are referenced where appropriate. However, clinical management is often dictated by a thorough understanding of the underlying pathophysiology. It is this deeper knowledge that underpins a lifetime of good clinical care. Our forebears knew it well, spending years on the basic biological sciences before following the clinical sciences and then clinical medicine. This book is about giving an understanding to clinical management. Many of the chapters discuss the non-pathological process of obstetric care and an appreciation of the normal transition to extrauterine life. Modern medicine allows us to better prepare for deviations from this otherwise natural process of pregnancy, gestation and birth. This book aims to clearly differentiate the normal from the pathological. Lastly, from before a newborn enters the world, parental expectations, experiences, dreams and anxieties will shape how families prepare for and adapt to their newborn child. Many of the common issues encountered are variations of normal, and hence this requires recognition by a confident and competent clinician to appropriately reassure families. Similarly, the recognition of the abnormal or pathological process before, during and after birth will allow for the appropriate assessment and management of both mother and baby.

xi

ACKNOWLEDGEMENTS Professor Norman Beischer died on 2 February 2015, as this book came to fruition. Along with his colleague editors of the first three editions of the book, particularly Professor Eric Mackay, he embodied a commitment and passion for teaching students of both obstetrics and midwifery that is—to this day perhaps—unequalled. His example is the inspiration for this latest edition. We have been very fortunate to have parents with a strong commitment to education, unending patience and a determination to give their children every opportunity. Each has had their particular professional, clinical and academic mentors. While we cannot acknowledge all those who guided us, we would particularly like to recognise the absolutely inspiring Sir Lance Townsend, Roger Pepperell, Christopher Targett, Graeme Ratten and all those others who, by their own example, showed us how to practise and teach. Such teachers and mentors cross our paths, often unexpectedly, throughout our journey from student to practicing clinician. These connections are truly priceless; the sharing of wisdom in a spirit of trust, warmth and generosity. These moments of inspiration shape us as doctors: they unite us, keep us grounded, remind us of the humanity of our work, encourage us to teach and allow us to directly contribute to the health and wellbeing of women, their children and their families. Teaching is a privilege and we have had the great fortune to see many of our wonderful students become our residents, then registrars and finally consultant colleagues. Some have authored chapters of this book but all those we have taught have, in truth, also taught us so much. Consultant colleagues—past and present—at the Mercy Hospital for Women and the Royal Women’s Hospital in Melbourne have authored almost all of the women’s health content of this book. Many did so while balancing incredibly demanding clinical schedules. We are extremely grateful to all of them. A textbook of this size is a monumental and time-demanding task. Nothing would be possible without the support and understanding of our families. Yet another evening passes: ‘The book?’ ‘Yes.’ An understanding life partner is priceless.

xii

LIST OF EDITORS Michael Permezel MD, MRCP(UK), MRCOG, FRANZCOG Professor of Obstetrics and Gynaecology, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia

Kypros Kyprianou MBBS, FRACP Paediatrician, Royal Children’s Hospital, Werribee Mercy Hospital, Epworth Freemasons Hospital and University of Melbourne, Melbourne, Victoria, Australia

Susan Walker MD, DDU, CMFM, FRANZCOG Professor of Maternal Fetal Medicine, Director of Perinatal Medicine, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia

xiii

LIST OF CONTRIBUTORS Julio Alvarez U MD Urogynaecolgy Consultant, Hospital Padre Hurtado, Santiago, Chile; Assistant Professor, Universidad del Desarrollo, Concepción, Chile Vivek Arora MBBS, MD, DNB, FRANZCOG, CGO Consultant Gynaecologic Oncologist, Royal Women’s Hospital and Western Health, Melbourne, Victoria, Australia Laurel Bennett MBBS, FRANZCOG Consultant Visiting Medical Officer, Northeast Health Wangaratta, Wangaratta, Victoria, Australia Jacqueline Boyle MBBS, FRANZCOG, MPH&TM, PhD Senior Staff Specialist, Monash Health, Clayton, Victoria, Australia; Head of Indigenous and Refugee Women’s Health Research, Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia Marilyn Clarke MBBS(Class II Hons), GradDipClinEpi, FRANZCOG Staff Specialist, Department of Obstetrics and Gynaecology, Grafton Base Hospital, Grafton, New South Wales, Australia

Alison Fung MBBS, FRANZCOG, CMFM, DDU Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia Megan Galbally MBBS, MPM, PhD, FRANZCP Head of Unit and Consultant Psychiatrist, Mercy Hospital for Women, Melbourne, Victoria, Australia Sonia R Grover MBBS, FRANZCOG, MD Clinical Professor, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; Director, Department of Paediatric and Adolescent Gynaecology, Royal Children’s Hospital, Melbourne, Victoria, Australia; Unit Head, Consultant Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia; Head of Family Planning Service, Consultant Gynaecologist, Austin Health, Melbourne, Victoria, Australia; Research Fellow, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Richard Hiscock MBBS, FANZCA Senior Consultant Anaesthetist, Mercy Hospital for Women, Melbourne, Victoria, Australia

Kathryn Anne Cook MBBS, FRANZCOG, FACSHM Obstetrician and Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia; Sexual Health Physician, Melbourne Sexual Health Centre, Carlton, Victoria, Australia

Lisa Hui MBBS, PhD, GradCertClinEpi, FRANZCOG, CMFM, DDU Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia; Senior Clinical Lecturer, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia

Kristina Cvach MBBS, MPHTM, FRANZCOG, CU Consultant Urogynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia

Neil Israelsohn MBBS(Hons), FRANZCOG Consultant Obstetrician and Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia

Megan KW Di Quinzio MBBS, MD, FRANZCOG Obstetrician Gynaecologist, Mercy Hospital for Women, Melbourne, Victoria, Australia

Sameer Jatkar MBBS(Hons), BA, MSc, MRMed, FRANZCOG Fertility Specialist, Monash IVF, Clayton, Victoria, Australia; Visiting Medical Officer, Monash Health, Clayton, Victoria, Australia

Peter L Dwyer FRANZCOG, FRCOG, CU Head of Urogynaecology Department, Mercy Hospital for Women and University of Melbourne, Melbourne, Victoria, Australia

Antonia McLaren Jones MBBS, BMedSci Fellow in Gynaecological Oncology, Mercy Hospital for Women, Melbourne, Victoria, Australia

Lenore Ellett MBBS(Hons), FRACGP, FRANZCOG Consultant Obststrician and Gynaecologist, Visiting Medical Officer, Mercy Hospital for Women, Melbourne, Victoria, Australia

Peter J Maher MBBS, FRCOG, FRACOG Director, Department of Endosurgery, Mercy Hospital for Women, Melbourne, Victoria, Australia; Clinical Professor, University of Melbourne, Melbourne, Victoria, Australia

Julia Francis MBBS(Hons) Obstetrics and Gynaecology Registrar, Mercy Hospital for Women, Melbourne, Victoria, Australia

xiv

Elizabeth Anne McCarthy MBBS, BMedSc, MD, FRANZCOG, CMFM, GradCertBiostatsEpi, DDU Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia; Senior Lecturer, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia

Michael John Rasmussen MBBS, MRCOG, FRANZCOG Consultant Obststrician and Gynaecologist, Clinical Director of Women’s and Children’s Health, Mercy Public Hospitals Inc., Melbourne, Victoria, Australia; Clinical Director of Gynaecology, Mercy Hospital for Women, Melbourne, Victoria, Australia

Kate McIlwaine MBBS(Hons), FRANZCOG Consultant Gynaecologist, Department of Endosurgery, Mercy Hospital for Women, Melbourne, Victoria, Australia

Emma Readman MBBS, FRANZCOG Consultant Gynaecologist Head of Unit, Mercy Hospital for Women, Melbourne, Victoria, Australia

Samantha Mooney MBBS(Hons), MRepMed, DRANZCOG Registrar, Mercy Hospital for Women, Melbourne, Victoria, Australia

Chris Russell MBBS, FRANZCOG Visiting Medical Specialist, Mercy Hospital for Women, Melbourne, Victoria, Australia

Patricia Moore MBChB, FRANZCOG, BA, PostgradDipBioethics Consultant Gynaecologist, Head of Early Pregnancy Services Unit, Royal Women’s Hospital, Melbourne, Victoria, Australia; Sessional Gynaecologist, Paediatric and Adolescent Gynaecology Unit, Royal Children’s Hospital, Melbourne, Victoria, Australia

Alexis Shub MBBS, FRANZCOG, PhD Specialist in Maternal Fetal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia; Senior Lecturer, University of Melbourne, Melbourne, Victoria, Australia

Ross Pagano MBBS, FRCOG, FRANZCOG Consultant Gynaecologist, Head of Vulvar Disorders Clinic, Royal Women’s Hospital, Melbourne, Victoria, Australia Gillian Paulsen MBBS(Hons), MPH, FRANZCOG Consultant Obstetrician, Mercy Hospital for Women and The Northern Hospital, Melbourne, Victoria, Australia; Clinical Lecturer, University of Melbourne, Melbourne, Victoria, Australia Adam Pendlebury MBBS, BMedSci, FRANZCOG Gynaecological Oncology Fellow, King Edward Memorial Hospital, Subiaco, Western Australia, Australia

Martien Snellen MBBS, MPM, FRANZCP Senior Perinatal Psychiatrist, Mercy Hospital for Women, Melbourne, Victoria, Australia Jeffrey Tan MBBS, MRCOG, FRANZCOG Consultant Gynaecologist, Oncology and Dysplasia Unit, Royal Women’s Hospital, Melbourne, Victoria, Australia Carol Vance MBBS, FRANZCOG Obststrician and Gynaecologist, Visiting Medical Officer, Mercy Hospital for Women, Melbourne, Victoria, Australia Peter Wein MBBS, FRANZCOG, GradDipEpidemBiostat Clinical Associate Professor, University of Melbourne, Melbourne, Victoria, Australia; Consultant Obstetrician, Mercy Hospital for Women, Melbourne, Victoria, Australia

Michael A Quinn AM, MBChB, MGO, MRCP, FRCOG, FRANZCOG, CGO Professor of Gynaecological Oncology, Royal Women’s Hospital and University of Melbourne, Melbourne, Victoria, Australia

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LIST OF REVIEWERS Donald Angstetra BSc(Med), MBBS, FRANZCOG Staff Specialist, Gold Coast University Hospital, Southport, Queensland, Australia; Senior Lecturer, Griffith University, Nathan, Queensland, Australia

Elizabeth Hurrion BMedSci, MBChB, MRCPCH, FRACP, GradDipClinEpid Senior Staff Specialist Neonatology, Mater Mothers’ Hospital, Brisbane, Queensland, Australia

Roland Broadbent MBChB, FRACP Associate Professor, Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand; Clinical Leader, Neonatal Services, Southern District Health Board, Dunedin, New Zealand

Linda McLaughlin BSc, MBBS, FRACP Neonatology Fellow, Mater Mothers’ Hospital, Brisbane, Queensland, Australia

Michael Carrette MBBS, FRANZCOG Senior Lecturer, Reproductive and Neonatal Health, James Cook University, Cairns, Queensland, Australia Vicki Clifton PhD NHMRC Senior Research Fellow, University of Adelaide, Adelaide, South Australia, Australia; Associate Professor, Conjoint Associate Professor, University of Newcastle, Callaghan, New South Wales, Australia; Editor, Placenta; Director of Clinical Research Development, Lyell McEwin Hospital, Adelaide, South Australia, Australia Girish Deshpande FRACP, MSc Staff Neonatologist, Nepean Hospital, Penrith, New South Wales, Australia Warwick Giles MBBS, FRANZCOG, DDU, PhD, CMFM, OAM Conjoint Professor, Faculty of Medicine, University of Newcastle and University of Sydney, Sydney, New South Wales, Australia

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Roger A McMaster-Fay MBBS, MRCOG, FRANZCOG Clinical Lecturer, Central Clinical School, University of Sydney, Sydney, New South Wales, Australia John Pardey MBBS, FRCOG, FRANZCOG Clinical Director, Women’s Health, Nepean Blue Mountains Local Health District, Penrith, New South Wales, Australia Karen Simmer PhD, FRCAP, FRCPCH Director, NICU, King Edward Memorial Hospital and Princess Margaret Hospitals, Subiaco, Western Australia, Australia; Professor Newborn Medicine, University of Western Australia, Crawley, Western Australia, Australia; Co-Director, NHMRC Centre of Research Excellence for Preterm Infants, Crawley, Western Australia, Australia Mariana S Sousa MD, PhD candidate University of New South Wales, Randwick, New South Wales, Australia

Section 1 ANATOMY AND PHYSIOLOGY Chapter 1

Reproductive anatomy and physiology

Chapter 2

Anatomy and physiology of pregnancy

Chapter 1  REPRODUCTIVE ANATOMY AND PHYSIOLOGY Peter Wein and Michael Permezel

KEY POINTS The anatomy and physiology of the female reproductive system can be understood in terms of its most important function, that of enabling conception, pregnancy and childbirth. The reproductive system plays other important roles in human physiology including sexual function, and through ovarian hormones which affect the tissues of the pelvic floor, bone density, vasomotor symptoms, lipid profile and cardiovascular health. The menstrual cycle should be viewed from four perspectives: hypothalamo-pituitary gonadotrophin secretion; ovarian follicular development and luteinisation; oestrogen and progesterone levels; and the endometrium. The following are the four phases of the menstrual cycle in succession. ■ Follicular phase: rising follicle-stimulating hormone (FSH), follicular development, rising oestrogen, endometrial proliferation. ■ Ovulatory phase: luteinising hormone (LH) surge, ovulation, luteinisation of the follicle, initiation of progesterone production, endometrial transition from proliferative to secretory. ■ Luteal phase: FSH and LH support, corpus luteum development, oestrogen and progesterone production, secretory endometrium. ■ Menstrual phase: declining LH resulting in luteolysis in the absence of a pregnancy, falling progesterone initiating endometrial shedding through ischaemic necrosis. The phases of sexual endocrinology extend from prepuberty (low levels of both gonadotrophins and sex steroids), through puberty (rising gonadotrophin and sex steroid levels), reproductive life (menstrual cycle, pregnancy or lactation), the climacteric (rising gonadotrophins, falling sex steroids) and postmenopause (high gonadotrophins, low sex steroids). For conception to occur, the fertilising spermatozoon and ovum must meet, and this usually occurs in the outer end of the uterine tube mid-cycle. The development of the mature sperm and ovum (spermatogenesis, oogenesis) is the result of a complex series of hormonal interactions between the hypothalamus, pituitary gland and gonad.

REPRODUCTIVE ANATOMY

Mons pubis

EXTERNAL GENITALIA

The mons pubis is a fibrofatty cushion lying anterior and superior to the junction of the two pubic bones (symphysis pubis). It is covered by hair, the distribution of which is gender-specific. In females, usually there is no extension upwards onto the abdominal wall.

The external genitalia are those structures visible on inspection. The different structures are shown in Figure 1.1.

Chapter 1  Reproductive Anatomy and Physiology

Sacrum Fallopian tube

Ureter

Ovary Round ligament

Uterus

Bladder

Posterior fornix

Pubis

Rectovaginal pouch of Douglas

Uterovesical pouch Cervix Urethra

Rectum and anal canal

Vagina

Perineal body Rectovaginal septum

FIGURE 1.1 

Midline view of the pelvic organs. The uterus is in the usual position of anteversion. Source: Courtesy of Prof. Norman Beischer.

Labia majora

Vestibule

The hair-covered, fibrofatty folds that extend from the mons above to the perineum below are the labia majora. They have both sweat and sebaceous glands, and are homologous with the scrotum in the male.

The vestibule comprises the area enclosed by the labia minora. The urethra and vagina open into it, as do the paired Bartholin’s and Skene’s ducts. It represents the lower portion of the embryological urogenital sinus.

Labia minora

Urethral meatus

The labia minora are enclosed by the labia majora and are smaller and more delicate than the labia majora. They are pink in colour and devoid of hair, but contain sebaceous glands and a few sweat glands. They are vascular rich and nerve endings are plentiful. Superiorly, they enclose the clitoris; inferiorly, they merge to form the fourchette, or posterior ring, of the vaginal introitus.

The external urinary orifice is situated 1 to 1.5 cm below the clitoris. It is often covered by the folds of the labia minora, which must be separated to expose it (e.g. for passing a catheter, as shown in Fig 1.2).

Clitoris The clitoris is the homologue of the male penis. It is composed of a vascular plexus (erectile tissue) arranged in a central corpus with two crura which are attached to the inferior rami of the pubis. The clitoris measures 1.5 to 2 cm in length, the terminal 0.5 cm being called the glans. The folds of the labia minora sweep upwards to enclose the clitoris, forming the prepuce above and the frenulum below.

Paraurethral ducts The paraurethral ducts (Skene’s ducts) come from the paraurethral glands (which have a lubricating function). Their tiny openings usually can be seen just below and beside the urethra.

Vaginal orifice The vagina opens onto the lower part of the vestibule. Before puberty, the orifice is closed by the hymenal membrane, which may have one or more small orifices in it. During reproductive life, the hymen is broken down and the interior of the lower vagina is visualised when the 3

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

A

B

FIGURE 1.2 

Technique of catheterisation. A The labia minora are separated to expose the urinary meatus. The vagina often has many folds (rugae) which simulate the urinary orifice. This woman has large thin labia, a relatively large clitoris and a patulous vagina. B A primigravida being catheterised preparatory to caesarean section. Note the sebaceous glands on the perineum, small thick labia minora and hence easy identification of the urinary meatus. Source: Courtesy of Prof. Norman Beischer.

labia are parted. The remnants of the hymen are visible around the vaginal orifice.

Bartholin’s ducts Bartholin’s ducts open onto the vestibule at its posterolateral aspect, just outside the hymen (Fig 1.3). The ducts are 1.5 to 2.0 cm long and run up to the paired Bartholin’s glands, which are situated posterolaterally (5 and 7 o’clock) above the constrictor muscles of the vagina (bulbocavernosus). The glands are pea-sized and are responsible for lubricating the introitus during sexual intercourse. Badly placed episiotomy incisions will either sever the ducts or involve them in the subsequent repair or fibrous scarring.

Perineum The area of the perineum is outlined by the vaginal fourchette anteriorly and the anus posteriorly (Fig 1.1). Deep to it is the perineal body, which lies between the anal canal 4

and the lower third of the posterior vaginal wall (Fig 1.4). It is this area that is incised in an episiotomy, where the introitus is enlarged to facilitate the birth of the baby or where lacerations can occur during the birth process.

INTERNAL GENITALIA Vagina The vagina is a musculomembranous tube which links the uterus to the vestibule. It is 8 to 12 cm in length and, in the resting state, the walls are opposed. It is capable of remarkable distension during the process of childbirth. Anteriorly, the vagina is close to the base of the bladder and the urethra, and posteriorly, to the pouch of Douglas, rectum and anal canal (Fig 1.4). If overdistension of the vagina occurs during childbirth, the fascial supports (vesicovaginal and rectovaginal septa) separating the vagina from the bladder and rectum tear, usually in the midline, allowing prolapse to occur (cystocele, urethrocele, rectocele).

Chapter 1  Reproductive Anatomy and Physiology

Dorsal vein of clitoris Bulbocavernosus muscle External urinary meatus

Perineal Internal pudendal

Veins

Vagina

Bulb of vestibule

Posterior fourchee

Bartholin’s gland and duct

FIGURE 1.3 

The bulbocavernosus muscles form a sphincter around the vagina, enclosing the vascular bulb of the vestibule in which the Bartholin’s gland is embedded posterolaterally. Source: Beischer NA, Mackay EV. Care of the pregnant woman and her baby. Artarmon: W.B. Saunders, 1978.

The lining of the vagina is thrown into folds like a concertina (allowing for expansion during childbirth) and these are known as rugae. The vagina has a stratified squamous epithelial lining, but no glands. Its moisture is provided chiefly by the secretion of the cervical mucous glands and, at the time of coitus, by vaginal transudation. When under the influence of oestrogen (i.e. during the reproductive years and especially during pregnancy), the vaginal squamous cells contain considerable glycogen that allows free growth of lactobacilli, which are normal inhabitants of the vagina. Since these organisms produce lactic acid, the pH of the vagina is acid (4.0 to 5.5) and this minimises the risk of ascending infection by other organisms to the endometrium, uterine tubes or peritoneal cavity. The uterine cervix projects into the upper 1 to 2 cm of the vagina, outlining the four fornices: anterior, posterior and lateral (left and right). The vagina passes through the muscular pelvic diaphragm. The muscles comprising the superficial perineal compartment join behind the vagina to form the perineal body (Fig 1.4).

Uterus The uterus has the critical role of housing and nurturing the embryo and fetus from implantation until birth. It is composed of two functional parts: a lower third that forms the uterine cervix and the upper two-thirds that form the uterine body. The non-pregnant adult uterus measures approximately 7.5 × 5.0 × 2.5 cm with a cavity length of approximately 6 cm. The uterine cervix has both vaginal and supravaginal components. The cervix is a strong pivotal point for

Clitoris 1 Ischiocavernosus

Vagina

2 Superficial transverse perineal

Bulb of vestibule

3 Levator ani pubococcygeus iliococcygeus 4 External anal sphincter 5 Gluteus maximus

Site of Bartholin’s gland Pudendal vessels Ischial tuberosity Perineal body

FIGURE 1.4 

Muscles of the perineum. 5

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

uterine stability, being attached to the pelvic walls by radiating fascial condensations called ligaments: pubocervical anteriorly, uterosacral posteriorly and transverse cervical (‘cardinal’) ligaments laterally. The cervix is delineated inferiorly by the external os and superiorly by the internal os. The shape of the external os is spherical in the nullipara, but usually transverse and more gaping in the multipara. In the latter, the reddish columnar epithelium lining the canal may be seen (perhaps exaggerated by ectropion formation), and also the small orifices of the cervical mucous glands. When the ducts of these glands are blocked by inflammation or scar tissue, small retention cysts form and these are obvious on the surface as nabothian follicles.

Uterine body The uterus is a hollow, muscular organ, the interior being roughly triangular in shape. The upper angles of the triangle are formed by the interstitial portions of the uterine tubes. The uterus is covered externally by the peritoneum, except the lower part anteriorly, where the peritoneum is reflected onto the bladder. It is at this loose attachment that the incision is made in a lower uterine segment caesarean section. The lower uterine segment lies at the junction of the uterus and cervix and while very narrow in the non-pregnant state, it expands during the third trimester of pregnancy and further in labour to some 10 cm in length. The uterus is globular in shape, but flattened in the anteroposterior direction. Normally, it is both anteverted (rotated forwards) and anteflexed (bent forwards on itself). In some 20% of women, the uterus is rotated backwards, lying more in relation to the rectum than the bladder. It is in this group that the rare complication of incarceration of the uterus occurs late in the first trimester of pregnancy, the enlarging uterus being caught in the hollow of the sacrum. The uterus is formed by the fused distal portions of the Müllerian ducts, the former the unfused proximal portions. Occasionally, evidence of this process going awry can be seen in the various duplications and deletions of the uterus which occur. The structure of the uterus is similar to that of most other hollow muscular organs in the body, although each of the three layers is specialised for the function of childbirth. 1. The endometrium or lining is composed of a columnar epithelium which dips into the submucosa in the form of branched, tubular glands. A feature of the endometrium is the typical coiled arteries, which also are under hormonal influence. They enlarge greatly during pregnancy (especially in the region of the placenta), forming the maternal contribution to the blood supply of the placenta. 2. The myometrium is the middle muscular layer and is composed of several interlacing layers of smooth muscle. During pregnancy, great enlargement of the 6

muscle fibres occurs, ready for the task of expelling the fetus in the process of parturition. In contrast to the uterine body, the cervix is fibromuscular with an approximate muscle mass of only 10%. 3. The serosa over the uterine body is continuous with the loose peritoneal covering the lower uterine segment. The cervix is covered by a serosa posteriorly but anteriorly lies in apposition to the posterior wall of the bladder. The blood supply of the uterus is from the uterine arteries on each side (Fig 1.5). These arise from the iliac arteries and pass down to the junction of cervix and uterus, where the cervical and vaginal branches are given off. The vessels then continue upwards at the side of the uterus in a tortuous manner, necessary to accommodate uterine enlargement during pregnancy, linking up with the ovarian arteries in the upper part of the broad ligament.

Uterine tubes The uterine tubes (also known as the fallopian tubes) are approximately 12 cm in length and act as a conduit for sperm to reach the ovum and for the ovum to transit from the ovary to the uterine cavity for implantation. The tube is composed of four parts: the interstitial part, which runs in the outer ‘cornu’ of the uterus; the isthmic part, a narrow portion comprising the inner one-third adjacent to the uterus; the ampullary part, a gradually widening trumpet-shaped outer third, which ends in a series of finger-like projections (the fimbrial part), which wrap themselves around the ovary at the time of ovulation. The Fallopian tube Uterus

Ovarian artery Round ligament Cervix

Uterine artery Anterior division of internal iliac artery

Azygos vaginal artery

FIGURE 1.5 

Vaginal arteries

Arterial blood supply to the internal genitalia. There is free anastomosis between vaginal, uterine and ovarian arteries. Coiling of vessels allows elongation as the uterus enlarges in pregnancy.

Chapter 1  Reproductive Anatomy and Physiology

inner portion of the tube is very narrow, and the epithelium is thrown up into a complex series of branching folds; hence, there is a strong tendency for blockage to occur should the tube become infected. The tubal epithelium is generously supplied with hair-like processes, called cilia, which beat gently in the direction of the uterine cavity to ‘encourage’ the ovum towards the uterus. Partial obstruction of the lumen or impairment of cilial function may result in implantation of the conceptus in the tube rather than in the uterus: a tubal ectopic pregnancy (see Chapter 8). The tubes lie at the top of the broad ligaments, which are composed of peritoneum, folded over the tubes and round ligaments like sheets on a line.

Round ligaments The round ligaments run from adjacent to the uterine cornua to the internal inguinal ring, which is located around the middle section of the inguinal ligament. They provide some anterior support for the uterus, especially during pregnancy when they enlarge markedly. Stretching may cause discomfort or pain (round ligament strain) which can be appreciated readily by gentle palpation at the sides of the uterus late in pregnancy.

Broad ligaments The broad ligaments are folds of peritoneum, lying between the uterus and the lateral pelvic wall. In the upper part lie the round ligaments and uterine tubes and at the base lie the uterine vessels and ureters. The remainder is taken up by delicate areolar tissue, vessels and nerves. Uterine perforation or rupture may occur into the broad ligament and, similarly, tubal ectopic pregnancy may rupture downwards into it.

Infundibulopelvic ligament As the lateral pelvic wall is approached, the blood vessels supplying the ovary sweep upwards out of the pelvic side-wall into the ovary.

Parametrium The tissue adjacent to the uterus in the base of the broad ligaments is called the parametrium, and is important because it represents one of the pathways in the spread of uterine infection, called parametriti, and also lymphatic spread of carcinoma of the cervix. The parametrium contains embryonic remnants related to the vestigial wolffian system of ducts and tubules from the vas deferens in the male but fail to develop in the female. Where remnants are clinically apparent in the female, they are termed Gartner’s duct cysts and usually lie deep within the anterolateral fornices of the vagina.

Ovaries The ovaries are situated on the back of the broad ligaments and are attached by a mesentery (mesovarium). Each ovary is almond-shaped and measures approxi-

mately 3 cm in length. The ovary has two key and related functions: the production of ova during the woman’s reproductive years and the secretion of gonadal steroid hormones. The ovaries have a yellowish-white irregular surface, often characterised by developing Graafian follicles or active or regressing corpora lutea. The ovarian and infundibulopelvic ligaments have already been mentioned, attaching the ovary to the back of the broad ligament and the pelvic side-wall respectively. In structure, the ovary possesses an outer cortex that contains primordial and developing follicles and specialised connective tissue (theca), and an inner medulla that is mainly composed of loose connective tissue and blood vessels. The blood supply of the ovary comes mainly from the ovarian arteries (which arise from the aorta), aided by the anastomosis with the uterine arteries. There are approximately 2 million primary oocytes during fetal life but a process of atresia means that there are only approximately 300 000 primary oocytes (germ cells) in the ovary at puberty. As there is usually only one oocyte released each month, approximately 1000 oocytes fail to reach maturity each month.

SKELETOMUSCULAR SUPPORTS Supporting the external and internal genitalia are the bony and fibromuscular structures which make up the birth canal.

THE BONY PELVIS This is made up of four bones joined together by ligaments. At the sides are the paired innominate (pelvic) bones. These are joined in front at the symphysis pubis. Behind, they articulate with the ala (or wings) of the sacrum forming the sacroiliac joints (Fig 1.6). The fourth bone, the coccyx, is loosely articulated with the lower border of the sacrum. Both the sacrum and the iliac bones are strong and heavy, since it is through them that the weight of the head and trunk is transferred to the legs. The innominate bone is composed of three separate elements: pubis, ischium and ilium. These ossify in early adulthood. The different parts of the bone are shown in Figures 1.7 to 1.9. The sacrum is composed of five fused vertebrae, and a large intervertebral disc separates it from the fifth lumbar vertebra above. The sacrum is directed backwards as well as downwards, and this throws its superior border into prominence as the sacral promontory. The sacrum is concave on its pelvic aspect, providing in part the characteristic curve of the birth canal. Looking into the pelvis from above, one can ascertain two parts: the false pelvis above and the true pelvis below. These are delineated by the iliopectineal line (Fig 1.6). The false pelvis can be appreciated on lateral view (Fig 1.9) as that part of the pelvis above the pelvic inlet. When viewed from the side (Fig 1.9), it can be seen that the birth canal anteriorly is made up only of 7

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

the symphysis pubis and is quite short (about 5 cm). Posteriorly, there is the sweep of the sacrum and coccyx (about 12 cm) which, when added to the fibromuscular perineal body, describes the curve of the birth canal. The dimensions of the true pelvis can be appreciated by studying three arbitrary planes—the pelvic inlet, the midpelvis and the pelvic outlet—the shape and Sacral promontory

Sacroiliac joint and ligament

dimensions of which are shown in Figures 1.8 and 1.9 and in Table 1.1. Four variations in pelvic shape are recognised (as listed in Table 1.2). Although the names are rarely used in clinical practice, it is helpful to know that an individual pelvis may be unusually wide or narrow in a particular dimension and either shallow or deep. The funnelling of the male pelvis with a narrow outlet relative to the inlet is also of clinical importance. Symphysis pubis

Iliopectineal line

Ischial tuberosity

Coccyx

Coccyx

Ischial spine

Sacrospinous and sacrotuberous ligaments

Sacrospinous and sacrotuberous ligaments

FIGURE 1.6 

The pelvic brim. View from above of a large articulated pelvis. The brim is almost round, the pubic arch is generous and there is minimal projection of the sacral promontory.

Sacrum

FIGURE 1.7 

The pelvic outlet. View of articulated pelvis from below. In order to escape injury, the coccyx must fold backwards during delivery of the head. Pelvic Outlet

Pelvic lnlet

Intertuberous diameter (11.5 cm)

Transverse (13.5 cm)

Anteroposterior (true conjugate) (11.5 cm)

FIGURE 1.8 

Anteroposterior diameter (11.5 cm)

The pelvic inlet and the pelvic outlet. The average dimensions of the inlet and outlet illustrated. 8

Chapter 1  Reproductive Anatomy and Physiology

Pelvic cavity This is the region between the pelvic inlet above and the pelvic outlet below, and is bounded by the pubic bones anteriorly, the curve of the sacrum posteriorly, and parts of all three components of the innominate bone laterally. The pelvic inlet is oval-shaped and wider transversely (Figs 1.6 and 1.8). The midpelvic plane (also known as the narrow pelvic plane) is at the level of the ischial spines. The ischial spines are important landmarks, as indicators of the type of pelvis and its size, but also as reference points for designation of the station of the presenting part. Because they are approximately midway down the birth canal (about 5 cm in the central axis), the head is assumed to be engaged when the vertex has reached this L5

S2

S1

S3 Ischial spine

S4 Plane of pelvic brim

S5

Coccyx Midpelvic plane Plane of pelvic outlet Curve of birth canal

FIGURE 1.9 

Sagittal view of the bony pelvis.

point, since the distance from the vertex of the skull to the maximum diameters of the head (biparietal and suboccipitobregmatic) is slightly less than 5 cm in the unmoulded state. The pelvic outlet is outlined by the subpubic arch, the ischial tuberosities, the sacrotuberous ligaments and the coccyx (Figs 1.7 and 1.8).

Pelvic inclination The lateral view of the pelvis indicates that the pelvic brim makes an angle of approximately 50° with the horizontal; this is called the angle of inclination. The inclination lessens as the birth canal is descended, being about 30° in the midpelvis and 10° at the outlet (Fig 1.9).

The pelvic joints The sacroiliac joints are partly cartilaginous, partly fibrous and are very strong. Despite this, pain is often experienced from approximately 20 weeks’ gestation as joint mobility increases with softening of the ligaments. Note that any weight bearing of the upper body on the legs must pass through the sacroiliac joint. The lumbosacral joint lies between the fifth lumbar vertebra and the sacrum. Because of the backward inclination of the sacrum, considerable strain also occurs here during pregnancy. In extreme cases (spondylolisthesis), the fifth lumbar vertebra projects downwards and forwards into the area of the pelvic brim. The two pubic bones are joined anteriorly at the symphysis pubis by fibrous tissue, although a layer of cartilage remains between them. It is through this cartilage that the operation of symphysiotomy is occasionally carried out in resource-poor settings to increase pelvic diameters to allow vaginal birth in cases of obstructed labour or social dystocia. Occasionally, there is abnormal separation of the pubic bones (pubic symphysis diastasis) in late pregnancy or the early puerperium. The condition is usually self-limiting,

TABLE 1.1  PELVIC MEASUREMENTS (AVERAGE). Antero-posterior diameter

cm

Transverse diameter

cm

Pelvic inlet

Upper symphysis to sacral promontory

11.5

Side to side across pelvic inlet

13.5

Midpelvic plane

Mid-symphysis to S2/S3

11.5

Bispinous

10.5

Pelvic outlet

Lower symphysis to coccyx

11.5

Intertuberous

11.5

TABLE 1.2  CLASSIFICATION OF PELVIS SHAPE. Type

Shape

Depth

Inlet versus outlet

Gynaecoid

Round apart from sacral promontory

Normal

Similar

Anthropoid

Anteroposterior wide, transverse narrow

Deep

Similar

Platypelloid

Anteroposterior narrow, transverse wide

Shallow

Similar

Android

Heart shape (very prominent sacrum)

Normal

Funnelling 9

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spontaneously resolving within weeks of childbirth. The sacrococcygeal joint is less fixed than the other joints, thereby allowing the coccyx to bend backwards as the fetus passes through the birth canal. However, undue displacement may overstretch the ligaments, giving rise to coccydynia (coccygeal pain) during the early puerperium.

Pelvic ligaments These are well developed in the pelvis because of the stresses to which the pelvic bones are subjected. Apart from the ligaments specifically related to the joints mentioned, there are two others of importance: the sacrospinous and sacrotuberous. These run from the sacrum to the ischial spine and ischial tuberosity respectively. Together with the coccyx and lowest part of the sacrum, they form the posterior aspect of the pelvic outlet.

The pelvic soft tissues The bony pelvis is clothed by a number of muscles, the chief of which form the floor of the pelvis and the perineum.

Levator ani The levator ani muscles run on each side from the back of the symphysis pubis and around the lateral pelvic wall on the fascia over the obturator internus muscle to the ischial spine and side of the coccyx, together with the special muscular bundle, the puborectalis. The puborectalis decussates or joins with its opposite number around the vagina and lower rectum. The urethra, vagina and rectum all pass through this muscular diaphragm, which is completed by fascial condensations on its upper and lower surfaces. The muscles of the two sides slope downwards and forwards in the form of a gutter, which assists rotation of the fetal head to occipitoanterior as it strikes against the pelvic floor. The puborectalis is important in helping to maintain closure of the outlet by drawing the different structures passing through it anteriorly towards the shelf of the symphysis pubis.

Urogenital diaphragm The urogenital diaphragm is a triangular-shaped muscular diaphragm through which pass the urethra and vagina. It occupies the space between the inferior borders of the ischiopubic rami (Fig 1.4) and extends posteriorly to the front wall of the rectum. On its deep aspect are two sets of muscles: the constrictors of the urethra and vagina, and the deep transverse perinei. Superficially, there are the ischiocavernosus muscles (passing from the ischiopubic ramus on each side up to the clitoris), the bulbs (erectile tissue) with the associated bulbocavernosus muscles, the superficial perineal muscles and the Bartholin’s glands. Between the vagina and rectum, the superficial and deep perineal muscles, including the anal sphincter, decussate and join to form the strong perineal body. Behind the anal canal, the sphincter muscles decussate to form the anococcygeal raphe. 10

Internal pudendal vessels and the pudendal nerve The internal pudendal vessels and the pudendal nerve pass forwards from the inner aspect of the ischial tuberosity across the fat-filled ischiorectal fossa (which lies between the tuberosity and the rectum) to supply the perineal structures.

REPRODUCTIVE PHYSIOLOGY THE MENSTRUAL CYCLE The menstrual cycle is initiated by the pulsatile secretion of gonadotrophin-releasing hormone (GnRH) from the hypothalamus. This in turn causes the secretion of the two gonadotrophins: follicle-stimulating hormone (FSH) and luteinising hormone (LH) from the anterior lobe of the pituitary gland. FSH and LH act on the ovary to cause follicular growth (especially FSH), ovulation (especially LH) and corpus luteum formation (also LH). They are simultaneously stimulating the secretion of oestrogen from the granulosa cells of the developing follicle (follicular phase of menstrual cycle) and then oestrogen plus progesterone from the lutein cells of the corpus luteum (luteal phase of cycle) (Fig 1.10).

Follicular phase FSH induces secretion of oestrogen by the granulosa cells in the developing follicle. Oestrogen has a growthstimulating effect on the blood vessels, stromal and epithelial cells of the uterine endometrium, producing a proliferative endometrium. There is also a stimulatory effect of oestrogen on the myometrial muscle cells, as well as on the duct tissues of the breast. Oestrogen also causes negative feedback on the hypothalamic–pituitary axis, progressively inhibiting further FSH secretion.

Ovulation Paradoxically. despite the negative feedback of oestrogen on the pituitary, rising oestrogen levels eventually trigger a massive peak of LH (the LH surge), which in turn causes the mature ovarian follicle to release the ovum (ovulation), approximately 30 hours later. Ovulation most commonly occurs on approximately day 14 of a 28-day cycle. The ovum passes into the fimbrial end of the uterine tube to await the potential arrival of ascending spermatozoa.

Luteal phase The space formerly occupied by the ovum is filled with blood and then granulation tissue, and the lining granulosa and theca cells develop under the continued secretion of LH to form the corpus luteum (yellow body). These specialised cells produce the second ovarian hormone, progesterone. Like oestrogen, progesterone has effects on the uterus, breasts and hypothalamic–pituitary system. In the uterus, oestrogen causes proliferation

Chapter 1  Reproductive Anatomy and Physiology

Ovarian cycle

Luteal phase

Follicular phase

Events in the ovary Developing follicle

Corpus luteum Ovulation

80

LH FSH (mU/mL)

LH

Oestradiol

FSH

Progesterone

Inhibin 60

Oestradiol (pg/mL) 40

Progesterone (ng/mL)

1000

10

800

8

600

6

1600

400

4

800

200

2

0

0

Inhibin (ng/mL)

0

20

0

0 Endometrial cycle

2 Menses

4

6

8

10

12

14 Days

Proliferative phase

16

18

20

22

24

26

28–0

Secretory phase

FIGURE 1.10 

Hormonal changes during the menstrual cycle. The menstrual cycle is a cycle of the hypothalamic–pituitary–ovarian axis, as well as a cycle of the targets of the ovarian hormones: the endometrium of the uterus. Therefore, the menstrual cycle consists of both an ovarian cycle (which includes the follicular phase, ovulation and the luteal phase) and an endometrial cycle (which includes the menstrual, proliferative and secretory phases).

Source: Boron WF, Boulpaep EL. Medical physiology updated edition. 2nd edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 55.9.

whereas progesterone causes increased cellular differentiation and inhibits any further proliferation.

Menstrual phase In the absence of fertilisation, falling gonadotrophin secretion from the pituitary causes corpus luteum degradation (luteolysis) with a consequent fall in oestrogen and progesterone menstruation thus ensues. Menstruation is essentially a normal response to progesterone withdrawal from an ‘oestrogen-primed’ endometrium.

Early pregnancy If fertilisation occurs and successful embedding takes place, the chorionic villi which surround the embryo (Fig 1.11) release human chorionic gonadotrophin (hCG). This hCG prevents regression of the corpus luteum, and

ensures that secretion of oestrogen and progesterone continues, allowing the embryo to develop in its endometrial bed (i.e. menstruation is prevented by sustenance of the corpus luteum).

Gametogenesis Gametogenesis is the process whereby the gametes (mature germ cells) are formed in the female and male gonads. Although only one ovum is produced each month compared with millions of spermatozoa in the male, the fundamental process (oogenesis, spermatogenesis) is the same. Essential to the understanding of the early development of the germ cells are: 1. the chromosome structure of the cells; and 2. the two basic forms of cell division. In both the female and male primary germ cells (and, 11

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

Cerebral cortex

Gonadotrophin-releasing factor Hypothalamus Neurosecretory cells to posterior lobe

Pituitary

Hypophyseal portal system to anterior pituitary lobe

Positive feedback

FSH LH

Negative feedback

Corpus luteum

Ovary

Graafian follicle

Uterus Oestrogen

Oestrogen + progesterone

FIGURE 1.11 

Hypothalamic–pituitary–ovarian–uterine interrelationships in the control of ovulation and menstruation. Source: Beischer NA, Mackay EV. Care of the pregnant woman and her baby. Artarmon: W.B. Saunders, 1978.

indeed, in all cells in the body except those gametes about to be joined in the process of fertilisation) there are 46 chromosomes (pairs of chromosomes 1 to 22 either XX or XY). In order for the number of chromosomes to remain constant when the ovum and sperm finally unite, each must shed half its complement. This special type of reduction division is called meiosis, as opposed to the process which occurs at all other times of cell division which is known as mitosis (Fig 1.12). Thus, there are stem cells in the ovary and testis which have the normal number of 46 chromosomes and these divide by ordinary mitosis to produce daughter cells: the primary oocytes and spermatocytes. When these divide by the process of meiosis to form the secondary oocytes and spermatocytes, there are only 22 autosomal chromosomes and 1 sex chromosome (X or Y) to each cell. Each daughter cell has lost half of its genetic 12

Primary oocyte XX First meiotic division

XX X

X

Primary spermatocyte

XY XY

Second meiotic division

X

Y

(First polar body) X Ovum

X

(Second polar body)

FIGURE 1.12 

X

X

Y

X and Y sperm

In normal gametogenesis, the ova all bear an X chromosome while half the spermatozoa bear X and half Y chromosomes.

Y

Chapter 1  Reproductive Anatomy and Physiology

material, but this will be restored when it unites with its partner at the time of fertilisation. It will be apparent that the oogonia (female germ cell) can only produce a daughter cell with an X chromosome, while the spermatogonia (male germ cell) can produce an X or Y spermatozoa. At conception, if the conjunction is XX, a female will result; if XY, a male.

THE PHASES OF REPRODUCTIVE LIFE FROM A SEX HORMONE PERSPECTIVE Prepuberty The hypothalamic–pituitary axis is hypersensitive to the negative feedback of the very low levels of endogenous sex hormones. As a result, the pituitary gonadotrophins (FSH and LH) remain at very low levels and the ovary is not stimulated to produce oestrogen and progesterone. In the absence of significant sex hormones, internal genitalia, external genitalia, breast development and secondary sexual hair remain in an infantile state.

Puberty The hypothalamic–pituitary axis develops progressively decreasing sensitivity to gonadal steroids and the levels of FSH and LH begin to rise which in turn stimulates the ovary to produce first oestrogen and then progesterone when levels are sufficient to induce ovulation.

Reproductive life Menstrual cycles

Pregnancy During early pregnancy, human chorionic gonadotrophin from the trophoblast cells maintains and stimulates the corpus luteum of pregnancy, which maintains oestrogen and progesterone at levels sufficient to sustain the endometrium and developing pregnancy. With establishment of the pregnancy, oestrogen and progesterone are produced by the placenta and the corpus luteum of pregnancy becomes non-essential from about the 13th week of gestation.

The climacteric The climacteric is the period surrounding the cessation of menses (menopause). Largely as a result of progressive attrition of follicles within the ovary, the ovary is depleted of oocytes and becomes increasingly refractory to stimulation by FSH and LH. As a result, the FSH and LH levels begin to rise as there is less negative feedback from the ovarian oestrogen and progesterone.

Postmenopause The ovary no longer has oocytes with their associated granulosa and lutein cells able to produce oestrogen and progesterone. High levels of pituitary gonadotrophins result. The ovarian stromal cells (which have the same embryological origin as granulosa cells) make small amounts of androstenedione that is converted in adipose tissue to oestrone. The oestrone is small in concentration but clinically important in mitigating the adverse effects of hypo-oestrogenism in the postmenopausal female.

The hypothalamic–pituitary axis stimulates the ovary in a cyclical manner. This results in menstrual cycles, most commonly of 28 days duration.

13

Chapter 2  ANATOMY AND PHYSIOLOGY OF PREGNANCY Michael Permezel and Peter Wein

KEY POINTS Following fertilisation in the outer third of the uterine tube, the conceptus reaches the uterine cavity by day 4 and implants at approximately day 6. The fertilised cell (zygote) divides to produce new cells (blastomeres) which form a cluster (morula). When the cluster develops a cavity, it is termed a blastocyst (Fig 2.1A). The various structures of the fetus are derived from three layers—the outer ectoderm supplying the nervous system and the skin, eye and ear; the middle mesoderm supplying the skeleton, muscles, connective tissue, haematopoietic system and urogenital system; and the inner endoderm supplying the gut, liver, pancreas, lungs, thyroid, parathyroid and thymus. The early trophoblast surrounds the embryo and interacts with the maternal spiral arteries, ultimately creating wide vascular channels that are the maternal blood supply of the placenta. The placenta is derived from the trophoblast as a specialised development of the portion that is closest to the underlying uterine decidua. Key functions include gas exchange, nutrient provision, waste product disposal and hormone production.

FERTILISATION The ovum is released into the peritoneal cavity and ‘captured’ by the fimbrial end of the uterine tube. Fimbrial cilia sweep the ovum towards the tubal ostium. Up to 98% of ova reach the uterine tube, demonstrating the efficiency of fimbrial capture and transmission of the ovum. On average, approximately 200 million sperm are ejaculated into the vagina. Only a few thousand will reach the cervical mucus, uterine body and uterine tube where they may have an opportunity to fertilise an ovum. The cervical mucus assists by nourishing the spermatozoa and acting as a place for temporary storage so that spermatozoa can be progressively released over several days. Spermatozoa can survive for up to 5 days in the cervical mucus but the ova can only survive 24 hours without fertilisation. This means that that pregnancy can occur with sexual intercourse up to 5 days before ovulation but only one day after. Transport of spermatozoa through the uterine body and tubes is aided by uterine and tubal contraction stimulated by prostaglandins in seminal fluid

and oxytocin released from the female posterior pituitary during orgasm. Of the approximately 200 million sperm ejaculated, only approximately 50 spermatozoa reach the distal tube. Figure 2.1A illustrates the development of the conceptus in its transition from ovary to implantation. The ovum remains surrounded by the cumulus oophorus, a ‘cloud’ of cells from the follicle that need to be dissolved by the sperm before it must penetrate a thick glycoprotein shell around the egg—the zona pellucida (Fig 2.1B and C). Hyaluronidase and proteolytic enzymes are released from the acrosomal head of the sperm (acrosomal reaction) and assist with this penetration along with mechanical forces related to sperm motility. Within a few minutes of sperm penetrating the zona, the ovum protects itself against the entry of any further spermatozoa (polyspermy). Chemical changes in the ovum cell membrane prevent sperm from binding and cause any bound sperm to fall off. Changes in the zona pellucida make it even more impenetrable to sperm.

Chapter 2  Anatomy and Physiology of Pregnancy

Zygote Zona pellucida

Morula

Inner cell mass

Blastocyst

A

B

Trophoblast

C

FIGURE 2.1 

The early changes in the fertilised ovum before implantation (which occurs on about day 20 of the menstrual cycle). A Diagram of the early changes. B An oocyte just after ovulation; it is surrounded by a clump of follicular cells in a clear, gelatinous matrix—the cumulus oophorus. C An 8-cell embryo with the spherical cells held in close proximity by the zona pellucida. Cell communication between the blastomeres commences at this stage. A few spermatozoa can be seen still adhering to the zona pellucida. Source: B and C from Beischer NA, Mackay EV. Care of the pregnant woman and her baby. Artarmon: WB Saunders, 1978.

15

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Fusion of the cell membranes of the sperm oocyte results in the formation of a single cell. Completion of meiosis within the oocyte is followed by combination of the genetic material from both ovum and sperm. The previously haploid cells, with 23 chromosomes each, now have formed a single nucleus with 46 chromosomes—the zygote.

PRE-IMPLANTATION DEVELOPMENT After formation of the zygote, rapid cell cleavage takes place by mitosis, with each pair of daughter cells (blastomeres) so formed having the 46 chromosomes of the parent blastomere. The blastomeres adhere to each other, eventually forming a cluster of cells termed the morula. This stage is the beginning of differentiation and the cells lose their totipotency (ability to form a complete individual) if separated away from the other cells. On day 4 after fertilisation, the conceptus passes into the uterus and prepares to embed in the endometrium, where it will differentiate and grow over the ensuing 9 months. At this stage, a fundamental change occurs in the cell mass. A fluid space appears and a division occurs into an inner cell mass, which will form the embryo (embryoblast), and an outer trophoblast, which will form the placenta (aided in part by the underlying maternal endometrium). This is the blastocyst and it is in this form that implantation takes place (Fig 2.1 and Table 2.1). Where the cluster of cells completely divides, monozygotic (identical) twinning results. If this occurs at days 1 to 3, the twins are dichorionic diamniotic; if at days 4 to 8, the twins are monochorionic diamniotic; and if at day 9 or longer, monochorionic monoamniotic.

IMPLANTATION Implantation occurs 6 to 8 days after fertilisation once the blastocyst has hatched from the zona pellucida. The primitive conceptus, after contact with the lining of the uterus, erodes through it and sinks into the deeper layers of the endometrium. The smaller blood vessels and the glands provide early nourishment as they interact with the trophoblastic cells over days 10 to 12. The subsequent development of the two elements—the embryo (later termed fetus) and the placenta—will now be considered separately.

EMBRYONIC AND FETAL DEVELOPMENT Table 2.1 lists the key phrases of development from the conceptus shortly after fertilisation through to term gestation. The inner cell mass flattens to form the embryonic disc at the start of the 2nd week after conception. The inner cell mass soon differentiates into three basic layers 16

(ectoderm, mesoderm and endoderm). From the dorsally placed ectoderm will derive the entire nervous system, the skin and the sensory organs, such as the eyes and ears. The intermediate mesoderm will form the bones, muscles, and connective tissue, as well as the vascular and urogenital systems. The ventrally placed endoderm is responsible for the gastrointestinal tract (including derivative organs such as the liver, gall bladder and pancreas), lungs, thyroid, parathyroid glands and thymus. By the 2nd week, the embryonic disc has become elongated and two cavities develop. The amniotic space appears dorsally, above the ectoderm. This space progressively enlarges over the next 10 weeks so that it covers the entire embryo except at one point—the body stalk— where the embryo is attached to the part of the trophoblast that is to form the placenta (Fig 2.2). By the 14th week of pregnancy, the amniotic sac fills the entire uterine cavity, pressing the non-placental trophoblast against the endometrium of the opposite wall. Ventrally, another space appears—the yolk sac—which is formed from endodermal cells. Unlike the amniotic sac, it never attains a large size although it carries out many essential functions prior to effective placental functioning. The extraembryonic coelom is a fluid-filled cavity which arises in the extraembryonic mesoderm surrounding the embryo. It splits the extraembryonic mesoderm into two layers: the somatic mesoderm, which, together with the trophoblast, forms the chorion; and the splanchnic mesoderm, which, with a fold of ectoderm, forms the amnion. The chorion forms a sac inside which the embryo and its amnion are suspended by the body stalk. As indicated earlier, continued growth of the amniotic cavity eventually obliterates this sac. Anomalies in this process of membrane development may present in the form of amniotic sheets or bands. Usually, amniotic sheets are readily visualised on ultrasonography and are harmless. In contrast, amniotic bands can cause a variety of fetal anomalies by hindering normal development (Fig 2.3). Originally, the extraembryonic coelom communicates with a similar but smaller space in the intraembryonic mesoderm—the intraembryonic coelom. As the embryo grows and folds, the two coelomic cavities become separated in the embryo forming the pleural, pericardial and peritoneal cavities. The body stalk provides the connection between the blood vessels of the fetus and those of the trophoblast (which is specialising to become the placenta). As development progresses, great elongation occurs in the stalk and it becomes the umbilical cord, containing the two arteries and a single vein. From weeks 3 to 8, the three embryonic layers progressively differentiate to provide the definitive organs of the body.

ECTODERMAL LAYER The ectodermal cells thicken in the midline to form the primitive streak that is the forerunner of the nervous

Chapter 2  Anatomy and Physiology of Pregnancy

TABLE 2.1  DEVELOPMENT OF THE CONCEPTUS, EMBRYO AND FETUS. Stage

Age*

I

1

Conceptus

Size

Characteristics Blastomeres form from progressive division of zygote to produce the morula (1–3 days), blastocyst (4–6 days) and trophoblast (7+ days).

(mm) II Embryo (5–10 weeks)

2

Inner cell mass differentiates into bilaminar embryonic disc. Primitive amniotic and yolk sac cavities. Trophoblast erodes maternal blood vessels and forms lacunae. Primitive uteroplacental circulation.

3

Chorionic sac measures 1 cm in diameter; villi around whole surface. Well-defined embryonic disc and body stalk. Somites forming. Fetal vascularisation of villi; intervillous space forming. Major developmental activity in nervous system and heart.

4

4–5

Fetal sac 2–3 cm. Somites forming to provide muscles, bones and nerves of trunk. Heart and pericardium prominent. Arm and leg buds forming. Branchial arches (maxilla, mandible, hyoid); otic pit and lens placode present. Adopting C-shaped curvature.

5

10–12

Amnion enveloping fetus and body stalk. Eyes, ears and nasal organs forming. Heart and circulation formed. Differentiation of thyroid gland and special outgrowths from the gut (liver, pancreas, gall bladder). Digital ridges indicate future fingers.

6

20–25

Head is large compared with the rest of the body. Digits well formed. Intestines enter coelom. Ears and eyes developing. Genital tubercle present. Lungs separating from gullet. Fetus begins to move.

7–8

40

Head rounded; eyes and ears still forming. Neck region delineated. Abdominal protrusion less marked. Definitive kidneys starting to develop; separation of urinary and rectal passages is complete; anal membrane ruptures. Facial clefts have closed. Beginning function of special endocrine glands.

(cm) III Fetus (11–40 weeks)

10

8

Ossification centres in most bones. Appearance of nails on fingers and toes. Functioning of nervous system at a primitive level (reflex responses). Teeth are beginning to form. Blood formation transferring from yolk sac and liver to bone marrow.

14

16

Sexual differentiation definite

18

Stage of organ growth rather than differentiation

22

Development occurring in the brain. Progressive budding, leading to maturation and increase in size in the kidneys, lungs and gastrointestinal tract.

26

36

30

42

34

46

38

50

Progressive appearance of centres of ossification, especially at ends of long bones.

*Weeks after conception

system. A longitudinal groove then develops within the primitive streak. Approximation of the edges of the neural groove convert it into the neural tube, which becomes the future spinal canal and ventricular system of the brain. The spinal column, derived from the mesoderm, develops around the neural tube. The cranial portion of the neural tube enlarges to form the brain.

Neuroblasts differentiate to form the white and grey matter of the brain. Primitive nervous reflex activity is seen as early as 8 weeks’ gestation. Whole body movements occur from 10 weeks’. At 17 to 19 weeks’, fetal movements are sufficiently strong to be first perceived by the mother (‘quickening’). The brain is highly susceptible to teratogenic 17

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

Somatic mesoderm

Chorion

Ectoderm Amniotic cavity Gut Fetus

Splanchnic mesoderm

Amnion

Ectoderm Coelom Yolk sac

Splanchnic mesoderm

Body stalk Allantois Endoderm

Placenta

FIGURE 2.2 

Diagram of 21-day embryo (3 weeks after fertilisation is the same as 5 weeks’ gestation in the language of the clinician).

FIGURE 2.3 

Medial view of the left leg of a 2-day-old female infant, a second twin of birth weight 1320 g born by breech extraction. Note gross oedema of the leg below the deep constriction caused by the amniotic band at the level of which were transverse fractures of the tibia and fibula. The fractures healed and the oedema resolved uneventfully after a relieving incision was made over the constriction. The amniotic band syndrome is rare (approximately 1 in 10 000 births). The band forms when the amnion ruptures and rolls into a cord, the fetus lying within the intact chorion.

18

agents, the critical period being from the 10th to the 30th days of embryonic life. Neuronal division occurs from fetal life until approximately 4 years postnatally. The eye develops as an outpouching of the forebrain at the side of the facial cleft. By 6 weeks’ there is a fusing of the optic vesicle and overlying lens placode. The optic vesicle becomes cup-shaped, with the narrow open end forming the pupil. The lens placode differentiates to form the lens. There are two layers: an inner vascularised pigment layer (retina) and an outer fibrous layer (choroid, sclera and cornea). Eyelid folds are fused until the sixth month (Fig 2.4); after the seventh month, the eye will respond to light. At birth, the infant fixes on patterns rather than colours; the optimum focal length is about 30 cm. The eye is highly susceptible to insult between the 18th and 30th days. The ear, like the eye, is a compound development that comes from the first pharyngeal pouch and the otocyst. Development occurs largely over the second half of the embryonic period (4 to 8 weeks’). The ossicles of the middle ear develop from the related mesenchyme, and the central nervous connections are established to the cochlear and vestibular portions. Myelination of auditory fibres occurs from about 24 to 26 weeks’. Sound perception develops slowly over the third trimester; it is geared to the type of noises heard in utero (especially vascular souffles).

MESODERMAL LAYER The mesoderm forms a number of internal structures by processes of proliferation and sculpturing, which are often quite complex. The cardiovascular system is seen initially as a simple network of tubes. In the thorax, the initially straight tube

Chapter 2  Anatomy and Physiology of Pregnancy

FIGURE 2.4 

This 2-day-old infant weighed 270 g at birth at 24.6 weeks’ gestation. She died at 3 days of age. The mother developed preterm premature rupture of the membranes (PROM) at 23 weeks’ gestation after several episodes of threatened preterm labour. Labour occurred 13 days after preterm PROM.

undergoes folding and division. Eventually the heart is formed—with its intricate system of chambers and valves—subserving first the requirements of the fetus where the lungs are by-passed, and later those of the baby, when the pulmonary circulation becomes operational. In the fetus, only 10% of the cardiac output goes to the lungs; of the blood in the descending aorta, 60% goes to the umbilical arteries (and the placenta) and the remaining 40% to the trunk and lower limbs. The heart rate reaches a peak in late embryonic life (approximately 170 bpm) and this slowly decreases to term (approximately 140 bpm). The pressure in the right side of the heart is higher than that in the left side, but this changes rapidly after birth. No nervous tissue is present in the placenta or umbilical cord, so blood flow must be under the control of local autacoids and humoral influences. Active compounds include a number of prostaglandins, angiotensin, bradykinin, serotonin, histamine and acetylcholine. The haematological system first develops in the mesoderm of the yolk sac (weeks 3 to 6), then the liver (weeks 6 to 36), and lastly in the bone marrow (week 20 onwards). Most of the early red blood cells are nucleated (erythroblasts) and contain a different type of haemoglobin. The embryonic haemoglobin gives way to fetal haemoglobin (Hb F) which contains 2 alpha and 2 gamma chains (α2γ2). This is an adaptation to the relative hypoxia of intrauterine life, as is the significantly higher haemoglobin concentrations (approximately 18 g/dL) at birth.

After birth, adult haemoglobin (Hb A), which contains two alpha and two beta chains (α2β2), rapidly increases from approximately 10% of all haemoglobin at birth to approximately 98% during infancy. White blood cells and lymphocytes appear in the peripheral blood late in the first trimester. The white cell count is low early in pregnancy—approximately 1 × 109/L at week 25—but reaches approximately 8 × 109/L at term. Immune globulins are produced after the first trimester, and the presence of an infection in fetal life can be inferred by finding disease-specific immunoglobulin M (IgM) in cord blood. Maternal immunoglobulin G (IgG) traverses the placenta from mother to fetus from about 15 weeks’ gestation and this progressively increases through pregnancy. The urogenital system is derived from swellings on the dorsal body wall. Ridges form and these invaginate to form tubes. The Wolffian is the male accessory duct system and the Müllerian is the female genital system. The gonads are populated by germ cells which have migrated from the primitive yolk sac, and these are juxtaposed to the upper part of the genital ducts. The testis can be distinguished from the ovary by about the 6th week. The luteinising-hormone-like activity of human chorionic gonadotrophin (hCG) is thought to accelerate testicular development, so that by the end of the first trimester fetal testosterone levels are comparable to adult male levels. The kidneys form from metanephric tissue which is invaded by an outpouching of the metanephric duct (the ureteric bud). As with other organs such as the lung and liver, repeated branchings occur until the final units of function are achieved (in this case the nephron, there being 1 million or more in each kidney). At the end of the first trimester, the fetal kidney is able to filter and reabsorb urine, but concentrating ability and acidification is poorly developed until after birth. The bladder forms when the urorectal septum descends and separates the bladder in front from the rectum/anal canal behind. The urethra is formed from grooves which appear on the vulva and close over; the female lacks the penile urethra, the folds remaining open to provide the labia minora. Glomerular filtration and tubular absorption rates are significantly less than in the adult on a surface area basis.

ENDODERMAL LAYER The endoderm becomes enclosed as the embryonic disc folds during the 4th week. The primitive foregut, midgut and hindgut are outlined during the 6th week; the midgut leads to the yolk sac at the umbilicus (Fig 2.2). The gastrointestinal system develops from the elongation and folding of the primitive foregut, midgut and hindgut. The foregut comprises the pharynx, oesophagus, stomach and proximal duodenum. The stomach rotates and its mesenteries form the greater and lesser omentum.

•

19

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•

The midgut extends from the duodenum to the left one-third of the transverse colon. The abdominal bulge seen in the embryo represents the midgut, which is too large to be accommodated in the abdominal cavity and herniates into the umbilical cord from weeks 8 to 12. Occasionally, this persists resulting in an exomphalos. Meckel’s diverticulum indicates the midpoint of the gut. Muscle tissue develops around the endodermal epithelium, and anatomical developments (formation of the appendix and caecum, rotation of the gut) occur in the embryonic period. The fetus swallows amniotic fluid from the end of the first trimester; the amount reaches 50 mL or more per hour in late pregnancy. The hindgut forms the remaining portion of the large bowel. Communication with the allantois ceases at approximately weeks 7 to 8 by the formation of the urorectal septum. Initially there is an occluding membrane or proctodaeum similar to that at the entrance to the foregut (the stomodaeum). This should break down by the end of the 10th week; failure to do so gives rise to the condition of imperforate anus. The respiratory system begins at the 3rd to 4th weeks’ with a tracheobronchial bud from the foregut which grows downwards in relation to the developing heart. There is progressive budding and vascularisation, with air sacs appearing in the terminal branches by about 20 weeks’. There are two types of lining cells: squamous and granular pneumatocytes; the latter, which appear at about the 6th month, produce surfactant that lowers surface tension in the alveolus. Primitive breathing movements can be observed by ultrasound as early as the 12th week of fetal life; they become progressively more frequent, deep and coordinated as gestation advances. The frequency of chest movement is approximately 50 per minute and such activity occupies approximately 50% of any observed time period in late pregnancy. The thyroid, parathyroid and thymus glands are all derived from the pharyngeal pouches over weeks 3 to 5; function usually commences late in the first trimester. The liver bud, which also forms the gall bladder, arises from the first part of the future duodenum. The liver is a comparatively large organ in fetal life, especially during the period of haematopoiesis. Gluconeogenesis occurs from the 10th week and glycogen storage is a feature of late fetal life. Bile formation commences in the fourth month, but many enzyme systems are relatively undeveloped until after birth. The pancreas forms from two buds and the acinar and islet cells develop side by side.

•

3. disposal of waste products back to the mother 4. hormone production. The placenta therefore functions for the fetus as its lungs, alimentary tract, liver and kidneys. To accomplish this effectively, it must bring the circulations of the fetus and mother into intimate contact but in a manner that minimises exposure of the fetus to undesirable chemicals, microorganisms or immunological attack.

PLACENTAL DEVELOPMENT Blastocyst As indicated previously, the mass of dividing blastomeres (the morula) becomes arranged into two groups: a smaller inner cell mass which develops into the embryo and a larger surrounding mass which forms the trophoblast and ultimately the placenta.

Early trophoblast The trophoblastic cells soon differentiate into an inner cytotrophoblast and an outer syncytiotrophoblast (Fig 2.5). The trophoblast invades the stroma and blood vessels in the decidual layer of the endometrium, a process that is critical to the development of a healthy placenta. The large maternal vascular channels supplying the placenta are derived from trophoblastic invasion of the spiral arterioles in the endometrium. Where this process is defective, maternal blood supply of the placenta is reduced and preeclampsia and/or fetal growth restriction may result. The early trophoblast elaborates human chorionic gonadotrophin (hCG) which sustains the corpus luteum in the ovary, thereby maintaining the levels of oestro­gen and progesterone and preventing menstruation. Progesterone

FIGURE 2.5 

THE PLACENTA The placenta has four critical functions: 1. gas exchange 2. provision of nutrients 20

Recently implanted embryo (aged 10 days) obtained at premenstrual curettage for the investigation of infertility. The primitive trophoblast has opened up sinusoids filled with menstrual blood in the endometrium. The inner cell mass has formed (magnification ×100).

Chapter 2  Anatomy and Physiology of Pregnancy

also encourages uterine relaxation, thereby reducing the likelihood that the rapidly expanding conceptus will be expelled by uterine muscular activity.

Formation of villi and the intervillous space From 12 days after conception, the trophoblastic cells send finger-like processes (villi) into the endometrium. Blood-filled spaces (lacunae) appear between the villi (Fig 2.5). In the mesenchymal core of the villi, fetal blood vessels develop and link through the body stalk with the fetal vascular system. By day 18, the villi have branched several times and both fetal and maternal blood vessels are functioning. The fetal vessels are separated from the intervillous blood lakes by the trophoblastic covering; the

fetal circulation is thus a closed one and does not mix directly with the maternal blood. The heart of the embryo starts to beat from approximately day 22 after fertilisation, creating a functional circulation.

Further changes in the trophoblast and decidua Early trophoblastic growth occurred over the entire circumference of the developing pregnancy (Fig 2.6). With further growth, the villi in contact with the deeper part of decidua (decidua basalis) continue to proliferate to form the chorion frondosum, while those in contact with the superficial part (decidua capsularis) atrophy, forming the chorion laeve (Fig 2.7). Thus, the fetal part of the placenta will be formed by the basal chorion frondosum,

FIGURE 2.6 

Complete miscarriage at 8 weeks’ gestation. Villi are present over the entire surface of the chorion. The limbs, eyes and ears have formed, and the abdomen is protuberant. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

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Fetal vein and arteries Chorion frondosum Intervillous space

Decidua capsularis

Chorion laeve

Decidua basalis

Amnion

Basal vein Septum Spiral arteriole Chorionic villi

Myometrium

FIGURE 2.8 

Circulation of the maternal blood around the chorionic villi; the latter are pulsating in the intervillous space due to the pumping of the fetal heart.

FIGURE 2.7 

Stage of development of fetus and placenta at 8 to 10 weeks’ gestation. The amnion lines the chorion laeve and fetal surface of the placenta, and becomes continuous with the epithelial covering of the umbilical cord.

and the maternal part by the decidua basalis subjacent to it. The chorion laeve subsequently loses its villi and becomes the outer layer of the membranes, expanded into the cavity of the uterus by the amniotic membrane which becomes the inner amniotic layer. Fusion of these two layers and obliteration of the uterine cavity occurs at approximately 13 weeks’.

Final development of the placenta By 14 weeks’, the placenta has attained its definitive form and, for the remainder of the pregnancy, the only changes are further branching of the villi and an increase in the intervillous space. The increase in size of the placenta is relatively less than that of the fetus so the fetal:placental weight ratio steadily increases through pregnancy, reaching a value of 6:1 at term. That is, a fetus of birth weight 3600 g at term would have (on average) a placenta of weight of approximately 600 g.

PLACENTAL STRUCTURE Anatomical and functional fetal placental units A schematic cross-section of the mature placenta is shown in Figure 2.8. From the basal area, maternal blood enters 22

the cotyledon via the spiral arterioles. There are approximately 100 such major arterioles supplying the placenta. The blood enters in the form of spurts or jets and cascades down over the villi, which are floating in the intervillous space like seaweed in the ocean. Oxygen and nutrients are provided in exchange for carbon dioxide and waste products from the villi. The deoxygenated blood is carried away by large veins, also situated at the basal area. The cotyledon is the unit of the placenta, and is based on the arteriolar vessels supplying it. Each cotyledon is functionally independent, although there is no clear separation of one from another, except by incomplete septa. The intervillous space is thus potentially traversable throughout the entire placenta. The 10 to 35 apparent subdivisions of the maternal surface of the placenta seen on inspection after delivery are also termed ‘cotyledons’, but are more properly termed lobules or lobes (Fig 2.9). These are anatomical rather than functional divisions, each containing a number of the latter. The mature placenta measures approximately 18 to 20 cm in diameter and its thickness ranges from 1 cm at the edge to 4 cm at the centre. The histological unit of the placenta is the villus. The finer fetal vessels (capillaries) form loops in the connective tissue core of the villus (Fig 2.10). As pregnancy progresses, there is an increase in the size and number of capillaries and, towards term, they lie close to the intervillous space, often with no perceptible trophoblastic cover.

Tissues separating maternal and fetal circulations The tissues separating fetal and maternal blood are cytotrophoblast, syncytiotrophoblast, connective tissue and

Chapter 2  Anatomy and Physiology of Pregnancy

A

B FIGURE 2.9 

The placenta at term. A Fetal surface showing how vessels ramify as they disperse from the insertion of the umbilical cord. They are covered by the glistening, transparent amnion. B Maternal surface showing the usual number (20) of fleshy cotyledons (lobules) packed together. There is no retroplacental clot nor macroscopic evidence of infarction or calcification. Source: Courtesy of Prof. Norman Beischer.

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FIGURE 2.10 

Section of a normal term placenta (magnification ×120). Note the rich vascularity of the villi, the thinness of the trophoblastic covering of the villi and the occasional collections (knots) of the syncytial cells. Source: Courtesy of Prof. Norman Beischer.

A FIGURE 2.11 

the endothelium of the fetal blood vessel. This barrier thins near term, creating increased efficiency in exchange of nutrients, waste products, gases and immunoglobulin between mother and fetus. Oxygen and carbon dioxide pass across the villus membrane. The fetal–maternal pressure gradient for carbon dioxide is quite low (0.9 kPa or 7 mmHg) because of a high diffusibility. The transfer of oxygen to the fetus depends partly on the difference in gradient (7.3 kPa or 55 mmHg), but also on the greater binding capacity of fetal haemoglobin relative to adult haemoglobin. The inner cytotrophoblast is mainly responsible for the production of the hCG and decreases in size as gestation advances and hCG levels decline. The outer syncytiotrophoblast produces oestrogen and progesterone and remains prominent until delivery, although it often becomes quite thinned out or gathered into groups of cells at the periphery of the villi (syncytial knots).

Fetomaternal haemorrhage Where there is a breakdown of the ‘barrier’ between fetus and mother, fetal erythrocytes may enter the maternal circulation. This may be responsible for the development of anti-red cell antibodies in the mother where an antigen is expressed by the fetus and not the mother (see Ch 22).

B

Velamentous insertion of the cord. A This cord inserted 10 cm from the nearest placental edge. The membranes are held to demonstrate the vessels and fetal surface of the placenta. B A bipartite (two-lobed) placenta with velamentous insertion of the cord. Source: Courtesy of Prof. Norman Beischer.

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Chapter 2  Anatomy and Physiology of Pregnancy

Large fetomaternal haemorrhages may cause fetal anaemia, fetal hydrops or even fetal death.

Placental calcification Placental calcification increases towards term and is probably a normal physiological process, since it is not more evident when the infant is stillborn. It is excessive in about 5% of placentas, resulting in a gritty maternal surface. Placental calcification has no well-established relationship with either fetal hypoxia or fetal growth restriction.

THE UMBILICAL CORD FIGURE 2.12 

Vasa praevia from a 28-year-old para 1 admitted with irregular contractions and spontaneous rupture of the membranes at 39 weeks’. Twelve hours later she had a sudden painless haemorrhage (200 mL) and the fetal heart became unrecordable; the cervix was 3 cm dilated. Four hours later she delivered a stillborn infant, birth weight 3390 g. Note velamentous cord insertion and torn vessel adjacent to the hole in the membranes. The perinatal mortality rate is high (50 to 80%) with vasa praevia, even if diagnosed quickly when haemorrhage occurs.

The umbilical cord has two umbilical arteries which carry deoxygenated blood from the fetus to the placenta, and a single umbilical vein which carries the oxygenated blood back to the fetus. It normally inserts towards the centre of the placenta, but may insert near the edge (battledore insertion) or even into the membranes (velamentous insertion) (Fig 2.11). This exposes the fetus to great risk if the path of the vessels lies across the cervical opening (vasa praevia) (Figs 10.3 and 2.12). The median length of the cord is 50 cm. True knots are present in approximately 0.75% of births (see Fig 33.8) but approximately 4% of stillbirths.

Source: Courtesy of Prof. Norman Beischer.

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Section 2 OBSTETRICS Section 2.1

Normal pregnancy

Section 2.2

Problems of early pregnancy

Section 2.3

Prenatal diagnosis

Section 2.4

Obstetric complications

Section 2.5

Medical and surgical disorders in pregnancy

Section 2.6

Common clinical scenarios and presenting problems in pregnancy

Section 2.7

Labour and birth

Section 2.7.1 Normal labour and birth Section 2.7.2 Induction of labour, instrumental delivery and casearean section Section 2.7.3 Intrapartum clinical problems Section 2.7.4 The puerperium and lactation Section 2.7.5 Global woman’s health and Indigenous women’s health

Section 2.1 NORMAL PREGNANCY Chapter 3

The prepregnancy consultation

Chapter 4

The first antenatal visit

Chapter 5

Antenatal care beyond the first antenatal visit

Chapter 6

Obesity and nutrition in pregnancy

Chapter 3  THE PREPREGNANCY CONSULTATION Michael Permezel

KEY POINTS The most important aspect of prepregnancy consultation is ensuring that it actually happens. This will be best achieved by measures that work towards avoiding unplanned pregnancies, seizing opportunities as women present for other reasons and educating women about the importance of the prepregnancy consultation. The first objective of a prepregnancy consultation is to ascertain any problems that may be relevant to a future pregnancy. Routine investigations should include an assessment of rubella immunity (if not already performed), varicella immunity (if uncertain) and a cervical smear (if due). If any issues are discovered, they should be thoroughly assessed (including investigations as needed), treatment optimised for pregnancy and the woman counselled with respect to what to expect in pregnancy. Of paramount importance in the advice to be given is the need for preconceptual folic acid. All women who may conceive should have measures in place to ensure that the developing embryo is not exposed to hazards such as alcohol, teratogenic drugs and radiation.

WHEN TO DO A PREPREGNANCY CONSULTATION? ‘Every woman every time.’ Each visit of a woman of reproductive age to a healthcare provider constitutes an opportunity for a prepregnancy consultation. This should be the case regardless of whether the visit is with a general practitioner or a specialist, and also whether for her or an accompanying child, so that each pregnancy is timed according to the woman’s choice and with appropriate periconceptual care as outlined in this chapter. The timetable of early embryogenesis means that critical development has already commenced before the menstrual period is missed and the woman has any idea she is pregnant. By the time of the usual occurrence of the first antenatal visit, many of the most important embryonic developments have taken place.

TIMING OF PREGNANCY The optimum timing of a pregnancy depends on a number of psychological, physical and social factors that will vary from couple to couple. If a pregnancy is not planned at this time, there is an obvious imperative of ensuring effective contraception is in place. Appropriate family planning advice is covered elsewhere in this book.

MATERNAL AGE CONSIDERATIONS IN THE TIMING OF PREGNANCY With advancing maternal age, there is a decline in fertility that can be detected on population studies as early as 32 years of age. This is initially of minimal consequence to most women but a more clinically relevant decline in fertility begins from about the age of 37 years, and then advances more rapidly after 40 years of age. Obstetric complications of advanced maternal age begin with the

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

increased risk of congenital anomalies and miscarriage and a long list of obstetric complications and procedures, including hypertensive disorders, gestational diabetes, placental insufficiency, uterine fibroids and caesarean section.

WHAT TO DO AT A PREPREGNANCY CONSULTATION There are three key tasks for the health practitioner to address when a pregnancy is planned: 1. screening to identify any issues that might impact on pregnancy 2. managing any clinical conditions found 3. giving general advice to all women planning a pregnancy.

SCREENING TO IDENTIFY ISSUES THAT MIGHT IMPACT ON PREGNANCY History and examination A full and detailed medical history will include age, presenting problem (e.g. how long they have already been trying to conceive), medical, surgical, obstetric, gynaecological, family, social, medications and allergy histories. Particular emphasis will be placed on information that could have relevance to early fetal disorders such as family history, environmental factors (e.g. chemicals or ionising radiation at work) and medications. A family history must also be obtained from the partner. The past obstetric history provides an opportunity to ‘debrief’ regarding concerns that might have surfaced since the last pregnancy. Anxieties about pain relief in labour, not getting to the hospital in time, previous obstetric complications and so on can often be alleviated quickly to the great relief of the woman and her partner. The clinical examination will follow the usual pattern beginning with general appearance, height, weight, vital signs, upper limb, head, neck, chest, abdomen and lower limb. Finally, any relevant neurological examination will be followed by a detailed gynaecological assessment. Gynaecological examination will begin with inspection of the external genitalia (e.g. previous female genital mutilation [FGM]), a speculum examination of the vagina and cervix and bimanual palpation of the uterus and adnexa. Particular note should be made of vaginismus in view of the implications for assessments during pregnancy and labour and the birth itself.

Investigations It is axiomatic in clinical medicine that investigations should only be undertaken if they are likely to impact on 30

clinical management. Sometimes extensive investigations are performed prior to pregnancy that have no clinical relevance until the woman is pregnant, and will likely be repeated then anyway. The following are the investigations that must be assessed as there are clinical consequences for the management of the woman prior to pregnancy.

Rubella and varicella immunisation status The obvious consequence of a rubella non-immune status is the need for vaccination prior to pregnancy. Failure to vaccinate prior to pregnancy will mean that the future embryo will be at risk of suffering the potentially devastating congenital rubella syndrome. Rubella vaccine cannot be administered during pregnancy because of perceived small risks from the vaccine itself. The same issues apply to varicella as to rubella but some will omit testing in the presence of a particularly definite clinical history of chickenpox.

Cervical smear Cervical screening should be performed according to recommendations. It is much preferred if cervical neoplasia is diagnosed prior to pregnancy so that treatment can be initiated in a timely manner. If high-grade cervical intraepithelial neoplasia is diagnosed in pregnancy, treatment will be deferred until the puerperium because of concerns that ablative treatment might cause excessive bleeding or precipitate a miscarriage.

MANAGING ANY CLINICAL CONDITIONS FOUND Clinical problems may require further assessment and optimisation of treatment. In rare cases, prognostic advice may lead to serious consideration with respect to whether a pregnancy should be undertaken at this time—or at all.

Diagnostic assessment Many conditions will require further assessment prior to a pregnancy. Some genetic testing of families may take weeks or months to define, especially if samples need to be sent overseas. Any planned imaging with plain X-rays or CT should be performed prepregnancy to minimise radiation exposure during early embryonic development. Prepregnancy diabetes will require knowledge of renal function including microalbumin excretion. A recent ophthalmologic assessment is also advisable.

Optimising treatment for pregnancy There are many medical conditions in which a change in treatment is recommended prior to embarking on a pregnancy. The following is not an all-inclusive list but contains examples that highlight some of the different reasons why therapy might be changed prior to pregnancy. Most anticonvulsant drugs are teratogenic and the need for these should be reviewed at a prepregnancy

Chapter 3  The Prepregnancy Consultation

consultation. In the presence of a prolonged seizurefree interval (say 2 years), consideration might be given to changing from polytherapy to monotherapy, a particularly teratogenic agent (e.g. valproate) to a less teratogenic anticonvulsant drug or even ceasing anticonvulsant medication altogether. In each case where there is a substantive change in therapy, a period of observation (say 6 months) is advised before embarking on a pregnancy. Some of the more common teratogenic medications include warfarin (usually switched to low-molecular-weight heparin for pregnancy) and ACE inhibitors (commonly replaced by antihypertensives with a long history of safety in pregnancy such as methyldopa or labetalol). Methotrexate should be ceased. Medication for asthma should generally be continued. There is good evidence that glucose control during early embryogenesis can limit the occurrence of congenital anomalies in the offspring of women with diabetes mellitus. Prepregnancy therapy should focus on optimum sugar control. This will usually mean switching to insulin if previously on an oral hypoglycaemic regimen. The insulin is commonly administered as a basal-bolus regimen or by continuous subcutaneous infusion for best control. Surgical conditions should, in general, also be managed preconceptually. Treatment of high-grade premalignant conditions of the cervix has already been mentioned but prepregnancy treatment is also advised for ovarian cysts that are unlikely to resolve spontaneously or for symptomatic gallstones. Apart from known contraceptives, not many drugs will actually reduce the likelihood of pregnancy, but sulfasalazine in the male is associated with low sperm counts.

Prognostic advice A few conditions are of such adverse prognosis in pregnancy that the woman must think very carefully if she wishes to proceed with a conception. Examples might include substantive renal impairment (successful pregnancy is very unusual with a serum creatinine of 300  µmol/L or higher and pregnancy probably accelerates progression to end-stage renal failure) and pulmonary hypertension where the maternal mortality approaches 50% in severe cases if the women elects to continue with the pregnancy. A woman with type 1 diabetes complicated by severe proliferative retinopathy and diabetic nephropathy and one healthy child may elect not to increase her family size further in the interests of maintaining her health, particularly eyesight and renal function, for as long as possible. Sometimes it may be a matter of deferring pregnancy pending correction of the underlying problem. The adverse obstetric consequences of morbid obesity are discussed elsewhere and there is an obvious necessity of prepregnancy weight loss, with or without surgical assistance.

GIVING GENERAL ADVICE TO ALL WOMEN PLANNING A PREGNANCY Preconceptual folic acid All women planning a pregnancy are advised to take preconceptual folic acid. The regimen is 0.5 mg daily with a dose of 5 mg recommended for women at risk, including those with a past or family history of neural tube defect, anticonvulsant drugs or with prepregnancy diabetes.

Getting pregnant While it might seem unnecessary to advise a couple on how to conceive, it is quite common for them to have significant misinformation regarding the likelihood of immediate conception and also the optimum timing and frequency of sexual intercourse. The median duration to conception is approximately 4 months and a couple should be also aware that only about 85% are pregnant after one year, with about half of the remainder conceiving in the second year. As far as the frequency of sexual intercourse is concerned, at least every second day leading up to ovulation is advisable to ensure there are spermatozoa present around the time of ovulation. While more frequent intercourse might lower the sperm count, it is most unlikely that this impacts adversely on conception rates. Certainly, having intercourse just once during the cycle on what is guessed to be the optimum day for conception is likely to have lower than normal pregnancy rates.

Smoking, alcohol and illicit drugs All women at risk of pregnancy should be aware of the risk posed to the early embryo by environmental toxins, even before she knows of the pregnancy. Many women would not be aware of the fetal risks of alcohol, and an important stage of fetal development would have passed if corrective action had not taken place before the onset of the next pregnancy. Although moderate alcohol consumption has not been shown to be embryotoxic, the wisest course of action is to for women planning a pregnancy to avoid alcohol altogether. While smoking is not teratogenic, there are increased risks of miscarriage and pregnancy complications including perinatal death. The motivation of an impending pregnancy is an ideal opportunity to tackle this addiction. Structured programs (e.g. ‘Quit’) aided by nicotine replacement are more likely to be successful than advice alone.

Pharmacological advice While it is sensible not to take any unnecessary medication in pregnancy, the woman should be advised that the simple analgesic, paracetamol, is considered safe in early pregnancy. She should make her doctor aware of a possible early pregnancy before she receives other prescribed medication. Diagnostic imaging with CT or X-rays (especially to the pelvic organs) should be strongly discouraged. 31

Chapter 4  THE FIRST ANTENATAL VISIT Michael Permezel

KEY POINTS The diagnosis of pregnancy is often clinical but a blood pregnancy test (serum β-hCG) is extremely accurate if there is any doubt. Gestational age is calculated from the first day of the last normal menstrual period. The most accurate assessment of gestational age will come from an ultrasound in early pregnancy, commonly at 12 weeks’ gestation. Screening for complications that may affect pregnancy should begin with a comprehensive history and examination. Investigations are extensive and include blood tests, imaging and a cervical smear (if due). Any conditions found need to be further assessed (including any additional investigations). Treatment of such conditions needs to be optimised for pregnancy and the woman should be counselled with respect to what to expect in pregnancy. Every pregnant woman requires detailed advice and discussion in early pregnancy. Topics that must be covered include diet, exercise, dietary supplements, medication use, smoking, alcohol, illicit drugs, sexual intercourse and occupational advice. A plan needs to be made for management of the pregnancy and, in particular, a discussion regarding available models of care and places of birth and the appropriateness of these to individual circumstances.

INTRODUCTION The first antenatal visit is a unique opportunity to establish a relationship between the primary carer and the pregnant woman. A motivated patient and a carer receptive to her needs constitute an important relationship over the months ahead. All too often the woman will present with preconceived ideas from friends who have either decided to alarm her with horror stories or, alternatively, mischievously encouraged the woman to adopt a minimalist care approach with the misguided notion that maternity care somehow causes most problems, when in fact the consequences of lacking such care are apparent, not only in the

developing world, but also in the more deprived or more ill-informed sectors of our own society.

DIAGNOSING PREGNANCY As with any medical diagnosis, pregnancy is diagnosed on history, examination and, where necessary, investigations. Common symptoms of early pregnancy include nausea, breast tenderness, nipple soreness and urinary frequency. Most notable is the first missed period— occurring approximately 2 weeks after fertilisation but most often 4 weeks from the first day of the last normal menstrual period.

Chapter 4  The First Antenatal Visit

Clinical examination is mostly unhelpful in the diagnosis of early pregnancy. Some softening of the cervical isthmus (Hegar’s sign) is detectable at 6 weeks’ but obvious uterine enlargement on bimanual palpation is probably not easily discerned until 8 weeks’ gestation. The uterus does not become palpable abdominally in most women until 12 weeks’ gestation, or even later if the uterus is deeply retroverted. Pregnancy tests rely on the detection of the placental hormone hCG which is produced uniquely by the trophoblast.

URINARY PREGNANCY TESTS (UCG) The urinary test may rarely have false positives and false negatives owing to some cross-reactivity with luteinising hormone (LH). Although mostly reliable, the consequences of telling a woman that she is not pregnant when in fact she is—and the reverse—are too serious to allow even rare mistakes.

SERUM β-hCG The blood pregnancy test is considerably more reliable than the UCG. Positive means pregnant, negative means not. Rare exceptions include trophoblast tumours producing hCG. A positive test may, of course, also occur as a result of a failed pregnancy, either within the endometrial cavity or in another ectopic location.

ASSESSMENT OF THE GESTATIONAL AGE—DATING THE PREGNANCY The importance of accurate dating cannot be overestimated, as without it there is a potential for misinterpreted tests and misguided scheduling of an induction of labour or elective caesarean section. The best opportunity for accurate dating will be in the first trimester when menstrual dates are more readily recalled and ultrasound is most accurate in defining gestational age.

FROM WHEN IS A PREGNANCY DATED? A pregnancy is dated from the first day of the last normal menstrual period, approximately 2 weeks before conception takes place. This oddity can be difficult to accept, both for patients and for new carers. A brief explanation that the dating is from when the unfertilised ovum first became responsive to maternal gonadotrophin may help reconcile this longstanding tradition of describing the gestational age of every human pregnancy as 2 weeks longer than it actually is. The most likely date of onset of spontaneous labour is approximately 266 days from ovulation or 280 days from the first day of the last normal menstrual period

(LNMP) if the cycle is regular and of 28 days’ duration. As stated earlier, this date is all-important for management of the pregnancy but unfortunately suffers from inconsistency of nomenclature. It can be variously termed expected date of confinement (EDC), expected date of delivery (EDD) or expected date of birth (EDB). EDD will be used in this book as EDB is used in some centres as an abbreviation for epidural block.

NAEGELE’S RULE The EDD can be calculated from the first day of the LNMP by adding 7 days and 9 months (Naegele’s rule). If the cycle is longer or shorter than 28 days, the EDD should be correspondingly adjusted as the duration of the luteal phase tends to be constant at about 14 days and a longer or shorter cycle will mean a correspondingly longer or shorter follicular phase—and therefore pregnancy. The LNMP cannot be relied on to calculate the EDD if the cycle is irregular or if the last period was that immediately following cessation of the combined oral contraceptive pill (OCP) as ovulation occurs a variable time after ceasing the combined OCP.

ULTRASOUND IN THE ASSESSMENT OF GESTATIONAL AGE Studies repeatedly show that an early ultrasound is more accurate than the LNMP in determining the EDD. Where an ultrasound has been performed before 13 weeks’ gestation, the EDD from that ultrasound would generally be used to determine the EDD. The gestational sac size can be measured early but as soon as a fetal pole is visible, the length of the embryo (crown–rump length [CRL]) gives the most accurate estimate of gestational age. CRL will guide the EDD from approximately 6 weeks’ gestation through to 12 weeks’ gestation and estimates should be within 3 days of the actual EDD. Beyond 12 weeks’, flexion and extension of the embryo mean that the CRL ceases to be of value and the breadth of the fetal head (biparietal diameter [BPD]) is used thereafter to determine the EDD. Prior to 20 weeks’, this should be within 7 days of the true EDD but with advancing gestations beyond 20 weeks’, the BPD becomes progressively less accurate such that it becomes only a very approximate guide in the third trimester of pregnancy.

OTHER MEANS OF DETERMINING THE GESTATIONAL AGE A woman may be very certain regarding the date on which conception occurred. This can be useful where an early ultrasound is not available and the woman is unsure of her menstrual dates. Similarly, where the pregnancy occurred through assisted conception (e.g. in-vitro fertilisation [IVF]), there can be considerable confidence establishing the EDD from the date of embryo transfer. 33

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SCREENING TO IDENTIFY ISSUES THAT MIGHT IMPACT ON THE PREGNANCY HISTORY A complete medical history is required as previously outlined in Chapter 3. Aspects include age, symptoms of pregnancy, medical and surgical history, obstetric and gynaecological history, medications and drug allergies, family history and social history. The latter must include information about smoking, alcohol and illicit drugs, as well as marital status, social supports and occupation. Gynaecological history should include reference to those conditions that might impact on pregnancy such as previous uterine or cervical surgery or genital herpes simplex infection.

EXAMINATION The clinical examination will follow the usual pattern beginning with general appearance, height, weight, vital signs, upper limb, head, neck, chest, abdomen and lower limb. Breast examination is important, as examination for breast lumps becomes increasingly difficult as gestation advances and breast cancer can progress rapidly in pregnancy, so early diagnosis is essential. Finally, any relevant neurological examination will be followed by a detailed gynaecological assessment. Gynaecological examination begins with inspection of the external genitalia (e.g. previous FGM) followed by bimanual palpation of the uterus and adnexa. A speculum examination of the vagina and cervix is performed if a Pap smear

or cervical swabs are indicated. Particular note should be made of vaginismus in view of the implications for assessments during pregnancy, labour and the birth itself.

INVESTIGATIONS—STANDARD RECOMMENDATIONS There are a large number of investigations that are needed in pregnancy because of therapeutic initiatives that will follow an abnormal test. A summary of these tests is provided in Table 4.1, with explanations of the terms used in the text that follows.

FULL BLOOD EXAMINATION (FBE OR FBC) This is necessary to exclude anaemia and acts as a screening test for thalassaemia and thrombocytopenia. Immune thrombocytopenia is one of the most common autoimmune conditions (see Ch 22). Screening for thalassaemia through a low mean corpuscular volume (MCV) is also important given the risk of thalassaemia major in the fetus should the father of the fetus also be a carrier.

BLOOD GROUP AND ANTIBODY SCREEN The blood group will detect the 15% of Caucasian women who are D-negative and require further screening during pregnancy (usually at 28 weeks’ and birth) and also prophylaxis with passive anti-D at prescribed times/events during pregnancy to minimise the risk of immunisation.

TABLE 4.1  INVESTIGATIONS COMMONLY RECOMMENDED AS ROUTINE IN EARLY PREGNANCY. Investigation

Rationale for performing the investigation

FBE (Hb, platelets, MCV)

Anaemia, thalassaemia

Blood group, antibody screen

Diagnose and prevent red cell isoimmunisation

Rubella antibodies, varicella antibodies (if uncertain of history), syphilis serology, Hep B, Hep C, HIV

Treat infection in current pregnancy (syphilis), take steps to reduce vertical transmission (Hep B, Hep C, HIV), vaccinate mother in puerperium (rubella, varicella), warn woman to present for zoster immune globulin if not immune and contact with varicella

MSU mcs

Diagnose and treat asymptomatic bacteriuria (6%)

Pap smear

Assess and monitor (treat in puerperium)

Serum screen for fetal aneuploidy

Screen for fetal anueploidy

12-week scans

Screen for fetal anueploidy (nuchal translucency), diagnose structural anomaly, identify multiple pregnancy

19-week scans

Diagnose structural anomaly, placenta localisation

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Chapter 4  The First Antenatal Visit

It is equally important that all women have an antibody screen at the first antenatal visit. Even women who are D positive may have antibodies against a variety of other red cell antigens such as c, E, K, Fya (see Ch 22).

MICROBIOLOGICAL SEROLOGY Rubella antibodies The obvious consequence of a rubella non-immune status is the need for vaccination early in the puerperium. A seronegative woman should avoid contact with unwell children in the first trimester and be re-screened for seroconversion if there is any possibility of rubella infection in early pregnancy.

Varicella antibodies The same issues apply to varicella as to rubella but some will omit testing in the presence of a particularly definite clinical history of ‘chickenpox’. A woman who is not immune to varicella should also be advised to present for prophylactic zoster immune globulin (ZIG) if she has contact with varicella (either chicken pox or shingles).

Syphilis Treponemal antibody tests are now commonly performed and are very specific. A reagin test such as the venereal disease research laboratory (VDRL) test or rapid plasma reagin (RPR) test may have false positives, including from the antiphospholipid syndrome. Therefore, the patient should be followed up even if a subsequent treponemal antibody test is reassuring.

Hepatitis B, Hepatitis C and HIV RANZCOG recommend screening for each of hepatitis B, hepatitis C and HIV. Despite a low prevalence, important therapeutic initiatives are indicated if the virus is present in order to minimise the risk of vertical transmission. Astonishingly, some other guideline writers do not mandate a recommendation for hepatitis C screening, even though it is by no means rare in the general population and all would take care to minimise invasive testing (e.g. fetal scalp electrode, fetal blood sampling) where the mother is a hepatitis C carrier.

MIDSTREAM URINE FOR MICROSCOPY, CULTURE AND SENSITIVITIES (MSU MCS) Approximately 6% of women will have asymptomatic bacteriuria at the first antenatal visit. Of these, up to onethird will go on and develop pyelonephritis if the bacteriuria is untreated.

CERVICAL SCREENING Cervical screening should be performed according to screening recommendation (listed in Chapter 61). Once the woman is pregnant, treatment of a high-grade cervical

intraepithelial neoplasia will be deferred until the puerperium because of concerns with respect to treatment causing excessive bleeding or precipitating a miscarriage.

SCREENING FOR DOWN SYNDROME See Chapter 9.

INVESTIGATIONS—ADDITIONAL THAT MAY BE CONSIDERED There are other investigations that may be considered in early pregnancy but at the time of writing this chapter they are not part of the routine recommendations of RANZCOG. These are summarised below.

HB ELECTROPHORESIS Hb E and Hb C will commonly not have a low MCV but can produce a transfusion-dependent anaemia if the partner has β-thalassaemia trait. Similarly, sickle cell anaemia needs to be excluded in women of relevant ethnicity.

SERUM FERRITIN Serum ferritin is indicated if there is an increased likelihood of iron deficiency (e.g. vegetarian). In centres of high prevalence of iron deficiency, serum ferritin may be routine in early pregnancy.

CHLAMYDIA SCREENING A cervical swab for chlamydia may be recommended to at-risk women, and is routine in some units for women under the age of 25 years.

VITAMIN D Vitamin D is obligated in those with dark skin and/or reduced sunlight exposure during pregnancy. The significance of low vitamin D for the offspring is awaiting further research, but supplementation is recommended if vitamin D is < 50 nmol/L and some will treat even in the range 50 to 75 nmol/L.

THYROID FUNCTION There is increasing evidence that subclinical hypothyroidism may have consequences for a pregnancy. While a large trial has now established that screening for hypothyroidism is unlikely to have substantive neurocognitive benefits in the offspring, there are still many clinicians who support screening for hypothyroidism in early pregnancy.1 This is to pick up the very small number of cases of severe hypothyroidism and also because there remains some evidence of a possible benefit for the index pregnancy—even if the level of thyroid-stimulating hormone (TSH) is in the subclinical range (i.e. 2.5 to 5.0 mIU/L). 35

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MANAGEMENT OF ANY CLINICAL CONDITIONS FOUND Clinical problems may require further assessment and optimisation of treatment. In rare cases, a very prognostic outlook may lead to a woman to question whether she should continue the pregnancy. Specific management of medical conditions at the first antenatal visit is discussed in the relevant chapters (10 to 27) detailing obstetric, medical and surgical disorders of pregnancy.

FURTHER ASSESSMENT, OPTIMISING TREATMENT AND PROGNOSTIC OUTLOOK Many conditions will need further evaluation, beginning with a detailed, directed clinical assessment (history and examination) and proceeding to relevant investigations. Obviously it is desirable to minimise exposure of a developing fetus to ionising radiation. There are many conditions in which a change in treatment is recommended in a pregnancy. Some of these are discussed in Chapter 3 and also in the chapters devoted to the relevant complications. Only rarely will the outlook be such that the parents give consideration to not proceeding with the pregnancy. If such a decision looks possible, on either maternal or fetal grounds, it is strongly preferred to provide the couple with the necessary detailed information and counselling at an early stage in pregnancy, requiring a degree of urgency from the healthcare providers.

GENERAL ADVICE All women need to be actively informed regarding important health choices that will impact on her pregnancy. The onus is on the health professional at the first ante­ natal visit to cover all the important areas of discussion. That discussion should be tailored to the patient’s needs and considered in the context of her background and a priori knowledge. She should be encouraged to purchase one of the better books that inform and educate around pregnancy and childbirth. At the same time, she should be warned of the hazards of taking too much notice of malicious friends or ramblings on the internet and to seek an early consultation if such has raised extreme levels of anxiety.

NUTRITION Listeria Listerial sepsis is covered elsewhere but may result in a septic miscarriage or lethal chorioamnionitis. Women should be appraised of the most likely sources of food poisoning. The avoidance of soft cheeses is applicable where such is made from unpasteurised milk. Also to be avoided are soft-serve ice-cream, raw fish (e.g. sushi, 36

smoked salmon, oysters), cold meats, salad bars and paté. More important for most women is proper food preparation and handling. Completely thaw before cooking and ensure all meat is cooked thoroughly—most importantly poultry. Take particular care with pre-prepared foods and those made with mayonnaise or crustaceans.

Healthy diet, particularly avoiding nutritional excess The epidemic of our time is obesity. Again, pregnancy is a time where the woman is attending her health practitioner on a regular basis and with added motivation. Reinforcing good dietary habits is an extremely important measure in preventative healthcare. There is good evidence that regular weighing of women at each ante­ natal visit will reduce the incidence of excessive weight gain in overweight patients.

Iron, iodine and calcium Most vegetarians are iron deficient although not necessarily so. Pregnant women who are not vegetarians should be encouraged to eat red meat. Vegetarians should be checked for iron deficiency (serum ferritin) and supplemented with oral iron if ferritin is low. Iodine deficiency is common in non-coastal areas. Salt should be used sparingly but of the iodised variety. Dairy products are a rich source of protein and calcium. Those women who are unable to take dairy may be advised to supplement with calcium tablets.

Multivitamin supplementation It is now common for pregnant women to be taking a proprietary multivitamin preparation suitable for pregnancy. There is clear evidence for periconceptual folic acid supplementation for the prevention of neural defects but the evidence for multivitamin use throughout pregnancy is more circumstantial. Many believe that over the last 50 or so years there has been a marked and progressive decrease in some adverse pregnancy outcomes including severe placental abruption and possibly severe preeclampsia. It has been suggested that better nutrition may be an explanation. A causative rationale has emerged in the form of homocysteine, which is a potential activator of endothelial cells. The levels of homocysteine are increased by mutations of the enzyme methyl tetra hydrofolate reductase but reduced by three key vitamins: folate and vitamins B6 and B12.

EXERCISE A light to moderate level of exercise is generally recommended in pregnancy. This may include continuing exercise programs at the gym or sporting club that preceded pregnancy. Strenuous exertion should probably be avoided as it has been linked to smaller birth weights. The health implications of this are uncertain but it could have adverse consequences in either the short or long term (see Ch 11). Intuitively, maternal hypoxia during exertion

Chapter 4  The First Antenatal Visit

may be detrimental to placental gas exchange and a good working rule is to exercise at a level at which conversation can still be continued.

ALCOHOL, SMOKING AND ILLICIT DRUGS Alcohol The wisest course of action is to avoid alcohol altogether in pregnancy. While the impact of a single episode of alcohol excess is likely to be small, there is no doubt that an alcohol intake of more than two standard drinks per day is associated with significant teratogenesis—fetal alcohol syndrome.

Smoking Smoking is definitely associated with increased risks of miscarriage and perinatal death. All smoking mothers and/or any smoking partners should be offered strategies to assist with complete smoking cessation. This is an example of using the added motivation of pregnancy and protecting the unborn child to achieve an extremely important health outcome for all the family.

Illicit drugs Cannabis, narcotics, cocaine, amphetamines and other illicit drugs all must be strongly discouraged in pregnancy. Each has its specific problems but notably cocaine use may be associated with the long-term consequences of preterm birth, placental insufficiency and placental abruption. Opioids may cause neonatal abstinence syndrome in which the unborn fetus is conditioned to the presence of the narcotic and has a withdrawal reaction in the early neonatal period with irritability, poor feeding and possibly seizures.

MEDICATIONS Women should be appraised of common medications that are almost certainly safe to administer in pregnancy, in their usual doses and in the absence of allergy. Examples would include paracetamol, metoclopramide (for early pregnancy nausea and vomiting) and commonly used penicillins (e.g. amoxycillin). Common asthma medication (e.g. salbutamol and/or corticosteroid inhalers) can and should continue. Mental health medication (see Ch 25) can usually be continued, weighing an uncertain but possible very low risk of fetal sequelae against a known maternal benefit. Some mental health medications (e.g. sodium valproate, lithium) are classified as category D (expected to be harmful to the fetus) yet may still be used in pregnancy occasionally where the benefit outweighs the risks. Constipation is a common pregnancy complication. All maternity healthcare providers should be able to advise on foods that are high in fibre, but women should also be informed that common laxatives are safe in pregnancy. The patient should be aware that all other

medication requires consultation, making sure that the administering doctor is aware that she is pregnant.

SEXUAL INTERCOURSE After such a long list of ‘don’ts’, the patient is often somewhat relieved to hear that there is no evidence to suggest that sexual intercourse is harmful in pregnancy. There is no evidence that preterm birth is increased by sexual activity, but pregnancy duration at term is, on average, a few days shorter in the sexually active woman. Sexual intercourse will generally be avoided within a week of any bleeding in pregnancy and certainly prohibited after rupture of the gestational membranes.

EMPLOYMENT Most women find they are physically fatigued in late pregnancy and a majority will choose to go on maternity leave from about 34 weeks’. However, a small proportion of women elect to work up until the day of the birth. There is evidence that physical work can both raise the blood pressure and increase the risk of preterm birth. If either of these issues are relevant in a particular pregnancy, then employment should probably be ceased.

TRAVEL Travel is seldom a problem in pregnancy until the last months. Long-duration air travel will predispose the patient to an increased risk of venous thromboembolism. Also, any event occurring during a long flight (e.g. antepartum haemorrhage, preterm labour) creates a serious situation in a location that can be many hours remote from any substantive medical care. A working rule might be that flights longer than a couple of hours are undesirable in anyone who is at increased risk of pregnancy complications and probably should be avoided in everyone after about 28 weeks’. Airlines may have various policies in this respect. Consideration should also be given with respect to areas of endemic infectious disease such as malaria or toxoplasmosis. The pregnant woman should carry a summary of relevant sections of her medical record and antenatal progress.

VACCINATIONS Influenza vaccine is safe and particularly important to administer in pregnancy. In general, live vaccines (e.g. rubella, varicella) are contraindicated but killed vaccines are relatively safe (e.g. influenza).

INFECTIONS CMV and toxoplasmosis can both be reduced by sensible handwashing before food preparation and after exposure to risk-prone events such as gardening (toxoplasmosis) or children at childcare (cytomegalovirus). 37

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BOOKING At the end of each first antenatal visit, an initial plan for the pregnancy should be made. Not a plan that cannot be changed, but a plan that sets the initial direction for care.

WHO? The first decision is with respect to the model of care. Who will be looking after the woman and her unborn baby, both during pregnancy and in labour? Nearly always this decision will mean some assessment of complexity and a search for specific complications as described previously. There are just about as many models of care as there are hospitals delivering maternity care, but the following is an overview of the types of care models and which women might be best suited to each.

The maternal fetal medicine (MFM) subspecialist These practitioners are highly skilled in the management of complex pregnancies and have additional training in obstetric ultrasound relative to most specialist obstetricians. While management of very complex pregnancies mostly lies with the specialist obstetrician, some conditions particularly benefit from the additional expertise of the subspecialist. Examples of cases commonly referred to the MFM might be intrauterine transfusion of the anaemic fetus or performing laser surgery of the connecting vessels in twin–twin transfusion syndrome. In most of the larger centres, the MFMs will have a prominent role. However, specialist obstetricians in medium-sized maternity hospitals will manage most of the complex cases themselves, referring only rare cases to an MFM and mostly even then only for advice rather than transferring patient care.

Specialist obstetrician All specialist obstetricians are skilled in the management of complex pregnancies as well as those without identified problems. They may do so within the public or private sector, often in partnership with registrars training to become specialists and always in collaboration with the hospital midwives.

preventative health precedents for the ongoing health of the woman and her family.

Midwife or training obstetrician care Women without additional complexity will commonly be offered care with a midwife or an obstetric resident in training.

Multidisciplinary care Some conditions require input from other specialists. A complex heart disease patient will need to be seen jointly by a specialist obstetrician, an obstetric anaesthetist and a cardiologist. In fact, input for almost every significant medical condition will usually benefit from health communication between the medical specialist and the obstetrician. Where patient numbers can justify it, the establishment of specialised multidisciplinary clinics allows healthy collaboration between different professional groups in the interests of patient care. This is perhaps exemplified by the pregnancy diabetes clinics where the obstetrician, endocrinologist, diabetic educator and sometimes an ophthalmologist or a paediatrician work jointly to achieve the best possible outcomes. Similarly, major disorders of mental health are best managed with a collaboration of treating psychiatrists, obstetricians and midwives.

WHAT PLACE OF BIRTH? Options regarding place of birth should be discussed, allowing an appropriate booking to be made. The major options will be a hospital maternity unit, an ‘alternative’ hospital-based birth centre that may be within a wellequipped hospital or free-standing, the latter without on-site access to operating theatres should unexpected complications develop (e.g. postpartum haemorrhage, acute fetal compromise). In Australia less than 1% of women choose to have a planned home birth. Even with formal arrangements for hospital back-up, most obstetricians believe that, although most home births will result in a favourable outcome, home birth has an unacceptably high risk exposure for both mother and child.

Shared care with a general practitioner obstetrician

REFERENCE 1) Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012;366(6):493–501.

The shared care general practitioner (GP) often has the great advantage of knowing the woman prior to pregnancy and the ability to meet many of her general health needs and those of her family. Importantly, the GP can enhance the doctor–patient relationship through the repeated visits of antenatal care. At such a time, most women will be more motivated than usual to take advice on important general health issues. These will not only benefit her unborn child but hopefully also will establish

FURTHER READING Joss-Moore LA, Lane RH. The developmental origins of adult disease. Curr Opin Pediatr 2009;21(2):230–4. Wax JR, Lucas FL, Lamont M, et al. Maternal and newborn outcomes in planned home birth vs planned hospital births: a meta-analysis. Am J Obstet Gynecol 2010;203(3):243.e1–8.

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Chapter 5  ANTENATAL CARE BEYOND THE FIRST ANTENATAL VISIT Michael Permezel

KEY POINTS The antenatal period serves as an opportunity for a spectrum of health promotion activities with repeated visits to a health professional at a time when most women are strongly motivated to provide a health environment for the developing baby. Pregnancy complications can be diagnosed early and management instituted. Placental insufficiency and preeclampsia deservedly receive particular focus. Each visit should include a brief history with specific inquiry regarding general wellbeing and fetal movements in pregnancies beyond 20 weeks’ gestation. Physical examination requires a standardised method of blood pressure measurement and fundal height determination as these will be important to compare from week to week, even if the examiner differs. Routine investigations in all women in the latter half of pregnancy include a full blood examination and test of glucose tolerance at 28 weeks’ and a vaginal swab for Group B streptococcus (GBS) at 36 weeks’. Women who are Rh-negative will additionally have their anti-D antibody level assessed at 28 weeks’ and injections of prophylactic anti-D at 28 and 34 weeks’, providing they have not developed endogenous anti-D production.

THE OBJECTIVES OF ANTENATAL CARE There are three key objectives of the routine antenatal visits.

HEALTH PROMOTION AND PREVENTATIVE MEDICINE Pregnancy offers a unique opportunity for health education that has the opportunity to impact not only on the pregnancy, but also the woman herself, her current and future children and her partner. The pregnancy provides very clear motivation. Repeated antenatal visits with a trusted and knowledgeable antenatal care provider

further increases the likelihood that advice will be followed. Issues can be raised, questioned, discussed and then revisited on repeated occasions throughout the pregnancy. Among those matters that may impact on both the pregnancy and future health of her family include dietary behaviours, exercise, weight control, smoking, alcohol and illicit drugs. Medical subjects such as the importance of immunisation and cervical smears can also be raised. Where conditions such as gestational diabetes, hypertension or mental health issues develop in pregnancy, these can be used to further educate in health areas that are likely to be of particular importance to that woman in the future. To not use the antenatal visits for health promotion is to waste one of the great opportunities to impact on the health of the population as a whole.

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

EARLY DIAGNOSIS AND MANAGEMENT OF PREGNANCY COMPLICATIONS Prior to 20 weeks’ but beyond the first antenatal visit, the emphasis is generally on early fetal wellbeing, particularly establishing the genetic and morphological health of the fetus. The approach to this is discussed in other chapters but largely will involve chasing up the results of tests organised at the first antenatal visit and also making sure that the patient attends for a morphology scan (typically organised for approximately 20 weeks’). Beyond 20 weeks’ (and assuming normal morphology), the focus of an otherwise uncomplicated pregnancy shifts towards early diagnosis of the two dominant conditions of late pregnancy: placental insufficiency and preeclampsia. Of course, a myriad of medical and obstetric complications are possible, but very specific attention is directed to both fetal wellbeing and the features of preeclampsia.

MATERNAL SUPPORT AND PREPARATION FOR BIRTH All women will have questions about labour and birth that need to be addressed during the antenatal period. Although information can be obtained from books, videos and antenatal classes, most women find it particularly reassuring to receive pertinent information from the antenatal clinic provider, particularly if that same person is to be also caring for her around the time of labour and birth.

ANTENATAL VISITS BEYOND THE FIRST ONE FREQUENCY OF VISITS There are various regimens recommended for antenatal visit frequency, balancing the costs to the woman and the community of excessive visit frequency against the possible delayed diagnosis of complications and other less tangible benefits of antenatal care, including maternal support and education.

THE TYPICAL ROUTINE ANTENATAL VISIT IN AN UNCOMPLICATED PREGNANCY History

providers should be confident in listening to and advising on management of the common symptoms of pregnancy, including headaches, heartburn, lower abdominal discomfort or round ligament pain, constipation, haemorrhoids, varicose veins (vulval as well as lower limbs), carpal tunnel syndrome oedema, muscle cramps, fainting or light-headedness and general fatigue.

Fetal movements Fetal movements are not commonly felt until approximately 17 weeks’ in a multigravida and 19 weeks’ if it is the first baby. The gestation tends to be later if the placenta is anterior. Where a woman still is not feeling movements beyond 20 weeks’, she may benefit from more frequent antenatal visits as a means of reassurance. Most women will soon perceive fetal movements if advised on what they should be expecting to feel and dedicate some time to concentrate on it. In the third trimester of pregnancy, maternal perception of fetal movements becomes an extremely important parameter in the assessment of fetal wellbeing. Most cases of stillbirth are preceded by many hours or days of no fetal movements. Every provider of antenatal care has an obligation to both inquire of fetal movements at each visit and provide the patient with some clear instruction as to what to expect in terms of fetal movements and what to do if that expectation is not met. Unfortunately, there is no uniform instruction as to how women should check fetal movements. One of three approaches is commonly used but ‘no specific instructions’ is not an option. 1. Check with meals: ‘Check that the baby moves a couple of times with each meal or in the half an hour or so thereafter. If it does, don’t worry until the next meal. If it doesn’t, have a cold, sweet drink and if still not, contact the hospital.’ 2. Count to 10: ‘Count each day until you have 10 movements. If you don’t have 10 movements by 6 pm at night or it is much later than usual, contact the hospital.’ 3. Usual pattern: ‘Get used to the pattern of your baby’s movements and contact the hospital if the baby is much quieter than usual.’ There has not been any significant comparative trial to establish which approach is most effective and because of the low incidence of adverse outcome, a randomised controlled trial is unfeasible. More onerous (e.g. ‘count to 10’) may have the least compliance, whereas less onerous (e.g. ‘usual pattern’ may be less sensitive) and a middle course (e.g. ‘check with meals’) may be best for a majority of women.

General wellbeing and symptomatology

Examination

As a first step, there should be a general inquiry regarding maternal wellbeing. There are many common symptoms that may be very important to the woman, even if of relatively minor medical significance. All antenatal care

After many years of largely ignoring maternal weight during pregnancy, the current obesity epidemic has led to some rethinking in this respect. Good research

40

Maternal weight

Chapter 5  Antenatal Care Beyond the First Antenatal Visit

indicates that self-monitoring maternal weight reduces the incidence of excessive weight gain in overweight and obese women. Although an issue that needs to be handled sensitively, it can be used to focus attention during pregnancy on sensible diet and exercise—extremely important aspects of health promotion for the woman and her family.

Blood pressure Particular care is taken with the accurate recording of blood pressure. This should be taken in standardised fashion with the patient seated, using the right arm at the level of the heart. Diastolic blood pressure (BP) is taken as sound disappearance (Korotkoff phase V) rather than muffling (phase IV).

Abdominal examination The woman should lie comfortably in the supine position, with the arms by the sides and the head well supported by a pillow. The bladder should be empty. The drapes are arranged to give access to the whole abdomen. Because of the occurrence of the supine hypotensive syndrome in some women, particularly in late pregnancy, the mother should be warned to lie on her side if she feels faint. Inspection The normal uterine contour is oval or pear-shaped; this is obliterated if there is an abnormal amount of intrauterine contents (multiple pregnancy and/or polyhydramnios). If the fetus is lying transversely, the fundus will be lower than expected and the transverse diameter will be widened. In the last 4 to 6 weeks, umbilical eversion is common and an umbilical hernia is noted for the first time in 1 to 2% of women. A pigmented line in the midline is common and termed the linea nigra. Palpation The four classical techniques of palpation are sometimes termed Leopold’s manoeuvres or grips (the latter term not accurately describing the procedure adopted). 1. Fundal palpation. The fundal height is estimated by placing the thenar surface of the left index finger at the highest point of the uterus and comparing this with accepted levels for different periods of gestation. This is the same palpation technique as used for a liver or spleen but with the left hand angling down instead of the right hand angling up. Before 20 weeks’, measuring the fundal height is not particularly useful as there is considerable variation from woman to woman. In general, the uterus will commonly be first palpable abdominally at approximately 14 weeks’ and reach the umbilicus at about 20 weeks’. Beyond 20 weeks’, the fundal height should be measured in centimetres from the top of the fundus down to the symphysis pubis and this measurement serendipitously approximates to the gestation in weeks. Because of descent of the head into the pelvis

in late pregnancy, the fundal height may not increase or even decrease as the head descends into the pelvis. Boxes 5.1 and 5.2 list the main reasons for the measured fundal height being greater or less than that expected for the gestational age. 2. Lateral palpation. This is used to ascertain the position of the back in those cases where the lie is longitudinal. The examiner remains in the same position, but the hands are moved down to the level of the umbilicus. With gentle pressure, supplemented with dipping movements, the resistance of the back is sought and its distance from the midline noted. This procedure is made easier if alternate hands are used to steady the trunk and push it towards the opposite examining hand. The fetal limbs will be on the side opposite the back; they are best felt by gliding the hands over the surface of the abdomen, seeking the mobile irregularities by which the limbs are characterised. If the lie is transverse, the characteristic features of the head and breech will be felt in each flank. 3. Pawlik’s grip. Here, the right hand only is used. The fingers are well spread and are placed in the suprapubic skinfold which runs out to each iliac fossa (Fig 5.1). With both this and the next palpation, gentleness must be exercised since the lower segment is more sensitive than the upper segment. Information is mainly derived from the thumb and middle finger, which move in a coordinated scanning fashion to

BOX 5.1  Causes of fundus greater than dates.

Wrong dates Maternal obesity Multiple pregnancy Large fetus Polyhydramnios Ovarian cyst Fibromyoma Hydatidiform mole

BOX 5.2  Causes of fundus less than dates. Wrong dates Small, growth-restricted fetus Oligohydramnios ✚ Placental insufficiency ✚ Rupture of the membranes ✚ Fetal renal insufficiency Transverse lie 41

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

hospitals but a common notation is 5/5, 4/5, 3/5, 2/5, 1/5 or 0/5 corresponding to 10, 8, 6 4, 2 or 0 cm of head being palpable above the pelvic brim. Auscultation The fetal heart becomes audible with the clinical Doppler instrument at about 12 weeks’ gestation. The point of maximal intensity is over the area of abdomen which is related to the left chest wall of the fetus, but is often only determined by trial and error. Generally, the site depends on the period of gestation and the presentation and position of the fetus. For example, in the second trimester, the fetal heart is usually heard best in the midline below the umbilicus; in breech presentations, it is located above (rather than below) the umbilicus; and in posterior positions, it is best heard well out in the flank, unless there is a significant deflexion. Although it is reassuring for the mother and clinician to hear a heartbeat, the greatest clinical importance of routine auscultation may lie in the rare detection of a fetal arrhythmia. Ectopic beats are not uncommon and mostly present no problem to the fetus. Significant bradycardias (e.g. heart block) or tachycardias (e.g. paroxysmal supraventricular tachycardia) may be treatable causes of fetal hydrops and require urgent assessment in a unit experienced in this highly specialised area of fetal medicine.

Urinalysis—proteinuria and glycosuria FIGURE 5.1 

The Pawlik method of palpation identifies the presenting part of the fetus and its station. Source: Courtesy of Prof. Norman Beischer.

determine which pole is presenting (breech or cephalic) and also whether it is mobile above the pelvic brim or fixed within the pelvis. Usually, Pawlik’s method is modified to a combined palpation, where the left hand is placed on the fundus in a mirror image of the right hand. A simultaneous comparison is thus available between what is felt in the upper and lower poles, and the examiner is more likely to be correct as to the presentation. 4. Deep pelvic grip. In this palpation, the examiner turns and faces the woman’s feet. The hands are placed over the sides of the lower uterus in the depression which lies medial to the anterior superior iliac spine and above the inguinal ligaments (Fig 5.2). Initially, the outline and nature of the presenting part is determined. The deep pelvic grip is particularly useful when the head is ‘fixed’ in order to determine how much of the head has entered the pelvis. The station (amount of descent) is determined from the amount of the presenting part (usually the head) which is out of the pelvis. Different notations are in use in different 42

There is a long tradition of testing for protein and glucose at each antenatal visit. With routine glucose tolerance testing as recommended overleaf, the added yield from urine testing of glucose is particularly low. Nevertheless, persistent glycosuria merits an early glucose tolerance test but most will be due to a lowered threshold for renal glycosuria in pregnancy. That is, even with normal blood glucose, sugar may appear in the urine in pregnancy. In contrast, urinalysis for protein at each antenatal visit is an important component of the antenatal visit. Although, most commonly, the hypertension precedes the proteinuria in preeclampsia, there are many cases where the proteinuria precedes the significant hypertension. The detection of ‘more than a trace’ of protein on urinalysis serves to alert the clinician that this may herald developing preeclampsia. If the blood pressure is normal, a urinary tract infection should be excluded and the proteinuria confirmed with a more formal urine collection (e.g. for urinary protein:creatinine ratio). Most importantly, the visit frequency should be increased (e.g. see the following week) so as to ascertain early if the blood pressure begins to rise.

Investigations There are essentially three occasions during pregnancy when investigations are requested.

First antenatal visit The investigations requested at the first antenatal visit are blood tests as specified elsewhere, a cervical smear if indicated, trisomy 21 screening (even though performed

Chapter 5  Antenatal Care Beyond the First Antenatal Visit

FIGURE 5.2 

Deep pelvic palpation.

Source: Courtesy of Prof. Norman Beischer.

approximately 12 weeks’) and the morphology scan (performed approximately 20 weeks’).

At 28 weeks’ gestation

Full blood examinationn There is a normal fall in haemoglobin during pregnancy with a trough at approximately 28 weeks’. For various reasons, particularly iron deficiency, the haemoglobin may fall excessively and therapy may be indicated. A lower limit of 105 g/L would generally be acceptable, with some dietary emphasis with respect to Fe and folate given if the Hb is in the range 105 to 110 g/L. If the patient does have anaemia then investigation is required and appropriate therapy instituted. Most commonly the serum ferritin will be low and oral iron recommended (see Ch 20). Glucose tolerance testing In 2012, the Australasian Diabetes in Pregnancy Society (ADIPS) made screening recommendations for the diagnosis of gestational diabetes mellitus (GDM). These recommendations were derived from the Hyperglycaemia Adverse Pregnancy Outcome (HAPO) study and

developed by the International Association of Diabetes in Pregnancy Societies (IADPSG), and endorsed by the World Health Organisation. ADIPS recommend that, in the absence of risk factors, all women have a fasting 75-g 2-hour oral glucose tolerance test (GTT) at 24 to 28 weeks’. If risk factors are present, screening should also occur in early pregnancy. The criteria for diagnosis are any one of the following:

• • •

fasting venous PG ≥ 5.1 mmol/L one-hour venous PG ≥ 10.0 mmol/L two-hour venous PG ≥ 8.5 mmol/L.

Previous testing regimens for low-risk women had recommended a non-fasting 75-g oral glucose challenge test (GCT) and proceeding to a full GTT only if the GCT 1-hour glucose was ≥ 8.0. This regimen will miss approximately 20% of GDM. Blood group antibody screen A blood group antibody screen tests the maternal plasma against a panel of red cell antigens in order to see if any 43

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

anti-red cell antibodies have developed. All women are screened at the first visit. Some units will screen all women again at 28 weeks’ but most units will only rescreen those women that are Rh(D)-negative simply because the cost-effectiveness of repeat screening is much lower in the Rh(D)-positive population and there is only a very low probability of developing clinically significant antibodies to non-D red cell antigens. For women who are Rh(D)-negative and do not have anti-D antibodies, prophylactic anti-D will be administered at 28 weeks’ and again at 34 weeks’.

At 36 weeks’ gestation As prophylactic anti-D is indicated at 34 weeks’ in the Rh(D)-negative women and Group B streptococcus screening (GBS) screening at 36 weeks’, it is common practice to do both of these at a single hospital visit from 34 to 36 weeks’ in women undertaking shared care with a clinician in the community. Group B streptococcus (GBS) screening Approximately 20% of women will have vaginal carriage of GBS in late pregnancy. In the absence of prophylaxis, about 1 in 200 neonates born to these women will get a

GBS infection of which up to 10% will be fatal, with significant morbidity in the survivors. Intrapartum prophylaxis will greatly reduce the risk of early onset neonatal GBS sepsis. There are essentially two approaches: ‘universal screening’ or a ‘risk-based approach’. Universal screening is recommended by the American College of Obstetrics and Gynaecology and preferred by a majority of Australasian units. In universal screening, all women are screened at approximately 36 weeks’ gestation with a low vaginal and perianal swab to determine whether they are carriers for GBS. GBS carriage is assumed without the need for screening where there has been GBS bacteriuria in pregnancy or there has been a previously affected neonate with early onset GBS disease. In the presence of GBS carriage (on swab or assumed), intrapartum antibiotic prophylaxis is recommended with intravenous penicillin. Where the woman is allergic to penicillin, cephazolin is usually the best choice unless the woman has a history of immediate hypersensitivity to penicillin. If this is the case, antibiotic sensitivities are required as some isolates are resistant to macrolides. If not resistant, clindamycin is the drug of choice; otherwise vancomycin should be used.

TABLE 5.1  FACTORS DETERMINING MODE OF BIRTH. Variable

Rationale

Favouring elective caesarean section

Favouring planned vaginal birth

Maternal tolerance of fetal risk in order to avoid medicalisation of caesarean section

All mothers prioritise fetal welfare but some will be intolerant even of a very small added risk of vaginal birth

Low

High

Likely future parity

Increasing risk of placenta accreta with increasing numbers of caesarean sections

Low

High

Likelihood of achieving a vaginal birth if attempted

Emergency caesarean section increases morbidity relative to the elective procedure

Low

High

Perceived added maternal morbidity of vaginal birth in the index pregnancy

For example, previous third- or fourthdegree tear

High

High

Perceived added maternal morbidity of caesarean section in the index pregnancy

For example, morbid maternal obesity

Low

High

Anticipated added fetal morbidity or mortality of planned vaginal birth

For example, breech presentation, active genital herpes in a mother in labour, previous caesarean section

High

Low

Anticipated added fetal morbidity or mortality of planned caesarean section

Respiratory distress syndrome more common with elective caesarean section, particularly relevant in maternal diabetes mellitus

Low

High

44

Chapter 5  Antenatal Care Beyond the First Antenatal Visit

TIMING AND MODE OF BIRTH TIMING OF BIRTH The median onset of spontaneous labour is 40 weeks’ from the first day of the LNMP, which equates to approximately 38 weeks from fertilisation. However, approximately 1 in 400 women will have a perinatal death or long-term disability for her offspring as a consequence of an event after maturity (38 weeks’). This does not mean that everyone should have their baby at 38 weeks’, but rather emphasises that those women with complications that make the risks of long-term consequences even higher are commonly offered early birth. Some of the more common conditions that mostly would be recommended to be delivered prior to 40.0 weeks’ include hypertensive disorders such as preeclampsia, intrauterine growth restriction, diabetes mellitus and twins. That is not to say that every incidence of these conditions must be delivered before 40 weeks’, but that recommendation would apply to most women. Other factors to consider are: 1. the severity of the condition; 2.

ripeness of the cervix for induction; and 3. priorities of the woman in terms of ‘what level of fetal risk’ is reasonable in order to avoid a medical intervention such as induction of labour.

MODE OF BIRTH While most women would rightly prefer a vaginal birth, there are increasing numbers of women who, having fully informed themselves of the pros and cons of elective caesarean section, choose that mode of birth. Factors that militate in favour of or against an elective caesarean section are given in Table 5.1. FURTHER READING International Association of Diabetes and Pregnancy Study Groups. Recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33(3):676–82. Centers for Disease Control and Prevention. Prevention of perinatal Group B streptococcal disease. Revised Guidelines. CDC; 2010.

45

Chapter 6  OBESITY AND NUTRITION IN PREGNANCY Alexis Shub

KEY POINTS

Good nutrition and healthy weight gain can improve maternal and perinatal outcomes. Folate supplementation is recommended prior to pregnancy and during the first trimester. Iodine supplementation is recommended during pregnancy. Iron and vitamin D supplementation may be necessary in at-risk groups. Pregnant women should be given food handling advice to minimise the risk of Listeria infection. Optimal gestational weight gain in pregnancy can optimise pregnancy outcomes. Weight gain targets have been developed for singletons and multiple pregnancies, and across different body mass index (BMI) strata.

INTRODUCTION For many women, pregnancy is a time of extra interest and care in diet and nutrition. Good nutrition and appropriate weight gain can improve pregnancy outcomes. Pregnancy is an ideal time to educate women about healthy lifestyle and to impact both on their own health and that of the next generation. Knowledge in the community of appropriate weight gain targets and nutritional practises in pregnancy is poor and obesity and excess gestational weight gain are common problems in our community. In some groups, additional nutrient supplementation is required. A dietary history and counselling should be part of the first antenatal visit. Topics to be covered include adequate intake of essential nutrients, total energy intake and food safety issues.

DIETARY GUIDELINES IN PREGNANCY Healthcare professionals caring for a pregnant woman have an opportunity to impact on each woman’s

pregnancy and also on her ongoing health and wellbeing and that of her family. A short dietary history should be taken at the first antenatal visit covering amount and variety of food eaten, the intake of fast foods and ‘extra foods’, foods that are higher risk in pregnancy and advice about weight gain. The body mass index (BMI) should be calculated and explained to the woman. Dietary guidelines in pregnancy are similar to those in the non-pregnant population, with an emphasis on consuming a wide range of foods including fruit and vegetables, low-fat dairy products, cereals and proteinrich foods. The additional caloric requirements for pregnancy are surprisingly low. There is no additional requirement in the first trimester. In the second trimester, a further 1.4 MJ (330 calories) per day is needed. Examples of how this can be met are: two serves of fruit, one egg and one carrot, or a low-fat cheese sandwich and one serve of fruit. The additional needs in the third trimester are 1.9 MJ (450 calories) per day, which can be met with the above examples plus an additional half cup of baked beans or one glass of low-fat milk. These additional needs are much lower than the need to ‘eat for two’ that is still widely believed. A typical

Chapter 6  Obesity and Nutrition in Pregnancy

pregnant and non-pregnant diet intake for each day is listed in Table 6.1, demonstrating the small increases required in pregnancy. For some women with more complex nutritional needs, a single visit or ongoing care in conjunction with a dietician may be needed. This includes women: with prepregnancy or gestational diabetes who are significantly underweight or overweight with underlying gastrointestinal pathology such as inflammatory bowel disease with severe or prolonged hyperemesis gravidarum with metabolic disorders such as phenylketonuria who are post-bariatric surgery with eating disorders with fluid restriction due to cardiac or renal disease with restrictive diets (e.g. vegans, restriction of multiple food groups) with very difficult social circumstances such as homelessness.

• • • • • • • • • •

VITAMIN AND MINERAL SUPPLEMENTATION For women with an adequate diet in Australia, good evidence only exists for routine supplementation with iodine and folate. In some subgroups there may be additional need for vitamin D, iron, vitamin B12 or high-dose folate supplementation. For many women, the most practical form of supplementation will be a pregnancy-specific multivitamin containing an adequate amount of folate and iodine. Non-pregnancy multivitamins should be avoided as they may contain excess amounts of vitamin A, which is teratogenic.

FOLATE Maternal intake of adequate folate in the periconceptual period and through the first trimester has been shown to

reduce the risk of fetal neural tube defects (spina bifida and anencephaly) and so is recommended for all women. Bread in Australia, with the exception of organic bread, is made with folate-fortified flour. Folate can also be obtained from fruit, green leafy vegetables and legumes. All women are advised to take folate supplementation of 0.5 mg from the time of planning pregnancy until 12 weeks’ gestation for this purpose. Woman at higher risk of having a baby with a neural tube defect (Box 6.1) are advised to take a higher dose of folate (5 mg). Folate may also have a role in reducing pregnancy complications such as abruption in woman with a poor diet.

IRON In pregnancy, around 4 to 5 mg of iron needs to be absorbed each day in comparison to 1.5 mg in nonpregnant women. The recommended dietary intake (RDI) is 27 mg. Many women will start pregnancy with low iron stores (low ferritin) without having iron deficiency anemia (low haemoglobin). Reference ranges for haemoglobin are lower in pregnancy, and non-pregnant ranges as reported by most laboratories will overdiagnose anaemia in pregnancy. There is variable evidence of the benefits of routine supplementation in women with an adequate diet who are not anaemic, with some suggestion of increased birth weights and less preterm delivery. Women who have iron deficiency anemia will need additional supplementation, with a specific iron supplement, containing at least 60 mg of iron daily. Women

BOX 6.1  Women requiring high-dose folate.

Previous baby with spina bifida or anencephaly Type 1 or 2 diabetes Women taking anticonvulsants Obesity

TABLE 6.1  CORE FOOD GROUP SERVES FOR NON-PREGNANT AND PREGNANT WOMEN. Cereals (breads, rice, pasta and noodles)

Vegetables and legumes

Fruit

Milk, yoghurt, cheese

Lean meat, fish, poultry, nuts and legumes

Extra foodsi

Women aged 19 to 60 (non-pregnant)

4–9

5

2

2

1

0–2.5

Pregnant women (all ages)

4–6

5–6

4

2

1–1.5

0–2.5

i

Foods that do not fit into the five food groups and are not essential to provide the nutrients the body needs. Source: National Health and Medical Research Council. Healthy Eating During your Pregnancy: Advice on Eating for You and Your Baby. Canberra: NHMRC. Online. Available: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n55h_healthy_eating_during_ pregnancy.pdf; 14 Dec 2014. Licensed under Creative Commons Attribution 3.0 Australia License.

47

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with additional iron needs in pregnancy, such as multiple births or decreased dietary iron intake (e.g. vegetarians), should also take iron supplements.

IODINE Overall in the Australian community, there is a mild iodine deficiency but it is difficult to measure an individual’s iodine status. Iodine is found in seafood and seaweed, but in very small amounts in other foods. In Australia it is a requirement that all salt used to make bread (except organic) uses iodised salt and this provides sufficient iodine for most of the population. Because pregnant women and women considering a pregnancy have a greater need for iodine, the National Health and Medical Research Council (NHMRC) recommends supplementation of 150 mcg/day. This is found in some pregnancy multivitamins and should be taken throughout the pregnancy. Further consultation with an endocrinologist should occur in women with underlying thyroid disease.

CALCIUM The total fetal need for calcium throughout the pregnancy is approximately 30 g. The RDI of calcium in pregnancy is 1000 mg/day, which is the same as in the non-pregnant population, as the increased needs of pregnancy are predominantly met by increased maternal absorption of dietary calcium. Calcium is not taken from maternal bone stores in pregnancy. Calcium supplementation may have a role in prevention of preeclampsia in women who are at high risk of preeclampsia and have a low dietary calcium intake.

VITAMIN D Vitamin D deficiency (< 50 mmol/L) and insufficiency (< 75 mmol/L) are common in the Australian obstetric population, especially in the southern states. Adequate vitamin D is very difficult to achieve from diet alone and is primarily obtained from sun exposure. This insufficiency has been linked to reduction in sun exposure due to increased skin cancer awareness and to the changing population demographics with an increase in women who are dark skinned or veiled. There is no current proven association between low maternal vitamin D and poor obstetric outcomes including gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) or preeclampsia.1 Low maternal vitamin D is, however, associated with an increased risk of neonatal hypocalcaemia and rickets, and women in high-risk groups should be screened in early pregnancy and treated with 2000 IU vitamin D daily if levels are below 50 mmol/L.

MERCURY Concern has been raised about the mercury content of fish, particularly in larger, longer-lived species, from naturally occurring mercury in the environment. High levels 48

of mercury may impact on fetal neurological development and so a reduced consumption of these is suggested in pregnancy. Pregnant women should eat shark (flake), broadbill, marlin and swordfish no more than once a fortnight and should not eat any other fish during that fortnight. Orange roughy and catfish should be eaten no more than once a week, and no other fish should be eaten during that week. Tinned tuna and salmon are safe to eat two to three times a week, as are other smaller fish not listed above. All these recommendations are based on a serving size of 150 g.

LISTERIA Pregnant women and other immunocompromised groups in the community are at higher risk of foodborne illness such as listeriosis; however, cases of listeria in Australia are uncommon. Listeria is caused by the aerobic and facultatively anaerobic gram-positive bacillus Listeria monocytogenes and is associated with consumption of contaminated food. Listeria in pregnancy is associated with miscarriage, still birth and preterm birth. Listeriosis should be considered in a pregnant women presenting with headache, fever, tiredness, aches and pains. Less common symptoms include diarrhoea, nausea and abdominal cramps. These symptoms may occur weeks after the contaminated food is eaten. Women should be advised to avoid the high risk foods listed in Box 6.2 and use careful safe food-handling practices.

WEIGHT GAIN IN PREGNANCY Optimal weight gain in pregnancy is associated with improved maternal and neonatal outcomes. Excess weight

BOX 6.2  Foods with increased risk of Listeria contamination. Foods to avoid include: cold meats from delicatessen counters and sandwich bars packaged, sliced ready-to-eat meats cold cooked ready-to-eat chicken (whole, portions or diced) pre-prepared or pre-packaged fruit or vegetable salads, including those from buffets and salad bars chilled seafood (such as raw oysters, sashimi and sushi), smoked ready-to-eat seafood and cooked ready-to-eat prawns soft, semi-soft and surface-ripened cheeses such as brie, camembert, ricotta, blue and feta refrigerated pate or meat spreads soft serve ice-cream unpasteurised dairy products.

Chapter 6  Obesity and Nutrition in Pregnancy

gain, even in women who begin pregnancy in the healthy weight range, is associated with increased rates of preeclampsia, macrosomia, babies that are small for gestational age, GDM, failed induction of labour, caesarean section and childhood obesity. Weight gain targets have been defined for each BMI category for singleton and twin pregnancies (Table 6.2). Weight gain targets have not been defined for the extremely obese woman, but many studies show that no weight gain, or even a small weight loss, in these women leads to acceptable outcomes. Overweight and obesity are increasingly common in the Australian community and throughout the world, with approximately 30% of women overweight and 20% of women obese in many centres. Women who are overweight or obese have increased rates of preeclampsia, gestational diabetes, operative delivery and thromboembolic disease.2 Their infants are more likely to be macrosomic, be growth restricted, have higher perinatal mortality and have higher rates of fetal abnormalities. Some of these risks are due to the underlying comorbidities associated with being overweight such as diabetes and hypertension; however, obesity itself appears to increase obstetric risk, which may result from the inflammation and endothelial dysfunction present in obese women. The risks to the mother and the baby increase in proportion to the BMI (Table 6.3). Worryingly, the infants of obese mothers and women with excess gestational weight gain have increased rates of obesity and cardiovascular disease into adult life.3 This probably results both from in utero programming (the epigenetic changes resulting from obesity and concurrent metabolic syndrome) and from lifestyle factors common to the families though infancy and childhood (including breastfeeding, eating habits and patterns of exercise). Outcomes for overweight and obese women in the antenatal and intrapartum period may also be compromised due to the practical implications of increased BMI. These include inadequate ultrasound imaging of fetal anomalies, less accurate clinical and ultrasound assessment of fetal growth, difficulty with intrapartum monitoring of the fetal heart rate and contractions, difficult intravenous access, lower success rate of regional analgesia and increased surgical difficulty for caesarean section.

Many trials have been performed to find the best way to minimise excess gestational weight gain, both in women with healthy weight gain and in the overweight and obese. Studies involving dietary intervention were most effective at minimising excess gestational weight gain, and also reduced preeclampsia and shoulder dystocia, without impacting on other obstetric outcomes. Many women are not aware of the guidelines for gestational weight gain and these should be explicitly discussed as part of routine antenatal care. Regular weighing in the antenatal period was stopped in many hospitals as it is a poor diagnostic or predictive test for preeclampsia or

TABLE 6.3  RISKS OF INCREASED BMI.* Healthy weight range

BMI 30–35

BMI > 40

Hypertension in pregnancy

1

3.2

6.5

Gestational diabetes

1

3.1

6.5

Caesarean section

1

2.0

3.0

Perinatal mortality

1

1.5

2.3

Preterm birth

1

1.2

1.6

Small for gestational age infant

1

1.1

1.6

Large for gestational age infant

1

1.3

1.6

* Adjusted odds ratios for age parity, smoking, ethnicity, insurance status, with healthy weight range as the reference range. Source: McIntyre DH, Gibbons KS, et al. Overweight and obesity in Australian mothers: epidemic or endemic? Med J Aust 2012; 196(3):184–8 © Copyright 2012 The Medical Journal of Australia— adapted with permission. The Medical Journal of Australia does not accept responsibility for any errors in adaptation.

TABLE 6.2  WEIGHT GAIN TARGETS FOR SINGLETON AND TWIN PREGNANCIES. BMI at beginning of pregnancy

Recommended weight gain (kg)

Rate of weight gain/week in 2nd and 3rd trimester

Recommended pregnancy weight gain for twins (kg)

Underweight (< 18.5)

12.5–18.0

500 g

N/A

Normal (18.5–24.9)

11.5–16.0

400 g

17.0–24.5

Overweight (25–29.9)

7.0–11.5

300 g

14.0– 22.5

Obese (≥ 30)

5.0–9.0

200 g

11.0–19.0 49

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IUGR; however, it provides an excellent opportunity for clinicians to discuss weight gain targets and improves gestational weight gain compliance. Many women welcome the opportunity to discuss their weight gain and reduce their risk of postpartum weight retention.

2) McIntyre HD, Gibbons KS, Flenady VJ, et al. Overweight and obesity in Australian mothers: epidemic or endemic? Med J Aust 2012;196:184–8. 3) Morandi A, Meyre D, Lobbens S, et al. Estimation of newborn risk for child or adolescent obesity: lessons from longitudinal birth cohorts. PLoS ONE 2012;7(11).

BARIATRIC SURGERY

FURTHER READING Food Standards Australia. Online. Available: http://www .foodstandards.gov.au Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines; Rasmussen KM, Yaktine AL, editors. Weight gain during pregnancy: reexamining the guidelines. Washington: National Academies Press; 2009. Thangaratinam S, Rogozińska E, Jolly K, et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012;344.

Bariatric surgery is becoming increasingly common in women of reproductive years, and will improve rates of spontaneous conception for many very obese women. Bariatric surgery appears to improve outcomes for the woman, with reduced rates of gestational diabetes and hypertension, but this may be at a cost to the fetus with increased risk of IUGR and perinatal mortality. These results may be more pronounced in women who have malabsorptive surgery rather than restrictive surgery, but restrictive surgery is more common in Australia. Pregnancies after bariatric surgery, especially malabsorptive procedures, require additional dietician input and increased fetal surveillance. REFERENCES 1) Harvey NC, Holroyd C, Ntani G, et al. Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess 2014 Jul;18(45):1–190.

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Section 2.2 PROBLEMS OF EARLY PREGNANCY Chapter 7

Hyperemesis gravidarum

Chapter 8

Bleeding in early pregnancy

Chapter 7  HYPEREMESIS GRAVIDARUM Neil Israelsohn

KEY POINTS Hyperemesis gravidarum is a specific condition with symptoms and effects over and above the common nausea and vomiting of early pregnancy. Pharmacological therapy is useful for those women who have not responded to the strategies mentioned in this chapter. A stepwise approach to therapy is recommended. Nausea and vomiting with atypical features (e.g. commencing after 12 weeks’ gestation) should not be considered to be hyperemesis gravidarum and needs exclusion of other causes.

DEFINITION Nausea and vomiting in the first trimester is one of the most common symptoms of early pregnancy and will affect the majority of women. Approximately 80% will experience some nausea and 50% will experience vomiting as well. Hyperemesis gravidarum is a specific condition with symptoms and effects over and above the common nausea and vomiting of early pregnancy. It affects approximately 1% of pregnancies. While definitions may vary, a common definition used is: ‘Intractable vomiting associated with weight loss of ≥5% of pre-pregnancy weight, dehydration and electrolyte imbalances which may lead to hospitalisation’.1

AETIOLOGY The exact aetiology of nausea and vomiting of pregnancy is still somewhat debated. It is thought that hormonal factors, specifically rising β-hCG and oestrogen levels, are the most likely primary factor. Other patient factors— gastrointestinal, vestibular, psychological, social and cultural—may mediate the patient’s response to the hormonal changes.

Higher levels of β-hCG (multiple pregnancy, molar pregnancy) are associated with more prevalent and severe nausea and vomiting.

CLINICAL FEATURES The term ‘morning sickness’ is truly a misnomer and women with nausea and vomiting in early pregnancy may experience these symptoms at any time of the day and often throughout the day. Symptoms often begin by 5 weeks’, peak between 11 to 12 weeks’ and resolve usually by 14 weeks’ gestation. Nausea and vomiting may continue into the second or third trimester in up to 20% of women. Symptoms may be aggravated by certain smells, preparing meals and eating particular foods. Fatigue may also increase the severity of symptoms. The psychological impact and effect on relationships and activities of daily living can be profound and warrants appropriate attention and care. Clinical features of severe dehydration, electrolyte disturbance and vitamin deficiency may be present in severe cases. Specifically, thiamine deficiency and the resulting Wernicke’s encephalopathy (ophthalmoplegia, ataxia, confusion) is a very rare, but serious, complication of protracted hyperemesis gravidarum.

Chapter 7  Hyperemesis Gravidarum

MANAGEMENT OF VOMITING IN PREGNANCY ASSESSMENT It is important to exclude other pathological causes of nausea and vomiting before ascribing it to pregnancy. Other causes may include (but are not limited to) gastritis, gastroenteritis, bowel obstruction, biliary colic, cholecystitis, appendicitis, pancreatitis, hepatitis, urinary tract infection and metabolic and neurological conditions. Investigations will depend on the clinical findings but should include: pelvic ultrasound to confirm gestation, exclude multiple pregnancy or molar pregnancy tests for renal function, electrolytes and liver function midstream urine for micro/culture/sensitivity to exclude urinary tract infection urinalysis for urinary ketones. Minor derangements of liver function tests are sometimes seen with hyperemesis gravidarum. Significant abnormalities should raise suspicion of an underlying gastrointestinal cause.

• • • •

TREATMENT FOR NAUSEA AND VOMITING OF PREGNANCY Reassurance regarding the self-limiting nature of the condition is often all that is needed for mild nausea and vomiting in pregnancy. Improving lifestyle factors including dietary changes and rest and avoiding precipitating factors is first-line treatment. Specifically, eating small, frequent meals that are low in fat content is commonly suggested. Ginger may be helpful. Women should drink small volumes often to avoid dehydration and take a multivitamin tablet if tolerated. Other non-pharmacological treatments include acupuncture and acupressure. A Cochrane review did not show a statistically significant effect in reducing the severity or duration of symptoms. Pharmacological therapy is useful for those women who have not responded to the aforementioned strategies. A stepwise approach to therapy is recommended. When oral medication is tolerated, first-line treatment is pyridoxine (vitamin B6). If further therapy is needed, simple antiemetics are prescribed such as doxylamine (Restavit©) or metoclopramide (Maxolon©). Both are classified as pregnancy category A drugs (i.e. taken by a large number of pregnant women without an increase in the frequency of malformation or other harmful effects). For the more refractory cases, ondansetron (Zofran) (pregnancy category B1, i.e. taken by only a limited number of pregnant women without an increase in the frequency of malformation or other harmful effects) would be the common third-line treatment.

If vomiting continues despite the measures mentioned, corticosteroids (e.g. oral prednisolone) can be effective in some cases, but the dose and duration should both be minimised in view of the maternal side effect profile with high doses or prolonged use.

Adjuvant therapies It is important to manage the coexisting oesophageal acid reflux associated with recurrent vomiting. Ranitidine 150 mg orally twice daily (pregnancy category B1) should be added to improve symptomatic relief.

TREATMENT FOR HYPEREMESIS GRAVIDARUM Patients with hyperemesis gravidarum will require admission for intravenous hydration and control of vomiting and associated biochemical disturbance. Admission may be to a dedicated pregnancy daycare centre, emergency department or inpatient ward depending on facilities available. Fluid replacement usually begins with 0.9% normal saline or Hartmann’s solution 1 L stat in the absence of any significant renal or cardiac condition. Further administration of intravenous fluids will be dictated by level of dehydration. Potassium replacement may be required—if administered intravenously, the rate should not exceed 10 mmol/hr. Oral potassium replacement is preferred if tolerated. Intravenous antiemetics are administered (metoclopramide or ondansetron). A water-soluble vitamin solution can be added to the intravenous hydration. Thiamine 100 mg intravenously/oral daily for 3 days may be required in extreme cases. Once the patient is tolerating light diet and fluids, she may be discharged. Ongoing management through a pregnancy day ward may be necessary (2 to 3 times per week) if the patient is unable to maintain a reasonable oral fluid intake at home. A dietician referral may be made as an inpatient or outpatient. Consideration of parenteral feeding or hyperalimentation may be necessary. REFERENCE 1) Miller F. Nausea and vomiting in pregnancy: the problem of perception—is it really a disease? Am J Obstet Gynecol 2002;186(5 Suppl Understanding): S182–3. FURTHER READING Arsenault MY, Lane CA. The management of nausea and vomiting of pregnancy. Clinical practice guideline 120. Society of Obstetricians and 53

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Gynaecologists of Canada (SOGC). October 2002. J Obstet Gynaecol Can 2002;24(10):817–23. Hiscock R, Palmer G. Nausea and vomiting in pregnancy. In: Gastrointestinal therapeutic guidelines. Version 5. Melbourne: Therapeutic Guidelines; 2011. Marley J, Chamberlain A, Goodman G. Corticosteroids— adverse effects. In: Therapeutic guidelines:

54

dermatology. Version 3. Melbourne: Therapeutic Guidelines; 2009. Matthews A, Dowswell T, Haas DM, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2010.

Chapter 8  BLEEDING IN EARLY PREGNANCY Neil Israelsohn

KEY POINTS Bleeding in early pregnancy should be considered to be an ectopic pregnancy until proven otherwise. Definitive management of miscarriage and ectopic pregnancy needs to be individualised depending on the patient’s clinical and social circumstances. Young, healthy women may compensate so effectively for significant blood loss as to have no/few signs of haemodynamic instability prior to haemodynamic collapse. Gestational trophoblastic disease should be considered in those with significant, persistent bleeding postpartum.

EARLY PREGNANCY BLEEDING

IS THE PREGNANCY VIABLE?

Early pregnancy assessment clinics (EPAC) are now common in hospitals managing pregnancy. They help to streamline the diagnosis and management of early pregnancy bleeding and provide a point of contact for ongoing medical care and support. Table 8.1 gives a simple differential diagnosis for bleeding in early pregnancy. In assessing the patient with early pregnancy bleeding, two important clinical questions need to be answered. 1. Is the pregnancy intrauterine? 2. Is the pregnancy viable?

Once an intrauterine pregnancy is confirmed, its viability should be determined. Serum β-hCG has little to offer in the management of an intrauterine pregnancy and the presence of fetal heart activity confirms viability. Any one of the following criteria is indicative of a failed pregnancy according to the guidelines of the Australian Society of Ultrasound in Medicine (ASUM): mean gestational sac diameter > 25 mm with no fetal pole fetal pole > 7 mm and no fetal heart activity inadequate growth of the gestational sac or fetal pole over the course of a week (i.e. < 1 mm per day). Poor prognostic features include a bradycardia (< 85 bpm) and significant subchorionic haematoma formation (Fig 8.2).

IS THE PREGNANCY INTRAUTERINE? All patients with bleeding and a non-localised pregnancy should be considered to have an ectopic pregnancy until proven otherwise. Ultrasound (usually transvaginal) and quantitative serum β-hCG form the basis for localising the pregnancy (Fig 8.1). The key component of this algorithm is the use of transvaginal ultrasound irrespective of the serum β-hCG. While intrauterine pregnancy contents are not expected to be visualised if the β-hCG < 1500 IU/L, an ectopic pregnancy with an inappropriate β-hCG for gestation may still be seen.

• • •

MISCARRIAGE A miscarriage is the presence of a non-viable intrauterine pregnancy before 20 weeks’. It is not necessary for there to be an embryo or fetus present. Clinically recognised miscarriage occurs in approximately 15% of pregnancies.

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TABLE 8.1  DIFFERENTIAL DIAGNOSIS OF EARLY PREGNANCY BLEEDING. Diagnosis

Cause

Not pregnant

In rare cases, a woman will have a false positive pregnancy test or for some other reason believe she is pregnant; bleeding may therefore be a menstrual period

Intrauterine pregnancy

Viable intrauterine pregnancy Non-viable (miscarriage, gestational trophoblastic disease)

Ectopic pregnancy

Most commonly tubal but may be ovarian, cervical or abdominal

Incidental cause for bleeding

Cervical polyp/cancer, ectropion, other genitourinary tract cause

Early pregnancy bleeding +/– pain Transvaginal ultrasound

Intrauterine pregnancy

Viable

Non-viable

Extrauterine pregnancy

Unlocalised pregnancy B-hCG < 1500 IU/L

Manage accordingly

B-hCG > 1500 IU/L

?Early intrauterine versus extrauterine pregnancy

Highly suspicious of ectopic pregnancy

Consider admission

Senior obstetric review

Repeat B-hCG in 48 hours Appropriate rise in B-hCG

Inadequate rise in B-hCG

Repeat ultrasound in 1 week

FIGURE 8.1 

Management of bleeding in early pregnancy.

If unrecognised biochemical pregnancies are included, the figure is much higher.

AETIOLOGY The aetiology of miscarriage is as follows. Chromosomal abnormalities. These are the most common cause of miscarriage and are responsible for approximately 50% of spontaneous miscarriages. Most of these abnormalities are non-recurring and include trisomies (e.g. trisomy 13), monosomy X (Turner syndrome) and polyploidies (triploidy and tetraploidy). The incidence of autosomal trisomies increases with advancing age. Endocrine. Poorly controlled endocrine disorders are risk factors for both infertility and miscarriage.

•

•

56

Preexisting diabetes, thyroid disease and hyperandrogenism (e.g. polycystic ovary syndrome [PCOS]) are associated with miscarriage. Obesity is also an independent risk factor for miscarriage. Although progesterone is essential for successful implantation and continuation of pregnancy, studies have shown neither a consistent correlation between progesterone levels and risk of subsequent miscarriage nor a benefit in reducing miscarriage with the use of exogenous progesterone. Thrombophilia. Antiphospholipid syndrome is a cause of recurrent miscarriage. The association of other hypercoagulable states and miscarriage is less certain as there are conflicting reports. It may be that thrombophilia has a greater association with late (> 10 weeks’) first trimester miscarriage.

•

Chapter 8  Bleeding in Early Pregnancy

Bleeding The amount of bleeding with a miscarriage is variable. In complete miscarriage, the loss is variable during the process but thereafter usually ceases entirely. In the majority of women with threatened miscarriage, the pregnancy continues uneventfully. The risk of loss is usually proportional to the amount of bleeding; if the loss continues or recurs or if there is any associated pain, the prognosis is less favourable. First-trimester bleeding predisposes to later pregnancy complications including preterm birth and preterm prelabour rupture of the membranes.

Pain

FIGURE 8.2 

Perigestational haematoma (H). CRL indicates crown–rump length of the fetus equivalent to 7 weeks’ and 6 days’ gestation on this scan.

•

Uterine abnormalities. Uterine malformations (bicornuate or septate) or fibroids (especially submucous) are implicated in recurrent pregnancy loss. Endometrial scarring (Asherman syndrome) also contributes to miscarriage risk. Chronic maternal disease. Significant maternal medical disease (e.g. cardiac, renal, connective tissue) is another risk factor in miscarriage. Toxins. Heavy tobacco use and heavy alcohol consumption are associated with an increased risk of sporadic miscarriage. Other risk factors are medications (e.g. methotrexate) and environmental toxins (e.g. arsenic, aniline dyes, benzene, ethylene oxide, formaldehyde, pesticides, lead, mercury and cadmium). Trauma. Invasive diagnostic procedures such as chorionic villus sampling (CVS) and amniocentesis are associated with small risks of miscarriage.

•

Pain is experienced as the uterus contracts or when the cervix is dilating and products of conception are being passed. The pain is felt in the lower abdomen or back, is usually cramp-like and follows the bleeding—in contrast to the sequence in ectopic pregnancy, discussed later in this chapter.

Passage of products of conception The passage of definite tissue defines incomplete or complete miscarriage. A confusing picture is presented when the decidual lining of the uterus is passed in ectopic pregnancy (decidual cast), since this simulates trophoblastic tissue (Fig 8.3). In many women, no fetus is passed at any time, since it is either absent (blighted ovum) or rudimentary and unnoticed.

CLASSIFICATION

Aetiology of recurrent miscarriage

Miscarriages were traditionally classified according to clinical criteria as listed in Table 8.2; that is, whether the cervix is open/closed, whether any products of conception have been passed and the size of the uterus relative to dates. More recently, however, ultrasound has played a more important role in the diagnosis and classification of miscarriage. The far greater availability of firsttrimester ultrasound has led to the diagnosis of significantly more missed miscarriages in asymptomatic women. Note that the term ‘missed miscarriage’ means a ‘non-viable pregnancy that has not yet had any vaginal bleeding’. It does not mean that the diagnosis has not been made.

The causes of recurrent miscarriage are similar to that for non-recurring miscarriage. With regards to chromosomal causes, parental balanced chromosomal translocations is a causative factor in approximately 4% of recurrent miscarriage.

INITIAL MANAGEMENT Assessment

•

•

CLINICAL FEATURES Pregnancy symptoms Symptoms and signs of pregnancy are usually present; pregnancy failure may be reflected by a diminution or cessation of typical pregnancy symptoms.

Take the patient’s history to elicit details of the presenting complaint as outlined in the Clinical features section. Clinical examination should include vital signs, abdominal palpation, speculum examination and bimanual palpation. The following investigations are useful: full blood examination (FBE), blood group and save serum, quantitative β-hCG and ultrasound. 57

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Generic treatment Resuscitation The amount of blood loss during miscarriage is highly variable. Fluid resuscitation is often not necessary; however, when the blood loss is heavy and ongoing, the patient will require a crystalloid or colloid infusion while

definitive management is being arranged. If there is evidence of severe haemodynamic compromise, the patient may need O-negative blood pending cross-match.

Passive anti-D for Rh-negative women

25 cm

Anti-D is not necessary for non-immunised, Rh-negative women who have a threatened miscarriage (i.e. bleeding with a viable pregnancy) before 10 weeks’. For other miscarriages, anti-D 250 IU intramuscularly is sufficient due to the small circulating volume of fetal red cells in the first trimester.

Explanation and support Emotional support is important during this time of loss. An explanation of the possible aetiology helps to reassure the woman and her partner that, in the overwhelming majority of cases, no act or omission has either caused the miscarriage or would have helped to prevent it.

FURTHER MANAGEMENT The plan for further management will depend on the type of miscarriage.

Threatened miscarriage 30 cm

Admission is rarely necessary. Reassure the patient regarding the ongoing viability of the pregnancy. Bleeding is seldom sufficient to require transfusion or intravenous fluid.

Complete miscarriage

FIGURE 8.3 

Decidual cast. After withdrawal of hormones due to death of the ectopic chorionic villi, the thickened endometrium is shed, usually in fragments as in menstruation, but sometimes as a single piece or decidual cast of the uterus, which may be mistaken for placental tissue (uterine abortion). Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

There is usually a history of significant bleeding, pain and the passage of products of conception followed by minimal blood loss, a closed cervix and a significant reduction in pain. The uterus is empty on ultrasound. The management is conservative. In the context of an empty uterus on ultrasound, a confident diagnosis of complete miscarriage can only be made if there is pathologic confirmation of products of conception or if the pregnancy has previously been localised as intrauterine. If neither of these criteria are met, one should suspect a possible ectopic pregnancy. In this case, quantitative β-hCG should be performed weekly to document return to non-pregnant levels and the patient

TABLE 8.2  CLASSIFICATION OF MISCARRIAGE. Miscarriage type

Cervix

Products of conception passed

Threatened miscarriage

Closed

No

Viable intrauterine pregnancy

Missed miscarriage

Closed

No

Non-viable intrauterine pregnancy

Inevitable miscarriage

Open

No

Non-viable intrauterine pregnancy; often low in the uterus

Incomplete miscarriage

Open

Yes

Retained products of conception

Complete miscarriage

Closed

Yes

Empty uterus; no extrauterine pregnancy

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Ultrasound findings

Chapter 8  Bleeding in Early Pregnancy

should be asked to present earlier if she experiences significant pain or bleeding.

Inevitable miscarriage While the patient will go on to pass the products of conception, this may occur after a variable amount of further bleeding and/or pain. Expectant or medical management is most appropriate. Occasionally patients will require a curette if there is sustained heavy bleeding.

Incomplete miscarriage This common presentation causes the most trouble from bleeding and shock; blood transfusion may be required in a few women. Cervical shock may occur if products become trapped within the cervix. This presents as bleeding, significant pain and often vagal/parasympathetic symptoms (bradycardia, hypotension, sweatiness and nausea/vomiting). Speculum visualisation of the cervix and removal of the products with sponge forceps may be necessary (Fig 8.4). It is often necessary to perform a curette to ensure complete removal of products of conception. If there is no

A

evidence of cervical tissue and bleeding is heavy and ongoing, ergometrine 0.5 mg intravenously may be trialled while theatre is arranged for an urgent curette. Usually, the bleeding is much less troublesome, and after the diagnosis has been made, ongoing management options are discussed, as detailed in the next section.

Missed miscarriage Ultrasound criteria for confirming a non-viable pregnancy are described earlier in this chapter. Where there is no suggestion of a septic miscarriage or haemodynamic instability, ongoing management may be expectant, medical or surgical. A Cochrane review has revealed that the rates of infection are similar for each management strategy. While the likelihood of success is a critical factor in determining ongoing management, other issues to consider include the patient’s: tolerance of potential ongoing bleeding and/or pain at home acceptance of having a complete miscarriage in a setting outside of the hospital

• •

B

FIGURE 8.4 

Incomplete miscarriage at 10 weeks’ gestation in a 21-year-old primigravida who presented with heavy vaginal bleeding and abdominal pain. A Placental tissue is seen protruding through the cervical os. Sponge-holding forceps grasp and remove the placental tissue. B Products of conception visible at a partly dilated external os. Source: Courtesy of Prof. Norman Beischer.

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• •

desire to avoid surgery/intervention access to medical services in the case of an emergency.

Expectant management Expectant management of a missed miscarriage is associated with more days of bleeding and unplanned surgical procedures as compared with surgical management. It can take up to 4 weeks for successful spontaneous miscarriage. Success rates are presented in Table 8.3.

Medical management Prostaglandin E1 (misoprostol) is used for medical management of miscarriage due to its low cost, ready availability and benign side effect profile. Side effects may include nausea, vomiting, diarrhoea, flushing and abdominal cramps. One common schedule is 800 mcg misoprostol PV followed by another 800 mcg 12 hours later if pregnancy products have not been passed. Medical management has greater rates of success as compared to expectant management yet still has a longer duration of bleeding and more unplanned procedures as compared with surgical management. Success rates are presented in Table 8.3.

Surgical management Cervical dilation and suction curette provides definitive management in almost all cases of missed or incomplete miscarriage. Minimal bleeding and period-like pain can be expected after the procedure. It is, however, associated with uncommon but potentially serious complications including anaesthetic risks and uterine perforation that may be associated with visceral or vascular damage. Uterine adhesions are very unlikely following a single curette in the absence of infection.

TABLE 8.3  SUCCESS RATES OF EXPECTANT, MEDICAL AND SURGICAL MANAGEMENT OF MISCARRIAGE. Management

Successful spontaneous miscarriage Missed/anembryonic miscarriage (%)

Incomplete miscarriage (%)

Week 1

30

53

Week 2

56

84

Day 3

71

93

Day 8

85

Medical

60

Septic miscarriage may complicate any of the forms of miscarriage but is mostly restricted to those where retained products are neglected. Historically, it was a consequence of criminally induced abortion. These rates have dropped significantly now that abortion is lawful in all Australian states, under certain conditions. In addition to the common symptoms of miscarriage, the patient will commonly have an offensive vaginal discharge, abdominal pain and fever. Common bacteria include anaerobic organisms (streptococci and Bacteroides) and enteric flora (E. coli). Severe infection may lead to septicaemia with ensuing shock, disseminated intravascular coagulation (DIC) and multi-organ failure. In the days of ‘backyard abortion’, Clostridium perfringens (welchii) was the responsible pathogen. Treatment involves broad-spectrum intravenous antibiotics and generally a curette, which is often delayed or performed under ultrasound guidance considering the increased risk of uterine perforation.

PROGNOSIS Most women are worried about both the immediate and long-term implications of bleeding in early pregnancy. Women should be reassured that bleeding in the presence of a viable pregnancy is usually benign and does not result in miscarriage. First-trimester bleeding may also be associated with a small increase in several pregnancyrelated complications: premature rupture of membranes, preterm labour, recurrent antepartum haemorrhage and growth restriction. Although not evidence-based, it may be worth considering cervical surveillance in women with significant and recurrent first-trimester bleeding.

SECOND-TRIMESTER MISCARRIAGE Second-trimester miscarriage affects approximately 1% of pregnancies. For pregnancies greater than 14 weeks’, medical management in a hospital setting is generally utilised in preference to surgical management. Misoprostol is the preferred oxytocic agent. Dilation and evacuation may be preferred in some circumstances by experienced clinicians.

RECURRENT MISCARRIAGE

Expectant

Surgical

Septic miscarriage

90–100

90–100

Recurrent miscarriage is defined as three or more successive miscarriages. It is estimated that recurrent miscarriage affects 1% of couples trying to conceive. Mostly this is idiopathic and no cause will be found in approximately 50% of couples. Investigations that can be undertaken include imaging of the uterus, endocrine profiling (especially thyroid), thrombophilia screening and parental karyotyping. However, even after three successive miscarriages there will be a live birth in approximately 70% women.

Chapter 8  Bleeding in Early Pregnancy

The chances are better in those with idiopathic recurrent miscarriage. If another miscarriage were to occur, the products of conception should be sent for karyotyping.

ECTOPIC PREGNANCY

The classical triad of symptoms is amenorrhoea (75%), lower abdominal pain (95%) and vaginal bleeding (75%). A similar picture may be seen with a miscarriage in progress.

PREDISPOSING FACTORS

An ectopic pregnancy occurs with the implantation of the conceptus outside the uterine cavity, usually in the fallopian tube (Fig 8.5) and rarely in the ovary, abdominal cavity or cervix (Fig 8.6). It occurs in approximately 1% of pregnancies.

The predisposing factors of an ectopic pregnancy are: previous ectopic pregnancy progesterone-only or emergency hormonal contraception intrauterine contraceptive device IVF tubal damage or adhesions. Kinking or narrowing of the tube will prevent the fertilised ovum making its way from the ampulla to the uterine cavity. Apart from the mechanical effect of the narrowing, damage to the cilia of the tubal epithelium will impede transport of the fertilised ovum. Common antecedents are chlamydial or gonococcal salpingitis, postabortal or postpartum salpingitis, and appendicitis. Endometriosis, congenital abnormalities and previous tubal surgery may also impair tubal function.

• • • • •

PATHOLOGY AND CLINICAL FEATURES Tubal pregnancy There are three main outcomes of a tubal ectopic pregnancy.

FIGURE 8.5 

Tubal pregnancy. The tube is grossly distended and has a thickened haemorrhagic wall which accounts for the unusually advanced duration of pregnancy (9 weeks’) before rupture occurred. Source: Courtesy of Prof. Norman Beischer.

Ampulla 55%

Isthmus 18%

Interstitial 4%

Ovary 2% Abdominal cavity 1%

FIGURE 8.6 

Fimbrial 20%

Relative frequency of sites of implantation of ectopic pregnancies.

Tubal abortion The conceptus is extruded out the fimbrial end of the tube. This is accompanied by colicky pain, followed by a more constant pain because of the presence of blood in the peritoneal cavity. The condition may settle spontaneously, but usually pain and bleeding continues and surgery is required.

Tubal rupture If the pregnancy progresses and tubal abortion does not occur, tubal rupture is inevitable (Fig 8.7). Acute rupture is associated with severe intraperitoneal bleeding and acute abdominal pain; often pain is also felt in the shoulder tip (due to irritation of the diaphragm by blood) and on defecation or passing flatus due to blood in the pouch of Douglas between the rectum and the upper vagina. Hypotension is a late sign of significant blood loss in this population and the patient may show few or no signs of haemodynamic instability before deteriorating rapidly in the face of ongoing concealed bleeding. A tachycardia alone should be considered to be highly significant in a patient with known or suspected ectopic pregnancy. The abdomen may exhibit signs of peritonism with generalised and rebound tenderness. Rupture may occur into the broad ligament, forming a broad ligament haematoma (Fig 8.7). Symptoms and 61

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signs of peritonitis are absent, but pelvic pain and tenderness are marked.

Missed tubal abortion

•

The embryo dies and usually is absorbed. The clinical features are those of early pregnancy, together with a brown or red vaginal loss and perhaps mild, lower abdominal pain. Often no pregnancy is located on ultrasound.

Other sites for ectopic pregnancy The following are other potential sites for an ectopic pregnancy. Cornual/interstitial pregnancy. The pregnancy is implanted in the proximal portion of the tube embedded within the uterine musculature. Because of the thicker muscular coat, such women usually present much later than is the case with the other types and rupture may be sudden and associated with

•

• • •

catastrophic blood loss. Pregnancy in a rudimentary uterine horn may present similarly. Cervical pregnancy. This is rare, but should be suspected when bleeding is heavy, particularly on vaginal examination. A small, firm uterus can be felt above the expanded cervix; this can be confused with the expansion caused by products of conception in the course of a miscarriage of an intrauterine pregnancy. Ultrasound will help to confirm the diagnosis (Fig 8.8). Uterine scar pregnancy. The pregnancy is located in the scar and is surrounded by myometrium and connective tissue (Fig 8.9). Heterotopic pregnancy. Concomitant intrauterine and extrauterine pregnancy is very uncommon, although it has a higher incidence among IVFconceived pregnancies. Abdominal pregnancy. This is an extremely rare occurrence and may take place due to primary implantation of a fertilised ovum in the peritoneal cavity or secondary implantation after a tubal abortion.

DIAGNOSIS Diagnosis of an ectopic pregnancy with the use of serum β-hCG and transvaginal ultrasound (Fig 8.10) is described earlier in the chapter (see Fig 8.1).

MANAGEMENT A ruptured ectopic pregnancy can present as a medical emergency and maternal collapse. There may be minimal information regarding preceding symptoms. A high level of suspicion should be maintained for any woman of

FIGURE 8.7 

Possible outcomes of tubal pregnancy are rupture into the peritoneal cavity, tubal lumen or broad ligament. Tubal missed abortion without rupture can occur asymptomatically and result in obliteration of the tubal lumen and later sterility. Note that the pregnancy distends the tubal wall, not its lumen; this explains why incision and expression often results in a patent tube. 62

FIGURE 8.8 

Cervical ectopic pregnancy. The body (B) of the uterus is empty. The cervix (C) is distended by the cervical ectopic pregnancy (E). This can often be confused with an inevitable miscarriage.

Chapter 8  Bleeding in Early Pregnancy

FIGURE 8.9 

Uterine scar pregnancy. The fundus (F) is seen with no gestational sac. The ectopic pregnancy (E) is located in the scar, outside of the uterine cavity and above the cervix (C), surrounded by myometrium.

FIGURE 8.10 

Tubal ectopic pregnancy. The adnexal mass (MASS) is seen medial to the left ovary (LO) in the ‘ectopic triangle’ between the ovary and lateral uterine wall.

reproductive age presenting with unexplained severe haemodynamic compromise or collapse. In these cases, it is important to secure intravenous access, take blood for FBE, cross-match 4 to 6 units of blood and perform a coagulation screen. Commence resuscitation with O-negative blood (or intravenous fluid if blood is not immediately available). Anaesthetics should be informed and arrangements made for an emergency laparotomy. In more subacute or asymptomatic presentations, the initial management is similar to that for the woman with suspected miscarriage: essentially intravenous access, blood tests ± intravenous fluid. Treatment of the ectopic pregnancy is generally either medical or surgical. Expectant management may be followed for women with low or declining β-hCG levels and no recognisable ectopic mass on ultrasound.

Medical treatment Methotrexate is a folate antagonist and inhibits DNA synthesis in rapidly dividing cells. The contraindications to medical treatment are listed in Box 8.1. The success rate of medical management in the absence of contraindications is 90%. Side effects of methotrexate are usually mild and include nausea, diarrhoea, stomatitis and gastritis. Less common but severe effects include pneumonitis, abnormal liver function and bone marrow suppression. Renal and liver impairment should be excluded before commencing therapy. There remains a risk of ectopic rupture during medical management. Return of β-hCG levels to normal may take several weeks and a delay of 3 months before conceiving again is generally recommended. It is important that patients are informed of these facts prior to

BOX 8.1  Contraindications to medical treatment. Haemodynamic instability or evidence of tubal rupture β-hCG > 5000 or tubal mass > 3.5 cm Fetal heartbeat Lack of access to timely medical assistance in the event of ectopic rupture Patient not able to comply with post medical treatment follow-up Contraindication to methotrexate (hypersensitivity, renal disease, breastfeeding etc.)

accepting medical treatment. They should be willing, and able, to present weekly for serum β-hCG measurements to ensure resolution of the ectopic pregnancy. Methotrexate may be given as a single injection or as a multi-dose regimen. A single-dose regimen includes the following. Day 1: Quantitative β-hCG. Administer methotrexate, 50 mg/m2 given as a single intramuscular injection. Day 4: Quantitative β-hCG. May rise between days 1 and 4. Day 7: Quantitative β-hCG. Test urea, electrolytes and creatinine; test liver function; and perform FBE. Clinical review. A quantitative β-hCG drop of ≥ 15% between days 4 and 7 is consistent with initial treatment success. Serum β-hCG should continue to be monitored weekly until

• • •

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< 5 IU/L. Patients should present if they experience significant abdominal pain and or bleeding. If the β-hCG level does not drop by 15%, consideration is given to either a second dose of methotrexate or surgical management. The multi-dose regimen has a similar success rate to the single dose for tubal ectopics; however, side effects are more common. It is generally only considered in cases of cornual, scar and cervical ectopic pregnancy.

Other treatment options

Surgical treatment

Live cervical, scar and cornual ectopics may be managed with intra-gestational potassium ± methotrexate injection.

Surgical management is indicated if medical treatment is contraindicated (as outlined earlier in Box 8.1) or if medical treatment fails or is declined by the patient.

Laparoscopy or laparotomy? Laparoscopy is appropriate for almost all ectopic pregnancies (even those with haemoperitoneum) except those with significant haemodynamic compromise. Ultimately the decision depends on the experience and skills of the attending gynaecologist and anaesthetic team.

Salpingectomy or salpingostomy? Laparoscopic salpingectomy (Fig 8.11) is the standard surgical treatment for tubal ectopic pregnancy. Research has shown similar rates of future intrauterine pregnancy and recurrent ectopic rates compared with medical management. Salpingostomy (incision of the affected tube with removal of the products of conception) is occasionally performed with a view to increasing future intrauterine pregnancy rates. Non-randomised studies suggest that

A FIGURE 8.11 

intrauterine pregnancy rates are greater after salpingostomy compared with salpingectomy ONLY in those with contralateral tubal disease. Against salpingostomy, there is increase in both persistent trophoblast requiring treatment and future ectopic pregnancy relative to salpingectomy.

GESTATIONAL TROPHOBLASTIC DISEASE CLASSIFICATION Gestational trophoblastic disease (GTD) encompasses a range of conditions characterised by a proliferative disorder of trophoblastic cells. These disorders can be broadly classified into benign or invasive/malignant (see Box 8.2) and are largely distinguished on histopathology.

Localised GTD Localised molar pregnancies are a result of aberrant fertilisation and as such are primary entities and cannot follow from a clinical pregnancy. Invasive GTD, on the other hand, may follow either a molar or clinical pregnancy including term, preterm, miscarriage or ectopic pregnancy.

B

Laparoscopic salpingectomy. A Shows the left ampullary ectopic pregnancy (E), the left ovary (LO) and the uterus (U). Free peritoneal blood is seen on the visceral and peritoneal surfaces. Evidence of parafimbrial blood clot. B Post-salpingectomy showing the left ovary (LO) and the uterus (U). 64

Chapter 8  Bleeding in Early Pregnancy

BOX 8.2  Classification of gestational trophoblastic disease. Localised (‘benign’) gestational trophoblastic disease (localised GTD) ✚ Partial hydatidiform mole ✚ Complete hydatidiform mole Invasive gestational trophoblastic neoplasia (invasive GTN) ✚ Invasive mole ✚ Choriocarcinoma ✚ Placental site trophoblastic tumour (PSTT)

Invasive GTN In the case of invasive moles, the degree of invasion may be local or may involve metastases, usually to the lungs or vagina. Invasive moles follow approximately 15% of complete moles and 3% of partial moles. The diagnosis is generally made clinically based on persistent β-hCG elevation after molar evacuation. Choriocarcinoma is a malignant disease characterised by abnormal trophoblastic hyperplasia and anaplasia, absence of chorionic villi, haemorrhage and necrosis. This malignant tumour of the trophoblast follows a hydatidiform mole in 50% of cases, normal pregnancy in 25% and miscarriage or ectopic pregnancy in 25% (see Fig 8.12).

PREDISPOSING FACTORS Rates vary significantly based on geographic region, ethnicity and maternal age. The condition is more common in Australasia (1 in 750 pregnancies) than in the United States, the United Kingdom and Europe (1 in 1500), but is most frequent in South-East Asia and Mexico (1 in 500). Choriocarcinoma is more common in older and younger women and there is a 1% recurrence risk if there is a past history of GTD.

HISTOPATHOLOGY AND CYTOGENETICS Complete and incomplete moles differ significantly in certain characteristics (Table 8.4). Complete molar pregnancy occurs as a result of fertilisation of an empty ovum with either two sperm or one that divides. The karyotype is generally 46XX (occasionally 46XY) and all of paternal origin. Partial molar pregnancy results from the fertilisation of an ovum with two sperm or one that divides resulting in triploidy 69XXY, 69XXX or, rarely, 69XYY. There is often a co-existing fetus that is prone to fetal death in utero and growth restriction. Partial moles have a much lower malignant potential.

FIGURE 8.12 

Choriocarcinoma. The woman was aged 17 and presented with a haemoperitoneum. As in 50% of cases, there was no preceding hydatiform mole. Uterine perforation necessitated hysterectomy. There were multiple pulmonary metastases but recovery was complete after hysterectomy. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

CLINICAL FEATURES AND PATHOLOGY Mole A hydatidiform mole is characterised by oedematous avascular villi with trophoblastic proliferation (Fig 8.13). Typically, a mole is initially diagnosed following an ultrasound performed because of vaginal bleeding (95%) in early pregnancy. Other clinical features may include hyperemesis gravidarum, theca lutein cysts (Fig 8.14), preeclampsia (may be before 20 weeks’ gestation), hyperthyroidism and vaginal passage of hydropic vesicles. Symptoms from metastatic spread of molar tissue may also occur (e.g. haemoptysis and/or pleuritic pain from spread to the lung).

Choriocarcinoma The clinical presentation of choriocarcinoma is varied depending on the antecedent pregnancy. Following a complete molar pregnancy, it may be diagnosed in asymptomatic women with routine β-hCG monitoring. 65

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TABLE 8.4  CHARACTERISTICS OF PARTIAL AND COMPLETE MOLES. Characteristic

Partial mole

Complete mole

Karyotype

69XXY, 69XXX, 69XYY

46XX or 46XY

Embryonic fetal tissue

Present

Absent

Villi

Focal hydropic villi

Diffusely hydropic

Theca lutein cysts

Uncommon

Common

Malignant GTN

3% Almost exclusively invasive mole

15% (invasive mole 90%, choriocarcinoma 10%)

FIGURE 8.13 

Section of a hydatidiform mole showing considerable trophoblastic proliferation. The chorionic villi show the typical enlargement (hydrops) and avascularity. Source: Courtesy of Norman Beischer.

FIGURE 8.14 

Uterus and bilateral theca-lutein cysts seen after hysterectomy at 18 weeks’ gestation in a woman with a hydatidiform mole. Suction curettage is the usual treatment of a hydatidiform mole. Source: Courtesy of Monash Health.

Following a normal pregnancy, persistent vaginal bleeding is the most frequent symptom. Vaginal bleeding after 6 to 8 weeks’ should prompt consideration of GTN along with the other more common conditions such as retained products of conception and endometritis. There may be evidence of metastatic tumour—vaginal metastases are present in 30% cases. These lesions are highly vascular and prone to bleeding. Patients may exhibit respiratory, gastrointestinal or neurological symptoms reflecting sites of distant metastases.

DIAGNOSIS Ultrasound Ultrasound of a complete mole reveals a central heterogeneous mass with numerous discrete anechoic spaces. There is no fetus or amniotic fluid (Fig 8.15)—unless there is a co-existent twin (4 to 6%, Figs 8.16 and 8.17). A partial mole may also have a co-existent fetus. A 66

choriocarcinoma appears as a hypervascular heterogeneous mass.

β-hCG

β-hCG is universally elevated as compared with other intrauterine or ectopic pregnancies. Occasionally, the diagnosis of a partial mole may only be made on histology of curettings from a suspected incomplete abortion.

MANAGEMENT Localised GTD Initial management The initial treatment is similar to that outlined for the woman with suspected miscarriage. Heavy bleeding may complicate this process, so adequate blood must be crossmatched. Suction curette is first-line management for complete and partial molar pregnancy. Hysterectomy

Chapter 8  Bleeding in Early Pregnancy

FIGURE 8.17  FIGURE 8.15 

Complete mole. Enlarged uterus showing hypoechoic vesicles consistent with a molar pregnancy.

Twin molar and normal pregnancy. The mother had severe preeclampsia at 16 weeks’ gestation. The fetus and attached placenta had a normal male karyotype but the separate molar tissue had a female karyotype and was thus a dizygotic twin. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

molar pregnancy, ongoing follow-up with serial β-hCG measurements for 6 months is important. Contraception should be commenced and if there is a trophoblast registry in the region, the case should be notified. Use of the oral contraceptive pill does not increase rates of invasive disease. The theca lutein cysts are managed conservatively although they may take months to resolve. Surgery may be necessary if torsion ensues.

Invasive GTN Initial management FIGURE 8.16 

Partial mole in association with triploidy 69. The mother had severe preeclampsia and was delivered at 24 weeks’. The single placenta was diffusely molar and the triploidy fetus had multiple abnormalities. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

would rarely be performed as first line management (Fig. 8.18). Tissue is sent in normal saline (not formalin) for histological analysis and karyotyping if necessary. If the diagnosis of a complete mole is established preoperatively, baseline investigations with a quantitative β-hCG and chest X-ray should be taken.

Follow-up Due to the possibility of persistent GTD (invasive molar pregnancy/choriocarcinoma), especially after complete

The preferred management of invasive GTN is with chemotherapy. Repeat curette is contraindicated due to the significant risk of maternal haemorrhage and uterine perforation. Chemotherapy is the cornerstone of management. ‘Staging’ into low- and high-risk groups takes place to determine the most appropriate chemotherapy. Low-risk women receive single-agent chemotherapy but the high-risk group are prescribed a multi-agent chemotherapeutic regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine [EMA/ CO]). Cure rates approach 100% for those treated with single-agent chemotherapy. For high-risk disease necessitating a multi-drug regimen ± adjuvant radiotherapy or surgery, cure rates are approximately 90%.

Follow-up

Once chemotherapy has been completed and β-hCG levels have returned to normal, the β-hCG levels should be monitored at monthly intervals for a further 12 months. The risk of relapse is 3% in the first year and rare after that. Pregnancy should be avoided during the first 12 months 67

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FIGURE 8.18 

Classic hydatidiform mole appearance from a hysterectomy specimen of a 56-year-old woman. Source: Courtesy of Monash Health.

after β-hCG returns to normal in order to facilitate β-hCG surveillance. An effective method of contraception should be used. The combined oral contraceptive pill is considered safe. Due to the risk of recurrence in subsequent pregnancies, women should have an ultrasound in the first trimester, placental histopathology and a serum β-hCG at 6 weeks’.

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FURTHER READING Hajenius PJ, Mol F, Mol BW, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev 2007. Luise C, Jermy K, May C, et al. Outcome of expectant management of spontaneous first trimester miscarriage: observational study. BMJ 2002;324(7342):873. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol 2010;203(6):531–9. Lurain JR. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol 2011;204(1):11–18. Mol BW, Matthijsse HC, Tinga DJ, et al. Fertility after conservative and radical surgery for tubal pregnancy. Hum Reprod 1998;13(7):1804–9. Neilson JP, Gyte GML, Hickey M, et al. Medical treatments for incomplete miscarriage (less than 24 weeks). Cochrane Database Syst Rev 2010;1. Royal College of Obstetricians and Gynaecologists. The management of early pregnancy loss. Green-top Guideline No. 25. London: RCOG; 2006. Scott F, Meagher S. Media release. Australasian Society for Ultrasound in Medicine (ASUM). Online. Available: ; [24 October 2011]. Soto-Wright V, Bernstein MMHP, Goldstein DP, et al. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995;86:775–9. Van Mello NM, Mol F, Opmeer BC, et al. Salpingotomy or salpingectomy in tubal ectopic pregnancy: what do women prefer? Reprod Biomed Online 2010;21(5):687–93. Zhang J, Gilles JM, Barnhart K, et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005;353(8):761–9.

Section 2.3 PRENATAL DIAGNOSIS Chapter 9

Screening, diagnosis and management of genetic and structural abnormalities in the fetus

Chapter 9  SCREENING, DIAGNOSIS AND MANAGEMENT OF GENETIC AND STRUCTURAL ABNORMALITIES IN THE FETUS Susan Walker

KEY POINTS The incidence of major birth defects is approximately 4%. Congenital defects may be due to genetic, infective or teratogenic influences, but the aetiology in many remains unknown. Screening for birth defects includes screening for Down syndrome and related aneuploidies, and a fetal anatomical survey with ultrasound. Other genetic conditions in high-risk families may be amenable to prenatal screening and diagnosis. Diagnostic tests for genetic abnormalities include amniocentesis and chorionic villus sampling, which have a miscarriage rate of 0.5 and 1% respectively. Cardiovascular and central nervous system abnormalities are the most common major structural abnormalities; however, renal, gastrointestinal, face and skeletal abnormalities may be detected with ultrasound, as may fetal tumours or hydrops. Management of families where a major structural abnormality has been identified is best undertaken by a multidisciplinary team addressing: the underlying cause; implications for the pregnancy, labour and delivery; newborn care and long-term prognosis; risk of recurrence; and options for the pregnancy, including continuation versus termination of the pregnancy.

INTRODUCTION The incidence of major birth defects—those associated with significant medical implications such as abnormalities of the central nervous system, the face or the cardiac, renal, gastrointestinal or skeletal systems—is approximately 4%. Minor birth defects such as skin tags are more common, but usually have no (or only minor) cosmetic implications. Many congenital defects have a genetic origin, whether from chromosomal defects (approximately 10%), single gene disorders (approximately 5%) or where inheritance is multifactorial (approximately 25%). Other defects may be a result of fetal infection, such as toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus (see Ch 19) or exposure to known teratogens. In the majority of cases, the aetiology remains

unknown. Congenital abnormalities may be part of a syndrome, where there is a collection of abnormalities in a characteristic pattern that are genetically linked. Screening for birth defects involves genetic screening for Down syndrome and related chromosomal disorders, and an anatomical survey with ultrasound, usually performed at 18 to 22 weeks’ gestation. Screening for other genetic disorders with important health implications but without a recognisable phenotype on ultrasound may be performed for disorders such as thalassaemia, cystic fibrosis and fragile X syndrome. Management of pregnancies where the fetus is known to have a fetal abnormality or serious medical condition requires the involvement of a multidisciplinary team. Counselling should address the implications of the diagnosis for the remainder of the pregnancy, labour and delivery,

Chapter 9  Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus

for postnatal care and the long-term implications. Some conditions may be amenable to in utero treatment, while most will involve postnatal surgery, medical treatment or ongoing surveillance. In some conditions, where the outlook is lethal, palliative care may be offered to the newborn. In conditions where a fetus is diagnosed with a serious or life-threatening condition, some families may consider adoption, while many will face the difficult decision of pregnancy termination.

GENETIC CONDITIONS SCREENING FOR ANEUPLOIDY Down syndrome (or trisomy 21) is caused by a complete or partial third copy of chromosome 21 (see Fig 9.1). It is the most common chromosomal abnormality associated with live birth, and the leading cause of intellectual disability associated with a recognisable chromosomal abnormality. Children with Down syndrome have a characteristic phenotype (Fig 9.2) including short stature, flattened nasal bridge, protruding tongue, epicanthic folds, short neck, single transverse palmar crease and hypotonia. Intellectual disability is universal, usually in the mild (IQ 50 to 70) to moderate (IQ 30 to 50) range. Up to 50% of newborns will have congenital heart disease and other structural abnormalities that may be identified prenatally, including duodenal or oesophageal atresia. Medical problems include hypothyroidism, hearing and eye abnor­malities, and an increased risk of

some malignancies. Behavioural and psychiatric problems are more common, as well as autism and early-onset dementia. Down syndrome affects approximately 1:600 to 700 pregnancies, although this depends on the maternal age of the population being studied, since the majority of pregnancies affected by trisomy 21 occur as a result of nondisjunction. Trisomy 21 from nondisjunction occurs when one gamete contributes 24 chromosomes (including two copies of chromosome 21) to the conceptus instead of the usual 23, resulting in 47 chromosomes. The karyotype for a female fetus with Down syndrome is shown in Figure 9.1 (written 47XX + 21). The majority of nondisjunction events are maternal in origin, and are more common with increasing maternal age. This explains the increased risk of miscarriage due to aneuploidy, and of live birth with Down syndrome, observed in older women. Less than 5% of cases of Down syndrome occur as a result of translocation, where the long arm of chromosome 21 is attached to another chromosome, usually chromosome 14. While the translocation is balanced (with a normal and complete complement of genetic material in the carrier parent), this has the potential to become unbalanced at the time of conception. Down syndrome is common. It has important medical implications. While not all families will decide to proceed with genetic screening, screening for Down syndrome, and access to diagnostic testing with amniocentesis or chorionic villus sampling (CVS), is considered an essential component of antenatal care. Historically, maternal age was the only screening test offered for Down syndrome, with all women aged 37 and over at the time of delivery offered invasive testing. However, this results in a screen positive rate of approximately 10% for a Down syndrome detection rate of only 30%. Population-based screening programs using serum screening, ultrasoundbased screening or a combination of both have vastly improved detection rates of Down syndrome, and it is recommended that all women be offered a screening test, regardless of maternal age. The recent arrival of cell-free fetal DNA as an advanced screening test has rapidly changed the landscape of aneuploidy screening, with superior sensitivity and specificity compared to other screening approaches. After Down syndrome, the chromosomal abnormalities most likely to result in live birth are trisomy 13 and trisomy 18, although both are almost inevitably lethal. Figure 9.2 provides a summary of the phenotypic features of trisomy 21, trisomy 18 and trisomy 13.

Screening tests for trisomy 21 Second trimester maternal serum screening FIGURE 9.1 

Trisomy 21 karyotype in a female fetus.

Source: Simpson JL, Elias S. Genetics in Obstetrics and Gynecology. 3rd edn. Philadelphia: WB Saunders, 2003. Figure 10.2.

Maternal serum analytes examined in the second trimester include alpha-fetoprotein, oestriol, β-hCG and inhibin. Gestation-specific reference ranges have been established and so maternal serum screening results are expressed as multiples of the median (MoM). Maternal blood is taken 71

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Epicanthic fold and flat facial profile

Intellectual disability Abundant neck skin

Simian crease

Congenital heart defects Intesinal stenosis

TRISOMY 21: DOWN SYNDROME Incidence: 1 in 700 births Karyotypes: Trisomy 21 type: 47, XX, +21 Translocation type: 46, XX, der(14;21)(q10;q10), +21 Mosaic type: 46, XX/47, XX, +21

Umbilical hernia Predisposition to leukaemia

Prominent occiput

Hypotonia

Intellectual disability Micrognathia

Gap between first and second toe

Low set ears Short neck Overlapping fingers

TRISOMY 18: EDWARDS SYNDROME

Congenital heart defects

Incidence: 1 in 8000 births Karyotypes: Trisomy 18 type: 47, XX, +18 Mosaic type: 46, XX/47, XX, +18

Renal malformations Limited hip abduction

Microphthalmia Polydactyly

Microcephaly and Intellectual disability

Cleft lip and palate

Rocker-bottom feet

Cardiac defects Umbilical hernia

Renal defects

TRISOMY 13: PATAU SYNDROME Incidence: 1 in 15 000 births Karyotypes: Trisomy 13 type: 47, XX, +13 Translocation type: 46, XX, +13, der(13;14)(q10;q10) Mosaic type: 46, XX/47, XX, +13

Rocker-bottom feet

FIGURE 9.2 

Characteristic phenotype and karyotype of fetuses with trisomy 21, trisomy 18 and trisomy 13.

Source: Kumar V, Abbas A, Fausto N, Aster J. Robbins and Cotran Pathologic Basis of Disease, Professional Edition. 8th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier.

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between 14 and 20 weeks’ gestation, with maternal age, weight, gestation and the presence of diabetes or a multiple pregnancy recorded. The pattern of biochemical abnormalities in a pregnancy affected by Down syndrome is a reduced alpha-fetoprotein and oestriol (the fetal contributors) and an elevated inhibin and β-hCG (the ‘placental’ contributors). The likelihood ratio corresponding to the maternal serum MoM is applied to the maternal a priori risk (the risk associated with her age alone) and a new risk is generated. The more maternal serum analytes that are examined, the higher the Down syndrome detection rate. When screening incorporates all four analytes, the detection rate in well-dated pregnancies is approximately 75% using a cut-off of 1:250 or higher and a false-positive rate of 5%. This means that 5% of women will screen positive, having an adjusted individual risk result between 1:2 (highest possible screen-positive risk) and 1:250 (lowest possible screen-positive risk), but almost all of these will turn out to be false-positives (i.e. they will be found to have an unaffected fetus at the time of diagnostic testing). The disadvantage of this test is the later gestation at the time of testing, and that the pregnancy needs to be accurately dated.

Screening with first-trimester nuchal translucency Fetuses with Down syndrome are more likely to have an increased fluid space (the nuchal translucency measurement) in the first trimester (Fig 9.3). This ultrasound is performed when the crown–rump length measures 48 to 84 mm, corresponding to a gestational age of 11 to 13 weeks. The Down syndrome detection rate using nuchal translucency measurement alone is approximately

A

75% using a cutoff of 1:300 or higher and a false-positive rate of 5%. While this test has comparable accuracy to second-trimester maternal serum screening, the advantage is the increased privacy offered by earlier screening; most families and clinicians would favour first-trimester screening and diagnosis. The disadvantage of nuchal translucency measurement is that it is operator dependent. For this reason, the Fetal Medicine Foundation provides only accredited sonographers with access to the software package that generates the customised risk.

Screening with first-trimester combined testing First-trimester combined testing refers to maternal serum screening in the first trimester, using pregnancy-associated plasma protein A (PAPP-A) and hCG combined with the nuchal translucency measurement. With first-trimester combined screening, patients have a blood test performed at 9 to 12 weeks followed by an ultrasound at 11 to 13 weeks (see previous section). The adjusted risk reflects the likelihood ratio generated by both the maternal serum screening and nuchal translucency results applied to the background maternal age risk. Not surprisingly, using the modalities of both ultrasound and maternal serum screening results in an improved sensitivity; the detection rate using first-trimester combined screening is approximately 90% at a cutoff of 1:300 and a false-positive rate of 5%.

Integrated testing: combining first- and secondtrimester screening The Down syndrome detection rate can be further increased (or the false-positive rate minimised) by modifying the first-trimester combined adjusted risk with

B

FIGURE 9.3 

Nuchal translucency measurement. A Normal nuchal translucency, measured with a well-magnified image, separate to the amnion and the neck in a neutral position. B Increased nuchal translucency associated with Down syndrome. Source: Adam, A, Dixon AK, Grainger RG, Allison DJ. Grainger and Allison’s Diagnostic Radiology. 5th edn. Philadelphia: Churchill Livingstone, 2007. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 53.11.

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second-trimester maternal serum screening (the integrated screening test). While not commonly performed, the detection rate using the five maternal serum analytes (PAPP-A in first trimester, plus alpha-fetoprotein, oestriol, inhibin and β-hCG in the second trimester) plus firsttrimester nuchal translucency is 90%, with a false-positive rate of only 2%. This minimises the risk of requiring a diagnostic test, with the attendant procedural loss, while retaining maximal sensitivity. The disadvantage of this test is that the final result is not available until the second trimester, but this may be minimised by the use of sequential or contingent screening. In the former approach, high-risk women on the basis of the firsttrimester results (e.g. > 1:50) are offered diagnostic testing, with the remainder being offered further testing in the second trimester to better quantify their risk. In the latter approach, three levels of risk are identified at the end of first-trimester testing: high-risk women (e.g. > 1:50), who are offered immediate diagnostic testing; lowrisk women (for e.g. < 1:2000) who are offered no further testing, given their extremely low risk; and intermediaterisk women (1:50 to 1:2000) who are then offered secondtrimester maternal serum screening to complete the integrated testing.

characteristic of the Down syndrome phenotype detectable with ultrasound which does not in itself pose any health risk to the fetus. Examples of soft markers include echogenic bowel, a short humerus or femur, clinodactyly of the fifth finger or a ‘sandal gap’ between the first and second toes. Nevertheless, such soft markers are found in approximately 15% of normal pregnancies, and so use of ultrasound alone as a screening test is inadequate. Ultrasound evaluation for structural abnormalities and soft markers may be used in combination with maternal serum screening with detection rates for Down syndrome increasing from approximately 80% to 90% in this setting. A normal second trimester ultrasound is associated with approximately halving the risk generated by maternal serum screening alone.

Abnormal maternal serum screening results: other implications

An exciting new development in the area of prenatal genetic diagnosis is non-invasive prenatal screening (NIPS) using cell-free fetal DNA (cffDNA) from the plasma of pregnant women. Circulating cell-free fetal DNA comprises approximately 10% of total maternal cell-free fetal DNA, and analysis of the fetal fraction of cell-free DNA is associated with detection rates of 99%, 95% and 90% for Trisomy 21, Trisomy 18 and Trisomy 13 respectively, with a false-positive rate of < 0.5%. cffDNA has the highest sensitivity and specificity of any screening test for Down syndrome. While initially only recommended for high-risk women, this technology has rapidly transitioned into clinical practice, and large datasets are confirming excellent test performance characteristics in low-risk women. Although this screening test has predictive characteristics that outperform previous screening tests, with very low false-positive and false-negative rates, it is important to note that it is not a diagnostic test. Confirmation with invasive testing is still necessary for patients with a screen positive result. Given the relatively high cost of this test, appropriate counselling is necessary for patients wishing to consider non-invasive prenatal diagnosis to ensure the limitations of this test, including failed fetal fraction, and the possibility of atypical findings are understood.

Very abnormal maternal serum results may be seen in a range of other pregnancy complications, even if the adjusted aneuploidy risk is low or chromosomal abnormalities have been excluded with diagnostic testing. Further evaluation is recommended in the following cases. First trimester ■ A low PAPP-A (< 0.4 MoM) is associated with a threefold increase in intrauterine growth restriction (IUGR) (positive predictive value 15%), intrapartum fetal distress, preeclampsia and stillbirth. ■ A low β-hCG (< 0.2 MoM) is associated with an increased risk of IUGR, with a positive predictive value of 15%. ■ The finding of a PAPP-A or β-hCG below these thresholds should prompt careful evaluation of fetal growth and wellbeing in late pregnancy, and avoiding post-term pregnancy. Second trimester ■ An elevated maternal serum alpha-fetoprotein in the second trimester (> 2.0 to 2.5 MoM) is associated with a range of structural defects including neural tube defects, exomphalos and gastroschisis. The finding of a maternal serum alpha-fetoprotein in this range should prompt a tertiary-level morphology ultrasound to exclude these and other structural defects. If no abnormality is confirmed, growth surveillance is recommended in late pregnancy. ■ A low oestriol (< 0.2 MoM) is associated with placental sulphatase deficiency, Smith-LemliOpitz syndrome and fetal death. Further evaluation is recommended in these cases.

Second-trimester ultrasound

Diagnostic tests

Approximately 50% of pregnancies affected with Down syndrome will have some clue on their routine morphology scan, such as a structural abnormality (e.g. a cardiac defect or cerebral ventriculomegaly), or a ‘soft marker’ of Down syndrome. A soft marker is a physical

Among women who screen as high risk for aneuploidy, the available diagnostic tests are chorionic villus sampling and amniocentesis. These are ultrasound-guided procedures done as an outpatient and do not require anaesthetic. Anti-D is given to all women who are

Non-invasive prenatal screening using cell-free fetal DNA

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•

•

Chapter 9  Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus

Rh-negative following any invasive procedure, and infective status for blood-borne viral infections should be noted on the referral. Chorionic villus sampling (CVS) is a procedure where a needle is passed into the chorionic (placental) plate and chorionic villi are aspirated (Fig 9.4). The procedure is most commonly performed between 12 to 14 weeks and is often the diagnostic test chosen after abnormal firsttrimester screening. The risk of miscarriage following CVS is approximately 1%. Amniocentesis is performed after 15 weeks’ gestation where approximately 10 to 15 mL of amniotic fluid is aspirated. The advantage of this test is the lower risk of miscarriage (approximately 0.5%), but this needs to be weighed against the problem of later diagnosis. Information that may be obtained from the genetic material taken at diagnostic testing includes fluorescent in-situ hybridisation, banded karyotype, microarray and single gene testing. Fluorescent in-situ hybridisation (FISH). This is a test where fluorescent-labelled probes attach to critical regions on individual chromosomes. The result is available in 48 hours, so FISH is a useful test to promptly exclude the major chromosomal abnormalities (trisomy 21, 18 and 13) and sex chromosome abnormalities (Fig 9.5). A FISH probe can be customised for other critical chromosomal regions to target a specific duplication or deletion (e.g. the 22q microdeletion associated with DiGeorge syndrome). Banded karyotype. Standard karyotyping involves examination of all chromosomes and will diagnose

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disorders of chromosome number (aneuploidy) or structure, such as deletions, duplications and translocations. The result from a banded karyotype takes approximately 2 weeks. Microarray (or molecular karyotype). Microarray analysis has successfully transitioned into prenatal clinical care. Microarray analysis enables detection of chromosomal deletions or duplications that are 100 times smaller than those identified on conventional karyotype. These small changes may be associated with significant phenotypic consequences. Nevertheless, microarray analysis carries the potential for findings of uncertain significance, and consultation with a genetic counsellor with attention to pre- and posttest counselling is recommended. Single gene testing. This can be performed on any prenatal sample for autosomal-dominant, recessive or X-linked conditions where the genetic defect is known. This includes conditions such as cystic fibrosis and thalassaemia.

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SCREENING FOR OTHER GENETIC CONDITIONS Cystic fibrosis Cystic fibrosis is one of the most common autosomalrecessive disorders, with a carrier frequency among Caucasian populations of approximately 1:25. This means the birth prevalence for cystic fibrosis is 1:2500 (1:25 × 1:25 × 1:4). Cystic fibrosis is a disorder of exocrine gland secretions causing an accumulation of thickened secretions that result in recurrent lung infections, malabsorption, infertility in males and shortened life expectancy. All newborns are screened for cystic fibrosis, but some families wish to know whether they are at risk prior to birth. Antenatal screening involves performing a cheek swab or blood test to check for the most common genes responsible for cystic fibrosis. Approximately 85% of carriers will be identified with this test. Diagnostic testing may be performed where both parents are confirmed to be carriers, where the risk to the fetus is 1:4.

Haemoglobinopathies

FIGURE 9.4

Transabdominal chorionic villus sampling.

Source: Gabbe SG, Niebyl JR, Galan HL, et al. Obstetrics: Normal and Problem Pregnancies. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 11.2.

Haemoglobinopathies may be divided into conditions of globin synthesis dysfunction (thalassaemias) or haemoglobin variants (such as sickle cell disease). Thalassaemia may affect either the alpha or beta subunit of the globin chain. Alpha-thalassaemia major (where all four genes coding alpha globin synthesis are missing) is incompatible with life since alpha chain synthesis is necessary for all haemoglobin types. Beta-thalassaemia major is associated with lifelong transfusion-dependent anaemia, a need for chelation therapy and shortened life expectancy. Women may be identified as being at risk (i.e. carriers) because of a personal or family history of thalassaemia. Screening among women without a known history may be based on: 1. assessment of full blood examination 75

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Interphase FISH

21

Y

13

18

X

21 13

18

Normal

Normal male

Trisomy 21

Trisomy 18

FIGURE 9.5

FISH on amniotic fluid cells to screen for aneuploidy.

Source: Lentz GM, Lobo RA, Gershenson DM, Katz, VL. Comprehensive Gynecology. 6th edn. St Louis: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 2.9.

parameters looking for evidence of an unexplained low mean cell volume (< 80 fl); 2. targeted screening of at-risk ethnic groups (African, South-East Asian and Mediterranean); or 3. universal screening with haemoglobin electrophoresis. Women found to have beta thalassaemia minor should be offered partner screening. If the partner is also found to have thalassaemia minor, they have a 1:4 risk of thalassaemia major in the offspring, and prenatal testing with chorionic villus sampling or amniocentesis should be offered.

reproductive carrier screening for a panel of conditions that are individually rare, but collectively common, is increasing as part of routine antenatal and preconception care. Families need to carefully weigh up the additional information obtained regarding their pregnancy against the financial cost and anxiety generated by unexpected findings. Genetic counsellors are invaluable in assisting with pre- and post-test counselling.

Other genetic conditions

PREVENTION OF STRUCTURAL ABNORMALITIES

Advice should be sought from a prenatal genetic counsellor regarding the place for prepregnancy or antenatal screening of other high-risk groups. Examples include screening of Ashkenazi Jews for Tay Sachs disease, and screening for Fragile X among families with a history of male autism or intellectual disability or those with a known family history of genetic conditions. Prepregnancy identification of high-risk couples enables them to consider assisted reproductive options such as preimplantation genetic diagnosis or use of donor gametes to minimise their risk of an affected child. The use of 76

STRUCTURAL ABNORMALITIES Some women are at higher than average risk for structural abnormalities. This includes women with a positive family history or who have had a previously affected pregnancy. Women with diabetes have an increased risk of malformations, with the risk directly correlated with Hb A1C at the time of conception. Some medications and social exposures are known to be teratogenic, including ACE inhibitors, lithium, warfarin, antiepileptic drugs (AEDs) and alcohol. Obesity is associated with a

Chapter 9  Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus

small but significantly increased risk of some structural abnormalities. Prevention of structural abnormalities thus includes advice on optimising medications, diabetic control and weight prior to pregnancy. Folic acid should be prescribed to all women contemplating pregnancy, and high-dose folate (5 mg daily) for women at increased risk of neural tube defects. This includes those with a previously affected child, women with diabetes, women receiving AEDs and obese women. Rubella and varicella are both potential teratogens, and vaccination prior to pregnancy is recommended.

DETECTION OF STRUCTURAL ABNORMALITIES The routine second trimester ultrasound is generally performed between 18 and 22 weeks’ gestation. Benefits of the routine second trimester ultrasound include accurate assignment of gestational age, diagnosis of multiple pregnancy, placental localisation and assessment of fetal anatomy. This targeted anatomical survey detects approximately 60% of major anatomical defects, with minor abnormalities more likely to be missed. Many major abnormalities may be detected as early as the first trimester, but even in the second trimester cardiac defects are less likely to be detected than central nervous system (CNS) or genitourinary abnormalities. The detection rate is limited by: the nature of some abnormalities (which may not become apparent until later in pregnancy) the gestation at the time of the ultrasound fetal position and number technical limitations including operator experience, ultrasound machine quality and maternal obesity which can seriously limit visualisation. Women known to be at high risk of structural abnormalities should have their ultrasound performed in a centre dedicated to obstetric ultrasound since detection rates are known to be higher in tertiary centres then in non-tertiary ones. This includes women with risk factors (see above), those who have had an increased nuchal translucency in early pregnancy or those who have suffered a teratogenic insult during pregnancy such as one of the TORCH infections (toxoplasmosis, other, rubella virus, cytomegalovirus and herpes simplex viruses). A brief overview of the most common abnormalities which have important perinatal implications now follows.

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aorta), abnormalities of venous return or abnormalities of rhythm or function. These lesions vary according to their risk of serious in utero consequences, such as heart failure and fetal hydrops, and important implications for neonatal care, such as cyanotic or ‘duct-dependent’ lesions. Women at increased risk of cardiac structural defects include those with a past or family history of congenital heart disease, women with diabetes or those exposed to teratogens such as AEDs and lithium, women with anti-Ro or anti-La antibodies or those with an increased nuchal translucency measurement in the first trimester. These women should have a detailed fetal echocardiogram performed in the second trimester, as should those with a suspected abnormality on screening examination. Follow-up with a paediatric cardiologist is advised if abnormalities are confirmed.

Abnormalities of the central nervous system Neural tube defects include anencephaly (where the cephalic portion of the neural tube fails to close, resulting in absence of the skull and most of the cerebrum), encephaloceles (where there is a skull defect and brain content herniates through the defect) and spina bifida (where there is a failure of closure of the dorsal aspect of the spine, with subsequent exposure of the meningesmeningocele and spinal cord myelomeningocele; see Fig 9.6). Anencephaly is universally lethal. The outlook for spina bifida depends on the level of the lesion, since the exposed spinal cord is dysplastic and motor and sensory function below the level of the bony defect is affected, resulting in varying degrees of paralysis, sensory dysfunction and disturbance of bowel and bladder function. The development of hydrocephalus will impact on neurodevelopmental outcome. The prognosis will be further affected by the presence of other chromosomal or structural abnormalities. The incidence of neural tube defects has dramatically reduced since the commencement of routine screening

Abnormalities of the cardiovascular system Abnormalities of the cardiovascular system are the most common type of structural abnormality with an incidence of 0.5 to 1%. These include septal defects (atrial, ventricular or atrioventricular septal defects), defects of the outflow tracts (such as tetralogy of Fallot, transposition of the great vessels and coarctation of the

FIGURE 9.6

Neonate with myelomeningocele.

Source: Townsend C, Beauchamp RD, Evers MB, Mattox K. Sabiston Textbook of Surgery. 19th edn. Philadelphia: Saunders, 2012. Figure 68.34.

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and folic acid supplementation. More recently, open fetal surgery has been shown to improve the outcome of children with spina bifida, where the spinal defect is closed via a hysterotomy incision prior to 26 weeks. This specialised surgery is not currently available in Australia and the benefits to the fetus need to be weighed against the maternal morbidity, including preterm birth and the risk of scar rupture in subsequent pregnancies. Nevertheless, this option may be appropriate for well-selected cases. Other CNS abnormalities diagnosed on ultrasound include: ventriculomegaly, which should trigger a series of further investigations looking for developmental, obstructive, chromosomal or infective causes; midline abnormalities, such as holoprosencephaly and agenesis of the corpus callosum; destructive lesions due to infection or haemorrhage; vascular malformations, such as the Vein of Galen malformation; or tumours. Neurosonography by those with experience in ultrasound evaluation of the fetal neural axis should be performed when an abnormality is suspected, and fetal magnetic resonance imaging (MRI) may be recommended, which provides additional useful information.

Abnormalities of the gastrointestinal system The most common abnormalities of the gastrointestinal system are developmental abnormalities of the anterior abdominal wall and, of these, exomphalos and gastroschisis are most common. Exomphalos (also termed omphalocele) is due to failure of return of the midgut to the abdominal cavity, which is usually completed by the end of the first trimester. Ultrasound shows a midline herniation of bowel (with or without liver) into the base of the cord, which is covered by peritoneum and amnion. Exomphalos is strongly associated with aneuploidy and other structural abnormalities. Where isolated, the outlook will depend on the size of the lesion and the ability to achieve successful postnatal surgical closure. Gastroschisis is a full-thickness paramedian abdominal wall defect where the small bowel herniates into the amniotic cavity unprotected by peritoneum (Fig 9.7). Matting of bowel loops and adhesion formation is common, and surgical resection of bowel loops may need to be performed at the time of abdominal wall closure. Gastroschisis is usually an isolated defect, but fetal growth restriction (FGR) in late pregnancy is common and early delivery is often indicated. Fetuses with abdominal wall defects need to be delivered in a facility where advanced neonatal resuscitation is available, and transfer to a surgical ward is usually arranged soon after delivery.

Abnormalities of the genitourinary system The most common abnormality of the genitourinary system is renal pelvis dilation, which may be mild (often resolving in the postnatal period) or severe (due to lower urinary tract obstruction). Bladder outlet 78

FIGURE 9.7

Gastroschisis. Note the protruding loops of small bowel, uncovered by peritoneum.

Source: Gabbe SG, Niebyl JR, Galan HL, et al. Obstetrics: Normal and Problem Pregnancies. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. E-Figure 21.3.

obstruction, typically due to posterior urethral valves in a male fetus, results in megacystis and severe hydronephrosis with anhydramnios. Amniotic volume assessment is crucial in determining the severity of a renal abnormality, since amniotic fluid is necessary for the fetal lungs to expand and develop normally. Severe renal abnormalities, such as bilateral renal agenesis or complete lower urinary tract obstruction, will be lethal because the subsequent anhydramnios results in lethal pulmonary hypoplasia. Lower grade obstruction, or abnormalities that are unilateral, should be followed up regularly during pregnancy with a plan for postnatal imaging and investigation.

Abnormalities of the face The most common facial abnormalities are cleft lip and/ or cleft palate. Women at risk include those with a family history and those on AEDs. Routine prepregnancy folate supplementation reduces the chance of clefting. Prenatal detection of an orofacial cleft should prompt a search for associated structural abnormalities and an amniocentesis should be offered. Prenatal referral to a paediatric cleft service is recommended to discuss neonatal management, including feeding advice and surgical repair, since surgical repair is associated with excellent cosmetic results (Fig 9.8).

Abnormalities of the skeletal system Skeletal dysplasias are a large group of disorders characterised by abnormal bone growth or development, and may affect only isolated bones or the entire skeleton. Evaluation of a suspected skeletal dysplasia should

Chapter 9  Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus

A

B

C

D

FIGURE 9.8

Preoperative (A), perioperative (B) and postoperative (C, D) view of unilateral cleft lip.

Source: Townsend C, Beauchamp RD, Evers MB, Mattox K. Sabiston Textbook of Surgery. 19th edn. Philadelphia: Saunders, 2012. Figure 69.4.

involve taking a history for skeletal dysplasias or familial short stature, careful evaluation for other structural abnormalities and FGR, performance of karyotype and referral to a centre with experience in evaluation of skeletal dysplasias. One of the most important assessments is the likelihood of lethality; this is mostly seen in severe skeletal dysplasias with extreme bone shortening and is due to underdevelopment of the fetal chest and resultant pulmonary hypoplasia.

Fetal tumours The most common fetal tumours are sacrococcygeal and cervical teratomas. Sacrococcygeal teratomas (SCT) particularly may undergo rapid growth during pregnancy, and be highly vascular. Accordingly, they may be responsible for high-output cardiac failure and development of fetal hydrops; haemorrhage into the tumour may also result in fetal anaemia. Management of pregnancies with 79

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a known fetal tumour includes frequent assessment of fetal wellbeing, consultation with a paediatric surgeon and possible evaluation with other imaging modalities such as MRI to plan postnatal surgical resection. Delivery may be challenging where tumours are large. Classical caesarean section may be necessary for a large SCT to facilitate delivery and minimise the risk of bleeding and trauma to the tumour at delivery. Where there is a large cervical teratoma, the neonatal airway may be compromised at delivery. In these circumstances, ex utero intrapartum therapy (EXIT) may be considered. The EXIT procedure involves delivering the fetal head by caesarean section under general anaesthetic while maintaining placental circulation until such time as an airway can be established. Such procedures require careful planning and can only be performed in a specialist centre with an experienced anaesthetic, obstetric and paediatric team.

Fetal hydrops Fetal hydrops is the description given to a fetus with fluid accumulation in two or more body cavities (pleural fluid, pericardial fluid, ascites or skin oedema; Fig 9.9). Hydrops may be due to conditions associated with cardiac failure, increased venous pressure or increased interstitial fluid accumulation. While hydrops has a large variety of causes, a useful acronym is CAUSTIC. Cardiac. This covers structural cardiac abnormalities (particularly those associated with high right atrial pressure, such as tricuspid atresia); high-output cardiac failure (e.g. due to fetal thyrotoxicosis or tumours); fetal arrhythmia (e.g. fetal congenital heart block or fetal tachyarrhythmias) and fetal

•

cardiomyopathy (including those due to infection or metabolic disorders). Anaemia. Fetal anaemia may be due to red blood cell isoimmunisation, feto-maternal haemorrhage, complications of monochorionic twinning or homo­ zygous alpha thalassaemia. Unexplained. A significant group of fetuses may be affected by hydrops due to an unknown underlying diagnosis. Structural. Structural abnormalities associated with hydrops include chest lesions that cause mediastinal compression and impair venous return as well as fetal or placental tumours. Twins. Monochorionic twins may be affected by twin-to-twin transfusion syndrome (TTTS; see Ch 14) which results in high-output cardiac failure in the recipient twin. Infective. Fetal infections such as toxoplasmosis, cytomegalovirus, rubella, syphilis and herpes simplex may result in hydrops due to the combined effects of myocardial inflammation and hepatitis (with decreased protein production) or specific mechanisms such as fetal anaemia due to parvovirus infection. Chromosomal. Chromosomal abnormalities include trisomy 21 or Turner’s syndrome (X0). In pregnancies complicated by fetal hydrops, a thorough evaluation should include establishing an underlying diagnosis. While some conditions such as fetal anaemia or TTTS may be amenable to in utero therapy, most fetuses with hydrops will not have a treatable cause and have a poor prognosis. The excessive placental size due to placental oedema makes the development of maternal preeclampsia (the so-called ‘mirror syndrome’) more likely. Accordingly, pregnancies complicated by fetal hydrops which are continuing require both careful fetal evaluation and close maternal surveillance.

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•

MANAGEMENT OF PREGNANCIES COMPLICATED BY FETAL GENETIC OR STRUCTURAL ABNORMALITIES FIGURE 9.9

Fetal hydrops. Longitudinal view of a fetus with skin oedema, ascites and a hydrothorax.

Source: Adam, A, Dixon AK, Grainger RG, Allison DJ. Grainger and Allison’s Diagnostic Radiology. 5th edn. Philadelphia: Churchill Livingstone, 2007. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 53.17.

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The application of genetic screening and fetal ultrasound in obstetrics has revolutionised the management of pregnancy and its potential complications. While normal findings improve positive feelings about the pregnancy and have been shown to promote earlier bonding, the finding of isolated or multiple serious abnormalities on prenatal ultrasound examination is inevitably stressful. Families require accurate information about the condition as quickly as possible. This is often best achieved with timely review in a multidisciplinary clinic with access to

Chapter 9  Screening, Diagnosis and Management of Genetic and Structural Abnormalities in the Fetus

obstetricians, paediatricians, genetic counsellors, medical geneticists, and ultrasonologists with experience in diagnostic and procedural ultrasound. Discussion within a multidisciplinary team has been shown to improve decision making about management of unborn infants with serious abnormalities. The counselling provided should be unbiased and respectful of the patient’s circumstances, culture, religion and beliefs, and be imparted with empathy and compassion. The information that needs to be provided includes confirmation of the abnormality, the likely aetiology, relevant associations, further investigations required and implications for the remainder of the pregnancy, labour and delivery, as well as the outlook for the patient’s unborn baby as a newborn and beyond, and the choices available to her regarding the future of the pregnancy. Retention of medical information at a time of stress is poor. A follow-up appointment should be planned soon after the disclosure interview, and frequent follow-up will be necessary. The provision of diagrams and written information can be valuable. Many patients will seek additional information on the internet; where possible, the names of recognised and reliable sites for information should be provided.

HISTORY AND EXAMINATION Once a fetal structural abnormality has been identified, a thorough medical, obstetric and family history should be performed. 1. Medical history (and examination where necessary) of both parents should be obtained, considering the possibility of unidentified autosomal-dominant traits (such as 22q11 deletion syndrome, myotonic dystrophy or tuberous sclerosis) that may be variably expressed or have a mild phenotype, escaping detection until adulthood. 2. Obstetric history should identify any potential teratogens, including medications, other drug exposures, infection and radiation. 3. Family history should be detailed, documenting a three-generation pedigree, noting particularly any children born with abnormalities, early deaths or consanguinity between the parents.

IMAGING The detection rate for structural abnormalities is higher in tertiary, compared to non-tertiary units. Because of this, all women with a suspected fetal abnormality should have a tertiary level ultrasound performed to optimise the information obtainable from prenatal ultrasound. This may include the use of 3D ultrasound, since this modality may be particularly useful in the assessment of facial and skeletal abnormalities. Fetal MRI may be of additional use, particularly when assessing brain abnormalities, lung abnormalities, complex abnormalities (particularly those requiring surgical planning) or when oligohydram-

nios is present. Parental imaging may occasionally assist with fetal diagnosis when the abnormality/abnormalities may represent an autosomal-dominant condition, such as polycystic kidney disease, or tuberous sclerosis.

ADDITIONAL TESTING Parental blood tests may be indicated if suspecting an X-linked, autosomal-recessive or autosomal-dominant genetic diagnosis, or where congenital infection may be a possible explanation for the ultrasound findings.

INVASIVE TESTING Fetal karyotype is indicated where the ultrasound findings are associated with an increased risk for aneuploidy. In the setting of structural abnormality, microarray (or molecular karyotyping) is recommended since studies suggest that 1 to 3% of fetuses with a structural abnormality will have an abnormality on microarray that would fail to be detected on conventional karyotype.

COUNSELLING Following confirmation of a fetal abnormality, the following areas should be addressed in counselling.

The likely aetiology and prognosis of the condition There will be cases where prediction of outcome is relatively straightforward and others where it is less so. External referral (e.g. to paediatric surgeon, renal physician) may be necessary to provide more detail on long-term management and the outlook for the baby.

The likely implications for the remainder of the pregnancy Potential obstetric complications may develop during the pregnancy related to the abnormality, such as poly­ hydramnios with anencephaly, preeclampsia with fetal hydrops, or an increased risk of preterm birth or IUGR.

The implications for labour and delivery Depending on the abnormality, delivery may need to be in a tertiary setting and, in some circumstances, timed delivery and/or caesarean section may be indicated.

Care of the newborn Depending on the abnormality, a paediatrician may be required immediately at delivery, or the baby may require admission to neonatal intensive care or transfer to another hospital.

The expected short- and long-term outcomes Parents will require information on the likely prognosis for the abnormality, the potential need for surgery or 81

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long-term medical treatment, the potential complications and how the condition and its treatment will impact on their child’s quality of life.

The risk of recurrence in future pregnancies In conditions with a known genetic diagnosis, the recurrence risk may be certain. In conditions where the underlying diagnosis remains unclear, the risk to a future pregnancy may remain uncertain, but become clearer with postnatal evaluation.

MAKING A DECISION Following this initial period of information gathering, patients will come to a decision regarding the future of the pregnancy.

Ongoing care Most families will elect to continue the pregnancy despite the presence of an abnormality, and the place and timing of ongoing care will depend on the nature of the abnormality, the presence of other maternal or fetal comorbidities, the need for ongoing ultrasound surveillance and the expected needs of the newborn. Most commonly, these women will remain under the care of a multidisciplinary maternal fetal medicine unit.

Lethal abnormalities Where a lethal abnormality has been diagnosed, and the family have decided to continue with the pregnancy, it is essential to consider the implications for the remainder of the pregnancy and the newborn period. This includes determining the place (if any) for monitoring during pregnancy or labour and addressing palliative care of the newborn. The importance of a multidisciplinary team including bereavement care and social work cannot be underestimated to ensure the family’s particular spiritual, cultural and social priorities are fully addressed.

birth registration, and the need for burial or cremation. (See also Ch 53.)

Surgical termination of pregnancy: dilation and curettage (D&C) or dilatation and evacuation (D&E) Access to surgical termination will depend on gestation and the experience of the operator performing this procedure, but is generally not available beyond 20 weeks. Because of the destructive nature of this procedure, the fetus will generally not be intact to see and hold, and postmortem information may be more limited.

Medical termination of pregnancy Medical termination of pregnancy involves induction of labour. It may be offered from 15 weeks’ gestation and is generally recommended after approximately 20 weeks’ gestation. Medical termination of pregnancy means the fetus is delivered intact, which can be preferable for obtaining postmortem information and so that families can see their baby after delivery. Feticide, where an ultrasound-guided injection of intracardiac potassium chloride is administered to the fetus to arrest the heart prior to delivery, may be necessary somewhere around 21 to 23 weeks. Cervical priming with multi-dose misoprostol (synthetic prostaglandin E1) is the preferred method of induction. Mifepristone (RU486) may be administered 48 hours prior to the scheduled induction to improve cervical and myometrial receptivity to prostaglandins. Following delivery, retained placenta occurs in approximately 15% of second trimester deliveries and dilation and curettage (D&C) may be required for retained products of conception. Seeing and holding their baby is an important part of saying goodbye for many families, and they may wish to create memories such as photographs, handprints and footprints, as well as considering an appropriate service or ceremony to farewell their baby.

Postmortem following fetal or neonatal loss in the setting of fetal abnormality

In some circumstances, families will consider they are unable to care for a child facing major health concerns. Adoption will be an option for some of these families. Information regarding adoption should be accessible to patients and the multidisciplinary team should develop an appropriate postnatal care plan to support the woman and her family.

Women and their families should be aware of the value of comprehensive postmortem examination, including imaging and genetic testing, which may help in postnatal counselling regarding the underlying aetiology and the risk of recurrence in future pregnancies. Clinicians should support families and encourage them to consider a complete autopsy, and examination of the placenta, by a perinatal pathologist to provide maximal information on the diagnosis and aetiology of the structural abnormality or abnormalities.

Abortion

Post-termination care

In the face of a serious abnormality, families may request an abortion. Legislative requirements on the upper gestational limit for termination of pregnancy vary from state to state in Australia, as does legislation surrounding

Suppression of lactation is recommended for any woman who delivers a fetus after 18 to 20 weeks. The patient’s general practitioner or referring doctor should be notified of the pregnancy outcome prior to discharge home.

Request for adoption

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Although many women will wish to return home soon after delivery, postnatal bereavement support is essential, and early postnatal review is recommended to assess physical and emotional recovery. Later postnatal review, including the results of investigations such as autopsy, will focus on grief support as well as discussing recurrence risks and plans for future pregnancies. FURTHER READING Gagnon A, Wilson RD, Allen VM, et al. Evaluation of prenatally diagnosed structural congenital anomalies. J Obstet Gynecol Can 2009;31(9):875–81. Noninvasive prenatal testing for fetal aneuploidy. Committee Opinion No. 545. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:1532–24.

Pugash D, Brugger PC, Bettelheim D, et al. Prenatal ultrasound and fetal MRI: the comparative value of each modality in prenatal diagnosis. Eur J Radiol 2008;68:214–26. RANZCOG. Prenatal screening for fetal abnormalities. RANZCOG Statements and Guidelines (C-Obs 35). Online. Available: ; [March 2015]. Savage MS, Mourad MJ, Wapner RJ. Evolving applications of microarray analysis in prenatal diagnosis. Curr Opin Obstet Gynecol 2011;23(2):103–8.

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Section 2.4 OBSTETRIC COMPLICATIONS Chapter 10

Antepartum haemorrhage

Chapter 11

Fetal growth restriction and assessment of fetal wellbeing

Chapter 12

Preterm labour, including cervical insufficiency

Chapter 13

The postdates pregnancy and rupture of the membranes before labour at term

Chapter 14

Multiple pregnancy

Chapter 15

Malpresentation

Chapter 10  ANTEPARTUM HAEMORRHAGE Neil Israelsohn

KEY POINTS Antepartum haemorrhage is defined as vaginal bleeding of ≥ 20 mL after 20 weeks’ gestation. Antepartum haemorrhage (APH) is a serious condition affecting approximately 3% of pregnancies. It accounts for a significant proportion of maternal morbidity and mortality. It is also responsible for up to 50% of very preterm birth and hence neonatal morbidity and mortality. The incidence of APH secondary to placenta praevia is increasing in parallel with the increasing caesarean section rate. Any painless bleeding in the second half of pregnancy must be assumed secondary to placenta praevia until proven otherwise. A vaginal examination should not be performed until placenta praevia is excluded. Placental abruption is a clinical diagnosis. The use of ultrasound and blood tests may be additive but will rarely make or refute the diagnosis.

AETIOLOGY

RESUSCITATION IF NECESSARY

The aetiology of antepartum haemorrhage (APH) is classically described by the site of bleeding, as outlined in Table 10.1. The main focus of attention in both diagnosis and management of APH is aimed at distinguishing between the two most common causes: bleeding from a low-lying placenta (placenta praevia) or from placental abruption. While vasa praevia is rare, it is associated with high neonatal morbidity and mortality and warrants exclusion in anyone presenting with vaginal bleeding. An unknown cause of APH is the most common finding.

Blood loss can be heavy and may be concealed within the uterus. A careful assessment must be made of volume status and correction made as needed. A large bore cannula should be inserted if there is any doubt and bloods should be taken for a haematological profile if moderate or severe abruption is a possibility.

INITIAL MANAGEMENT OF AN APH OF UNKNOWN AETIOLOGY WHERE AND WHO? The woman should be admitted to hospital and carefully assessed by an experienced obstetric team.

ASSESS FETAL WELLBEING Clinically, the mother should report on fetal movements and the fundal height assessed. Ultrasound and cardio­ tocography are both indicated to further evaluate fetal wellbeing.

DETERMINE AETIOLOGY This involves an initial clinical assessment noting the following principles. Placenta praevia is typically recurrent painless small bleeds associated with a non-tender uterus and a high presenting part or malpresentation (because the placenta occupies the lower uterine segment).

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TABLE 10.1  AETIOLOGICAL CLASSIFICATION OF ANTEPARTUM HAEMORRHAGE. Aetiology

Site

Placenta praevia

Placenta: low lying

Placental abruption

Placenta: not low lying (variable location)

Incidental

Cervix and lower genital tract (e.g. cervical polyp)

Uterine rupture

Uterine non-placental

Vasa praevia

Fetal

Unknown cause

Unknown

•

A placental abruption of moderate or severe degree will be painful and associated with a tense tender uterus. Incidental bleeding commonly follows sexual intercourse or clinical examination. The site is usually apparent on speculum examination (remembering that digital vaginal examination is prohibited until the placental site has been determined and praevia excluded). An ultrasound is indicated to determine placental site and thereby exclude placenta praevia. Management thereafter will be determined by the diagnosis.

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PLACENTA PRAEVIA DEFINITION The incidence of placenta praevia is approximately 1 in 250 pregnancies > 20 weeks’ gestation. Placenta praevia is defined as a placenta that inserts wholly, or in part, into the lower uterine segment. It either overlies, or is proximate (≤ 2 cm) to, the internal cervical os. Placenta praevia is often described as mostly anterior or posterior and is then further classified according to ultrasound criteria. Minor: the leading edge of the placenta lies within the lower segment (≤ 2 cm), up to the edge of the cervical internal os. Major: the placenta lies over the internal os. This classification has largely replaced the older classification of Grade 1, 2, 3, 4 placenta praevia shown in Figure 10.1. Several studies have shown that more than 90% of placentas that are considered ‘low lying’ at the 20 week’ scan will no longer be in the region of the cervix at the time of delivery. Apparent ‘placental migration’ was thought to occur during the second and third trimesters owing to the development of the lower uterine segment.

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First (lateral)

Second

Third

Minor

Fourth (central) Major

FIGURE 10.1

Degrees of grades of placenta praevia. The amount of bleeding is proportional to the extent to which the placenta encroaches on the lower uterine segment.

However, it is now believed that the placenta does not move but rather grows towards the better vascularised fundus. Placental tissue in the relatively under-vascularised lower segment/cervix undergoes atrophy. In some cases this atrophy results in placental vessels unsupported by placental tissue (vasa praevia). There is a higher chance of persistence of a low-lying placenta at delivery if: diagnosis is later in pregnancy the placenta is posterior there has been a prior caesarean section if the placenta overlaps the os > 25 mm. Placental bleeding is thought to occur when small changes in the cervix or lower uterine segment cause shearing forces, and partial separation, at the placental attachment site.

• • • •

PREDISPOSING FACTORS The following factors can predispose a woman to placenta praevia: previous caesarean section advanced maternal age increased parity in vitro fertilisation smoking.

• • • • •

CLINICAL FEATURES The classic presentation of placenta praevia is that of painless bleeding in the second and third trimesters. This is not absolute, however, and it should be noted that bleeding from placenta praevia may stimulate some contractions and hence cause some pain. Any painless bleeding in the second half of pregnancy must be assumed

Chapter 10  Antepartum Haemorrhage

secondary to placenta praevia until proven otherwise. A vaginal examination should not be performed until placenta praevia is excluded. Bleeding occurs in 90% of women with placenta praevia. Approximately one-third will bleed prior to 30 weeks’, one-third between 30 and 36 weeks’ and onethird after 36 weeks’ gestation. Most women with a placenta praevia who have had one bleed will likely bleed again. However, the amount and timing is unpredictable. Placenta praevia may also be associated with an unstable lie or malpresentation in late pregnancy. The majority of placenta praevia are asymptomatic and diagnosed at the routine 19- to 20-week ultrasound.

Haemoglobin should be optimised with administration of iron and/or folate supplements as necessary. Ultrasound should be repeated at 32 to 34 weeks’ and include a growth assessment. Advise the woman to avoid sexual intercourse.

DIAGNOSIS

Timing and mode of birth

While clinical suspicion is important in the diagnosis and management of placenta praevia, the definitive diagnosis is generally made with ultrasound. Transvaginal ultrasound is both safe and more accurate than transabdominal imaging in diagnosing placenta praevia. A high index of suspicion is warranted if the clinical scenario suggests a placenta praevia (painless bleeding, mobile presenting part, abnormal lie) irrespective of the previous ultrasound result (Fig 10.2). When discovered at the routine 20-week ultrasound, a follow-up ultrasound should be performed at 32 to 34 weeks’ to confirm persistence of placenta praevia and to exclude vasa praevia and placenta accreta.

Symptomatic placenta praevia (any gestation): vaginal bleeding

MANAGEMENT Asymptomatic placenta praevia: no vaginal bleeding Management of asymptomatic placenta praevia should begin with explaining the diagnosis, including the risk of provoked and unprovoked vaginal bleeding.

Outpatient versus inpatient The woman can usually be an outpatient until 34 weeks’ but then hospitalisation is usually recommended—even in the absence of bleeding for those with a major placenta praevia. Outpatient care requires close proximity to the hospital, mobile communication and preferably the presence of a responsible adult at all times. Delivery should occur at 37 weeks’ if the placenta praevia is major or 38 weeks’ if it is minor. However, delivery will be necessary earlier in the event of heavy continued bleeding. Mode of delivery will be by caesarean section if the placenta is ≤ 2 cm of the internal cervical os. Where a minor placenta praevia has been diagnosed early in the third trimester, a repeat scan at 36 to 37 weeks’ may be warranted—especially if the fetal head is beginning to engage.

If the woman presents with symptomatic placenta praevia with vaginal bleeding, she should be admitted to hospital—for any gestational age.

Resuscitation Obtain intravenous access. Intravenous fluid should be delivered as needed. A blood transfusion may be indicated if there has been substantial blood loss.

Initial investigation Full blood examination, blood group and hold/crossmatch and a coagulation profile (if there is significant vaginal bleeding) comprise the initial blood tests. Fetal wellbeing should be assessed with cardiotocography if > 26 weeks’ gestation.

Treatment

FIGURE 10.2

Anterior placenta praevia.

Corticosteroids (for fetal lung maturity) are indicated if delivery is anticipated prior to 34 weeks’ and is not imminent. Magnesium sulfate (MgSO4) should be considered (for neuroprotection) if delivery is anticipated before 30 weeks’. (Note that delivery should not be delayed if there is ongoing, severe bleeding or fetal compromise.) Tocolysis may be used in selected cases where the bleeding is relatively minor but has initiated labour prior to 34 weeks’. Delivery (by caesarean section) is indicated by: any bleeding at a gestation > 36–37 weeks’ moderate, ongoing blood loss > 34 weeks’

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•

heavy bleeding with maternal haemodynamic compromise or unremitting bleeding at any gestation.

Outpatient versus inpatient after an episode of bleeding Patients with a major placenta praevia and a moderate to severe bleed will generally remain inpatients until delivery. However, patients may be considered for outpatient management on a case-by-case basis if circumstances allow as mentioned earlier this chapter.

Operative management: caesarean section Where heavy blood loss is anticipated (e.g. suspicion of placenta accreta), a midline skin incision should be employed with general rather than regional anaesthesia. Excessive blood loss from the lower segment at caesarean section is common as the less muscular lower segment does not contract well. In addition to oxytocin and ergometrine, other measures that may be needed to control bleeding include PGF2alpha, suturing the bleeding placental site vessels in the lower uterine segment, uterine artery ligation, balloon tamponade or hysterectomy.

VASA PRAEVIA DEFINITION AND INCIDENCE Fetal vessels traverse within the membranes over the region of the internal os. This condition results from either a velamentous cord insertion or fetal vessels running between two lobes of placenta (Fig 10.3). Incidence is approximately 1 in 2500 pregnancies.

CLINICAL CONSEQUENCES Undiagnosed vasa praevia may be associated with a perinatal mortality of up to 70%. In contrast to the loss of maternal blood with placental abruption or placenta praevia, the bleeding with a vasa praevia is fetal. The vessels are at risk of rupture with either spontaneous rupture of the membranes or amniotomy.

DIAGNOSIS The diagnosis can be made antenatally with ultrasound. Vasa praevia should be actively sought in those with a velamentous cord insertion or succenturiate lobe and on third trimester ultrasound in all women who had a lowlying placenta at 20 weeks’. It may also present as vaginal bleeding after amniotomy or spontaneous rupture of membranes. Severe fetal compromise follows soon afterwards.

FIGURE 10.3

Vasa praevia. The mother reported decreased fetal movements after passing a ‘cupful’ of bright blood vaginally at 37 weeks’ gestation. The infant was stillborn at 3100 g. The arrows show the ends of the torn fetal vessel from which the fetus bled to death. More commonly, bleeding from vasa praevia occurs at the time of membrane rupture during labour.

section is commonly recommended at approximately 36 weeks’ to avoid the possibility of premature, prelabour rupture of membranes and potential fetal exsanguination.

PLACENTA ACCRETA Placenta accreta is a life-threatening condition where there is morbid adherence of the placenta to the myometrium. In this situation, placental separation is difficult and commonly associated with life-threatening haemorrhage, often necessitating hysterectomy. It most commonly occurs where an anterior placenta praevia occurs at the site of one or more previous caesarean sections. Placenta accreta is discussed in detail in Chapter 36.

PLACENTAL ABRUPTION DEFINITION AND INCIDENCE Placental abruption is defined as the partial or total detachment of the placenta from the placental/decidual interface prior to delivery of the fetus. Placental abruption occurs in approximately 1% of pregnancies. The recurrence rate is approximately 10% in subsequent pregnancies.

MANAGEMENT

PREDISPOSING FACTORS Placental bed ischaemia

While there is no definitive agreement on the management of antenatally detected vasa praevia, elective caesarean

The most common mechanism for abruption appears to be ischaemia of vessels in the placenta bed producing necrosis

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Chapter 10  Antepartum Haemorrhage

of anchoring villi and placental separation. Predisposing factors are therefore those of placental insufficiency: hypertensive disorders, including underlying hypertension and preeclampsia; it is important to recognise that placental abruption may be the presenting feature of severe preeclampsia thrombophilia, which remains somewhat controversial; stronger association of poor pregnancy outcome, including abruption, with certain thrombophilias (e.g. antiphospholipid syndrome), antithrombin III deficiency, homozygote genetic thrombophilia or compound heterozygote genetic thrombophilia smoking, cocaine use chorioamnionitis (e.g. following preterm prelabour rupture of the membranes).

• •

• •

Uterine trauma Much less commonly, the anchoring villi are sheared by traumatic injury, most often due to blunt trauma to the abdomen as a result of a motor vehicle accident.

Multiple pregnancy or polyhydramnios The normal cause of placental separation is the shearing force created between the uterine wall and the placental surface as the uterine volume reduces after birth. This same mechanism may lead to an abruption with rupture of the membranes in the presence of polyhydramnios or after birth on one twin prior to delivery of the other.

CLINICAL FEATURES AND CLASSIFICATION Placental abruption is a clinical diagnosis. The classic presentation is that of vaginal bleeding associated with abdominal and/or back pain. The pain is often constant in nature. Contractions will often be present and are usually of a high frequency but low intensity. However, they may also reflect typical labour-like contractions in strength and frequency. As there is often a mixture of concealed and revealed bleeding, the amount of vaginal bleeding is often a poor indicator of the degree of placental separation. As such, vaginal bleeding may be slight and seemingly inconsequential, or severe and life-threatening.

Mild abruption

FIGURE 10.4

Moderate placental abruption covering approximately one-third of the placental surface.

• •

haemodynamic compromise or disseminated intravascular coagulation (DIC) fetal compromise.

Severe abruption Severe abruption leads to fetal death in utero due to a large placental abruption. There is uterine pain and a tense, tender uterus with maternal haemodynamic compromise and DIC.

MANAGEMENT Mild abruption Initial management Generally, the woman should be admitted to hospital even though symptoms and signs are minimal and there is no evidence of maternal or fetal compromise. Careful assessment is needed to ensure that a more severe situation (moderate abruption) is not evolving. If the woman is less than 34 weeks’, corticosteroids will be administered in anticipation of a possible preterm birth.

Further management

In mild abruption, the clinically well patient will have minimal pain or uterine tenderness. There is no fetal compromise and revealed blood loss is less than 200 mL. Presumably, this is due to a marginal placental bleed with minimal separation.

The main concerns are either a repeat abruption of greater severity or evolving placental insufficiency (that may have been causal as well as consequential to the original presentation). Ultrasounds should be performed at least fortnightly for fetal wellbeing and delivery should be expedited at approximately 38 weeks’.

Moderate abruption

Moderate abruption

Moderate placental abruption (Fig 10.4) is diagnosed where any of the following are present and the fetus is alive: tense tender uterus revealed blood loss > 200 mL

Initial management

• •

Who and where? The woman should be admitted to an area where both mother and fetus can be monitored closely. The 89

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anaesthetist and paediatrician should be alerted that early delivery may be needed. Stabilisation Stabilisation involves the following steps. 1. Volume status assessment and replacement as needed. 2. Haematological assessment with correction of anaemia and replacement of platelets and clotting factors as needed. 3. Fetal wellbeing assessment with continuous cardiotocography. 4. Kleihauer on maternal blood to asses fetomaternal haemorrhage. 5. Anti-D administration if mother is Rh-negative. 6. Fetal lung maturity and neuroprotection: if birth is not imminent, corticosteroids if less than 34 weeks’ and MgSO4 if less than 30 weeks’.

Further management Further management involves continued intensive assessment of fetal wellbeing in anticipation of fetal compromise. Delivery should occur if there is: maternal haemodynamic compromise or DIC fetal compromise gestation > 34 weeks’. Prompt caesarean section is indicated if there is fetal compromise but major maternal morbidity or death is a real risk when a caesarean is performed in the presence of coagulopathy. Every effort should be made to stabilise the patient and correct the hypovolaemia and coagulopathy prior to delivery.

• • •

Severe abruption Where the fetus is dead, the mode of delivery is usually vaginal, especially as these patients often labour readily. Caesarean section is occasionally required for the control of severe ongoing bleeding or in the case of contraindicated vaginal birth. All attempts should be made to correct hypovolaemia and haematological disturbances prior to caesarean section. Hysterectomy may occasionally be needed for control of postpartum haemorrhage (Fig 10.5).

BLEEDING FROM THE CERVIX OR LOWER GENITAL TRACT CERVICAL ECTROPION A speculum examination to exclude cancer is especially important in those women with recurrent small bleeds who have not had a recent speculum or Pap smear.

CERVICAL POLYPS Cervical polyps usually do not require removal in pregnancy as this may provoke significant further bleeding. 90

FIGURE 10.5

Hysterectomy specimen of a Couvelaire uterus. The uterus has patches of black from the blood within the subserosal uterine muscle. Complete recovery is usual but there is often associated disseminated intravascular coagulation.

CARCINOMA OF THE CERVIX A speculum examination to exclude cancer is especially important in those women with recurrent small bleeds who have not had a recent speculum or Pap smear. FURTHER READING Ananth CV. Placental abruption in term and preterm gestations. Evidence for heterogeneity in clinical pathways. Obstet Gynecol 2006;107:785–92. Neilson JP. Interventions for treating placental abruption. Cochrane Database Syst Rev 2010. Oyelese Y, Smulian JC. Placenta praevia, placenta accreta, and vasa praevia. Obstet Gynecol 2006;107(4):927–41. Royal College of Obstetricians and Gynaecologists. Placenta praevia, placenta praevia accreta and vasa praevia: diagnosis and management. Green-top Guideline No. 27. London: RCOG; 2011. Royal College of Obstetricians and Gynaecologists. Antepartum haemorrhage. Green-top Guideline No. 63. London: RCOG; 2011. Tikkanen M. Placental abruption: epidemiology, risk factors and consequences. Acta Obstet Gynecol Scand 2011;90(2):140–9.

Chapter 11  FETAL GROWTH RESTRICTION AND ASSESSMENT OF FETAL WELLBEING Alexis Shub

KEY POINTS Fetal growth restriction (FGR), refers to babies who have failed to reach their optimal growth potential. Small for gestational age (SGA) describes babies where the birth weight is less than the 10th percentile for gestation. Low birth weight (< 2500 g) or very low birth weight (< 1500 g) are weight-based descriptions. Such definitions are less useful as they do not differentiate between the preterm baby, the term growth-restricted baby and the preterm growth-restricted baby. Small for gestational age may be due to constitutional influences on growth or FGR. FGR is most commonly due to placental insufficiency, but can also be due to congenital infections or fetal genetic/structural malformations. FGR is the single biggest risk factor for stillbirth and compromise during labour. Risk factors for FGR include hypertension, preeclampsia, diabetes, smoking, obesity and advanced maternal age. Early-onset FGR usually refers to FGR occurring before 32 to 34 weeks’, and is most commonly due to uteroplacental insufficiency, although infection or fetal abnormality should be considered. Late-onset FGR occurs after 32 to 34 weeks’, and is most commonly constitutional or due to uteroplacental insufficiency. Ultrasound is the mainstay in investigation of the small fetus, to assess: ■ fetal size and weight ■ blood flow in the umbilical artery (umbilical artery Doppler assessments) and Doppler assessments of fetal circulation, where indicated ■ parameters of fetal wellbeing (amniotic fluid volume and biophysical profile). FGR at term should be managed with delivery. Management of FGR in the preterm period needs to balance the risks of in utero asphyxia and stillbirth with the risks associated with preterm birth. Multiparameter surveillance, primarily involving ultrasound, is used most commonly to help decide the best time to deliver the severely preterm growth-restricted fetus.

FETAL GROWTH RESTRICTION Detection and management of fetal growth restriction (FGR) is one of the primary aims of antenatal care. Undetected FGR is a leading cause of stillbirth. Growthrestricted babies are more likely to suffer antenatal and

intrapartum stillbirth, suffer neurocognitive deficits and have long-term health problems in childhood and in adult life (Fig 11.1). FGR can be caused by maternal, fetal or placental factors. One of the difficult problems in the antenatal period is differentiating the constitutionally small, but well, baby from the baby with FGR who is at

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risk of antenatal and postnatal complications. Detection of FGR during the antenatal period may enable the cause of abnormal fetal growth to be determined. Detecting FGR also provides intervention opportunities to reduce the risk of intrauterine or intrapartum death.

WHY IS A FETUS SMALLER THAN EXPECTED? Babies may be constitutionally small (the well small baby from the small mother) or pathologically small, and it may not be apparent antenatally which diagnosis applies. Sixty per cent of babies that are small for gestational age (SGA) are constitutionally small and experience no extra complications; these need to be differentiated from babies with FGR who require additional surveillance and intervention. Conversely, identifying the constitutionally small baby prevents unnecessary additional intervention. Babies may have fetal growth restriction but be above the 10th percentile for gestation, having failed to achieve their growth potential. Assessment of the adequacy of fetal growth has to include the optimal birth weight for that baby. Factors that need to be included are primarily the mother’s height and weight, but babies tend to be heavier with increasing parity, and male babies are slightly heavier than females. The use of personalised growth percentiles has been shown to more accurately identify the cause of stillbirth so that many babies that were described as an unknown cause of stillbirth can be defined as FGR

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175 Morbidity Mortality

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60 75

50 40

50

30 20

Perinatal mortality (per 1000)

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10 > 10 10

9

8

7

6

5

4

3

2

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3800 g) Small fetus (preterm e.g. < 36 weeks’ or growth restricted) Placental insufficiency Fetal head extension (Fig 15.3) Footling breech presentation Evidence of cephalopelvic disproportion (e.g. previous obstructed labour, short stature) 123

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A

B

FIGURE 15.3

Burns-Marshall method of delivering the head. A The baby hangs with back uppermost to flex and promote engagement of the head. B The head is delivered by traction on the feet as they are swung upwards; the head is born by extension as it rotates around the symphysis.

fetal abnormality and head extension) will have been performed and the mother educated with respect to her specific roles in the conduct of the birth. In particular, she will have been informed of the importance of not pushing until the cervix is fully dilated and then the necessity of delivering the breech by expulsive effort from the mother. This is because traction by the accoucheur before the head is deep in the pelvis will cause head extension, with potentially catastrophic outcomes. Where the breech has not been diagnosed antenatally, the above two key aspects of ‘detailed assessment’ and ‘maternal education’ are likely to be deficient and not easily accomplished with a woman in established labour. Continuing with a vaginal breech birth in such 124

circumstances is likely to be associated with increased perinatal risk.

First stage of labour The general care, observations and management are similar to that for a cephalic presentation. As with all births, but even more so for a breech presentation, there should be ready access to immediate caesarean section. A recommendation for continuous electronic fetal monitoring is mandatory. An electrode can be attached to the buttock if necessary, taking care to avoid the genitalia. The passage of meconium is common and not necessarily indicative of fetal compromise. An increased likelihood of emergency anaesthesia should limit oral intake

Chapter 15  Malpresentation

to clear fluids only. Assessment of progress of labour should be vigilant and any delay in progress in the active phase of labour should lead to a recommendation for caesarean section. A vaginal examination should be performed as soon as the membranes rupture to exclude cord prolapse. Epidural anaesthetic for pain relief will have the desirable effect of preventing pushing until full dilatation of the cervix has occurred and the breech is on the perineum. This will be particularly important in the preterm situation where the head is relatively large and the smaller breech may slip through a partially dilated cervix, with subsequent head entrapment by the cervix. However, the downside of an epidural is substantial in that the mother will have reduced expulsive forces in the second stage of labour when, unlike cephalic presentations, there is no option of traction to deliver the body and aftercoming head—at least not until the head is deep within the pelvis and can no longer extend.

Second stage of labour: assisted breech delivery In all cases, an accoucheur skilled in vaginal breech delivery should be in attendance as accoucheur or supervisor. A paediatrician should be in attendance or immediately available.

no stage is there any traction through the atlanto-occipital joint.

Delivery of the shoulders The baby is rotated 90° to deliver the anterior shoulder beneath the pubic symphysis (Fig 15.4). The arm is then delivered by sweeping the humerus across the chest. The baby is then elevated to bring the posterior shoulder into the hollow of the sacrum. The body is then rotated 180° and lowered so that the previously posterior shoulder is also delivered beneath the symphysis pubis and then returned to back uppermost. This is termed Løvset’s manoeuvre. Extended arms are usually a consequence of traction being applied in delivery of the trunk. When this occurs, a hand is introduced into the vagina and each forearm is swept in an arc over the baby’s face (it is usually easier if the posterior arm is delivered first).

Delivery of the aftercoming head After delivery of the shoulders and arms, the baby is allowed to hang downwards while the mother continues to push in order to flex the head and facilitate engagement of the head in the pelvis. When the hair line becomes visible beneath the symphysis, the head is deeply engaged in the pelvis. The final delivery of the

Preparation The woman is placed in the lithotomy position when the breech is visible and the perineum distending. The bladder is emptied by catheter if necessary. If there is no epidural, perineal infiltration with 1% lignocaine and a pudendal nerve block should be performed.

Delivery of the breech and legs The accoucheur is not committed to a vaginal birth until the first (anterior) cheek of the buttock is delivered and the anus is visible. If delivery needs to be expedited in second stage before this point, a caesarean section should be performed. An episiotomy is performed routinely in nulliparas and in multiparas if the perineum is tight. The breech is then born by maternal expulsive effort. If the legs are flexed, they are freed as the breech passes through the introitus. If the legs are extended, they can be delivered by pressure in the popliteal fossa (Pinard’s manoeuvre) to flex them down.

Delivery of the trunk With continued maternal effort, the lower trunk is delivered to the level of the umbilicus. A loop of umbilical cord should be brought down to avoid tension on the cord. A warm cloth is placed over the buttocks and legs, and the baby grasped by the pelvic girdle as excessive abdominal pressure is liable to cause serious injury to such structures as the liver and spleen. The back is rotated uppermost (sacroanterior) to produce the most favourable diameters for the aftercoming head (occipitoanterior). At

FIGURE 15.4

Lövset’s manoeuvre for delivery of the posterior arm by rotation through 180° to the anterior position where it appears beneath the symphysis pubis. The baby is grasped by the pelvic girdle to avoid injury to the abdominal organs. 125

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A

B

FIGURE 15.5

Forceps delivery of the aftercoming head. A The occiput must be anterior (posterior fontanel beneath the symphysis pubis). B When the mouth appears the infant can breathe, although the greatest diameters of the head are still negotiating the narrow pelvic plane and outlet.

aftercoming head can be by forceps (Fig 15.5) or manual traction. With a forceps delivery of the aftercoming head, the assistant elevates the fetus and holds the arms out of the way to enable access of the blades to the sides of the head. Note that the traction force is being applied to the softer parietal bones in this case, rather than the harder base of the skull with a cephalic presentation forceps delivery. With the manual technique (Mauriceau–Smellie– Veit), the fetus is placed on the accoucheur’s arm, straddling it with arms and legs; flexion of the head is maintained by the middle finger placed in the baby’s mouth and the ring and index fingers beside the nose on the alveolar ridge (Fig 15.6). The index finger of the other hand pushes on the region of the occiput to further increase flexion. The head is delivered by drawing the body downwards and then forwards over the mother’s abdomen.

FIGURE 15.6

The Mauriceau–Smellie–Veit technique for delivery of the head is particularly useful when deflexion has caused failure of engagement.

Management of head entrapment Most problems are experienced as a consequence of head extension when traction is applied from below through the atlanto-occipital joint. (In contrast, maternal pressure from above on the vertex will lead to increased head flexion.) Patience is required and the head will usually engage with further maternal effort. If extension is severe, an experienced accoucheur is needed to pass a hand along the hollow of the sacrum up to the head in order to flex it manually. Symphysiotomy may be necessary but requires an accoucheur familiar with this procedure. If the baby is small or the presentation footling, the trunk may slip through a cervix which is not fully dilated. 126

Maternal effort may still achieve delivery of the head but on occasions it will be necessary to incise the cervix, classically at the 2, 6, and 10 o’clock positions (Dührssen’s incision).

Breech extraction Having gone to considerable lengths in the previous section to emphasise that one should never pull on the breech from below for fear of causing both extended arms and head extension, it must be acknowledged that the procedure of breech extraction is sometimes employed

Chapter 15  Malpresentation

for delivery of a second twin. With an epidural in situ, careful pressure by an assistant on the vertex may help maintain flexion of the head along with maternal effort. There are two reasons why some traction is allowable for a second twin. First, the traction force on the atlantooccipital joint is considerably less as the soft tissues have already been distended by the first twin birth. Second, a twin is usually small relative to the pelvis, and a minor degree of head extension should still result in diameters that are able to pass through the pelvis. If the second twin is known to be large, breech extraction should not be attempted and a caesarean section will be needed if delivery of the second twin must be expedited before an instrumental delivery is possible.

PROGNOSIS The perinatal mortality and long-term morbidity are increased in breech presentations both by virtue of the reason for the breech presentation and also consequences of the breech delivery itself. Fetal structural, abnormalities, neurological deficits and tight nuchal cords are all more common in breech presentations. Cord prolapse and head entrapment will be the two most common complications of the birth itself, causing long-term sequelae.

TRANSVERSE/OBLIQUE LIE: SHOULDER PRESENTATION If labour begins when the lie is transverse or oblique, the shoulder is the part that presents; that is, the part first felt on vaginal examination. There is no mechanism for

A

B

delivery in such cases and either the lie must be corrected or a caesarean section performed. The incidence at term (37 weeks’) is approximately 1 in 200 pregnancies.

PREDISPOSING FACTORS Predisposing factors are as for breech presentation, but there is a particular preponderance for high parity. The grand multipara has little tone in the uterus or anterior abdominal wall and therefore little form to the uterine cavity to drive the fetus to a cephalic presentation. However, as gestation advances in late pregnancy, there is still considerable fetal growth and less and less room for the fetus to lie transverse or obliquely. The majority of these transverse or oblique lies therefore correct spontaneously in late pregnancy. Placenta location remains an important predisposing factor for transverse lie (Fig. 15.7).

DIAGNOSIS Unless obscuring features are present (such as multiple pregnancy or obesity), transverse and oblique lies are relatively easy to diagnose. The general appearance of the abdomen often gives the first clue to transverse lie, because of lateral expansion. Furthermore, there is no fetal pole palpable in the fundus or lower uterus. The rounded, hard, ballottable fetal head will then be palpated in one flank or the other, with the softer breech on the opposite side. Confirmation by ultrasonography in the antenatal clinic or labour ward is very straightforward and within the skill range of all care providers.

C

FIGURE 15.7

Transverse lie. A Fundal placenta with fetus facing upwards. B The central (type 4) placenta praevia would prevent either fetal pole entering the pelvis. C Neglected transverse lie with prolapsed arm in labour. Uterine rupture would be imminent. 127

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MANAGEMENT Determine aetiology (look for a cause) Only a very small number of pregnancies will be found to have a transverse or oblique lie at 36 weeks’ or beyond. The history and examination should be reviewed. In the absence of an obvious cause (e.g. grand multiparity, placenta praevia), ultrasonography is indicated to exclude important predisposing factors such as fetal abnormality or a previously undiagnosed placenta praevia.

External cephalic version ECV is usually relatively easy with an oblique or transverse lie, but a high proportion revert almost immediately to their original position. It is obviously pointless to do repeated ECVs when the procedure is having no lasting impact on the malpresentation.

Admission to hospital If the abnormal lie persists to 38 weeks’, the safest course may be for the woman to be admitted to hospital until the lie corrects or a caesarean section is performed. The principal concern in late pregnancy is prolapse of the cord at the time of labour or prelabour rupture of the membranes. In hospital there is an opportunity for an immediate vaginal examination and prompt caesarean section if the cord is palpable. Cord prolapse at home carries a high mortality rate, and having the patient remain at home should be considered only if she lives adjacent to the hospital and there is someone with her all the time to take her immediately to the hospital should labour begin or the membranes rupture.

What happens in hospital? If the condition is due mainly to laxity of the uterus in a woman of high parity, it is likely that as full term approaches, the lie will stabilise longitudinally. The woman is reviewed daily to see if this has occurred and is discharged from hospital only if the lie has been stable longitudinally for 48 hours. Correction to longitudinal before labour becomes progressively less likely at or beyond the due date, and most will resort to caesarean section at this time. A common situation is an older woman of high parity who is more likely to have complications like hypertension or diabetes mellitus that would lead to a recommendation for birth at about 39 weeks’.

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If labour commences with the lie oblique or transverse, external cephalic version may be performed and the membranes ruptured in the hope that a longitudinal lie will establish. This course of action carries a significant risk of cord prolapse and should be contemplated only if immediate recourse to caesarean section is available.

Caesarean section for a transverse or oblique lie This can be a difficult procedure as the lower uterine segment may be poorly formed and a limb will be difficult to grasp if the back is down. If there is adequate liquor, internal version to either cephalic or breech is accomplished relatively easily during the caesarean birth. With no liquor and the back down, particularly if the lower segment is poorly formed, the wisest course of action may be to perform a vertical incision in the lower uterine segment that can be extended into the upper segment (classical caesarean section) if delivery proves difficult. FURTHER READING American College of Obstetricians and Gynecologists. External cephalic version. ACOG Practice Bulletin No. 13. Obstet Gynecol 2000, reaffirmed 2009;95(2):1–7. Hannah ME, Hannah WJ, Hewson SA, et al. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000;356:1375–85. Hofmeyr GJ, Kulier R. External cephalic version for breech presentation at term. Cochrane Database Syst Rev 2000;(2):CD000083. RANZCOG. Management of breech presentation at term. RANZCOG Statements and Guidelines (C-Obs 11). Online. Available: ; [March 2015]. Rietberg CT, Elferink-Stinkens PM, Visser GHA. The effect of the Term Breech Trial on medical intervention behaviour and neonatal outcome in the Netherlands: an analysis of 35 453 breech infants. BJOG 2005;112(2):205–9. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat caesarean deliveries. Obstet Gynecol 2006;107:1226–32.

Section 2.5 MEDICAL AND SURGICAL DISORDERS IN PREGNANCY Chapter 16

Hypertensive disorders of pregnancy eclampsia

Chapter 17

Thromboembolism, cardiac disorders and respiratory disease

Chapter 18

Bacterial infections in pregnancy

Chapter 19

Viral and protozoan infections in pregnancy

Chapter 20

The blood: anaemia; thrombocytopenia and coagulopathy

Chapter 21

Gastrointestinal, hepatobiliary, gynaecological and renal problems

Chapter 22

Autoimmune and isoimmune disease in pregnancy 

Chapter 23

Diabetes mellitus

Chapter 24

Neurological disease

Chapter 25

Mental health disorders during the perinatal period

Chapter 16  HYPERTENSIVE DISORDERS OF PREGNANCY ECLAMPSIA  Michael Permezel

KEY POINTS Gestational hypertension is hypertension developing in pregnancy but without systemic effects, and affects approximately 10% of pregnancies. Preeclampsia is a major cause of both maternal and perinatal morbidity and mortality. Preeclampsia is unique to pregnancy, appearing after 20 weeks’ gestation and disappearing within days of delivery, and is characterised by generalised vasospasm, platelet aggregation, increased capillary permeability and widespread tissue ischaemia. Primary causes of preeclampsia include immunological issues, vascular disease and conditions associated with a large placenta (hyperplacentosis). Mild preeclampsia requires close surveillance of both fetal condition and progress of the disease, with a possible role for antihypertensive drugs. Delivery should occur at 38 weeks’ or earlier if indicated by fetal condition or disease progression. Severe preeclampsia requires intensive nursing care, stabilisation and delivery. Stabilisation includes: prophylaxis of eclampsia, control of blood pressure, management of intravascular volume status, attention to platelets and clotting factors, renal and liver function, and close fetal surveillance with corticosteroids for fetal lung maturity if less than 34 weeks’. Eclampsia occurs with almost equal frequency in the antenatal period and the puerperium. Most cases of eclampsia have not previously been diagnosed with preeclampsia at the time they present. Eclampsia requires acute management of the generalised tonic clonic convulsion, stabilisation as for severe preeclampsia and prompt delivery.

CLASSIFICATION OF HYPERTENSION IN PREGNANCY Hypertension in pregnancy can be defined as either a systolic blood pressure (SBP) ≥ 140 mmHg and/or a dia­ stolic blood pressure (DBP) ≥ 90 mmHg (Korotkoff phase 5), elevated recordings being made on at least two occa­ sions, some hours apart. Severe hypertension is defined as an SBP ≥ 160 mmHg and/or DBP ≥ 110 mmHg. Classification suffers from lack of uniformity in defi­ nition. A simple approach is as follows.

1. Preexisting or chronic hypertension: hypertension in pregnancy that is present before 20 weeks’. 2. Gestational hypertension: hypertension in pregnancy after 20 weeks’ gestation in a previously normo­ tensive woman without evidence of systemic involvement. 3. Preeclampsia: hypertension in pregnancy after 20 weeks’ gestation in a previously normotensive woman with evidence of systemic involvement including the one or more of the following. ■ Renal: significant proteinuria, renal insufficiency (serum creatinine > 90 µmol/L), oliguria.

Chapter 16  Hypertensive Disorders of Pregnancy Eclampsia 

Haematological: thrombocytopenia, haemolysis, disseminated intravascular coagulation. ■ Hepatic: serum transaminases raised, epigastric or right upper quadrant pain. ■ Neurological: convulsions, hyperreflexia with sus­ tained clonus, severe headache, persistent visual disturbance, stroke. ■ Pulmonary: oedema. ■ Placental: abruption, fetal growth restriction. 4. Chronic hypertension with superimposed preeclampsia. 5. Other related disorders (eclampsia, HELLP syndrome: a manifestation of severe preeclampsia with haemol­ ysis, elevated liver enzymes and low platelets).

aggregation and microthrombus formation. There is hypersensitivity to circulating vasoconstrictors such as angiotensin II and reduced response to vasodilators such as nitric oxide. The fundamental issue in preeclampsia is that the widespread endothelial dysfunction is secondary to a factor liberated from an ischaemic placenta. The conse­ quent generalised tissue ischaemia also affects the pla­ centa, thereby exacerbating the process in an escalating cycle of positive feedback, culminating in severe pre­ eclampsia and possibly eclampsia. Teleologically, it makes sense that the ischaemic placenta will initially drive the blood pressure higher to aid placental perfusion. In pre­ eclampsia, the process has escalated to the extent that the ischaemia also affects the placental circulation, making perfusion worse rather than better.

CHRONIC HYPERTENSION

What is ‘factor X’?

The incidence ranges from 1 to 2%. Essential hyperten­ sion is responsible for over 90% of cases (other causes include renal disease, endocrine disorders and collagen vascular disease). Under careful supervision, patients should be taken off antihypertensive medications with adverse side effects such as ACE inhibitors and diuretics. If antihypertensive treatment is necessary, suitable first-line agents include methyldopa, labetalol and nifedipine. Maternal risks include exacerbation of hypertension, superimposed preeclampsia and placental abruption. Fetal risks are directly related to the degree of hyperten­ sion, and are increased in pregnancies where antihyper­ tensive treatment is necessary. Careful surveillance of maternal and fetal wellbeing during pregnancy is necessary. In cases where antihyper­ tensive treatment is administered, delivery at 38 to 40 weeks’ is indicated.

Much research has been directed to a possible agent that is liberated by an ischaemic placenta that has widespread effects on endothelial function, resulting in systemic vasospasm and platelet aggregation. There are many putative candidates and, at the time of writing, there are probably multiple factors that contribute to the endothe­ lial ‘activation’. Pre-eminent candidates at this time include an increase in antiangiogenic factors sFlt-1 and soluble endoglin and a reduction in circulating VEGF and placental growth factor. Probably all contribute, perhaps to different degrees in contrasting patients and their clinical scenarios. This research will hopefully point to new initiatives for early diagnosis, prevention and man­ agement of this common but potentially devastating disease.

■

GESTATIONAL HYPERTENSION There is a wide geographical variation but the average incidence is about 10%. Predisposing factors are similar to those of preeclampsia, with obesity being prevalent among women with gestational hypertension. Management is largely directed to careful surveil­ lance on an outpatient basis, looking for evidence of sys­ temic involvement that would indicate the development of preeclampsia. Clinical surveillance should be increased through more frequent outpatient visits supplemented by regular investigation of renal and liver function, plate­ lets, urinalysis and assessments of fetal wellbeing. Deliv­ ery is indicated at 38 to 40 weeks’ gestation depending on the severity.

PREECLAMPSIA PATHOPHYSIOLOGY The widespread endothelial dysfunction results in vasospasm, increased capillary permeability, platelet

PREDISPOSING FACTORS There are three classical pathways to initiate placental ischaemia as the trigger for the positive feedback process (Fig 16.1). Among the more common predisposing factors are a new partner, cohabitation of less than 6 months, essential hypertension and obesity. Overriding this is a genetic predisposition to the disease, which is reflected in the incidence being three to four times greater if a first-degree relative suffered from preeclampsia. That is, not all women will develop pre­ eclampsia with the same aetiological impetus.

Deficient placentation There is a fundamental requirement in mammalian evolution for maternal immunological tolerance of trophoblastic antigens of paternal origin. Failure of this mechanism results in an abnormal interaction between invading trophoblast cells and the decidua, with defective invasion of the muscular layer of the spiral arteries in the decidua and myometrium by the cytotrophoblast early in placentation. Failure to convert the spiral arteries to lowresistance vascular channels leads to a diminished utero­ placental blood supply (Fig 16.2). 131

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Deficient placentation

Maternal vascular disease

Excessive placental size

Failure of immunological tolerance

Hypertension, renal disease, SLE

Twins, diabetes, hydatidiform mole placental hydrops

Placental ischaemia sFlt-1, soluble endoglin Endothelial dysfunction: vasospasm, capillary permeability platelet aggregation, microthrombus formation

Cardiovascular

,

Neurological Renal

Haematological Hepatic

FIGURE 16.1 

Pathogenic pathways of preeclampsia.

Maternal vascular disease

Renal

Women with vascular diseases are also more likely to develop preeclampsia. This includes hypertension (essen­ tial or secondary), renal disease, diabetes mellitus and diseases of the connective tissues. The incidence is also increased in women with obesity. Both the hereditary and acquired thrombophilias appear to increase the risk of preeclampsia in case control studies.

The serum uric acid level becomes elevated relatively early in the progress of the disease. It reflects increased distal tubular reabsorption in the presence of reduced renal perfusion and correlates with the risk of placental insufficiency. Urinary protein is increased in normal pregnancy, but is abnormal if it is greater than 300 mg/ 24 hours or 30 mg/mmol on a spot urinary protein : cre­ atinine ratio. Oliguria and renal insufficiency (serum cre­ atinine > 0.09 mmol/L) are later changes.

Excessive placental size A large placenta (hyperplacentosis) is seen in multiple pregnancy, diabetes mellitus, hydatidiform mole and hydrops fetalis, all of which predispose to the develop­ ment of preeclampsia.

CLINICAL FEATURES Typically, the patient with preeclampsia is asymp­ tomatic.

Cardiovascular Increased capillary permeability causes generalised oedema affecting in particular the feet, hands and face. Hypertension is a direct consequence of the generalised vasospasm and it therefore, to some extent, represents a marker of the severe tissue hypoxia seen in the disease. Unchecked severe hypertension (> 170/110) can result in fatal maternal intracranial haemorrhage; placental abrup­ tion is more likely, particularly in early-onset disease. Pulmonary oedema may occur as a consequence of leaky pulmonary capillaries, making overenthusiastic volume replacement unwise. 132

Haematological Thrombocytopenia reflects increased platelet turnover, and the platelet count is a further parameter that may be used to monitor progress of the disease. Disseminated intravascular coagulation usually occurs later but is par­ ticularly hazardous and mandates delivery.

Hepatic Small haemorrhages and hypoxic swelling of the liver results in epigastric pain, tenderness at the right costal margin and elevation of transaminases and/or bilirubin. Rarely, rupture of the liver capsule may occur with poten­ tially difficult-to-control haemorrhage that may be fatal (Fig 16.3). Pancreatitis has even been reported, although this too is rare.

Neurological Other features of particularly serious cases include effects on the eye, brain, liver and lungs. The woman may experi­ ence visual blurring as a consequence of retinal arterial

Chapter 16  Hypertensive Disorders of Pregnancy Eclampsia 

NORMAL Placenta Cytotrophoblast stem cells

Anchoring villus cytotrophoblast column

Decidua

Myometrium

Tunica media smooth muscle

Cytotrophoblast Syncytiotrophoblast

Maternal blood

Bloo d flow

Spiral artery

Floating villus Cytotrophoblast

Maternal endothelial cells

Endovascular cytotrophoblast

PREECLAMPSIA Placenta Cytotrophoblast stem cells

Anchoring villus cytotrophoblast column

Decidua

Maternal endothelial cells

Cytotrophoblast Syncytiotrophoblast

Myometrium

Maternal blood

Less bloo d flow

Fetal blood vessel Floating villus

Tunica media vascular smooth muscle layer

Spiral artery

Cytotrophoblast

FIGURE 16.2 

Abnormal placentation in preeclampsia. In normal placental development, invasive cytotrophoblasts of fetal origin invade the maternal spiral arteries, transforming them from small-calibre resistance vessels to high-calibre low-resistance vessels capable of high blood flow. In preeclampsia, cytotrophoblasts fail to adopt an invasive endothelial phenotype. Invasion of the spiral arteries is shallow and they remain small-calibre high-resistance vessels, resulting in later placental ischaemia. Source: Mount DB, Pollak MR. Molecular and Genetic Basis of Renal Disease. Philadelphia: Saunders, 2007. Copyright © 2007 Saunders, An Imprint of Elsevier. Figure 25.1.

ischaemia. Inspection of the optic fundi may reveal arterial spasm or even exudates/haemorrhage. Similar changes in cerebral arterioles may result in headaches, hyperreflexia and convulsions (eclampsia). Typically, ischaemic stroke involves the occipital lobes (Fig 16.4).

Placental Fetal compromise results from placental insufficiency with intrauterine growth restriction (Fig 16.5), fetal

hypoxia and even fetal death. Forewarning may be obtained by assessment of fetal wellbeing using ultra­ sound and CTG in addition to clinical parameters. Placen­ tal abruption may result in rapid fetal demise and represents a considerable danger for the mother as well. The course of the disease is variable but may be very rapidly progressive. Borderline or labile blood pressure elevation may advance to a life-threatening crisis in the space of a week or less. In other cases, the early course 133

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is benign—only to develop rapidly at a later gestation. Although preeclampsia is more common in nulliparas, it is important to remember that the disease can be severe and of sudden onset in multiparas. The signs of pre­ eclampsia (or eclampsia) may first be observed during labour or after delivery.

Site of liver laceration with sutures in situ

Unruptured subcapsular hematoma

FIGURE 16.3 

Subcapsular hematoma of the liver in a fatal case of eclampsia.

Source: Management of Acute Obstetric Emergencies. Barton, John R., M.D.; Sibai, Baha M., M.D.. Published January 2, 2011. Pages 125–135. © 2011.

DIFFERENTIAL DIAGNOSIS Apart from gestational hypertension, the other most common cause of raised blood pressure in pregnancy is chronic hypertension. The most useful distinguishing feature is the gestation at onset. Apart from the uncom­ mon instance of a hydatidiform mole, preeclampsia almost always begins after 20 weeks’ gestation. Retro­ spective diagnosis of chronic hypertension may be made when the disease is persistent after delivery. Proteinuria may be a consequence of underlying renal disease. Differentiation from severe preeclampsia can be extremely difficult as there is often hypertension and oedema as well. The dilemma is often to what extent the clinical picture is explained by underlying renal disease versus an element of superimposed preeclampsia. The latter has more sinister implications for the fetus and rapid deterioration in maternal health. Intensive surveil­ lance of fetal and maternal wellbeing is imperative in such a situation. In unusual cases, phaeochromocytoma

At onset

FLAIR

DWI

FIGURE 16.4 

Occipital lobe lesions in a woman with eclampsia. A 23-year-old primigravida woman at 30.5 weeks’ gestation awoke with a headache, nausea and vomiting, followed by a generalised tonic–clonic seizure. On presentation to the hospital, her blood pressure was 160/100. She was obtunded with mild right arm and leg weakness, hyperreflexia, and a right Babinski’s sign. Axial fluid-attenuated inversion recovery (FLAIR) images done on presentation show the high-intensity lesions involving the white and gray matter of both occipital lobes. Source: Schapira AHV. Neurology and Clinical Neuroscience. St Louis: Mosby, 2006. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 112.3A.

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Chapter 16  Hypertensive Disorders of Pregnancy Eclampsia 

BOX 16.1  Features of severe preeclampsia. Severe hypertension not controlled with medication Renal insufficiency; heavy proteinuria (> 5 g/24 hours) Hepatocellular enzymes markedly elevated; jaundice Severe thrombocytopenia; disseminated intravascular coagulation Neurological sequelae including stroke and convulsions (eclampsia) Pulmonary oedema

management by predetermined hospital protocols and that delivery is indicated in most cases within 24 to 48 hours of the diagnosis. The specific serious complica­ tions denoted in Box 16.1 are absolute indications for deliv­ ery on maternal grounds, regardless of gestational age.

MANAGEMENT FIGURE 16.5 

Severe intrauterine growth restriction in preeclampsia at 36 weeks’ compared to a normally grown term fetus. The growth-restricted fetus weighed 1930 g at 36 weeks’ from a mother with severe preeclampsia. Source: Courtesy of Prof. Norman Beischer.

or antiphospholipid antibody syndrome should be excluded as a possible underlying cause. Dependent oedema of the legs is common in preg­ nancy and may be exaggerated by prolonged standing, multiple pregnancy or individual variations in lymphatic drainage. Some swelling of the fingers (tightness of the rings) may occur in normal pregnancy, but significant generalised oedema should always alert the clinician to the possibility that preeclampsia may be developing. Rare differential diagnoses that may be considered include lupus nephritis, haemolytic-uraemic syndrome (HUS), thrombotic thrombocyopenic purpura (TTP) and acute fattly liver of pregnancy.

CLASSIFICATION OF PREECLAMPSIA There is no consensus as to how preeclampsia should be classified according to severity. Differentiating mild and moderate disease separately is not necessarily of critical importance as there are no major differences in manage­ ment through this spectrum of the disease. Close monitor­ ing is required and delivery should take place with fetal maturity. In contrast, the diagnosis of ‘severe preeclamp­ sia’ denotes that the disease requires intensive inpatient

The aim of therapy is to manage the major sequelae of the disease, recognising that there will be little impact on the underlying disease process until delivery, which must be effected at the most appropriate time for both mother and fetus. Management therefore depends on the severity of the preeclampsia, the gestational age and fetal wellbeing. Little is to be gained in continuing pregnancy when the fetus is mature but with severe disease at very immature gestations, delivery is sometimes temporarily deferred with intensive surveillance and possibly treat­ ment. Where an absolute maternal indication for delivery is present, delivery must be effected regardless of gesta­ tional age or fetal considerations.

Management of preeclampsia without severe features Mild preeclampsia is somewhat of a misnomer since it is never a condition to be taken lightly. Initial assessment is required of both disease severity and fetal condition. Disease severity will be determined by symptoms (oedema, epigastric pain, visual disturbance, headache), clinical signs (blood pressure monitoring, hyperreflexia) and investigations. Investigations in the woman with pre­ eclampsia should include FBE, urinary protein : creatinine ratio, serum uric acid, platelet count and hepatic trans­ aminases. Fetal surveillance should include clinical parameters such as maternal perception of fetal move­ ment and clinical assessment of fundal height, along with CTG and ultrasonography with estimated fetal weight, amniotic fluid volume, fetal activity and Doppler mea­ surement of umbilical vessel blood flow. 135

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The disease progression is unpredictable. Women with mild preeclampsia should be managed in hospital or with recurrent pregnancy day assessment admissions where the patient is assessed once or twice weekly for symptoms, clinical features (especially blood pressure) and the above investigations. Antihypertensive drugs are indicated with a SBP ≥ 160 mmHg or DBP ≥ 100 mmHg. With SBP 140 to 160 mmHg or DBP 90 to 100 mmHg, there is a trend towards benefit, but larger randomised controlled trials are underway to more definitively determine an overall net gain. Magee et al. suggest tighter control of blood pressure results in fewer episodes of severe hyperten­ sion.1 Methyldopa has a long history of safe use in preg­ nancy but has side effects of lethargy and depression and may increase the risk of deep vein thrombosis (DVT). It is increasingly being replaced by drugs with better side effect profiles such as labetalol and nifedipine. Delivery is indicated at fetal maturity (38.0 weeks’) or earlier if there is evidence of significant fetal compromise or there is rapid disease progression towards severe preeclampsia.

Management of severe preeclampsia The presence of severe preeclampsia marks a quantum change in management. Intensive observation and treat­ ment must be instituted and termination of the preg­ nancy is required, almost regardless of the period of gestation. At very premature gestations, control of severe hypertension with drugs and/or lesser degrees of protein­ uria may permit delivery to be deferred temporarily, although frequently the presence of fetal compromise makes delivery indicated anyway. Poorly controlled blood pressure or evidence of other organ damage (renal, hepatic, neurological, haematological, pulmonary) are absolute indications for delivery at any gestational age (Box 16.1).

Where and who manages the patient? After establishing the diagnosis of severe preeclampsia, the woman should be admitted to an appropriate area of the hospital equipped for intensive nursing. The anaes­ thetic service should be informed and an obstetric physi­ cian may be consulted, but the primary responsibility for care must remain with the obstetric team. The paediatric team should be informed if the patient is preterm.

Stabilisation prior to delivery A number of principles of management for stabilisation of the disease prior to delivery need to be followed accord­ ing to an established hospital protocol for the condition. These principles are (in order): 1. convulsion prophylaxis 2. blood pressure monitoring and treatment 3. intravascular volume assessment and volume replace­ ment as required 136

4. haematological profile, liver and renal function tests, with appropriate treatment if deranged 5. fetal surveillance.

Convulsion prophylaxis Convulsions are potentially life-threatening to both mother and fetus. Prophylaxis is certainly indicated in the presence of hyperreflexia and some units will use prophylaxis in all cases of severe preeclampsia. Therapy should precede antihypertensive therapy, as magnesium sulfate will have a vasodilatory effect of its own and will also offer some protection against convulsions that may be precipitated by too rapid lowering of the blood pres­ sure. The best choice for convulsion prophylaxis is mag­ nesium sulfate. Anticonvulsant therapy should be continued until at least 12 to 24 hours after delivery. Magnesium sulfate has had a long history of use, and apart from decreasing central nervous system excitability, the vasodilatation induced appears to get at the cause of the problem (focal cerebral ischaemia). A loading dose of magnesium sulfate (4 g = 8 mL of a 50% solution given intravenously over 15 minutes) is followed by a continu­ ous infusion (1 to 2 g per hour = 2 to 4 mL of a 50% solution). Blood levels should be checked 8-hourly (thera­ peutic range 2 to 4 mmol/L). Overdosage may result in serious respiratory depression and can be reversed with intravenous calcium gluconate (10 mL of a 10% solution).

Blood pressure control Control of severe hypertension is necessary to prevent complications such as cerebral haemorrhage and placental abruption. Severe hypertension in pregnancy (SBP ≥ 160 or DBP ≥ 110) should be regarded as a medical emergency. Nevertheless, rapid and excessive lowering of blood pres­ sure may aggravate ischaemia in areas of persistent vaso­ spasm in the brain or placenta. A DBP of 90 to 100 mmHg is therefore desirable. Hydralazine and labetalol are alter­ natives for intravenous bolus administration to lower blood pressure and can be followed by an infusion.

Intravascular volume status The intravascular compartment is much reduced in severe preeclampsia as a consequence of chronic veno­ constriction. However, central venous pressure and venous return are maintained for the same reason. Prob­ lems can occur with the administration of venous compartment dilators (magnesium sulfate and anti­ hypertensives), which may result in a significant fall in central venous pressure and consequently cardiac output, further compromising tissue perfusion. Practically, the jugular venous pressure and hourly urine output act as barometers of central venous pressure. If these are reduced, then an intravascular fluid bolus is indicated. Failure of a urine input to increase with fluid is an indica­ tion for expert management with a possible need for a central venous pressure (CVP) line. If fluid replacement

Chapter 16  Hypertensive Disorders of Pregnancy Eclampsia 

is necessary, colloidal or crystalloid solutions can be used. There are pros and cons of both approaches. Excessive infusion can be fatal with the development of lifethreatening pulmonary oedema in the presence of ‘leaky’ pulmonary capillaries. For this reason, most units will insist on a CVP line before intravascular volume is expanded substantially.

lift-out forceps or vacuum extraction should take place. Ergometrine is contraindicated for the third stage and oxytocin (5 units intravenously) should be used instead.

The puerperium

Transfusion of platelets and/or fresh frozen plasma/ plasma concentrates may be required as judged by hae­ matological studies. If the platelet level is < 30 × 109/L, 6 units of platelets should be administered and the level should be > 50 × 109/L for delivery. Clotting factors should be replaced with fresh frozen plasma if the pro­ thrombin time or partial thromboplastin time is pro­ longed. Seriously impaired renal function or jaundice require expert medical assistance and are extremely adverse developments.

After delivery, the pathophysiological abnormalities are reversed fairly rapidly; for example, the low renal perfusion/output and depressed platelet levels usually return to normal in 3 to 4 days. If the disorder is severe and has occurred in the second or early third trimester, recurrence is likely in the succeeding pregnancy. The woman should be investigated in the puerperium for any residual hypertension and for an underlying disorder such as renal disease, systemic lupus erythematosus (SLE) or the antiphospholipid syndrome. The patient should be followed up at 6 weeks. In addition to a clinical review, FBE, urea and electrolytes, LFT uric acid and urinary protein should be assessed to ensure all have normalised.

Fetal surveillance and therapy

Future treatments

Haematology, liver and renal function

Fetal surveillance usually consists of continuous cardioto­ cographic monitoring up until the time of delivery. If delivery is to be deferred, ultrasound for fetal growth, amniotic fluid volume and Doppler studies along with daily CTG are essential. Corticosteroids are indicated if delivery is likely before 34 weeks’. Magnesium sulfate administered for convulsion prophylaxis will have a dual purpose with fetal neuroprotection indicated at gesta­ tions less than 30 weeks’.

Delivery An absolute rule is that the woman is assessed (and stabi­ lised where possible) with respect to anticonvulsant pro­ phylaxis, blood pressure control, blood volume status, haematology, renal function and liver function before embarking upon delivery. Epidural analgesia is useful in reducing pain, stress and the level of blood pressure but is contraindicated if there is severe thrombocytopenia or dis­ seminated intravascular coagulation. A decision regarding the timing and route of delivery is made on the basis of careful monitoring of the maternal and fetal condition.

Mode of delivery It is an axiom in obstetrics that women with severe pre­ eclampsia labour well after amniotomy and are often found to have an unexpectedly favourable cervix despite a very premature gestation. In some women with severe preeclampsia, caesarean section will be required because of fetal distress, a markedly unfavourable cervix, breech presentation or antepartum haemorrhage; however, severe preeclampsia of itself is not an indication for cae­ sarean section. There will be occasional exceptions to this rule when the condition of the mother is serious or dete­ riorating rapidly. The neonatal paediatrician and anaes­ thetist should be warned in advance so that appropriate arrangements can be organised. Prolonged pushing is contraindicated if the blood pressure is high, and a

Currently there are no medical therapies to treat the underlying pathophysiology of preeclampsia. Consider­ able research is being performed in an attempt to identify treatments that might reduce sFlt-1 and soluble endoglin and stabilise the disease process. Statins are cholesterollowering drugs with vasoprotective properties and have been shown to reduce sFlt-1 in preeclamptic mice models. The StAmP trial is currently investigating whether pravas­ tatin can reduce sFlt-1 secretion in preterm preeclamptic patients. Extracorporeal removal of sFlt-1 or the adminis­ tration of VEGF are other proposed treatments currently being explored.

Prophylaxis Prevention of preeclampsia necessitates an appreciation of the predisposing factors. Specific therapy of aetiologi­ cal conditions may reduce the risk of preeclampsia; for example, control of SLE with anti-inflammatory drugs, control of essential hypertension with antihypertensives or low-molecular-weight heparin for antiphospholipid syndrome. There is a generally accepted benefit of low-dose aspirin in preventing preeclampsia among those at increased risk. This needs to be commenced early in preg­ nancy to be effective and should be 100 mg daily. Calcium supplementation has also been demonstrated to reduce the risk of preeclampsia and so should be recommended, particularly in high-risk women and those with low dietary calcium intake. Folic acid supplementation in a multivitamin preparation may also contribute to a lower­ ing of preeclampsia risk (possibly through a reduction in homocystine levels) but vitamin C and vitamin E have been shown to be ineffective. Closely allied with prevention of preeclampsia is timely diagnosis. Antenatal care is obviously important in every pregnancy but closer clinical monitoring is nec­ essary in the presence of a predisposing factor for 137

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preeclampsia. The search continues for a reliable test to identify those women destined to develop preeclampsia. Raised blood pressure in the second trimester appears as reliable as any other test and as yet there is no reliable early pregnancy laboratory or ultrasound marker of future preeclampsia. The search continues.

HELLP SYNDROME HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) is a special variant of severe preeclampsia. It is important to distinguish it from similar conditions of acute endothelial cell damage such as haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Management is the same as severe preeclamp­ sia, with added attention to the haematological and bio­ chemical disturbances.

ECLAMPSIA Eclampsia is a generalised tonic-clonic seizure as a con­ sequence of pregnancy-related cerebral hypoxia. Eclamp­ sia is a very serious complication because of the high risk to the life of the mother and baby. Early diagnosis and active treatment of preeclampsia will enable the avoid­ ance of eclamptic fits in the majority of cases.

PATHOGENESIS The basic disorder is cerebral hypoxia, brought about by intense vasospasm and contributed to by cerebral oedema. Eclampsia may be more likely in women with a lower inherent threshold for convulsions. Imaging will demonstrate cerebral haemorrhage or thrombosis in a small number of these women.

INCIDENCE Eclampsia occurs in approximately 1 in 1500 deliveries. It is obviously considerably less common than preeclamp­ sia (1 in 50 pregnancies). There is, however, a wide geo­ graphical variation due partly to differing standards of antenatal care and partly to poorly understood factors such as diet and climate.

CLINICAL FEATURES In approximately 50% of women, eclampsia precedes the onset of labour; a small number first present in labour but most of the remaining 50% present in the early puerperium. Severe headache, visual disturbance, drowsiness, irri­ tability, restlessness, and twitching or jitteriness may precede the convulsion, as may other systemic features of severe preeclampsia. The convulsion is typical of a generalised tonic-clonic seizure. Usually there is a preictal stage or aura and the 138

woman is dissociated from her surroundings. This is fol­ lowed by a tonic stage, lasting approximately 30 seconds, when the skeletal muscles are in a generalised spasm: because of the virtual cessation of respiration, the woman becomes cyanosed. This stage gives way to the clonic stage of alternate muscular spasm and relaxation, which lasts up to 2 to 3 minutes. In this stage, the woman is at considerable risk of self-injury (tongue biting, striking herself against unyielding surroundings, or falling out of bed). Finally, there is the postictal stage of reduced level of consciousness, which lasts for a variable period, some­ times hours, depending on the number of fits, degree of vasospasm and cerebral hypoxia.

DIAGNOSIS Eclampsia should not present a diagnostic dilemma if preceded by severe preeclampsia. In the absence of obvious preeclampsia, other causes of convulsions need to be considered. Such conditions include maternal hypotension (‘fainting fit’), idiopathic epilepsy, intra­ cranial neoplasia, cerebrovascular accident, local anaesthetic toxicity (inadvertent intravenous injection), alcohol withdrawal and metabolic disturbances (e.g. hyponatraemia, hypoglycaemia).

PROPHYLAXIS OF ECLAMPSIA Prevention of eclampsia is largely via early diagnosis and prompt treatment of severe preeclampsia. This implies that the obstetric team is vigilant during the antenatal, intrapartum and postnatal periods to the symptoms and signs of preeclampsia and in no way underestimates the potentially catastrophic sequelae of the condition.

MANAGEMENT OF ECLAMPSIA The aims are to provide initial first aid for the convulsion, then stabilisation as for severe preeclampsia, and finally termination of the pregnancy as soon as practicable.

Convulsion first aid First aid for convulsion should be as follows. 1. Prevention of injury. The woman should positioned so as to protect her from physical injury. 2. Airway and oxygen. A rubber airway placed in her mouth will inhibit tongue-biting and protect the airway. Oxygen should be provided by means of a mask or nasal catheter. Artificial ventilation with bag and mask may be necessary in the early postictal phase, particularly if large amounts of diazepam were required. 3. Posture. The woman should be nursed in the semi­ prone position to facilitate drainage of the airway and to minimise pulmonary aspiration. 4. Anticonvulsant. Diazepam or clonazepam intrave­ nously remains the most effective means of stopping

Chapter 16  Hypertensive Disorders of Pregnancy Eclampsia 

a convulsion. Loading with 4 g magnesium sulfate should occur as soon as feasible. 5. Transport. If the woman is to be transferred to hos­ pital, it is desirable that a doctor or nurse accompany her in the ambulance.

STABILISATION PRIOR TO DELIVERY As for severe preeclampsia, the woman should be admit­ ted to an area of the hospital that is equipped for inten­ sive nursing care. If there is an impaired conscious state, neurological observations should be performed and the woman nursed in a semiprone position. Further fits should be anticipated with the availability of oxygen, bag and mask, rubber airway, reliable intravenous access and diazepam. Management is then similar to that discussed under severe preeclampsia: 1. prevention of further fits (magnesium sulfate, phe­ nytoin or diazepam) 2. blood pressure monitoring and control 3. intravascular volume assessment 4. haematology 5. renal and liver function 6. fetal surveillance.

EXCLUDE INTRACRANIAL PATHOLOGY Intracranial imaging is needed at some stage to exclude intracranial pathology, but stabilisation as above is the first priority.

DELIVERY Delivery should be expedited as soon as the woman is stabilised. In most circumstances this will be by cae­ sarean section, but some women will be able to give birth vaginally if the fits are controlled on magnesium sulfate infusion and the cervix is very favourable.

PROGNOSIS Maternal death may occur in relation to eclampsia. This is most commonly due to cerebral haemorrhage, with

renal or cardiac failure being less common. Other serious complications include pulmonary oedema, disseminated intravascular coagulation, psychosis and cortical blind­ ness. In surviving women, there is usually complete recovery of function. Perinatal death occurs in 10 to 15% and is due mainly to hypoxia and prematurity. REFERENCE 1) Magee L, Von Dadelszen P, Rey E, et al. Less tight versus tight control of hypertension in pregnancy. NEJM 2015;372(5):407–17. FURTHER READING Altman D, Carroli G, Duley L, Magpie Trial Collaboration Group, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002;359(9321):1877–90. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122(5):1122–31. Koopmans CM, Bijlenga D, Groen H, HYPITAT study group, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009;374(9694):979–88. Lowe SA, Bowyer L, Lust K, et al. The SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust NZ J Obstet Gynaecol 2015;55(1):11–16. Roberts JM, Bodnar LM, Lain KY, et al. Uric acid is as important as proteinuria in identifying fetal risk in women with gestational hypertension. Hypertension 2005;46(6):1263–9. Wen SW, Chen XK, Rodger M, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 2008;198:45, e1–7.

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Chapter 17  THROMBOEMBOLISM, CARDIAC DISORDERS AND RESPIRATORY DISEASE Michael Permezel and Lisa Hui

KEY POINTS Thromboembolism ■ The hypercoagulation of pregnancy increases the risk of thromboembolism and is one of the more common direct causes of maternal death. A high index of clinical suspicion is required in the symptomatic patient followed by definitive investigation and treatment with low-molecular-weight (LMW) heparin if the diagnosis is confirmed. ■ In women with predisposing factors for thromboembolism, daily self-administered LMW heparin is indicated, ceasing with labour and recommencing 6 hours postpartum. Cardiac disease ■ Substantial changes occur in cardiovascular physiology during pregnancy, most notably a 40% increase in cardiac output with diminished cardiac reserve. ■ Some of the more common symptoms (e.g. oedema, dyspnoea) and signs (e.g. systolic flow murmur) of normal pregnancy need to be carefully assessed to exclude underlying cardiorespiratory disease. ■ More women with severe forms of congenital heart disease are surviving to reproductive age, leading to a particularly challenging obstetric population. Pulmonary hypertension (of any cause) has a particularly poor prognosis in pregnancy, as does Marfan’s syndrome with aortic involvement and any heart disease with severe compromise. ■ Management of the cardiac patient requires a multidisciplinary approach, ideally with prepregnancy assessment and counselling. Optimisation of medication for pregnancy includes a consideration of whether there is a need for thromboembolism or infectious endocarditis prophylaxis. ■ Cardiovascular disease, particularly pulmonary hypertension, may exacerbate in the puerperium. ■ In peripartum cardiomyopathy, the physiological events around labour, birth and the early postpartum period culminate to produce life-threatening cardiac insufficiency in a woman with no prior history of cardiac disease but a presumed inherent sensitivity to these changes. Respiratory disease ■ An increase in ventilation by about 40% is associated with decreased respiratory reserve in pregnancy. ■ Asthma is the most common preexisting respiratory condition in women of childbearing age. Deterioration of lung function during pregnancy may occur with moderate or severe disease, and adherence to medication is essential. Short-acting beta-sympathomimetics and corticosteroids are regarded as safe to continue in pregnancy.

Chapter 17  Thromboembolism, Cardiac Disorders and Respiratory Disease

THROMBOEMBOLISM

PREVENTION

Pregnancy, and particularly the puerperium, is associated with an increase in clotting factors to help meet the haemostatic challenge of delivery. Venous stasis and blood vessel injury also contribute to the prothrombotic state of pregnancy. Deep vein thrombosis occurs in about 0.1% of women during pregnancy or the puerperium and about 50% of these are asymptomatic. Pulmonary thromboembolism occurs in about 10% of women with a deep vein thrombosis, and 1 in 50 000 pregnant women die as a result of this complication. With preeclampsia and haemorrhage, this is one of the three major causes of maternal mortality. The most important risk factor for venous thromboembolism in a pregnant woman is a prior history of deep venous thrombosis or pulmonary embolism. Other predisposing factors are given in Table 17.1.

Steps to prevent thromboembolism are imperative and include: 1. early mobilisation after delivery or surgery; and 2. prophylactic anticoagulant therapy with lowmolecular-weight (LMW) heparin for women at increased risk. It is important that this is continued into the early puerperium when the risk is greatest.

CLINICAL FEATURES AND DIAGNOSIS Deep vein thrombosis The woman may report pain or swelling of the leg. Clinical examination reveals the leg to be tender in the calf or thigh, oedematous and warm. The diagnosis can be confirmed by colour flow imaging with ultrasound of the lower limb deep veins.

Pulmonary embolism Clinical features vary considerably according to the size of the embolus. At one extreme there may be complete occlusion of the major arteries to the lung with maternal hypotensive collapse, while in contrast a small embolus can often be totally asymptomatic. Between these extremes, obstruction to a small- or medium-sized vessel may result in shortness of breath, chest pain or haemoptysis. Diagnosis is confirmed by CT pulmonary angiography.

TABLE 17.1  PREDISPOSING FACTORS FOR THROMBOEMBOLISM. Congenital thrombophilia

Acquired

Hyperhomocysteinaemia

Obesity

Factor V Leiden mutation

Smoking

Prothrombin gene mutation

Prolonged bed rest

Protein S deficiency

Surgery, infection

Protein C deficiency

Antiphospholipid syndrome, thrombocytosis

Antithrombin III deficiency

Cardiac disease, hypoproteinaemia

TREATMENT Treatment is with LMW heparin, initially at full anti­ coagulant dose levels, but it may be reduced to prophylactic dose for the remainder of pregnancy and the puerperium. The LMW heparin is discontinued when spontaneous labour occurs or 12 hours before planned delivery and recommenced 6 hours postpartum. If longterm anticoagulation is needed, warfarin can be commenced in the early postpartum period as it does not pass into breastmilk. Side effects of long-term LMW heparin include haemorrhage and thrombocytopenia. Warfarin (unlike heparin) crosses the placenta, and may produce chondrodystrophy, optic atrophy and haemorrhagic problems in the fetus. Insertion of an inferior vena cava filter is reserved for those women with repeated emboli despite anticoagulation, or women with a contraindication to anticoagulation. Surgical thrombectomy would be considered as a life saving measure if there has been a massive pulmonary embolism.

CARDIAC DISORDERS PHYSIOLOGICAL CHANGES IN PREGNANCY The cardiac output increases by about 40% in pregnancy but may double with maternal effort in the second stage of labour. This physiological adaptation is not only in response to the increased demands of the uteroplacental circulation but also other organs (e.g. renal). Both stroke volume and heart rate increase. The cardiac work increase is partly offset by reductions in both peripheral resistance (afterload) and blood viscosity with the physiological anaemia of pregnancy. The cardiac work rises through pregnancy and plateaus early in the third trimester. The hyperdynamic circulation commonly results in a soft ejection systolic murmur along the left sternal edge. It should be distinguishable from pathological murmurs by being quieter (grade 1 or 2), having an absence of other abnormalities, and the normal splitting of the second heart sound (widening with inspiration and closing with expiration). The normal ECG in pregnancy may show some left-axis deviation. Suspicious cardiovascular symptoms that suggest a pathological cause include severe dyspnoea, paroxysmal nocturnal dyspnoea, syncope with exertion, haemoptysis or chest pain with exertion. 141

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AETIOLOGY Congenital anomalies are the most common maternal cardiac problems in pregnancy. Problems may occur in combination (e.g. tetralogy of Fallot). Of particular sinister prognosis is Eisenmenger’s syndrome, where there is a left-to-right shunt through a septal defect or patent ductus in childhood, characterised by severe longstanding pulmonary hypertension and eventually a rightto-left shunt resulting in cyanosis. Rheumatic heart disease is still a major problem globally. Other causes of cardiac insufficiency in pregnancy include tachyarrhythmias, viral myocarditis, idiopathic cardiomyopathy, ischaemic heart disease and pulmonary hypertension of any aetiology.

CLASSIFICATION BY SEVERITY The New York Heart Association classification is as follows: grade 1, normal exercise tolerance; grade 2, breathless on moderate exertion (heavy household work); grade 3, breathless on less-than-moderate exertion (light household work); grade 4, breathless without significant activity.

CLASSIFICATION BY PATHOPHYSIOLOGY It is useful to have a concept of how the heart is com­ promised in order to predict performance during pregnancy or response to stresses such as general or regional anaesthesia. 1. Pump failure is a defective myocardial performance and may be due to ischaemia, idiopathic cardiomyopathy or viral myocarditis. 2. Volume load (preload) includes valvular regurgitation and high-output states (anaemia, thyrotoxicosis, peripheral shunting). Pregnancy has a similar effect on the heart. 3. Pressure load (afterload) may be intrinsic (aortic or pulmonary stenosis) or extrinsic (systemic or pulmonary hypertension). 4. Tachyarrhythmias may increase in frequency in pregnancy, particularly paroxysmal supraventricular tachycardia. 5. Reduced ventricular filling may be due to mitral/ tricuspid stenosis or reduced venous return.

CLINICAL FEATURES OF HEART DISEASE IN PREGNANCY The demands of the antenatal period will be a stress on the already limited cardiac reserve, further exacerbated during labour. Cardiac failure ensues when the cardiac reserve cannot meet the demand. In women at risk of endocarditis, pregnancy and its interventions increase 142

the risk of this complication. The hypercoagulable state of pregnancy may combine with a sluggish circulation to cause thrombosis and/or embolism. If the circulation is particularly poor, there is a risk of placental insufficiency with intrauterine growth restriction.

PROGNOSTIC FACTORS The conditions that have a particularly poor prognosis in pregnancy are pulmonary hypertension, Marfan’s syndrome with aortic involvement or grade 4 heart disease of any cause. In these circumstances, pregnancy should be advised against and termination considered if pregnancy occurs. Myocardial infarction is very rare in pregnancy unless the woman has multiple risk factors, such as a strong family history, hypertension, diabetes and a history of smoking. This condition is very serious, however, and carries a significant mortality.

MANAGEMENT Prepregnancy It is essential that a woman with cardiac disease be assessed before pregnancy with respect to both the nature of the lesion and the severity of diminished cardiac reserve. Assessment may include electrocardiogram, echocardiography and cardiac stress test. Treatment should be optimised in anticipation of a pregnancy, bearing in mind the relative benefits and disadvantages of maintenance therapy such as anticoagulants, vasodilators and antiarrhythmics. Corrective surgery, if necessary, should take place before conception as cardiopulmonary bypass may not provide adequate uteroplacental perfusion. If maternal prognosis is poor, appropriate contraceptive advice is required. Anticoagulation with warfarin is usually contraindicated because of the risk of teratogenic sequelae in the fetus including saddle nose, basophilic stippling of bones, microphthalmia, optic atrophy and intellectual disability. LMW heparin is usually substituted for warfarin as soon as a pregnancy is confirmed. In the case of a mechanical prosthetic heart valve, LMW heparin may be combined with aspirin. Angiotensin-converting enzyme (ACE) inhibitors are contraindicated in pregnancy because of an impact on fetal renal function, and beta-blockers have been associated with intrauterine growth restriction and should be used with caution. Appropriate immunisations should be performed prior to pregnancy (e.g. influenza, pneumococcal, tetanus, rubella). Genetic counselling regarding the risk of congenital heart disease in the baby should also be offered.

Antenatal Where medication is inappropriate for pregnancy, this should be adjusted as above. If the maternal prognosis

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during pregnancy is very poor, termination should be offered. The woman needs to be booked under spe­ cialist care with frequent obstetric and cardiologist review. In pregnancy, early diagnosis and prompt treatment of any deterioration in cardiac condition is imperative. Minimisation of aggravating factors is also important. Anaemia is obviously a potential aggravating factor, as is excessive weight gain. Prophylaxis against thromboembolism should be considered if the cardiac defect specifically predisposes to this complication (e.g. pulmonary hypertension) or prolonged bed rest is necessary. Additional fetal surveillance should include ultrasonography in the third trimester to detect intrauterine growth retardation.

Timing and mode of delivery Spontaneous labour is usually preferred to an induction as it should be more efficient and therefore place less demand on cardiac reserve, particularly if the cervix is unripe. In most conditions, vaginal delivery is preferable to elective caesarean section. There may be some possible exceptions (e.g. pulmonary hypertension, coarctation of the aorta) that benefit from elective caesarean section rather than vaginal delivery, but such decisions should be made only after consultation between obstetrician, anaesthetist and cardiologist. If caesarean section is undertaken, a discussion regarding tubal ligation at the time of surgery may be appropriate.

Intrapartum management: first stage Where there is a lesion at risk of bacterial endocarditis, an intravenous line is required for the infusion of prophylactic antibiotics. Amoxycillin (or vancomycin if the patient has a penicillin allergy) and gentamicin are suitable agents. Care must be taken not to infuse excessive intravenous fluid that may precipitate cardiac failure. The woman must be observed closely in the labour ward. In addition to the routine observations, regular checks of jugular venous pressure and lung bases for crepitations should be performed. The patient’s oxygen saturation should be monitored with pulse oximetry. If the woman is not anticoagulated, epidural analgesia may be administered with careful control of intravascular volume to avoid hypotension, but this is contraindicated in aortic stenosis and hypertrophic obstructive cardiomyopathy, and may also be hazardous in mitral stenosis or pulmonary hypertension. In these women, the epidural administration of opioid drugs alone can provide safe analgesia.

Second stage of labour The woman’s head and shoulders should be elevated during labour and delivery, with the legs dependent.

Specifically, the lithotomy position should be avoided because of the risk of acute pulmonary oedema. Forceps or vacuum extraction should be used to avoid prolonged pushing in the second stage.

Third stage of labour These women withstand blood loss poorly and prophylaxis against postpartum haemorrhage is necessary, even though ergometrine is contraindicated. Oxytocin 10 units by slow intravenous injection should be administered after completion of the second stage. In the event of a postpartum haemorrhage, intravenous ergometrine should be given, as the two reasons for avoiding it initially (excessive preload and afterload) are no longer present and hypovolaemia in these women can have catastrophic sequelae.

Puerperium Rapid haemodynamic alterations occur at this time that may precipitate right or left heart failure. This includes a physiological ‘autotransfusion’ of blood volume into the circulation from the contracted uterus and mobilisation of extracellular fluid. Women with mitral stenosis are particularly at risk of pulmonary edema during this period due to restricted left vetnricular filling. Pulmonary hypertension commonly deteriorates in the early puer­ perium, possibly as a consequence of progesterone withdrawal. Attention is given to the prevention of thromboembolism by early mobilisation and prophylactic LMW heparin. Contraception is important, as unwanted pregnancies may unnecessarily risk deterioration in maternal cardiac condition. The combined oral contraceptive pill is undesirable because of the thromboembolic risk, but progestogen-only contraception is safe. An intrauterine contraceptive device may risk endocarditis. Laparoscopy may be relatively contraindicated in these women (cardiac embarrassment from pneumoperitoneum), as is general anaesthesia (risk of thromboembolism). Vasectomy of the partner or tubal ligation at the time of cesarean section are suitable options if permanent contraception is desired.

PERIPARTUM CARDIOMYOPATHY This is a rare condition (about 1 in 2000 pregnancies) where a cardiomyopathy develops for the first time in the peripartum period. It often presents with sudden maternal decompensation at the time of a peripartum event such as a preeclampsia or postpartum haemorrhage. Cause is likely to be a preexisting sensitivity to peripartum events such as the withdrawal of oestrogen, a known positive inotrope. Treatment is along the usual lines for a dilated cardiomyopathy. Even when recovery appears complete, there is a high recurrence rate in any subsequent pregnancy. 143

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RESPIRATORY DISEASE PHYSIOLOGICAL CHANGES IN PREGNANCY Ventilation is increased in pregnancy by about 40%. There is no significant change in the respiratory rate so the increase in minute volume is largely met by an increase in tidal volume due to a direct effect of progesterone on the central respiratory centre. The increased ventilation causes a reduction in maternal carbon dioxide tension in maternal blood, which facilitates gas exchange across the placenta. Oxygen exchange is aided by the differing oxygen dissociation curves for fetal and adult haemoglobin. In the third trimester, there is a considerable fall in expiratory reserve volume and residual volume due to upward pressure by the uterine fundus on the diaphragm. Episodic mild shortness of breath sometimes occurs mid-pregnancy as an awareness of the increased respiratory work. It is not exercise related and not nocturnal. It requires careful clinical assessment to identify any underlying cardiorespiratory disease before attributing the symptom to physiological reasons.

ASTHMA This is the most common disease affecting the lungs in pregnancy. There is no uniform pattern of the disease in pregnancy. Mild asthma has little effect on pregnancy but with moderate or severe asthma there is an increased risk of intrauterine growth restriction, preterm birth and preeclampsia. Most drugs used for asthma are relatively safe in pregnancy, including the beta-sympathomimetics and corticosteroids. As in non-pregnant women, potential adverse effects will be lessened with inhaled rather than oral medication. Caution should be exercised with the administration of prostaglandins for cervical ripening, induction of labour or postpartum haemorrhage.

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Prostaglandin F2-alpha is particularly prone to cause bronchoconstriction. Anti-inflammatory drugs postpartum may exacerbate asthma. Management of asthma in pregnancy is similar to that in the non-pregnant state. Adherence to medication is even more important than usual in the interests of both the mother and the offspring. It is important that the carer educates the mother with respect to the risk–benefit equation, strongly favouring any needed medication. Peak expiratory flow should be checked regularly as a guide to therapy. The basic aim of drug therapy is to pro­ vide bronchodilator and anti-inflammatory activity. For mild intermittent asthma, inhaled beta-sympathomimetic (e.g. salbutamol or terbutaline) for occasional symptom relief may be all that is needed. If attacks are more frequent, prophylaxis with an inhaled corticosteroid (e.g. beclomethasone, budesonide) should be instituted to reduce beta-agonist dependence. Antibiotics should be used if there is associated infective bronchitis. Short courses of oral corticosteroids may be needed for exacerbations and hospitalisation may be necessary for severe attacks. FURTHER READING Lewis G, editor. The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer—2003–2005. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH; 2007. McLintock C, Brighton T, Chunilal S, et al. Recommendations for the prevention of pregnancyassociated venous thromboembolism. ANZJOG 2012;52:3–13. Murphy VE, Schatz M. Asthma in pregnancy: a hit for two. Eur Respir Rev 2014;23(131):64–8. Royal College of Obstetricians and Gynaecologists. Cardiac disease and Pregnancy. Good Practice Guideline No. 13. London: RCOG; 2011 June. Online. Available: ; [16 Dec 2014].

Chapter 18  BACTERIAL INFECTIONS IN PREGNANCY Peter Wein

KEY POINTS Bacterial infection in pregnancy remains a challenge due to increasing antibiotic resistance, changing common organisms and patterns of infection. Normal physiological changes of pregnancy and lactation put the pregnant woman at increased risk of infection. Preterm premature rupture of the membranes and prolonged labour are prime causes of ascending infection and chorioamnionitis. The human immunodeficiency virus (HIV) has seen the return of infections thought to be conquered, such as syphilis and tuberculosis. Infection is often ‘silent’ in terms of clinical features. A high index of suspicion is thus necessary if the wellbeing of the mother, fetus and neonate is to be maintained.

INFECTIONS BY SITE The mother is predisposed to infection in four classical sites: the uterus, urinary tract, breast and (depending on the mode of birth) either the perineal or abdominal wound. Infection is particularly common in pregnancy owing to the relative immune suppression, together with physiological changes such as urinary tract dilatation and stasis. Even a normal confinement leaves every woman with a large healing placental site, tantamount to a surgical wound in a potentially contaminated area; many also have an episiotomy or sutured laceration in close proximity to bowel bacteria. The neonate with immature defence mechanisms is at particular risk of bacterial infections. This will be more pronounced in the premature neonate or, less commonly, a neonate compromised by specific immune deficiencies (e.g. neonatal alloimmune neutropenia). A variety of organisms may be involved, both aerobic and anaerobic, reflecting the microflora of the lower birth canal. The fetus is also at risk from microorganisms acquired transplacentally, originating in the mother’s bloodstream.

Infection of the mother during pregnancy usually affects the fetus directly, but indirect manifestations such as fever and endotoxin liberation (e.g. from vaginal or urinary tract infection) may precipitate premature rupture of the membranes and/or premature labour. When treating infection in the pregnant or puerperal woman, the possible effects on the fetus or newborn of drugs given to the mother should be remembered. Antibiotics should never be given indiscriminately; most of the treatable infections have relatively specific drug regimens.

REPRODUCTIVE TRACT INFECTION CHORIOAMNIONITIS Pathology Infection of the fetus, secundines (placenta and membranes) and amniotic fluid is secondary to infection

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or colonisation of the mother by pathogenic microorganisms. When the infection arises in the vagina, the membranes and amniotic fluid are involved primarily; the baby and placenta are involved secondarily. The organisms reflect the normal vaginal flora—mixed aerobic and anaerobic bacteria—or intercurrent disease. Bacteria can gain access to the fetus via the nasopharynx during normal ‘breathing’ movements in utero.

Predisposing factors The usual situation is preterm premature rupture of the membranes (PPROM), with ascent of pathogens from the cervix/vagina. The presence of a cervical suture increases the risk of infection and, if present, should usually be removed if the membranes rupture irrespective of the gestation. Chorioamnionitis can occur with intact membranes and prolonged labour, the latter causing a breakdown of the normally effective barrier. Transplacental infections can occur during pregnancy in the absence of premature rupture of the membranes or labour. There may be an unnoticed or mild illness in the mother (e.g. listeriosis). The primary damage is seen in the placenta or in the fetal liver.

Diagnosis Early signs are often absent or minimal; with a more established infection, there may be maternal and/or fetal tachycardia, maternal fever, uterine tenderness and odour. Full blood examination will show an increased white blood cell count, with a neutrophilia and left shift. Acute phase reactants such as C-reactive protein (CRP) levels are usually elevated, although the rise in CRP may not occur until after clinical chorioamnionitis and a need for expedited delivery is apparent. The cardiotocography commonly shows a fetal tachycardia. If the diagnosis is in doubt, amniocentesis is very occasionally performed, enabling amniotic fluid microscopy and culture and a definitive diagnosis. This may be difficult where there is oligohydramnios as a consequence of PPROM.

Management Established chorioamnionitis requires delivery, and failure to expedite birth may result in a maternal death. The major issues are the mode of birth and the most appropriate antibiotics. In women with PPROM, there is good evidence that prophylactic treatment with erythromycin reduces the incidence of chorioamnionitis. In established chorioamnionitis, the usual combination of antibiotics while awaiting identification of a specific organism is as follows: amoxycillin/ampicillin 2 g intravenously 6-hourly plus gentamicin 5 to 6 mg intravenously 24-hourly for three doses (if normal renal function) plus metronidazole 500 mg 8-hourly. Gentamicin should only be used as empiric therapy for 72 hours. If there is an organism isolated that is only

• • •

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sensitive to gentamicin, further dosing should be guided by serum levels.

POSTPARTUM ENDOMETRITIS Pathology The ‘childbed fever’ that was the great scourge of the 19th century was due to Streptococcus pyogenes (Group A strep) and led to one of the greatest ever simple advances in medicine—handwashing before attending a birth. This was instigated by Ignaz Semmelweiss in 1852. The common organisms now are those colonising the vagina and perineum including Group B streptococci (GBS), coliforms and anaerobes. The placental site is usually infected first, after which spread occurs to the surrounding tissues, resulting in parametritis and pelvic peritonitis but rarely general peritonitis or septicaemia (see Ch 41).

Predisposing factors Predisposing factors include prolonged labour greater than 12 hours, multiple vaginal examinations, operative delivery (both vaginal and caesarean birth) and retention of products of conception. Infection complicates caesarean section in 5 to 10% of elective and 10 to 30% of emergency cases. Prophylactic antibiotics (usually a firstgeneration cephalosporin) significantly decrease post­ operative infection.

Management Management includes resuscitation as necessary, identification of the organism if possible (although the infection is often polymicrobial) and broad-spectrum antibiotics until the organism is identified.

POSTABORTAL ENDOMETRITIS Predisposing factors Predisposing factors include preexisting infection (e.g. Chlamydia) and retained products of conception.

Pathology The usual organisms are lower genital tract flora. Illegal (‘backyard’) abortion was historically associated with Clostridium perfringens and commonly fatal.

Diagnosis The patient presents with a combination of increased bleeding, pelvic pain, fever and offensive discharge. Examination may show fever, lower abdominal tenderness, cervical motion and forniceal tenderness on pelvic examination, and the presence of a vaginal discharge. Cervical swabs should be taken for Gram stain and culture and polymerase chain reaction (PCR) testing for Chlamydia.

Management For mild to moderate disease, oral treatment with amoxycillin and clavulanate and a single dose of azithromycin

Chapter 18  Bacterial Infections in Pregnancy

(repeated after 7 days) is appropriate. Severe disease is treated with intravenous amoxycillin, gentamicin and metronidazole as for chorioamnionitis. Ultrasound examination may be required to determine if there are significant retained products of conception. If there are, curettage may be necessary to remove the nidus of infection.

URINARY TRACT INFECTION PATHOGENESIS Microorganisms grow more readily in the urine of pregnant women, possibly due to differences in pH and the greater amounts of sugar and amino acids that escape reabsorption in the renal tubules. In addition, there is some obstruction to urine flow in the ureters, and decreased smooth muscle tone due to progesterone. The risk of urinary tract infection (UTI) in pregnancy is thus increased and is further aggravated by catheterisation and trauma to the urethra and bladder during delivery. In the great majority of women with urinary infection, a coliform or other gram-negative organism is cultured. In about 6% of women in early pregnancy, significant bacteriuria (> 108 colony-forming units/L) will be found in a midstream specimen of urine (MSU). If untreated, approximately one-third of these women will develop acute pyelonephritis, with increased rates of prematurity and perinatal mortality. Universal screening for asymptomatic bacteriuria is therefore recommended at the first antenatal visit. As the infection is only diagnosed by the results of urine culture, the organism and sensitivity are known and so the most appropriate antibiotic can be used. Depending on sensitivities, the usual antibiotics are amoxicillin, cephalexin, amoxycillin with clavulanate or nitrofurantoin. The infection should be treated for 5 days and the urine retested 1 week after treatment finishes. If it persists or recurs, the infection is retreated. If the infection recurs again, suppressive treatment with a low dose of antibiotic (nitrofurantoin 100 mg at night) can be used for the duration of pregnancy. UTIs that persistently recur may indicate an abnormality of the upper urinary tract (stone or congenital malformation), and renal ultrasound examination may be helpful.

ACUTE PYELONEPHRITIS Acute pyelonephritis is suspected when there are symptoms of urinary tract infection together with fever and loin pain. Bacteraemia (in about 20% of patients) and severe sepsis can occur, so it should be treated aggressively. Initial investigation is with MSU, blood cultures, full blood examination and renal function tests. Empiric treatment should be commenced with ampicillin 2 g intravenously 6-hourly plus gentamicin 5 to 6 mg intravenously 24-hourly for three doses (if normal renal function). Once the patient is

symptomatically improved and afebrile for 48 hours, she can be switched to the appropriate oral antibiotics for a total of 10 days. A ‘proof of cure’ urine culture should be performed at least 48 hours after the end of the course. As there is a significant risk of recurrence, prophylactic nitrofurantoin 100 mg at night should be used for the remainder of the pregnancy.

BREAST INFECTION PATHOGENESIS The chief predisposing causes of puerperal mastitis are stagnation of milk in poorly drained lactiferous sinuses and trauma from suckling. It is probable that the invading bacteria (almost always Staphylococcus aureus) come from the baby rather than the mother. The baby is colonised from the hospital environment and therefore these organisms are usually penicillin-resistant.

DIAGNOSIS The mother will present with pain and redness in the breast, often localised to one quadrant. With more severe infection, very high fevers (40°C), rigors and generalised symptoms may occur.

MANAGEMENT Mastitis should be treated promptly with a broadspectrum antibiotic to prevent a breast abscess. Women who are clinically well can be treated with oral dicloxacillin (or clindamycin if allergic to penicillin). However, some women develop a marked pyrexia, and may need treatment with intravenous flucloxacillin. Symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDS) and cold compresses will relieve the symptoms. It is vital to ensure the breast is emptied. The best way to do this is to continue breastfeeding. If a breast abscess is suspected, it can be confirmed with ultrasound examination. In most cases, the abscess can also be drained using ultrasound guidance to aspirate the pus. If this fails, occasionally formal incision and drainage is necessary (Fig 18.1). Candida albicans is also often diagnosed as a cause of shooting breast and nipple pain. (See Chs 39 and 41 for more details.) It is not clear whether Candida really causes these symptoms or whether treatment with antifungal drugs helps.

SPECIFIC ORGANISMS TRANSPLACENTAL (HAEMATOGENOUS) INFECTIONS Full details of Chlamydia and gonorrhoea infections can be found in Chapter 54. This section will deal with special features of these infections relating to pregnancy. 147

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[Treponema pallidum haemagglutination]). There are a number of causes of false-positive reagin tests, including the anticardiolipin syndrome.

Management A

B

FIGURE 18.1 

Breast abscess is an avoidable complication of breastfeeding if an antibiotic is given at the onset of localised redness and tenderness with or without pyrexia. A There is a painful fluctuant lump often deep within the breast without involvement of overlying skin. B Treatment is a wide incision in a radial direction from the nipple into the depth of the abscess cavity over the most dependent area with adequate drainage.

Syphilis Epidemiology This ancient disease is caused by the spirochaete, Treponema pallidum. It has largely been controlled in areas where antenatal care is adequate because of routine serological testing of all women at the first antenatal visit. However, syphilis is still relatively common in rural and regional Indigenous populations and in less-developed countries. It is estimated that there are 500 000 perinatal deaths in the world every year due to maternal syphilis, with a similar number of babies born with congenital syphilis. Detection and treatment is highly cost-effective, with an estimated cost of about $10 per life saved.

Sequelae The spirochaete crosses the placenta and causes congenital syphilis. This is associated with significant perinatal mortality, as well as osteochondritis, rash of palms and soles, nasal discharge, hepatosplenomegaly, anaemia, IUGR, fetal hydrops, microcephaly, pneumonitis, nephrosis, thrombocytopenia, petechial rash, uveitis, chorioretinitis, leukaemoid reaction and the typical ‘saddle nose’.

Diagnosis Although syphilis is rare, the consequences of untreated maternal syphilis are serious. There is an inexpensive, reliable test and a very effective low-cost treatment, so universal screening at the first antenatal visit remains cost-effective. High-risk populations, where syphilis may be contracted during pregnancy, should be retested at 28 weeks’ gestation. If the serology is positive on screening (usually RPR [rapid plasma reagin] or Venereal Disease Research Laboratory [VDRL]), a more detailed study is made to confirm the presence of the disease by specific anti-treponemal testing (FTA [fluorescent Treponema antibody] and TPHA 148

Treatment requires an adequate course of penicillin: benzathine penicillin 1.8 g intramuscularly for early syphilis (< 12 months) or benzathine penicillin 1.8 g intramuscularly for three doses at weekly intervals if the duration of the disease is more than 12 months or unknown. Because the alternatives to penicillin have not been shown to prevent congenital syphilis, patients who are allergic to penicillin should be desensitised then treated with penicillin. In addition, the woman’s partner should be tested and treated if serology is positive. It is also important that the disease be notified and sexual contacts examined. The baby should be carefully examined and investigated with syphilis serology, which should be less than four times the mother’s titre. If both are negative, the baby should receive a single dose of benzathine penicillin 37.5 mg/kg intramuscularly.

Listeriosis Listeria monocytogenes is a ubiquitous environmental gram-positive organism. Although uncommon, infection of the mother with Listeria monocytogenes may have serious consequences for the infant. The organism is ingested with poorly cooked meat or seafood, pates and smallgoods, contaminated soft cheese, soft-serve ice cream or vegetables that have not been adequately washed. It can grow in refrigerated products, so pregnant women should not eat at-risk foods that have been stored for more than 24 hours. Typically, the mother has a non-specific, flu-like febrile illness; back pain and rigors may also be present. It can lead to premature labour, fetal death or a severe disseminated fetal infection (lung, liver, central nervous system) resulting from transplacental transmission. Meconium staining of the amniotic fluid is common even in the late second trimester. Unless the diagnosis is thought of and energetic treatment given, the baby has a high risk (25 to 50%) of dying. If the diagnosis is clinically suspected, blood cultures and genital tract cultures should be performed. There may a place for amniocentesis and culture of amniotic fluid. Treatment of suspected or documented infection is with intravenous ampicillin 2 g 6-hourly.

Chlamydial infection Untreated genital Chlamydia trachomatis infection in pregnancy increases the risk of PPROM, preterm labour and preterm birth. The baby has about a 30% risk of conjunctival infection and a 15% risk of pneumonia. These outcomes can be prevented by simple treatment of pregnant women with genital chlamydial infection. However, it is unclear whether screening all or some pregnant women for Chlamydia is an effective policy. The Centers for Disease Control and Prevention (United

Chapter 18  Bacterial Infections in Pregnancy

States) recommends screening of all pregnant women. The Royal Australasian College of Obstetricians and Gynaecologists recommends that ‘selective testing for Chlamydia should be considered for those who may be at increased risk (e.g. less than 25 years)’ and the National Institute for Clinical Excellence (NICE) in the United Kingdom suggests that Chlamydia screening should not be offered as part of routine antenatal care. Testing should definitely be performed in women with symptoms, or those who are at high risk. Testing can be performed by nucleic acid amplification tests of vaginal swabs or urine. The recommended treatment is a single 1-g dose of oral azithromycin. The patient should be tested for gonorrhoea. Sexual contacts should be followed up and treated. A test of cure should be performed in not less than 3 weeks.

prolonged induction-delivery interval after artificial rupture of the membranes.

Gonorrhoea

Prevention

Neisseria gonorrhoea infection in pregnancy is very rare in Australia. If untreated, it is associated with an increased risk of preterm delivery. The baby is at risk of a severe gonococcal conjunctivitis, ophthalmia neonatorum, which can lead to blindness if not treated. In the United States, routine prophylaxis for this condition with topical erythromycin is still mandated in many states. Women with symptoms of cervicitis, those with chlamydial infections and those who have had sexual contact with men who have had gonorrhoea should be tested as described above. The appropriate treatment is ceftriaxone 250 mg intramuscularly and azithromycin 1 g orally, both as a single dose. Again, contact tracing and test of cure are vital.

Awareness of the condition and the introduction of prophylaxis have led to a marked decline in the incidence of the early-onset disease. The most effective method used to reduce early-onset disease is the culture-based approach; all pregnant women are tested at 35 to 37 weeks’ gestation by a vaginal and anorectal swab cultured in selective medium. Women who test positive and other women with risk factors receive intrapartum antibiotics prophylaxis. The indications for treatment are listed in Box 18.1. The prophylaxis of choice is benzyl penicillin where GBS is the principle concern. If chorioamnionitis is suspected, broad-spectrum antibiotic therapy that includes an agent known to be active against GBS should replace GBS prophylaxis. It is important at the first antenatal visit to characterise accurately ‘penicillin allergy’. Women who state that they are allergic to penicillin but do not give a history of immediate-type hypersensitivity to penicillin (anaphylaxis, angioedema, respiratory distress or urticaria) should receive intrapartum prophylaxis with cefazolin. Those who have immediate-type hypersensitivity to penicillin or any other beta-lactam should receive an alternative antibiotic guided by the antenatally determined antibiotic sensitivity of the GBS. If this is not available, clindamycin is a common alternative, but up to 20% of GBS have resistance to clindamycin. The recommended approach to antibiotic choice is shown in Figure 18.2.

GROUP B β-HAEMOLYTIC STREPTOCOCCUS Epidemiology This gram-positive coccus is present in the vagina at some time during pregnancy in approximately 20% of women; it often can also be isolated from the rectum in such women. About 50% of the babies born to colonised women are themselves colonised; of these, about 1% develop serious early-onset Group B streptococcal disease, so that the overall prevalence of this condition in untreated populations is about 1/1000 (20% × 50% × 1%). Prior to treatment of women at risk of having a baby with early-onset disease, this was the most common micro­ organism causing serious infection in the newborn.

Clinical features Group B streptococcus can cause asymptomatic bacteriuria (see above); these women are at a particularly high risk of having an affected baby. Premature labour and premature rupture of the membranes are more common. Approximately 1.5 to 2.0% of women will experience puerperal infection (uterine), chiefly as a complication of

Neonatal sequelae There are two main syndromes. The first is an early-onset septicaemia, sometimes with meningitis or pneumonia, often presenting as an idiopathic respiratory distress syndrome/cardiovascular collapse. While prematurity is a risk factor, most cases occur in term babies because there are more of them. There is a significant associated mortality of at least 5% even if treated promptly, with a 20% risk of severe morbidity in the survivors. The second main syndrome is the late-onset form. This is seen usually after the first week of life, the baby being lethargic, anorexic and jaundiced; meningitis is a common complication.

MYCOPLASMAL AND UREASPLASMAL INFECTION The female genital tract of sexually active women is often colonised by mycoplasmal organisms (Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum). There is an association between these organisms and chorioamnionitis, premature labour, puerperal and neona­ tal infection. However, it is not clear whether asymptomatic woman colonised with these organisms benefit from 149

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Patient allergic to penicillin? Yes

No

Patient with a history of any of the following aer receiving penicillin or a cephalosporin?¡¡ • Anaphylaxis • Angioedema • Respiratory distress • Urticaria

Penicillin G, 5 million units IV initial dose, then 2.5—3.0 million units¡ every 4 hrs until delivery or Ampicillin, 2 g IV initial dose, then 1 g IV every 4 hrs until delivery

Yes

No

Isolate susceptible to clindamycin¡¡¡ and erythromyciniv ?

Cefazolin, 2 g IV initial dose, then 1 g IV every 8 hrs until delivery No

Yes

Vancomycin, 1 g IV every 12 hrs until delivery

Clindamycin, 900 mg IV every 8 hrs until delivery

¡

Doses ranging from 2.5 to 3.0 million units are acceptable for the doses administered every 4 hours following the initial dose. The choice of dose within that range should be guided by which formulations of penicillin G are readily available to reduce the need for pharmacies to specially prepare doses. ¡¡ Penicillin-allergic patients with a history of anaphylaxis, angioedema, respiratory distress or urticaria following administration of penicillin or a cephalosporin are considered to be at high risk for anaphylaxis and should not receive penicillin, ampicillin or cefazolin for GBS intrapartum prophylaxis. For penicillin-allergic patients who do not have a history of those reactions, cefazolin is the preferred agent because pharmacological data suggests it achieves effective intra-amniotic concentrations. Vancomycin and clindamycin should be reserved for penicillin-allergic women at high risk for anaphylaxis. ¡¡¡ If laboratory facilities are adequate, clindamycin and erythromycin susceptibility testing (box 3) should be performed on prenatal GBS isolates from penicillin-allergic women at high risk for anaphylaxis. If no susceptibility testing is performed, or the results are not available at the time of labour, vancomycin is the preferred agent for GBS intrapartum prophylaxis for penicillin-allergic women at high risk for anaphylaxis. ¡v Resistance to erythromycin is oen, but not always, associated with clindamycin resistance. If an isolate is resistant to erythromycin, it might have inducible resistance to clindamycin, even if it appears susceptible to clindamycin. If a GBS isolate is susceptible to clindamycin, resistant to erythromycin, and testing for inducible clindamycin resistance has been performed and is negative (no inducible resistance), then clindamycin can be used for GBS intrapartum prophylaxis instead of vancomycin.

FIGURE 18.2 

Recommended regimens for intrapartum antibiotic prophylaxis for prevention of early-onset Group B streptococcal (GBS) disease.i Broader spectrum agents, including an agent active against GBS, might be necessary for treatmeant of chorioamnionitis. Abbreviation: IV = intravenously. Source: Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Online. Available at http://www.cdc.gov/mmwr; 19 November 2010;59(RR-10).

treatment. Many clinicians would only treat colonisation with these organisms in the presence of PPROM or cervical insufficiency. If a Mycoplasma hominis infection is to be treated, the best drug in pregnancy is clindamycin. M. hominis is resistant to macrolides (e.g. erythromycin), and the best drug, doxycycline, is contraindicated in the second and third trimesters. Ureaplasmas are sensitive to macrolides, 150

but more to the newer agent clarithromycin than erythromycin. They are not sensitive to clindamycin.

TUBERCULOSIS Tuberculosis is not specifically affected by pregnancy, nor does it have any specific adverse effects on pregnancy

Chapter 18  Bacterial Infections in Pregnancy

BOX 18.1  Indications and non-indications for intrapartum antibiotic prophylaxis to prevent early-onset Group B streptococcal (GBS) disease.i Intrapartum GBS prophylaxis indicated Previous infant with invasive GBS disease GBS bacteriuria during any trimester of the current pregnancyii Positive GBS vaginal-rectal screening culture in late gestationiii during current pregnancyii

Unknown GBS status at the onset of labour (culture not done, incomplete or results unknown) and any of the following: ✚ delivery at < 37 weeks’ gestation ✚ amniotic membrane rupture ≥ 18 hours ✚ intrapartum temperature ≥ 38.0°C ✚ intrapartum nucleic acid amplification tests (NAAT)i positive for GBS

Intrapartum GBS prophylaxis not indicated Colonisation with GBS during a previous pregnancy (unless an indication for GBS prophylaxis is present for current pregnancy) GBS bacteriuria during previous pregnancy (unless an indication for GBS prophylaxis is present for current pregnancy) Negative vaginal and rectal GBS screening culture in late gestationiii during the current pregnancy, regardless of intrapartum risk factors Caesarean delivery performed before onset of labour on a woman with intact amniotic membranes, regardless of GBS colonisation status or gestational age

i

Adapted from Centers for Disease Control and Prevention. Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines from CDC, 2010. MMWR 2010 Nov 19;59(No. RR10). Online. Available: http://www.cdc.gov/mmwr/pdf/rr/rr5910.pdf; 16 Dec 2014. ii Intrapartum antibiotic prophylaxis is not indicated in this circumstance if a caesarean delivery is performed before onset of labour on a woman with intact amniotic membranes. iii Optimal timing for prenatal GBS screening is at 35 to 37 weeks’ gestation.

apart from its effects on the mother. It often becomes known in pregnancy because that may be the first time a woman who has recently emigrated from a high-risk area seeks medical care. The investigation, diagnosis and treatment of tuberculosis are the same in pregnancy as in non-pregnant women. Chest X-rays can be performed with adequate shielding of the fetus. If active tuberculosis is diagnosed, it should be initially treated with isoniazid, rifampicin, ethambutol and pyrazinamide. FURTHER READING Capoccia R, Greub G, Baud D. Ureaplasma urealyticum, Mycoplasma hominis and adverse pregnancy outcomes. Curr Opin Infect Dis 2013;26(3):231–40.

Centers for Disease Control and Prevention. Prevention of perinatal Group B streptococcal disease. Revised guidelines from CDC, 2010. Recommendations and Reports 2010;59(RR10):1–32. Online. Available: . Semmelweiss IP. Die Ätiologie, der Begriff und die Prophylaxis des Kindbettfiebers (‘The etiology, concept and prophylaxis of childbed fever’) 1861. CA Hartleben’s Verlags-Expedition, Pest. Online. Available: ; [30 Nov 2014]. Therapeutic Guidelines. Antibiotic. Version 15. Melbourne: Therapeutic Guidelines Limited; 2014.

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Chapter 19  VIRAL AND PROTOZOAN INFECTIONS IN PREGNANCY Susan Walker

KEY POINTS Infections during pregnancy can be considered as predominantly harmful to the mother (where she may be susceptible to more severe complications such as with varicella pneumonia), the fetus only (e.g. rubella, which may have only minor or subclinical manifestations in the mother but devastating effects on the fetus) or to both. Infection in pregnancy may be detected: ■ during routine antenatal screening (e.g. rubella, syphilis, hepatitis B, hepatitis C and HIV) ■ by screening for seroconversion following suspected contact (e.g. parvovirus or varicella) ■ following suspicion of clinical illness (e.g. herpes simplex) ■ following prenatal diagnosis of suspected fetal malformation associated with congenital infection (e.g. toxoplasmosis, cytomegalovirus). A summary of management of viral and protozoal infections in pregnancy is provided in Table 19.1. Simple hygiene measures can reduce the risk of congenital infection and should be provided to all pregnant women (Boxes 19.1 and 19.2). Prevention of serious maternal and perinatal morbidity can be achieved with prepregnancy rubella and varicella vaccination. Prevention of serious maternal and infant morbidity is possible with influenza vaccination during pregnancy. Prevention of serious infant morbidity due to pertussis may be achieved either with cocooning (vaccination of close contacts) or vaccination of women in late pregnancy to provide passive protection to the newborn.

INTRODUCTION Viral and protozoal infections may have serious consequences for the mother, fetus and neonate. A summary of the maternal, perinatal and fetal risks together with prevention and treatment strategies is found in Table 19.1.

CYTOMEGALOVIRUS Congenital cytomegalovirus (CMV) is the most common form of infective neurological handicap in the developed world. Approximately 50% of Australian women are seronegative and 1% will seroconvert (primary infection)

during pregnancy. Women at increased risk of seroconversion include daycare workers (8% seroconversion/ year) and parents of children shedding CMV (24% seroconversion/year). The majority of maternal infections will be silent since CMV infection in immunocompetent adults is generally asymptomatic. While congenital CMV can be the result of non-primary infection, the risk of fetal transmission and infant sequelae is highest with primary infection. The risk of fetal transmission with maternal primary infection is approximately 40%. Among infected fetuses, 10 to 15% will be symptomatic at birth, with symptoms such as jaundice, hepatosplenomegaly, hydrops, thrombocytopenia, anaemia, microcephaly, seizures and chorioretinitis (Fig 19.1).

Maternal sequelae

Nil; seroconversion in pregnancy = 1%

Mild maternal illness

Mild maternal illness

Maternal varicella may be complicated by severe pneumonia

Maternal infection may be more severe in pregnancy

Primary infection more likely to disseminate in pregnancy

Infection

Congenital cytomegalovirus (CMV)

Rubella

Parvovirus

Varicella

Measles

Herpes simplex virus (HSV)

Infection within 1 week of delivery may result in severe neonatal infection Neonatal infection more likely with primary infection and lesions at delivery

Fetal sequelae only with primary infection

Suppressive aciclovir from 36 weeks’ in women with recurrent attacks; caesarean within 6 hours of rupture of membranes or labour onset if active lesions at time of delivery

Prepregnancy vaccination; post-exposure prophylaxis with immunoglobulin

Continued

Observation, isolation, swabs and/or treatment of newborn if significant exposure

Neonatal surveillance

Aciclovir for maternal or neonatal disease Prepregnancy vaccination; zoster immunoglobulin (ZIG) within 96 hours of contact if mother nonimmune

Risk of severe neonatal varicella if maternal infection within 2 weeks of maternal infection

Up to 2% risk of congenital varicella syndrome; infection may be confirmed with amniocentesis No congenital syndrome

Middle cerebral artery peak systolic velocity (MCA PSV) surveillance for fetal anaemia for 12 weeks post maternal exposure and follow with intrauterine transfusion (IUT) if necessary

Hygiene advice; avoid contacts

In infected fetuses, fetal loss risk = 10%; fetal hydrops with infection risk 15% < 20 weeks’

Consider abortion if confirmed infection early pregnancy

Surveillance for fetal defects; consider administration of CMV hyperimmunoglobulin (HIG)

Risk of fetal infection = 50%

Prepregnancy vaccination

Hygiene advice (see Box 19.1)

Management

Cardiac abnormalities, eye abnormalities, deafness, neurodevelopmental delay

Infants symptomatic at birth = 10%; symptomatic later = 10%

Fetal infection risk = 40%; confirmed with amniocentesis

Prevention strategy

High-risk multiple abnormalities in first trimester; uncommon sequelae after 20 weeks’

Perinatal sequelae

Fetal infection

TABLE 19.1  SUMMARY OF VIRAL AND PROTOZOAL INFECTIONS IN PREGNANCY.

Chapter 19  Viral and Protozoan Infections in Pregnancy

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154

Maternal sequelae

No impact on disease course

No impact on maternal disease course

No impact on disease course

Mild mononucleosislike illness

Maternal illness worse in pregnancy; severity related to degree of partial immunity

Pregnancy significant risk factor for major respiratory morbidity with influenza infection

Infection

Human immunodeficiency virus (HIV)

Hepatitis B

Hepatitis C

Toxoplasmosis

Malaria

Influenza

FGR; neonatal death

Infant sequelae due to preterm birth and consequences of maternal infection

Miscarriage; preterm birth; stillbirth

No congenital syndrome but increased stillbirth risk

Infant sequelae highest with early pregnancy infection

Overall fetal infection = 50%; transmission increases with gestation; confirmed with amniocentesis

Treatment dictated by disease severity and local resistance patterns Oseltamivir, symptomatic/ supportive treatment; isolation; vaccination of healthcare workers Vaccination during pregnancy to reduce risk of maternal and infant serious respiratory morbidity

Spiramycin from time of maternal infection; pyrimethamine-sulfadiazine combination with folinic acid if confirmed fetal infection > 18 weeks’

Maternal follow-up plus follow-up of infant and family members

Antivirals to reduce viral load in late pregnancy in women with high viral load; maternal follow-up plus follow-up of infant and family members

Neonatal ART; surveillance to confirm no infant infection

Management

Avoid travel to endemic areas; avoid mosquito contact and take chemoprophylaxis

Hygiene and food advice (see Box 19.1)

Minimise invasive procedures; avoid breastfeeding if nipples cracked or bleeding

Transmission risk = 5%; almost exclusively in RNA-positive women

No congenital syndrome

Antiretroviral therapy (ART) during pregnancy and delivery; caesarean if detectable viral load; avoid breastfeeding

Prevention strategy

Hepatitis B immune globulin and vaccine at birth; minimise antenatal and intrapartum invasive procedures

Perinatal transmission approximately 25% in the absence of interventions

Perinatal sequelae

Peripartum transmission results in perinatal infection in 1% with low viral load; up to 10% with high viral load

No congenital syndrome

No congenital syndrome

Fetal infection

TABLE 19.1  SUMMARY OF VIRAL AND PROTOZOAL INFECTIONS IN PREGNANCY—cont’d.

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Chapter 19  Viral and Protozoan Infections in Pregnancy

BOX 19.1  Advice for CMV seronegative women in order to minimise the risk of seroconversion during pregnancy. Wash hands with soap and water for 15 to 20 seconds after handling body fluids, dirty laundry or children’s toys, changing nappies, bathing or feeding young children. Do not share food, drinks or eating utensils with young children. Do not put a dummy in your mouth or share a toothbrush with a young child. Avoid contact with saliva when kissing a child. Clean toys, countertops and so on that come into contact with children’s urine or saliva.

FIGURE 19.1

CMV disease in a 2-day-old infant causing jaundice, hepatosplenomegaly and pneumonia requiring intubation and ventilator support. Source: Courtesy of Prof. Norman Beischer.

Of these infants, approximately 10% will die and 50% will be left with permanent sequelae. Among infants with congenital CMV who are asymptomatic at birth, 10 to 15% will become symptomatic later, most commonly with sensorineural hearing loss. While no country has yet implemented universal screening for CMV, this position may change if trials currently underway demonstrate that fetal CMV infection can be reliably prevented, or its sequelae minimised, by antenatal interventions.

MANAGEMENT OF THE SERONEGATIVE MOTHER Women known to be seronegative should be given advice on how to minimise primary infection in pregnancy (Box 19.1). These interventions have been shown to reduce the risk of seroconversion in pregnancy.

MANAGEMENT FOLLOWING SEROCONVERSION Following the diagnosis of maternal primary CMV, fetal infection can be confirmed with amniocentesis, performed after 21 weeks’ gestation and 7 weeks after mater-

nal infection. The presence of CMV polymerase chain reaction (PCR) in the amniotic fluid confirms fetal infection. Trials underway are examining the role of CMV hyperimmune globulin (CMV HIG) to reduce the chance of fetal transmission among women with primary infection in pregnancy.

MANAGEMENT OF THE INFECTED FETUS In fetuses with confirmed infection, discussion with parents needs to include: 1. surveillance for evidence of fetal sequelae, using serial ultrasound and, possibly, fetal MRI; 2. the potential for in utero therapy with CMV HIG or antivirals, such as valaciclovir; and 3. their options if they elect to terminate the pregnancy. Among fetuses with evidence of damage on antenatal imaging, sequelae at birth are almost inevitable. Although normal imaging provides some reassurance, serious sequelae may still occur despite normal antenatal imaging, particularly sensorineural hearing loss. Accordingly, all newborns where the mother has had primary infection in pregnancy should be carefully followed up after delivery.

RUBELLA Due to widespread vaccination programmes, congenital rubella syndrome has now been almost eliminated in developed countries. However, when maternal infection occurs, particularly during the first trimester, the effects on the fetus can be profound. Although the majority of pregnant women are immune, it is recommended that routine testing for rubella antibodies be carried out at the first antenatal visit. If she is immune, she can be reassured; if not, she should be immunised in the puerperium. If the vaccine is inadvertently given in early 155

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pregnancy, there is no indication for abortion; to date, there have been no cases of congenital rubella syndrome in fetuses born to women inadvertently exposed to the vaccine during pregnancy. Other advice to seronegative women includes contact avoidance, and the importance of presenting for serological testing in the event of suspected exposure (see below).

MATERNAL INFECTION The infection is usually spread by droplets and after an incubation period of 2 to 3 weeks, a fine rash appears which lasts for 1 to 5 days. The rash is not characteristic, but lymphadenopathy (usually suboccipital, postauricular and cervical), together with joint pain and swelling (particularly of the wrists and fingers), are suspicious. The infected patient is highly infectious for 1 week before and 2 weeks after the appearance of the rash. Unfortunately, there is no rash in 50% of rubella infections, and 50% of rubella-like rashes are due to other conditions. If a woman presents after suspected contact, she should have her rubella antibodies checked. If she has IgG antibodies prior to the onset of the rash, then the antibodies represent prior infection. If the titre is low or negative, a further test 2 to 3 weeks later should be carried out. Acute rubella is diagnosed in the presence of: 1. a fourfold rise in rubella IgG titre between the acute and convalescent serum specimens; and 2. the appearance of rubella-specific IgM. Rubella IgM antibodies appear 1 week after the onset of infection and persist for approximately 1 month. Post-exposure prophylaxis with human

A FIGURE 19.2

immunoglobulin has not been shown to be effective in preventing the risk of infection in non-immune contacts.

FETAL INFECTION The fetus is infected by transplacental passage of the virus during the stage of maternal viraemia. The risk of transmission causing sequelae are highest in the first trimester. Congenital rubella infection can cause fetal growth restriction (FGR), fetal death in utero, congenital malformations and neurodevelopmental delay. The most common malformations include cataracts, deafness and cardiac abnormalities (Fig 19.2). The effect on the fetus is largely related to gestational age, with cardiac and eye abnormalities more likely with infection in the first trimester and hearing loss with maternal infections up to 18 weeks’ gestation. The incidence of defects is 80 to 85% in the first trimester, whereas congenital defects are uncommon with infection after 18 to 20 weeks’ gestation and FGR is the only consequence of late-pregnancy infection.

DIAGNOSIS AND MANAGEMENT OF FETAL INFECTION Faced with the high likelihood of multiple, severe abnormalities, most families will elect for abortion following confirmed rubella infection in early pregnancy. Confirmation of fetal infection may be difficult but, if requested, PCR on chorionic villus appears the most useful. The

B

A Congenital rubella syndrome (purpuric rash, hepatosplenomegaly, bilateral cataracts, pulmonary stenosis, placental insufficiency) in a 1-day-old small for gestational age infant, birth weight 2110 g at 38.2 weeks’ gestation. B Cataract in the left eye displayed when the infant shown in A was aged 7 days. Source: Courtesy of Prof. Norman Beischer.

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place of intravenous immunoglobulin (IVIG) is controversial, but may prolong the incubation period and provide some fetal protection. Human immunoglobulin is only recommended for women with confirmed rubella infection who do not wish to terminate the pregnancy.

DIAGNOSIS IN THE NEWBORN Diagnosis in the newborn relies on demonstration of a rubella-specific IgM antibody or infant IgG rubella antibody level that persists at a higher level than the maternal antibody (remembering that maternal IgG crosses the placenta). Rubella can also be cultured from neonatal fluid such as a throat swab, urine, cerebrospinal fluid (CSF) or blood. In addition, nucleic acid testing is available in many centres for the detection of rubella virus. Infants with congenital rubella may continue to excrete the virus for over a year.

PARVOVIRUS B19 Parvovirus B19 (or ‘slapped cheek’ infection) can occur in both a sporadic and endemic form, and is transmitted by droplet spread. Sixty per cent of women are seropositive; of the remaining 40%, the risk of seroconversion during pregnancy depends on the nature of exposure. If they are a teacher in a daycare centre or school and exposed, 20 to 30% of susceptible women will seroconvert while 50% will seroconvert if there is a positive household contact.

MATERNAL INFECTION While the facial rash sparing the mouth, nose and eyes (‘slapped cheek’), followed by a truncal rash, is characteristic in young children, many adults will be asymptomatic. The most common symptom in adults is a transient symmetrical polyarthropathy, lasting weeks to months. Most women will thus only be diagnosed following seroconversion after a known contact. Parvovirus IgM-specific antibody is usually detectable by the third day after symptoms and usually disappears within 30 to 60 days, but may persist for up to 120 days. Parvovirus IgG antibody is detectable by day 7 of the illness and usually persists for life. Paired sera, 2 to 4 weeks apart, should be performed to detect seroconversion.

FETAL INFECTION Fetal transmission occurs in 50% of cases, and parvovirus may be associated with fetal loss and the development of fetal hydrops, but is not associated with congenital malformation. Transient isolated pleural or pericardial effusions may also be seen and are presumed to be due to pleural or myocardial inflammation. Generalised hydrops is usually due to severe fetal anaemia because parvovirus replicates in rapidly proliferating cells such as red blood cell precursors. The risk of fetal loss following maternal

parvovirus infection is estimated at approximately 10% prior to 20 weeks’ and < 1% after 20 weeks’. The risk of hydrops is approximately 15% with infection prior to 20 weeks’ (when circulating fetal red cells have the shortest half-life), compared to less than 5% after 20 weeks’. Accordingly, weekly ultrasound surveillance is recommended to look for evidence of fetal hydrops or fetal anaemia by measuring the middle cerebral artery peak systolic velocity (MCA PSV). Surveillance is recommended for 12 weeks after maternal exposure; 85% of cases requiring transfusion are diagnosed within 10 weeks’ of maternal infection. In fetuses with signs of severe anaemia, intrauterine transfusion (IUT) is indicated.

VARICELLA (CHICKENPOX) MATERNAL INFECTION The varicella zoster virus (VZV) is highly contagious and because of this, many children contract varicella before reaching adolescence. In addition, many children receive varicella vaccination and so susceptible pregnant women are uncommon. The incubation period for varicella zoster virus is 10 to 21 days. If a non-immune woman is exposed to varicella zoster, she should be offered zoster immunoglobulin (ZIG) if the exposure was within the past 96 hours. The purpose of ZIG is to reduce the occurrence of maternal disease, but it is not 100% effective and a woman who has received ZIG may still develop chickenpox, albeit with milder manifestations. Maternal varicella may be severe, including pneumonia, which develops in 10 to 20% of patients. If maternal varicella occurs, then a woman should be considered for antiviral therapy (aciclovir) if she presents within 24 hours of rash onset to reduce the severity of maternal disease. Antivirals may also be considered after 24 hours in the setting of progressive symptoms or in an immunocompromised host.

FETAL INFECTION ZIG is not known to reduce the risk of fetal sequelae from maternal varicella infection. The risk of congenital varicella syndrome depends on the trimester that the mother is infected. The risk with maternal infection prior to 12 weeks’ is 0.4%, rising to 2% between 12 and 20 weeks’ gestation. Fetal infection can be confirmed with varicella PCR on amniotic fluid, although a negative PCR does not exclude the diagnosis. The fetal anomalies that can result from congenital varicella syndrome include FGR, limb hypoplasia, eye damage, skin lesions and brain atrophy, so review with detailed ultrasound is recommended at least 5 weeks following maternal infection, as is consideration of repeat imaging if the amniocentesis is positive. Neonatal follow-up is indicated whenever a mother has varicella during pregnancy. 157

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INFECTION OF THE NEWBORN Neonatal varicella may occur when VZV transmission occurs just prior to delivery; it has a mortality of up to 30%. Infants of mothers with varicella within 2 weeks of delivery are at risk, but neonates born to mothers who have clinical varicella within 5 days prior to 2 days after delivery are at the greatest risk, as they acquire the infection without the protection of passive transfer of maternal IgG. Isolation, post-exposure prophylaxis and treatment needs to be considered in these cases.

MEASLES This infection is caused by a paramyxovirus. The incubation period is 10 to 14 days. It is rare in pregnant women because of lasting immunity from childhood infection or immunisation. Approximately 10 days after exposure, clinical symptoms comprising of fever, coryza conjunctivitis and cough develop. During the next 2 to 3 days, Koplik’s spots may appear (tiny, granular, slightly raised white lesions) followed by a generalised maculopapular skin rash. The rash starts on the head and neck then spreads to the trunk and upper extremities. The lower extremities are usually involved by day 3 of the rash. The clinical course may be altered by receipt of immunoglobulin, and may be given to non-immune pregnant women up to 7 days following contact with measles. In pregnancy, measles is associated with an increased risk of preterm labour and pregnancy loss but there is no congenital syndrome. However, severe disease in the mother can result in pneumonia, encephalitis, myocarditis and hepatitis. If infection is acquired within a week of delivery, there is a significant risk of neonatal mortality, especially in the premature baby. In such cases, immunoglobulin may be given to the mother and baby.

HERPES SIMPLEX VIRUS The seroprevalence of herpes simplex virus (HSV) 1 is approximately 70% and HSV 2 approximately 15%. While historically HSV 1 was considered to be mostly associated with non-genital infections (lips, mouth, eyes) and HSV 2 with genital infections, HSV 1 has increased in prevalence and is now considered the infective agent in approximately 40% of genital infections. The major concern with herpes infection in pregnancy is perinatal transmission and neonatal disease.

MATERNAL INFECTION The immunosuppression accompanying pregnancy means that gingivostomatitis and vulvovaginitis of pri­ mary infection is more likely to disseminate in pregnancy. Women with primary infection should be treated with oral aciclovir for 7 to 14 days. Recurrent attacks are 158

usually short and self-limiting, not usually requiring treatment during pregnancy, although suppressive ther­ apy may be considered from 36 weeks’ gestation (see below) or in the setting of frequent recurrences.

INFANT INFECTION Infection of the neonate is far more likely with primary HSV than during recurrent episodes or asymptomatic shedding (30% versus < 2%). Symptoms in the infant usually appear after an incubation period of 3 to 6 days. The spectrum of clinical disorder is wide and is often considered in three broad groups: skin and/or mucosal disease, encephalitis and disseminated HSV with severe multi-organ dysfunction. The mortality rate of encephalitis and disseminated HSV is high; local HSV has a low mortality rate, but a high risk of dissemination if untreated.

MANAGEMENT IN PREGNANCY Women with first-episode HSV in pregnancy should be treated with 7 to 14 days of oral aciclovir. Women with recurrent herpes who have active lesions or prodromal symptoms at the time of labour or rupture of membranes should be delivered by caesarean section, ideally within 6 hours of membrane rupture. In women with recurrent herpes, routine surveillance with vaginal or cervical swabs in late pregnancy are not recommended because of their poor predictive value. Prophylactic aciclovir from 36 weeks’ until delivery has been shown to reduce the rate of clinical recurrence at the time of delivery, to reduce asymptomatic shedding and to reduce the rate of caesarean section.

HUMAN IMMUNODEFICIENCY VIRUS (HIV) With the introduction of combination antiretroviral therapy the life expectancy of people living with human immunodeficiency virus (HIV) has increased and HIVrelated mortality has significantly reduced. Therefore, many women infected with HIV are choosing to have children. In addition, universal screening for HIV in pregnant women is now recommended in most countries around the world resulting in women often being diagnosed with HIV for the first time during pregnancy. Optimal management of HIV and pregnancy is essential to maximise the mother’s health, minimise transmission to partners and to prevent HIV transmission to the newborn.

MATERNAL HIV In the absence of interventions, vertical transmission from mother to infant occurs in 15 to 25% of cases. In resource-rich settings, the reported rate of transmission

Chapter 19  Viral and Protozoan Infections in Pregnancy

(with interventions including maternal and neonatal antiretroviral therapy [ART], avoidance of breastfeeding and consideration of caesarean section) is reduced to between 0.1 and 1%. ART should be offered to all women with HIV to reduce the risk of mother-to-child transmission. ART is usually a three-drug combination with the aim of viral suppression. The time to commence ART needs to be individualised according to maternal and perinatal indications. ART should be continued during the intrapartum period, whether during labour and delivery or caesarean section. While caesarean section is generally recommended to minimise transmission in women with a detectable HIV viral load in their blood, current data does not confirm an additional benefit of caesarean section over vaginal birth in women with an extremely low viral load.

DIAGNOSIS OF HIV IN THE INFANT While the diagnosis of HIV infection in adults is readily established by the detection of HIV antibodies, the situation is more complex in babies born to HIV-positive women. During the pregnancy, the fetus passively acquires maternal HIV antibodies across the placenta. Therefore, all babies born to HIV positive women will test positive to HIV antibodies for at least the first 6 months of life. It may take up to 18 months for a baby to clear these maternal antibodies. For this reason, a sensitive technique based on nucleic acid (the polymerase chain reaction [PCR]) is used to detect the presence of HIV in babies. Multiple negative tests up until the age of 3 months are required to confirm an uninfected status in exposed infants. In uninfected babies, it is recommended that the child have an HIV antibody test at 12 to 18 months to confirm the baby has cleared all the passively acquired HIV antibodies. If a PCR is positive, the test is always repeated as soon as possible (on a new sample) before it is confirmed that the baby is infected.

HEPATITIS B Transmission with hepatitis B may be either horizontal through sexual contact and blood products or vertical, from mother to child. The likelihood of chronic carriage depends on the timing of infection, with infection during infancy associated with a 90% rate of chronic carriage, compared with only 10% if infected during adulthood. In Australia, the prevalence of chronic hepatitis B is just under 1% with high-risk groups including immigrants from countries where hepatitis B is endemic, people engaging in high-risk sexual activity and injecting drug users.

MANAGEMENT OF THE PREGNANT WOMAN WITH CHRONIC HEPATITIS B Acute hepatitis B in pregnancy has a similar course as outside pregnancy, with often an initial flu-like upset

(malaise, anorexia, fatigue) giving way to nausea, fever, liver tenderness and jaundice; the urine is dark and the stools are pale. There is a 10% perinatal transmission rate with acute hepatitis B. Screening for chronic hepatitis B is recommended for all pregnant women since studies confirm that approximately 50% of chronically infected adults are unaware that they are infected until screened. The standard test available is the hepatitis B antigen (HBsAg) enzyme immunoassay (EIA or ELISA). All HBsAg-positive pregnant women should be tested for HBeAg and should have HBV DNA measured, since the risk of vertical transmission depends on the maternal viral load. The higher the viral load, the greater the risk of transmission despite interventions such as hepatitis B immunoglobulin and birth dose hepatitis B vaccination. Liver function tests should be performed each trimester for assessment of liver inflammation. Chronic hepatitis B is associated with potential long-term sequelae in the mother such as cirrhosis of the liver and hepatocellular carcinoma, and women identified in pregnancy should be referred to a specialist clinic for ongoing surveillance and management. If the mother has been found to be a carrier on routine testing, her partner and any previous children should be tested and all counselled regarding current and future management. Women requiring invasive prenatal testing should be counselled about the potential for perinatal trans­ mission, particularly if the viral load is high. Amniocentesis is preferred to chorionic villus sampling and transplacental passage of the needle should be avoided if possible.

MANAGEMENT OF THE INFANT Reducing the risk of exposure includes minimising invasive procedures in labour. Post-exposure prophylaxis includes administration of hepatitis B immunoglobulin within 12 hours of delivery together with intramuscular hepatitis B vaccine, followed by similar doses of vaccine at 1 and 6 months of age or 2, 4 and 6 months of age depending on the local immunisation schedule. Infants of women with a high viral load are at a higher risk of failed post-exposure prophylaxis and becoming infected. The risk of the infant being infected following post-exposure prophylaxis is estimated at 1% among antigen-negative mothers, rising to nearly 10% in the setting of high viral load. Recent trials have confirmed that giving antiviral treatment (such as tenofovir) to women in the third trimester who have a high viral load can significantly reduce the viral load (and hence, risk of transmission) by the time of delivery. Hepatitis B has been found in colostrum and breastmilk but as long as the baby receives immunoglobulin and birth dose vaccine, there is no evidence that there is an increased risk of transmission via breastfeeding. 159

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HEPATITIS C Hepatitis C is transmitted by blood so risk factors for infection include injecting drug use, receipt of blood products (particularly prior to routine blood product screening), tattoos and residence in endemic countries. The risk of transmission to the infant is approximately 5%, with the risk almost exclusively confined to women with detectable hepatitis C RNA in the blood. The risk of transmission is also higher among women co-infected with HIV. Women found to be hepatitis C positive during pregnancy should have an assessment of viraemic status performed and liver function tests checked. They should be referred to a viral hepatitis clinic and counselled regarding partner and family contacts, similar to hepatitis B. Caesarean section is not recommended for women who are hepatitis C positive, although invasive procedures during pregnancy and in labour should be minimised. There is no evidence that infants who are breastfed are at a higher risk of infection with hepatitis C, but direct infant contact should be minimised if the nipples are cracked or bleeding.

PROTOZOAL INFECTIONS TOXOPLASMOSIS Toxoplasma gondii is an obligate intracellular parasite. Cats are the definitive host, and oocytes are shed into cat faeces. Humans and other animals become intermediate hosts through ingestion of contaminated food or water. Women may become infected in pregnancy directly through ingestion of cysts or by eating undercooked meat, where bradyzoites may live dormant in cysts in animal muscle indefinitely. Advice for women on minimising the risk of toxoplasmosis in pregnancy can be found in Box 19.2.

Maternal infection Sixty per cent of adults are seronegative and susceptible to primary infection. Infection in immunocompetent adults is usually asymptomatic, but may present as a mononucleosis-like illness. Primary infection is diagnosed with the appearance of toxoplasmosis-specific IgM or IgG seroconversion.

Fetal infection The risk of transmission is 50% overall with an increase from approximately 15% in the first trimester to 45% in the second trimester and 70% in the third trimester. Fetal infection can be confirmed with amniocentesis performed approximately 1 month after maternal infection. The risk of infant sequelae is highest in the first trimester, and includes ventriculomegaly, microcephaly, chorioretinitis, FGR and fetal loss. Ultrasound surveillance is recommended for fetuses known to be infected. 160

BOX 19.2  Advice for women in order to minimise the risk of toxoplasmosis infection in pregnancy. Avoid ingesting soil by carefully washing fruit and vegetables before eating and washing hands carefully after gardening. Avoid raw or undercooked meats by washing food-preparation surfaces carefully, cooking meat to 66°C or higher or freezing meat for at least 24 hours at −12°C. Avoid travel to underdeveloped countries (particularly South America) where more virulent strains predominate. Avoid drinking contaminated water. Oocytes are only infective if matured outside the cat for 2 to 3 days, so avoid contact with old cat faeces (e.g. in the garden) and changing the cat litter tray.

Treatment in pregnancy Treatment of toxoplasmosis in pregnancy is associated with a lower risk of fetal transmission and sequelae. Treatment with spiramycin, which concentrates (but does not cross) the placenta, is recommended from the time of maternal seroconversion to reduce fetal trans­ mission. If fetal infection is subsequently confirmed with amniocentesis, then spiramycin should be changed to pyrimethamine-sulfadiazine combination with folinic acid. Paediatric follow-up of infected infants after delivery is necessary.

MALARIA Malaria is a preventable and treatable parasitic infection caused by five species of plasmodia. It is transmitted by mosquitoes and associated with significant maternal and perinatal morbidity and mortality. Pregnancy is associated with an increased risk of parasitaemia and severe disease; the WHO estimates that 10 000 maternal deaths each year are as a result of malaria in pregnancy. The severity of malarial infection is inversely related to disease prevalence. In areas of low immunity, pregnant women are more likely to experience severe symptoms such as hypoglycaemia, cerebral malaria, severe anaemia, acute pulmonary oedema and death. Malarial parasites reside and multiply in the placenta, contributing to spontaneous abortion, preterm birth, stillbirth and neonatal death; malaria is estimated to be responsible for 200 000 infant deaths worldwide each year. Individuals living in endemic areas develop partial immunity and malarial infection is more likely to be mild, associated with maternal anaemia and impaired fetal growth. Malaria should be suspected in women returning from a malaria-endemic area with a febrile illness.

Chapter 19  Viral and Protozoan Infections in Pregnancy

Diagnosis should be made by peripheral blood smears and rapid diagnostic tests. Treatment needs to be individualised, taking into account gestation, disease severity and the likelihood of drug resistance. Women should be advised not to travel to malaria-endemic areas while pregnant. If unavoidable, they should consider chemoprophylaxis with hydrxoychloroquin or mefloquine, and avoiding contact with mosquitoes by covering exposed skin, staying indoors between dusk and dawn, applying insect­ icide containing diethyltoluamide (DEET) and using insecticide-impregnated nets.

VACCINATIONS RUBELLA Women planning pregnancy should have an assessment of their rubella immunity performed, given the potential for serious sequelae of congenital rubella syndrome (see the section on rubella earlier in this chapter). Women coming from resource-poor settings are those most likely to be non-immune. Those found to be non-immune should have the measles, mumps, rubella (MMR) vaccination prior to pregnancy and be advised to avoid conception for 28 days following vaccination. The vaccine can be safely administered while breastfeeding.

VARICELLA Women planning pregnancy should also have an assessment of their varicella immunity status, given the potential for serious maternal and fetal sequelae of primary infection in pregnancy (see the section on varicella earlier in this chapter). Women found to be non-immune should be vaccinated prior to pregnancy and advised to avoid conception for 28 days.

INFLUENZA Influenza vaccination during pregnancy is an essential part of antenatal care. Pregnancy is associated with an increased risk of severe morbidity and mortality from influenza, likely due to a combination of the cardiorespiratory changes and immunomodulation associated with pregnancy. Women suspected of having influenza should be treated with antivirals (oseltamivir 75 mg twice daily for 5 days) and antipyretics, provided with appropriate supportive care and receive treatment for secondary bacterial infections. Healthcare workers in contact with pregnant women should be vaccinated every year. The most effective means of reducing the risk of influenza in pregnancy is with administration of the influenza vaccine. The influenza vaccine has also been shown to reduce the risk of infant respiratory morbidity. This is because of the ‘triple benefit’ of maternal vaccination: 1. transplacental passage of maternal IgG; 2. passage of secretory IgA in breastmilk; and 3. cocooning (i.e. those most likely to infect the newborn are close contacts,

so vaccination of the parents indirectly protects the infant). It is estimated that only five vaccination doses are necessary to prevent one case of serious maternal or infant respiratory illness. Influenza vaccination safety is well established. No study to date has shown an adverse consequence of inactivated influenza vaccine in pregnant women or their offspring. Influenza vaccination is recommended for all pregnant women regardless of gestation, and is usually available from February each year in the Southern Hemisphere. Unvaccinated pregnant women should be immunised at any time during influenza season as long as the vaccine supply lasts.

TETANUS, DIPHTHERIA AND PERTUSSIS (DTPA) Prevention of pertussis in the newborn is important because of the high morbidity and mortality in this condition among infants less than 3 months of age. To reduce the risk of infant pertussis, vaccination of the mother and other household contacts (cocooning) is one means of protecting them; the other is to administer dTpa to women after 20 weeks’ during each pregnancy to provide transplacental passive protection for the infant in the first vulnerable months. This latter approach is currently recommended by the Centers for Disease Control and Prevention in the United States and by the Department of Health in the United Kingdom, although Australian guidelines are yet to endorse these recommendations.

OTHER VACCINATIONS Advice on other vaccinations that may be relevant to pregnant women (e.g. those with special health needs or planning travel) can be found in the Australian Immunisation Handbook. FURTHER READING Arshad M, El-Kamary SS, Jhaveri R. Hepatitis C virus infection during pregnancy and the newborn period—are they opportunities for treatment? J Viral Hepat 2011;18(4):229–36. Australian Technical Advisory Group on Immunisation. The Australian immunisation handbook. 10th edn. Canberra: Australian Government Department of Health; 2013. Centers for Disease Control and Prevention. CDC guidelines for vaccinating pregnant women. Online. Available: ; [30 Nov 2014]. Dijkmans AC, de Jong EP, Dijkmans BA, et al. Parvovirus B19 in pregnancy: prenatal diagnosis and management of fetal complications. Curr Opin Obstet Gynecol 2012;24(2):95–101. Giles ML, Visvanathan K, Lewin SR, et al. Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv 2012;67(1):37–44. 161

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Giles ML. HIV and pregnancy—how to manage conflicting recommendations from evidence-based guidelines. AIDS 2013;27(6):857–62. Hui L, Wood G. Perinatal outcome after primary maternal cytomegalovirus infection in the first trimester: a practical update and counseling aid. Prenat Diagn Jan 2015;35(1):1–7. Hutchinson BJ, Palma-Dias R, Walker SP. Universal cytomegalovirus screening: time for reappraisal? Fetal Matern Med Rev May 2014;25(2):117–33. Kaye A. Toxoplasmosis: diagnosis, treatment, and prevention in congenitally exposed infants. J Pediatr Health Care 2011;25(6):355–64. Knight M, Lim B. Immunisation against influenza during pregnancy. The benefits outweigh the risks. BMJ 2012;344:e3091.

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Lazzarotto T, Guerra B, Gabrielli L, et al. Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy. Clin Microbiol Infect 2011;17(9):1285–93. Palasanthiran P, Starr M, Jones C, et al., editors. Management of Perinatal Infections. Sydney: Australasian Society for Infectious Diseases; 2014. Women’s Health Committee. RANZCOG College statement: influenza vaccination during pregnancy (C-Obs 45); Nov 2013. Online. Available: ; [30 Nov 2014].

Chapter 20  THE BLOOD: ANAEMIA, THROMBOCYTOPENIA AND COAGULOPATHY Lisa Hui and Michael Permezel

KEY POINTS The expansion of blood volume in pregnancy results in a ‘physiological haemodilution anaemia’ with a haemoglobin threshold of 10.5 g/dL for the diagnosis of anaemia in late pregnancy. The major cause of anaemia in pregnancy is iron deficiency. Folic acid deficiency and the haemoglobinopathies are the other two common causes. All women should have a full blood examination and red cell indices at the first antenatal visit and then a haemoglobin check again at 28 weeks’. Abnormalities should be investigated and corrected. Couples at risk for hemoglobinopathies should be offered testing to determine the risk of a severely affected child. The most common cause of thrombocytopenia in pregnancy is the relatively benign condition of gestational thrombocytopenia. Other causes included preeclampsia, immune or thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, systemic lupus erythematosus (SLE), drugs, infection and bone marrow neoplasia. Disseminated intravascular coagulation is a serious condition characterised by intravascular activation of the clotting pathway. Obstetric causes include placental abruption, postpartum haemorrhage, prolonged fetal death, severe preeclampsia, amniotic fluid embolism, septicaemia and sustained hypotension. There is a secondary consumption of clotting factors and platelets, which produces a haemorrhagic diathesis. Treatment is by replacement of deficient blood factors and correction of the basic disorder.

ANAEMIA

DEFINITION

PHYSIOLOGY

Anaemia can be defined by a haemoglobin value < 11.5 g/dL in the first trimester, or < 10.5 g/dL in later pregnancy.

The blood volume increases 35% in pregnancy. As the plasma volume increases more than the red cell volume, there is a resulting 10% fall in the Hb level known as the ‘physiological anaemia of pregnancy’. Adult red blood cells predominantly contain Hb A (composed of two alpha and two beta globin chains), with a small amount of Hb A2 (two alpha and two delta chains). Fetal red cells, however, contain predominantly Hb F (two alpha and two gamma chains), which has a different oxygen dissociation curve to adult haemoglobin. The oxygen affinity of Hb F is higher at lower partial pressures, which facilitates transfer of oxygen across the placenta.

CLINICAL SEQUELAE Non-specific tiredness and fatigue are common pregnancy symptoms but will be exacerbated by anaemia. Anaemia is associated with an increased risk of intrauterine growth retardation, preterm labour and puerperal sepsis. The impact of a relatively moderate postpartum haemorrhage may be catastrophic. Inheritance of a severe fetal anaemia must be considered where both parents have a haemoglobinopathy.

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PRINCIPAL CAUSES OF ANAEMIA IN PREGNANCY Anaemia during pregnancy is most commonly caused by: 1. iron deficiency; 2.folic acid (or B12) deficiency; and/or 3. haemoglobinopathy.

Iron deficiency

Vitamin B12 deficiency Vitamin B12 deficiency is rare in pregnancy. It may be due to autoimmune pernicious anaemia, dietary deficiency (e.g. vegan diet), or disease of the terminal ileum (e.g. Crohn’s disease). Serum B12 levels may be spuriously low in pregnancy and serum holotranscobalamin is required for a more confident diagnosis.

Physiology

Haemoglobinopathies

Approximately 4 mg of elemental iron is needed daily during pregnancy and lactation. Usually only about 10% of dietary iron is absorbed but this increases to about 20% in pregnancy and lactation. The total amount of iron stored in the body (excluding red cells) may be up to 1200 mg, but many women have iron stores depleted by a poor diet, menorrhagia or previous pregnancies.

Classification

Incidence and predisposing factors Iron deficiency accounts for about 90% of anaemia in pregnancy, except in communities where the haemoglobinopathies are prevalent. Iron deficiency anaemia is more common where iron stores have been depleted by: 1. dietary deficiency 2. malabsorption syndromes 3. excessive loss (grand multiparity, menorrhagia, antepartum haemorrhage, hookworm infestation).

Diagnosis The diagnosis is suggested by a hypochromic microcytic anaemia on full blood examination (FBE) and confirmed by a low-serum ferritin. It is critical to exclude co-existent thalassaemia as this can have major implications for family planning and prenatal diagnosis.

Folate deficiency Predisposing factors Folate deficiency may occur through the following. 1. Dietary deficiency. Folate is present in leafy green vegetables, legumes and some fruits, and is readily destroyed by excessive cooking. 2. Increased demand such as any haemolytic anaemia (e.g. haemoglobinopathy), multiple pregnancy, anticonvulsant drug therapy (especially phenytoin).

Clinical sequelae Apart from anaemia, folate deficiency is associated with an increased risk of neural tube defects and may elevate homocystine levels with possible thrombophilic sequelae.

Prevention All women are recommended to have at least 3 months’ preconceptual supplementation with folic acid 0.5 mg daily as prophylaxis against neural tube defects. Where there is a predisposing factor (e.g. haemoglobinopathy, multiple pregnancy, anticonvulsant drug therapy), 5 mg/ day is recommended. 164

Haemoglobinopathies are inherited anomalies of haemoglobin synthesis. Definitive diagnosis usually involves a combination of haemoglobin electrophoresis and DNA testing. 1. Thalassaemias are quantitative defects in haemoglobin production affecting either the alpha or beta globin chains. 2. Haemoglobin variants are qualitative defects of haemoglobin synthesis, in which an abnormal form of haemoglobin is being produced (e.g. Hb S [sickle cell disease]).

Beta-thalassaemia This is a single gene condition predominantly seen in people of Mediterranean, Middle Eastern, Indian subcontinent and South-East Asian backgrounds. A person with a single gene mutation (‘beta thalassaemia minor’) is called a carrier and is usually asymptomatic. Beta thalassaemia carriers are usually healthy, but have a mild haemolytic anaemia with Hb levels typically 8 to 10 g/dL in the third trimester. The principal relevance to pregnancy, however, is the one in four risk of betathalassaemia major in the child if the partner is also affected with beta-thalassaemia minor. Beta-thalassaemia major is a severe transfusion-dependent anaemia that manifests in early childhood, and prenatal diagnosis should be offered to couples at risk.

Alpha-thalassaemia Alpha thalassaemia genes are most common in people of Asian origin, but are also found in people of African, Middle Eastern and Mediterrean background. The genetics are more complex than beta thalassaemia as there are four (rather than two) gene loci coding for the alphachain. Between one and four of these genes may be affected. A single gene deletion does not usually affect the haemoglobin level; two gene deletions produce a mild anaemia. Three gene deletions produce a more severe anaemia (Hb H disease) that may be transfusion dependent and four gene deletions are incompatible with postnatal survival and result in hydropic fetal death (Barts hydrops). Haemoglobin electrophoresis is normal for one and two gene deletions but Hb H (beta4-tetramer) may be present on haemoglobin electrophoresis when three genes are absent. The mean corpuscular volume (MCV)

Chapter 20  The Blood: Anaemia, Thrombocytopenia and Coagulopathy

is normal with a single gene deletion but usually reduced with two and three gene deletions. Diagnosis is with DNA analysis. Barts hydrops is only possible if both parents have at least a two-gene deletion in a heterozygous pattern (−/−, +/+) rather than (+/−, +/−), and prenatal diagnosis should be offered to these couples.

Sickle cell haemoglobin (Hb S) Sickle cell disease is an autosomal recessive disorder caused by a beta globin gene mutation that leads to the production of an abnormal form of haemoglobin (Hb S). The homozygous form (sickle cell disease) is characterised by hemolysis and vaso-occlusive complications. Sickle cell trait is the heterozygous form of the disease. It does not cause serious morbidity in pregnancy, but is associated with increased risk of urinary tract infections. The genes for sickle cell disease are most common in people of African, Middle Eastern, Southern European, Indian, Pakistani and Caribbean origin. The importance for the pregnancy is the risk of sickle cell disease in the offspring if the partner is also affected. Again, prenatal diagnosis is offered if both parents are affected. Women with sickle cell disease are at increased risk of complications during pregnancy. The incidence of sickle cell crises is probably increased by pregnancy. Complications include pneumonia, pyelonephritis, miscarriage, preeclampsia and prematurity.

Other haemoglobinopathies Combinations of haemoglobin variants, thalassaemia or other haemoglobin variants may produce a severe anaemia, and antenatal diagnosis should be considered where such a combination in the fetus is genetically possible. For example, the combination of sickle cell trait and beta-thalassaemia minor may have a clinical condition similar to sickle cell disease. Haemoglobin E/beta-thalassaemia is a severe transfusion-dependant anaemia.

PREVENTION OF NUTRITIONAL ANAEMIAS Folic acid supplementation is indicated in all women at prepregnancy counselling to reduce the risk of neural tube defect. Iron supplementation is not routinely recommended but those at risk should be screened with serum ferritin.

Screening for anaemia in pregnancy The haemoglobin level is checked at the first visit and again at about 28 weeks’. If there is excessive loss at birth, a further check should be made postpartum. Red cell indices are performed at the first antenatal visit to detect haemoglobinopathies; although these will not all have anaemia, the majority will have a reduced MCV. Haemoglobin electrophoresis should be performed routinely at the first antenatal visit in ethnic groups at increased risk of haemoglobinopathy.

MANAGEMENT OF ANAEMIA IN PREGNANCY Determine aetiology of anaemia A clinical history may reveal dietary deficiency, gastro­ intestinal disorders, menorrhagia or other blood loss. Physical examination should note hepatosplenomegaly or lymph node enlargement. FBE with red cell indices will enable categorisation as follows. Hypochromic microcytic anaemia may be iron deficiency and/or a haemoglobinopathy. Serum ferritin will screen for iron deficiency. Haemoglobin electrophoresis and DNA analysis will detect the haemoglobinopathies. Normocytic or macrocytic anaemia require a reticulocyte count, renal function, serum folate and B12. If B12 is low, serum holotranscobalamin should be used to confirm. Bone marrow examination is indicated if there are any suspicious features or the anaemia is inexplicably refractory to treatment.

• •

Iron deficiency anaemia Assessment Iron deficiency anaemia in pregnancy does not usually require further investigation, as gastrointestinal pathology is not commonly present. Nevertheless, appropriate tests should be performed if the clinical assessment is suggestive of chronic gastrointestinal blood loss.

Treatment Oral iron supplementation is the first-line treatment in early pregnancy. Unless the woman is not taking, tolerating or absorbing the oral iron, the haemoglobin level should rise by about 1 g/week. If oral iron is not tolerated, if response is poor or if more rapid haemoglobin elevation is needed, an intravenous iron infusion can be administered.

Folate or vitamin B12 deficiency All women should be treated with 0.5 mg daily of preconceptual folic acid as prophylaxis against neural tube defects. Folate deficiency is treated with folic acid (5 mg daily). The cause (dietary, increased demand, malabsorption) is usually apparent clinically. Vitamin B12 deficiency is rare in pregnancy. The aetiology should be determined (e.g. strict vegan, autoimmune, Crohn’s disease) and appropriate intramuscular replacement instituted.

Haemoglobinopathies Assessment of the genetic implications of these inherited disorders (e.g. thalassaemia, sickle cell) is imperative due to their increased red blood cell turnover. Central to the determination of fetal risk is full assessment of the male partner with FBE, Hb electrophoresis and DNA analysis. Thalassaemia carriers should take folic acid 165

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supplementation and ferritin levels should be checked to exclude co-existent iron deficiency due to their increased requirements. Sickle cell disease requires specialised treatment to minimise the risk of sickle cell crises.

THROMBOCYTOPENIA The normal platelet count is 150 to 400 × 109/L. Surgical bleeding or postpartum haemorrhage may occur if platelets are < 50 × 109/L. Spontaneous bleeding may occur with platelets < 30 × 109/L. Box 20.1 lists the causes of thrombocytopenia in pregnancy.

GESTATIONAL THROMBOCYTOPENIA This is defined as thrombocytopenia of mild or moderate degree (75 − 150 × 109/L) and detected for the first time during late pregnancy, with the platelet count returning to normal within 7 days of delivery. It occurs in about 5% of all pregnancies and is responsible for about 65% of all cases of thrombocytopenia in pregnancy. The cause is most probably an increase in physiological platelet turnover. Gestational thrombocytopenia is very rarely (< 1% of affected pregnancies) associated with severe fetal thrombocytopenia.

PREECLAMPSIA Thrombocytopenia is a relatively common occurrence in preeclampsia and particularly the special variant of preeclampsia known as HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). Treatment is by appropriately timed delivery.

IMMUNE THROMBOCYTOPENIC PURPURA In immune thrombocytopenic purpura (ITP) there is normal or increased production of platelets, but these are destroyed by antiplatelet antibodies. Treatment should be instituted if the platelet count falls below 75 × 109/L.

BOX 20.1  Causes of thrombocytopenia in pregnancy. 166

Gestational thrombocytopenia Preeclampsia Immune thrombocytopenic purpura (ITP) Disseminated intravascular coagulation Thrombotic thrombocytopenic purpura (TTP) Drugs (e.g. heparin, quinine) Infections SLE Haematological malignancies

Prednisolone and/or immunoglobulin infusions are the principle modalities of therapy. In severe cases, intrapartum platelet transfusions may be required to facilitate safe birth and anaesthesia.

Newborn sequelae Since the antiplatelet antibodies cross the placenta, the newborn may also have thrombocytopenia. The period of highest risk for newborn bleeding complications is around days 2 to 5 of life, when the platelet count is at a nadir. Maternal platelet and circulating antibody levels do not reliably predict the severity of thrombocytopenia. The strongest predictor of newborn thrombocytopenia is a past history of an affected newborn. However, in most situations this history is not present and the mode of delivery is determined by the usual obstetric indications. Where there are concerns regarding severe fetal thrombocytopenia, avoiding a traumatic instrumental birth is desirable. However, just as importantly, a scar on the uterus will predispose to a future placenta accreta in a woman with compromised platelets.

THROMBOTIC THROMBOCYTOPENIC PURPURA Thrombotic thrombocytopenic purpura (TTP) is a rare medical emergency characterised by widespread microthrombi as a consequence of vascular endothelial cell damage. Multiple organs may be affected, including the central nervous system, liver, kidney and placenta. It may be very difficult or impossible to distinguish TTP from HELLP syndrome, and TTP probably has a very similar pathogenesis. It usually requires plasmapheresis and replacement with fresh frozen plasma. In contrast to preeclampsia, the course of the disease is not dramatically improved by delivery.

COAGULATION DISORDERS DISSEMINATED INTRAVASCULAR COAGULATION Pathogenesis Tissue thromboplastins are the normal activators of the extrinsic coagulation pathway in response to local tissue damage. Rich sources of thromboplastins include the placenta and amniotic fluid. When there is systemic release of thromboplastins into the bloodstream, disseminated intravascular coagulation (DIC, ‘microvascular clotting’) occurs with consumption of platelets and clotting factors (especially fibrinogen factors V, VII, VIII ) and tissue ischaemia, which may result in secondary damage to the kidneys, liver, lung and brain. Red blood cells encountering fibrin strands in the small blood vessels may become fragmented (microangiopathic haemolytic anaemia).

Chapter 20  The Blood: Anaemia, Thrombocytopenia and Coagulopathy

Aetiology The causes of DIC in pregnancy are as follows: 1. placental abruption, but this is uncommon unless the abruption is severe enough to cause fetal death 2. postpartum haemorrhage 3. sepsis, particularly involving the genital tract (septic abortion, chorioamnionitis) or haemolysis (e.g. Cl. perfringens, E. coli) 4. amniotic fluid embolism 5. severe preeclampsia 6. sustained hypotension which causes widespread endothelial damage with resulting intravascular coagulation. 7. fetal death in utero, but generally only if the fetus is at least 20 weeks’ size and period of death is greater than 4 weeks.

Clinical features DIC presents almost invariably with a haemostatic problem, either as genital tract bleeding from the placental site or persistent bleeding from the wounds (vaginal tears, caesarean section, venepuncture sites).

Investigations The following investigations are indicated. 1. Blood film and platelet count. Evidence of microangiopathic haemolysis with fragmentation of red cells may be present. Platelet count is reduced. 2. Coagulation profile. Activated partial thromboplastin time (APTT) and prothrombin time will be prolonged. 3. Fibrinogen. This may be depleted (normal range in pregnancy 4 to 6 g/L; coagulation fails at levels < 1 g/L).

Treatment The basic treatment principles are removal of the precipitating cause if possible, correction of aggravating factors and replacement of missing coagulation factors and platelets. Correction of aggravating factors such as shock, hypothermia and hypoxia is important. This includes blood transfusion if necessary and oxygen administration. Replacement of clotting factors is most effectively done with fresh frozen plasma. Clotting factor concentrates such as fibrinogen concentrate or cryoprecipitate may be required. Platelets should be maintained > 50 × 109/L in the presence of active bleeding by the administration of fresh packs of group-compatible platelets. Any aetiological condition should be treated promptly, often by

delivery of the fetus. Anticoagulants (e.g. heparin, streptokinase) do not have a role in obstetric DIC complicated by bleeding. Similarly, antifibrinolytic drugs (epsilonaminocaproic acid, aprotinin) are not helpful.

INHERITED ANOMALIES OF COAGULATION FACTORS Von Willebrand’s disease There is typically a history of epistaxis, heavy menstrual loss, easy bruising and operative/postoperative haemorrhage. The basic defect is in the factor VIII-related antigen (von Willebrand’s factor) leading to a relative deficiency of factor VIII and a platelet function disorder. Diagnosis is made on the basis of a prolonged bleeding time and an assay of von Willebrand’s factor. The main effect in pregnancy is a tendency to postpartum haemorrhage. The likelihood of this is best gauged by the woman’s past history and an estimation of factor VIII level in late pregnancy. If lower than about 40% of normal, fresh frozen plasma, cryoprecipitate or desmopressin acetate (except in type IIB disease) is indicated. The anti-fibrinolytic agent tranexamic acid may also be used in the peripartum period to reduce the risk of postpartum haemorrhage. Since this is an autosomaldominant inherited disorder, there is a possibility of a haemorrhagic diathesis in the neonate.

OTHER COAGULATION FACTOR DISORDERS The most common congenital disorder, haemophilia, is an X-linked recessive disorder and therefore affects almost exclusively males. It has been observed that some 10% of carrier females will exhibit a tendency to excessive bleeding, and fresh frozen plasma may be required at the time of delivery. In a female carrier with a male offspring, there will be a 50% probability of an affected baby with implications for prenatal diagnosis and mode of birth. FURTHER READINGS RANZCOG. RANZCOG College statement: routine antenatal assessment in the absence of pregnancy complications (C-Obs 03b); March 2013. Online. Available: ; [30 Nov 2014]. RCOG. Management of sickle cell disease in pregnancy. Green-top Guideline No. 61. July 2011. Online. Available: ; [16 Dec 2014].

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KEY POINTS Appendicitis in pregnancy can be difficult to diagnose because of the expanded differential diagnosis and the altered anatomy, as the appendix is both lifted and partially obscured by the expanding uterus. Cholestasis of pregnancy is associated with an increase of stillbirth, but both symptoms and liver function can be largely normalised with ursodeoxycholic acid treatment. Acute fatty liver of pregnancy (AFLP) has many features in common with preeclampsia and is characterised by hepatic functional impairment (jaundice, coagulopathy, hypoglycaemia) that is usually out of proportion to the abnormalities in hepatic enzyme levels. Incarceration of a retroverted pregnant uterus may occur at approximately 14 weeks’ gestation and results in acute urinary retention. Resolution is usually effected with urinary catheterisation; surgical correction is rarely necessary. Fibromyomas are common in obstetric patients. Fundal height measurements may no longer reflect fetal growth. Complications include red degeneration of the fibroid and malpresentation. Ovarian cysts may be of any type but luteal cysts are particularly common in early pregnancy. Complications include torsion as the uterus expands. Surgical removal is best performed early in the second trimester and would commonly be recommended for cysts of 6 cm or more diameter. Urinary tract infections complicate approximately 6% of pregnancies. They are often asymptomatic but approximately one-third will progress to pyelonephritis if left untreated. Minor degrees of renal functional impairment predispose to preeclampsia and preterm birth. More severe degrees (e.g. serum creatinine > 0.3 mmol/L) are rarely associated with a successful outcome. Prospects are much better post-transplantation.

THE GASTROINTESTINAL AND HEPATOBILIARY SYSTEMS ACUTE APPENDICITIS Appendicitis complicates about 1 in 1000 pregnancies. Miscarriage or preterm labour can be precipitated by the intraperitoneal infection. The diagnosis is more difficult because of the upward displacement of the appendix

(Fig 21.1) and confusion with pregnancy complications. The differential diagnosis of abdominal pain in pregnancy includes round ligament strain, ovarian cyst complication (e.g. torsion), red degeneration of a fibromyoma, gastroenteritis and pyelonephritis. Treatment is appendicectomy, which can be more difficult with the uterine enlargement. Laparoscopy is difficult once the uterine size has attained 16 weeks or so. In late pregnancy, caesarean section may be performed at the same time to enable better access to the appendix.

Chapter 21  Gastrointestinal, Hepatobiliary, Gynaecological and Renal Problems

BOX 21.1  Causes of jaundice in pregnancy.

9 months’ 6 months’ 3 months’

McBurney point

Haemolytic ✚ Septicaemia (e.g. Clostridium, E. coli) Hepatocellular ✚ Viral hepatitis ✚ Severe preeclampsia, HELLP syndrome ✚ Acute fatty liver of pregnancy ✚ Medications ✚ Autoimmune chronic active hepatitis Obstructive ✚ Cholestasis of pregnancy ✚ Cholelithiasis ✚ Drug-induced ✚ Primary biliary cirrhosis ✚ Pancreatic carcinoma

hepatocellular enzymes as well as elevated bile salts. Rarely, vitamin K malabsorption may lead to a bleeding tendency. Premature labour is relatively common and there is a marked increase in the risk of stillbirth.

Management FIGURE 21.1

The increasingly elevated position of the appendix in pregnancy as gestation advances.

JAUNDICE Jaundice is traditionally classified into three categories: haemolytic, hepatocellular and obstruction (Box 21.1). Causes may be either consequential to, or independent of, the pregnancy. Clinical features suggesting cholestasis include pruritus, dark urine and pale stools. Biochemical tests will also help differentiate between hepatocellular damage and obstruction. Hepatocellular damage is associated with an increase of predominantly unconjugated bilirubin and hepatocellular enzymes. Caution must be exercised in interpreting alkaline phosphatase levels due to the placental production. An ultrasound examination is helpful in demonstrating dilatation of the biliary tree in cases of extrahepatic obstruction.

Cholestasis of pregnancy Pathogenesis Cholestasis of pregnancy is due to an oestrogen-sensitivity effect and exhibits a familial tendency. It may be frequently recurrent in successive pregnancies and may even occur with the combined oral contraceptive pill.

Clinical features Pruritus, particularly of the palms and soles, is characteristic. Liver function tests usually show some elevation of

Other causes of obstructive jaundice should be excluded. Increased surveillance of fetal wellbeing is indicated (e.g. ultrasound, cardiotocography). Ursodeoxycholic acid is usually effective in controlling symptoms and normalising liver function tests. Induction of labour is indicated at 37 to 38 weeks or earlier if liver function deteriorates on ursodeoxycholic acid. The condition resolves rapidly after pregnancy.

Acute fatty liver of pregnancy Pathogenesis Like severe preeclampsia, acute fatty liver is unique to pregnancy, more common in primigravidas and extremely uncommon before the late second trimester. Interestingly, about 25% of cases are due to an autosomal recessive condition (LCHAD deficiency) in the fetus that impacts on the mother by the transplacental passage of hepatotoxic fetal-derived fatty acids.

Clinical features This potentially fatal syndrome comprises malaise, fatigue, epigastric discomfort and vomiting. Jaundice soon follows. There is a significant leucocytosis, abnormal transaminases, hyperbilirubinaemia, hypoglycaemia and often coagulopathy.

Management The woman should be placed in an intensive care unit: intravenous fluids are administered, together with albumin, dextrose and clotting factor replacement with fresh frozen plasma. The pregnancy should be terminated, usually by urgent caesarean section. 169

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Cholelithiasis and acute cholecystitis

Clinical features

Cholelithiasis is another disease in women of childbearing age. Gallstones are present in approximately 3% of women in pregnancy. Biliary colic is usually caused by a stone in the cystic duct or common bile duct. The pain is severe, tends to be constant and usually lasts for 12 to 15 hours. Acute cholecystitis is rare in pregnancy. The condition is treated conservatively with antibiotics and analgesia. Surgery is rarely necessary during pregnancy and usually can be deferred until the puerperium.

Mid-trimester miscarriage, preterm labour and preterm premature rupture of the membranes are possible consequences. Malpresentation may result from the altered shape of the uterine cavity. Uterine abnormalities are frequently detected as an incidental finding at the time of the obstetric ultrasound, laparoscopy, curettage or caesarean section (Fig 21.2).

THE REPRODUCTIVE SYSTEM CONGENITAL DISORDERS OF THE MÜLLERIAN SYSTEM Types of anomaly Approximately 1% of women have one of the following anomalies. 1. Faulty midline fusion. The anomaly may involve the uterus, cervix, vagina or a combination of these. The extreme form is represented as a completely separate system on each side (uterus didelphys). 2. Faulty development of one duct gives rise to incomplete, non-canalised or absent structures on that side (e.g. unicornuate uterus). There are often anomalies of the renal tract on the same side.

Management Obstetric management is usually expectant, but the caesarean section rate is increased, usually as a result of malpresentation. A vaginal septum can be stretched markedly during labour and can be incised between clamps and ligated.

FEMALE GENITAL MUTILATION Female genital mutilation (FGM) is an important obstetric issue and needs a clear understanding of not only the physical considerations but also the psychological, social and legal considerations. In order to birth vaginally, surgical enlargement of the introitus is usually necessary and most often best accomplished by division of adherent labia in the anterior section of the perineum, sometimes termed an anterior episiotomy. This can be performed antenatally or in labour. In most jurisdictions it is illegal to recreate the anatomy of the FGM postpartum by suturing the labia back together.

FIGURE 21.2

Uterus didelphys found at caesarean section. The non-pregnant half of the duplicated system is also hypertrophied by the hormones of pregnancy. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

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INCARCERATION OF THE UTERUS The uterus lies in a retroverted position in around 20% of women. Although spontaneous correction occurs late in the first trimester in the great majority, the growing uterus occasionally becomes incarcerated in the hollow of the sacrum. With continued growth, there is pressure on the bladder neck and the woman experiences increasing difficulty in voiding, leading to complete urinary retention (Fig 21.3). The condition is relieved by the insertion of a Foley catheter, which is left to drain. The uterus can then be pushed gently out of the pelvis with the woman in the knee/chest position if spontaneous correction does not occur.

UTEROVAGINAL PROLAPSE IN PREGNANCY

Management usually involves replacement with a ring pessary and periods of recumbency. Vaginal birth can be undertaken. Although there is considerable improvement in the puerperium, surgery is eventually likely to be needed.

MOTOR VEHICLE ACCIDENT IN PREGNANCY The woman may suffer uterine rupture, placental abruption and/or pelvic fracture as a result of motor vehicle injury. Seat belts should be worn as they minimise the risk of fatal injury. Following a significant traumatic injury to the abdomen, prolonged fetal cardiotocographic monitoring (e.g. 4 hours) should be undertaken in view of the possibility of placental abruption or even traumatic uterine rupture (Fig 21.5).

This becomes more likely with increasing parity. The condition improves after the fourth month as the uterus becomes abdominal in position, but may recur late in pregnancy because of the weight of the uterus (Fig 21.4).

FIGURE 21.3

Incarceration of a retroverted gravid uterus may occur at about 12 to 14 weeks’ when it fills the pelvis. The cervix is displaced upwards and anteriorly, causing the urethra to become elongated, and may obstruct, causing urinary retention.

FIGURE 21.4

Cervical hypertrophy and prolapse at 39 weeks. The cervix pulled up in labour and the woman had a normal vaginal birth. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

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FIGURE 21.5

Uterine rupture following a motor vehicle accident at 36 weeks’. The uterine rupture was discovered 2 hours after the car accident at caesarean section because of a poor cardiotocograph. Source: Courtesy of Prof. Norman Beischer.

UTERINE FIBROMYOMAS Clinical features About 1% of pregnancies are complicated by fibromyomas, particularly in older women. While most commonly asymptomatic, fibromyomas do increase in size during pregnancy and may cause malpresentation, obstructed labour (cervical fibroid) or postpartum haemorrhage (bleeding submucous fibroid). About 10% of these women will experience red degeneration (infarction), which causes severe abdominal pain and needs to be considered in the differential diagnosis of an acute abdomen in pregnancy. Torsion or bleeding from a subserous fibroid are rarer complications. The diagnosis of uterine fibromyomas can usually be confirmed by ultrasonography. 172

Management Myomectomy is virtually never indicated other than for torsion of a pedunculated subserous fibroid. Pain in association with red degeneration may be treated with analgesics. If a caesarean section is needed, care with the uterine incision should be taken to avoid transection of a fibromyoma and any temptation to perform a myomectomy should be resisted.

OVARIAN CYSTS AND TUMOURS Ovarian tumours are potentially serious because of their liability to develop complications in pregnancy. Twothirds of the tumours are cystic: originating in the corpus luteum (luteal cyst), covering epithelium (serous or mucinous cystadenoma), germinal elements (cystic teratoma,

Chapter 21  Gastrointestinal, Hepatobiliary, Gynaecological and Renal Problems

dermoid) or vestigial remnants (parovarian cyst). Solid tumours are usually fibromas.

Clinical features Diagnosis is usually incidental at the time of an obstetric ultrasound. Clinical problems may arise when the tumour itself complicates (torsion, haemorrhage, incarceration, necrosis, rupture, infection, malignancy) or the tumour impacts on the pregnancy (obstructed labour from a cyst deep in the pelvis, malpresentation).

Management Small cysts (< 6 cm) with a simple internal structure on ultrasonography can be followed conservatively, as they are likely to be functional in nature (corpus luteum cyst) and resolve spontaneously. Women should be advised of the symptoms of torsion and the importance of prompt presentation. Endometriotic cysts are also best managed conservatively. Larger cysts, or those with ultrasound features of neoplasia, are best treated surgically early in the second trimester. Surgery in the first trimester is more likely to cause an interruption to the pregnancy, and is reserved for women with complications such as torsion. Where a cyst is discovered late in pregnancy, removal is deferred until early in the puerperium, or at caesarean section if this is the mode of birth for other reasons.

therapy or a combination of both is usual. Occasionally a microinvasive lesion may be treated more conservatively with cone biopsy where preservation of childbearing is a high priority. The major factors influencing treatment are the stage of the disease, the gestational age at diagnosis and the parity/desire for children. On occasions, a difficult decision must be made with respect to whether a delay in therapy can be justified to enable fetal viability at the risk of maternal progression of disease.

THE URINARY SYSTEM PHYSIOLOGICAL CHANGES IN PREGNANCY The smooth muscle relaxant properties of progesterone combine with some ureteric compression to produce considerable dilatation of the renal pelvis and ureters, so-called physiological hydronephrosis (Fig 21.6). Renal blood flow and glomerular filtration rate increase by about 40% in pregnancy. There may be glycosuria in the presence of a relatively normal blood glucose (lowered renal threshold for glucose). Normal values for proteinuria are < 150 mg/24 hours in the normal adult but increase to < 300 mg/24 hours in preg-

CERVICAL INTRAEPITHELIAL NEOPLASIA Clinical features With routine cervical cytology, features suggestive of cervical intraepithelial neoplasia (CIN) may be found in about 0.5% of pregnant women. The lesion is asymptomatic unless it progresses to invasive carcinoma. Such an outcome appears to be exceedingly uncommon during pregnancy, with few cases reported in the literature.

Management High-grade abnormal cervical cytology in pregnancy should be assessed with colposcopy, repeat cytology and target biopsy if needed. Cone biopsy is performed only if microinvasion is suspected colposcopically or on target biopsy. As progression of CIN to invasive cancer is exceedingly rare during pregnancy and treatment may compromise the pregnancy, management of appropriately assessed CIN is conservative (colposcopic reviews) until after the pregnancy. Between 6 and 12 weeks postpartum, the lesion should be re-evaluated and if high-grade CIN is present, it can be removed.

CERVICAL CARCINOMA

FIGURE 21.6

Invasive cervical carcinoma is exceedingly rare in pregnancy. There may be watery or blood-stained discharge or frank bleeding. Radical treatment by surgery, radio-

Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

Physiological hydronephrosis of pregnancy.

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nancy. The frequency of micturition increases consequent on an increase in total urine produced and the pressure effects exerted by the enlarging uterus on the bladder.

LOWER URINARY TRACT INFECTION The predominant organism in urinary tract infection (UTI) is Escherichia coli, which is responsible for about 80% of infections. Enterococcus faecalis, Aerobacter aerogenes, Klebsiella, Proteus and β-haemolytic streptococci are less common urinary tract pathogens and more suggestive of underlying renal pathology.

Clinical features Asymptomatic bacteriuria is found in about 6% of women when screened at the first antenatal visit. Clinical pyelonephritis will develop in about one-third of these women while being very uncommon in those without bacteriuria on initial screening. These women are also at increased risk of obstetric complications, particularly preterm labour. Symptomatic UTIs may occur at any time but are more common in pregnant than non-pregnant women.

Management

CHRONIC RENAL INSUFFICIENCY Aetiology Causes include chronic pyelonephritis, chronic glomerulonephritis and polycystic kidney disease. Glomerulonephritis may be classified according to aetiology (e.g. idiopathic, familial, lupus, diabetic), histology (e.g. diffuse or focal, membranous or proliferative) or clinical picture (e.g. nephritic, nephrotic, benign haematuria). The incidence appears to be decreasing with the reduced prevalence of streptococcal infections.

Clinical features Anaemia, preeclampsia, premature labour, fetal growth retardation/placental insufficiency and perinatal mortality are all increased in the presence of renal disease. Severe impairment of renal function (serum creatinine > 0.2 mmol/L) has a poor prognosis and successful pregnancy is rarely seen with serum creatinine > 0.3 mmol/L or with a woman requiring dialysis. Progression of glomerulonephritis may occur with superimposed preeclampsia, and recurrent urinary tract infection may aggravate the course of chronic pyelonephritis.

Diagnosis is confirmed with a properly collected midstream urine microscopy, culture and sensitivities. Appropriate antibiotic therapy is commenced, often amoxicillin unless antibiotic sensitivities indicate otherwise. A further urine specimen should be tested after completion of the course and at intervals of 2 to 3 months during the pregnancy. If bacteriuria recurs, nocturnal antibiotic prophylaxis is usually recommended (e.g. nitrofurantoin 100 mg at night).

Management

ACUTE PYELONEPHRITIS Clinical features

Pregnancy

In the absence of screening for asymptomatic bacteriuria, 2% of women will develop acute pyelonephritis. The woman complains of dysuria and frequency of micturition, pain in the flank radiating to the loin, fever and chills; anorexia and vomiting are often associated. Loin tenderness, fever and tachycardia are usually present. Rarely, serious infections may be associated with septicaemic shock.

Management Diagnosis is confirmed on urine microscopy. Antibiotic therapy should be instituted on clinical grounds before the urine culture result is available, and the parenteral route may be chosen for a more rapid response or because of vomiting. Analgesics are often needed, and fever should be treated with tepid sponging and antipyretic medication. An adequate fluid intake is essential and an intravenous infusion is necessary if there is nausea or vomiting. Follow-up in the puerperium should look for an underlying cause (e.g. calculi). 174

Prepregnancy Full assessment of the severity, nature and aetiology of the renal disease should take place. If the prognosis is poor, effective contraception is required. A woman needing renal transplantation in the near future should have this performed before pregnancy. Where the cause is treatable (e.g. lupoid nephritis), the disease should be controlled before commencing a pregnancy. An accurate assessment of gestational age is essential. An early ultrasound should be performed if there is discordance among clinical findings. Routine screening for other problems (clinical and investigations) must not be omitted. If the renal disease has not been recently assessed, this needs to be done with respect to cause and severity. Treatment of the renal disease should be optimised for pregnancy. If immunosuppressants are being used, some modification may be required. Occasionally, an extremely poor prognosis for mother and fetus leads to a recommendation of pregnancy termination. The woman should be booked into a suitably equipped hospital with specialist obstetric and renal physician care. Subsequent antenatal care should be directed towards the potential complications in pregnancy. The renal disease itself requires close surveillance as a serious deterioration in renal function mandates delivery. Anaemia should be anticipated and iron/folate supplement should be given. Preeclampsia is particularly prevalent and care should be initially directed at prevention (rest, blood pressure control, low-dose aspirin, calcium supplementation) and early diagnosis through more frequent antenatal

Chapter 21  Gastrointestinal, Hepatobiliary, Gynaecological and Renal Problems

visits. The latter can be difficult as the features of preeclampsia mimic those of chronic renal disease. The timing of delivery will be very much dependent on fetal growth and maternal progress. With significant renal impairment, it is unlikely that the pregnancy would be allowed to proceed beyond 38 weeks’ gestation.

Pregnancy after a renal transplant Pregnancy is not contraindicated by a prior renal transplant, but the woman’s condition should be stable, with minimal hypertension, proteinuria or evidence of graft rejection. Immunosuppressant drugs can be used cautiously, even in the first trimester. The incidence of spontaneous abortion, premature labour, preeclampsia and urinary tract infection are all increased. If a caesarean section is performed, care must be exercised to avoid the pelvic kidney.

ACUTE URINARY RETENTION Incarceration of a retroverted pregnant uterus Late in the first trimester, a retroverted uterus may become ‘incarcerated’ between the hollow of the sacrum and the rear of the pubic symphysis. Pressure is exerted on the bladder neck and proximal urethra as the uterus expands forwards. The retention may be masked by incontinence, which is due to overflow. The condition is usually cured by catheterisation, with the catheter indwelling for 24 to 48 hours, sometimes aided by the prone position and manual anteversion of the uterus.

Intrapartum urinary retention The fetal presenting part may cause occlusion at the level of the bladder neck. The resulting bladder fullness is discomforting to the woman, encourages infection and

inhibits uterine contractions. If neglected, serious damage to the base of the bladder may result, even to the extent of fistula formation. The other cause of intrapartum urinary retention is epidural analgesia since the woman is often unable to void.

Postpartum urinary retention Bruising at the bladder base or perineal discomfort from an episiotomy or lacerations may reflexly inhibit bladder function, making micturition difficult. It should be remembered that the bladder has a poor tone after delivery and considerable distension may occur without the usual discomfort or urgent desire to micturate. If voiding has not occurred by about 12 hours, a urinary catheter should be passed. A full bladder may give a false idea of the height of the uterine fundus.

STRESS INCONTINENCE Statistics indicate that about 5% of women have this problem prior to pregnancy, about 30% during and about 10% after delivery. Deterioration of urinary control is more likely with a large infant and a prolonged second stage, and less likely after caesarean section. FURTHER READING Bacq Y, Sentilhes L, Reyes HB, et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology 2012;143(6):1492–501. Phelan ST. Renal disease in pregnancy ambulatory issues. Clin Obstet Gynecol 2012;55(3):829–37. Wei Q, Zhang L, Liu X. Clinical diagnosis and treatment of acute fatty liver of pregnancy: a literature review and 11 new cases. J Obstet Gynaecol Res 2010;36:751–6.

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Chapter 22  AUTOIMMUNE AND ISOIMMUNE DISEASE IN PREGNANCY Michael Permezel and Gillian Paulsen

KEY POINTS Antibodies may cross the placenta and impact on the fetus. The antibody transfer progressively increases through pregnancy, from very little before, say, 16 weeks’ and then only gradually increasing until an exponential increase at term. In the case of autoantibodies, the fetus usually has a similar condition to that of the mother; for example, immune thrombocytopenia (ITP) produces thrombocytopenia in the fetus and autoimmune hyperthyroidism can produce hyperthyroidism in the fetus. These and other examples are discussed in this chapter. An unusual exception is that autoimmune salivary and lacrimal gland disease (Sjögren’s) can produce heart block in the fetus due to differing antigenic expression. Isoantibodies (also known as alloantibodies) do not impact at all on the mother but can have lethal consequences for the fetus. Most important are the anti-red blood cell isoantibodies, but there are also less common conditions where isoantibodies are directed against white cells or platelets. Disease severity of anti-red blood cell antibodies is largely reflected by the level (titre) of the antibody and ranges from mild jaundice at one extreme through severe anaemia to hydropic fetal death at the other. All women are screened for anti-red blood cell antibodies at the first antenatal visit and those that are Rh-negative are re-screened at 28 weeks’. Prophylaxis against immunisation from fetomaternal haemorrhage is only available for the D antigen through administration of passive anti-D at times of bleeding, trauma, birth and also prophylactically at 28 and 34 weeks’ gestation.

BACKGROUND The conceptus is antigenically foreign and therefore immunologically ‘privileged’ in not being rejected. This immunological tolerance is a product of both specific features of the conceptus that limit the presentation of antigens to the mother and changes in the maternal immune response—both specific to the fetal antigens as well as a degree of general immune suppression. Placental insufficiency and preeclampsia may sometimes be the result of insufficient immunological tolerance. The immune system of the fetus becomes progressively more competent as the pregnancy advances. The

immune competence of the fetus and subsequent neonate is further enhanced by progressively increasing transfer of maternal antibody across the placenta as the pregnancy advances. The obvious downside of this antibody transfer is the potential for antibodies directed against fetal tissues to cross the placenta and have adverse effects on the fetus. Where an antibody crosses the placenta and is directed against an antigen that the fetus possesses but not the mother, it is termed an isoantibody and the condition is called isoimmunisation. The problem is most common with red cell antigens but may also occur with the various platelet or leucocyte antigens.

Chapter 22  Autoimmune and Isoimmune Disease in Pregnancy

The fetus may also be involved, indirectly, by the transfer of harmful maternal autoantibodies, usually producing a variation of the problems seen in the mother. The antibodies may be organ specific, examples of which include myasthenia gravis, autoimmune thyroid disease and immune thrombocytopenic purpura. Alternatively, antibodies may be against more widespread antigens such as the antinuclear factors (ANF or ANA) in systemic lupus erythematosus (SLE). Antiphospholipid antibodies are particularly harmful to the conceptus in that they are associated with an increased risk of spontaneous abortion and widespread intravascular thrombosis, including the placenta. In these conditions, the adverse affect on the pregnancy may be mediated more by the impact of the disorder on the maternal vascular perfusion of the placenta rather than the binding of the antibody to tissues within the fetus.

AUTOIMMUNE DISEASE IN PREGNANCY Early in fetal life when the immune system is immature, it accepts as normal all the developing tissues around it; they are recognised as ‘self’. As the system matures, it is able to differentiate between self and non-self. Occasionally, there is a breakdown in the system and the immune system starts to attack its own tissues by production of an autoantibody. These antibodies can be directed against many different tissues and cause problems in the mother as the antibody binds to the maternal antigen against which it is directed. In pregnancy, these harmful antibodies may cross the placenta and cause clinical problems for the fetus that may continue into early neonatal life. Table 22.1 summarises the features of some of the autoimmune diseases

which may complicate pregnancy and which are not covered in other chapters. The following facts should be remembered. 1. Antibodies of the IgG type pass freely across the placenta and affect the fetus. In contrast, IgM does not cross the placenta. 2. The clinical manifestation in the fetus is usually similar to the mother but differences in antigenic expression may lead to entirely different consequences; for example, anti-Ro or anti-La antibodies producing Sjögren’s syndrome in the mother (dry mouth and dry eyes due to binding of the antibody to the salivary and lacrimal glands respectively) but heart block in the fetus due to binding of the antibody to the conducting system within the heart. 3. The fetus (and newborn) may be affected in the absence of maternal features (the fetal tissues are more susceptible to the antibodies), or after the mother has been treated (e.g. by thyroidectomy in the case of Graves’ disease or splenectomy in the case of immune thrombocytopenic purpura). 4. The fetal disorder is usually self-limited (2 to 3 months), but permanent damage may occur (e.g. heart block in the case of antibodies to the cardiac conducting system). The following conditions are examples of maternal autoimmune disease that may impact on the fetus.

IMMUNE THROMBOCYTOPENIC PURPURA Clinical features In immune thrombocytopenic purpura (ITP), an antiplatelet autoantibody causes thrombocytopenia in the

TABLE 22.1  AUTOIMMUNE DISEASES THAT MAY IMPACT ON THE FETUS. Disorder

Antibody

Maternal clinical features

Pregnancy effects

Systemic lupus erythematosus (SLE)

Anti-dsDNA

Renal disease, skin lesions, polyarthritis

Miscarriage, IUGR, preeclampsia, preterm labour

Antiphospholipid syndrome

Anticardiolipin

Thrombosis

Miscarriage, IUGR, preeclampsia

Sjögren’s syndrome

Anti-Ro, anti-La

Dry mouth, dry eyes

Congenital heart block

Immune thrombocytopenia

Antiplatelet

Thrombocytopenia

Thrombocytopenia

Autoimmune hypothyroidism

Anti-thyroperoxidase (anti-TPO), antimicrosomal

Hypothyroidism

Hypothyroidism

Autoimmune hyperthyroidism

Anti-TSH receptor

Hyperthyroidism, goitre, exophthalmos

Hyperthyroidism including CCF, IUGR goitre

Myasthenia gravis

Anti-acetylcholine receptor

Maternal muscle weakness

Fetal muscle weakness, rarely arthrogryposis 177

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mother. The condition may have presented with a bleeding tendency but in pregnancy it is most likely to be diagnosed in the course of a routine full blood examination at the first antenatal visit. Most concern in pregnancy will be around the risk of postpartum haemorrhage for the mother, but the fetus may also be thrombocytopenic and at particular risk of traumatic haemorrhage at birth. It is, however, very uncommon for the fetus to be severely affected and in general the thrombocytopenia is less severe than that seen with neonatal alloimmune thrombocytopenia (NAIT) discussed later in this chapter. Predicting the fetal platelet count is difficult and maternal antiplatelet antibody levels are not helpful. The maternal platelet count is a guide and the fetus may be at particular risk where the maternal platelet count is low in spite of a past maternal splenectomy, being indicative of severe disease.

Management ITP is variously treated with corticosteroids (e.g. oral prednisolone) with or without the addition of immunoglobulin therapy (usually by weekly infusion). The intention is usually to maintain the platelets at a level of more than 50 × 109/L during pregnancy and at a level where the anaesthetist would be comfortable inserting regional analgesia if necessary, mostly around 80 × 109/L.

A

B

AUTOIMMUNE HYPERTHYROIDISM (GRAVES’ DISEASE) A thyroid-stimulating autoantibody (TSaab) (more commonly termed TSH-R autoantibody) binds to and stimulates the thyroid-stimulating hormone (TSH) receptor, producing hyperthyroidism in both mother and fetus. Usually the disease has been diagnosed before the pregnancy. If not, astute observation is needed since there is considerable overlap in symptoms and signs with the changes of normal pregnancy. Goitre and tachycardia (particularly if persisting during rest or the Valsalva manoeuvre) are very suspicious; weight loss (this may be obscured by the normal increase in pregnancy), exophthalmos, pretibial oedema, vomiting, diarrhoea and hand tremor are other signs which should lead to laboratory investigation. Preeclampsia, congestive cardiac failure and fetal morbidity are more likely in the untreated mother. In the baby, hyperthyroidism is rare but may arise from transplacental passage of the thyroid-stimulating autoantibody. Usually, the effect of the TSaab is counteracted by concomitant antithyroid drugs, which also cross the placenta. Neonatal thyrotoxicosis may be seen where the mother has no requirement for antithyroid drugs, despite high levels of circulating TSaab (e.g. previous I131 or thyroidectomy) (Fig 22.1).

C

FIGURE 22.1

Graves’ disease in pregnancy. A Hypothyroid 21-year-old mother who experienced Graves’ disease at age 7 years and was treated by subtotal thyroidectomy. She was given maintenance therapy with daily thyroxine throughout pregnancy. B Her infant girl was born at term with severe Graves’ disease, goitre and exophthalmos that persisted for 6 months. C The child was healthy at 20 months old.

Source: Gleason CA, Devaskar, SU, eds. Avery’s Diseases of the Newborn. 9th edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 9.6.

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The diagnosis is confirmed by an elevated free T4 value (normal range 10 to 19 pmol/L) and a very low TSH level (< 0.5 mU/L). The woman should be screened for thyroid antibodies (stimulatory or inhibitory), which may cross the placenta and affect the fetus. Fetal surveillance is indicated with fetal heart rate assessment at each antenatal visit and serial ultrasounds to detect evidence of IUGR or evolving CCF. Most women are now treated with antithyroid drugs such as carbimazole or propylthiouracil, which block the uptake of iodine by the gland and hence the formation of the thyroid hormone. Another action of propylthiouracil is to block the peripheral conversion of T3 to T4 (the more active tissue hormone). Propylthiouracil is the preferred drug for the breastfeeding mother because of a lower concentration in milk. It is usually possible to reduce the dose progressively during the second half of pregnancy, the free T4 being kept near the upper limit of normal. During the course of pregnancy, the free T4 and TSH should be checked every month. An exacerbation is often observed postpartum and an increase in drug dose may be necessary. Maternal side effects of antithyroid drugs include rash, pruritus, nausea, fever and leukopenia. In Graves’ disease, the fetal sequelae of antithyroid drugs are counterbalanced by the transplacental passage of TSaab. Fetal hypothyroidism may occur where the antithyroid drugs are required in the absence of TSaab. Such a clinical situation may arise with an active thyroid adenoma. A selective beta-adrenergic blocking drug may be useful early in treatment to control quickly the sympathetic effects of the disease. Subtotal thyroidectomy is rarely necessary during pregnancy as good control can usually be achieved medically. The neonate should be examined for evidence of goitre, hypothyroidism or hyperthyroidism and cord blood should be sent for measurement of free T4 and TSH. The presence of a thyroid nodule will require referral and usually fine needle biopsy.

AUTOIMMUNE HYPOTHYROIDISM (HASHIMOTO’S DISEASE) Antithyroid peroxidase or ‘non-stimulatory’ anti-TSHreceptor antibodies may cause thyroid dysfunction in both mother and fetus. The classical features of hypothyroidism are a general slowing of body functions (tiredness, constipation, bradycardia, puffy/dry skin, cold sensitivity, decreased mental alertness, impaired memory and depression/irritability). On investigation, T4 levels are low and TSH is elevated. In the untreated condition, pregnancy is unlikely to occur; if it does, there is an increased incidence of miscarriage, preeclampsia, cardiac dysfunction and postpartum haemorrhage. The puerperium may be complicated by lactation difficulty or a puerperal mental illness, especially depression. The fetus may be affected by transplacental passage of an antithyroid antibody which

may result in congenital hypothyroidism (cretinism). In general, the fetus should be protected during pregnancy by adequate treatment of the mother but may need supplementation through early infancy. If the mother has established hypothyroidism, replacement with thyroxine will be necessary, the usual dose ranging from 100 to 200 mcg/day. The dose should be titrated to the serum free thyroxine level and the serum TSH. Thyroxine levels should be maintained in the upper normal range (and low for TSH) as the fetus may be dependent on transplacental passage of thyroxine if its own thyroid has been adversely affected by the antibody. An increase in thyroxine dose is usually required in pregnancy.

MYASTHENIA GRAVIS In myasthenia gravis, there is an autoantibody against a protein in the neuromuscular junction, causing muscle weakness in the mother. Like other autoimmune conditions, the antibody crosses the placenta and can cause the neonate to have transient muscle weakness, sometimes of clinical significance. Rarely, the impact on fetal muscular function is profound and there may be lethal contractures in relation to an absence of muscular function (arthrogryposis).

SYSTEMIC LUPUS ERYTHEMATOSUS Systemic lupus erythematosus (SLE) is a clinical definition but is characterised by the presence of antidsDNA antibodies in approximately 90% of cases. Other antinuclear antibodies such as anti-Ro and anti-La or antiphospholipid antibodies may co-exist. The anti­ bodies cross the placenta but the impact on the pregnancy may be more a reflection of the maternal vascular disease than the direct impact of the antibody on the fetus. Like autoimmune thyroid disease, SLE is particularly prevalent in women of childbearing age, affecting approximately 1/1000 women in pregnancy. The likelihood of adverse outcomes increase with renal involvement, hypertension and periconceptual disease activity. Pregnancy complications include miscarriage and stillbirth, preeclampsia, preterm birth and placental insufficiency. Management should be multidisciplinary, with obstetrician and physician working together to minimise complications. Disease flares are usually managed with corticosteroids but other drugs such as hydroxychloroquine are sometimes used, although hydroxychloroquine is relatively contraindicated in early pregnancy (category D). Where anti-Ro/La or anti-phospholipid antibodies are co-existent, these may have the dominant effect on the pregnancy outcome.

ANTIPHOSPHOLIPID SYNDROME This is an important autoimmune condition because of a particular tendency to impact adversely on pregnancy. 179

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There may be some overlap of this condition with SLE as some women have both antinuclear and antiphospholipid autoantibodies, but it is best viewed as a distinct entity. Clinical features in the mother are largely a consequence of both arterial and venous thromboses throughout the body, with a predilection for the placental bed. Recurrent miscarriage is the most common presentation but the syndrome may also be associated with intrauterine fetal death, severe growth restriction or preeclampsia. Diagnosis can be made by demonstration of the autoantibody or the ‘lupus’ anticoagulant. The latter is a real misnomer since it is associated with thrombosis rather than a bleeding tendency and is a feature of the antiphospholipid syndrome rather than SLE. In management of the antiphospholipid syndrome, anticoagulant therapy is of prime importance and this may be combined with antiplatelet drugs or even immunosuppression in extreme cases. Even moderate levels of antiphospholipid antibodies would often not be treated in the absence of a history of clinical sequelae.

ANTI-RO AND ANTI-LA SYNDROMES These are antibodies directed against cytoplasmic ribonucleoproteins Ro and La. In the mother, these antibodies characteristically cause Sjögren’s syndrome (dry mouth and dry eyes), a photosensitive rash or even an SLE-like syndrome. Potential clinical features in the fetus include the photosensitive rash (5%) and complete heart block (2%). The risk is greater if there is a previously affected child (16%) or two previously affected children (50%). The heart block is permanent and may be fatal. Onset may be as early as 18 weeks’ and may be associated with a myocarditis of variable severity, from antibody binding to the fetal cardiac muscle as well as the cardiac conducting system. Detection of fetal arrhythmias is the key objective of auscultation of the fetal heart at each antenatal visit—in all pregnancies, not just those with anti-Ro or anti-La. Where there is a high risk of heart block (e.g. previously affected pregnancy), the P-R interval of the fetal cardiac cycle may be measured to anticipate impending heart block. Salbutamol can be beneficial if bradycardia is causing heart failure, but treatment may be limited by maternal side effects. Dexamethasone (sometimes supplemented by plasmapheresis) may benefit any myocarditis but will not reverse the heart block. These may be instituted prophylactically if there have been poor outcomes in previous pregnancies. Early neonatal therapy will depend on the degree of heart failure but a pacemaker may be necessary. If the fetus survives the neonatal period, the outlook is generally good but a small number will have irreversible myocardial damage that leads to neonatal death or ongoing myocardial insufficiency. 180

RED CELL ISOIMMUNE DISEASE IN PREGNANCY PATHOPHYSIOLOGY In red cell isoimmunisation, the fetus has red cell antigens that the mother does not possess. The mother is able to make an anti-red blood cell antibody that does not affect her but can cause haemolysis in the fetus.

WHICH ANTIGENS? The most common red cell antigen that is responsible is the D antigen at the rhesus locus. Approximately 85% of all red cell immunisation is related to the D antigen. Some of the other, more common antigens that may be responsible are listed in Table 22.2. Antibodies against other antigens may not cause clinical problems for the fetus because either they are predominately IgM (e.g. anti-A, anti-B, anti-P) or the fetal red cell does not express that antigen (anti-Le). The rhesus or Rh factor or D antigen is present in approximately 85% of Caucasians, 95% of African Americans and 99% of Asians and is so named because it is present in the rhesus monkey. In the preprophylaxis era, it was responsible for 98% of all cases of red cell isoimmunisation affecting pregnancy but now as many of 15% are caused by other anti-red blood cell isoantibodies, particularly anti-c, Kell, E and Duffy.

How did the mother acquire the anti-red blood cell isoantibody? Blood transfusion Although all blood administered is ABO and Rh group compatible, there is generally no matching for all the other red cell antigens capable of initiating an immune

TABLE 22.2  RED CELL ANTIGENS AND HAEMOLYTIC DISEASE OF THE NEWBORN. Red cell antigens associated with haemolytic disease of the newborn

Red cell antigens not associated with haemolytic disease of the newborn (or only mild disease)

Rhesus antigens: D, c, E, C

Rhesus antigen: e

Kell (K), Kidd (Jka and Jkb), Duffy (Fya and Fyb)

ABO antigens: A and B

M, N, S, s

Lewis (Le) P, P1

Chapter 22  Autoimmune and Isoimmune Disease in Pregnancy

response. The mother will not have a ‘transfusion reaction’ as such when she is first exposed to that antigen; however, this will serve as a primary immune stimulus and antibody production will be initiated that might impact on a current or future pregnancy.

Fetomaternal haemorrhage The fetus will usually inherit one or more major blood group factors from the father which are absent in the mother. When fetal red cells leak across the placenta into the mother’s circulation, she may react to these ‘foreign’ red cell antigens by forming isoantibodies. As little as 0.1 mL of fetal blood may lead to a maternal primary immune response.

Consequences of anti-red blood cell isoantibodies If anti-red blood cell isoantibodies are IgG in type, these will pass across the placenta from the mother to the fetus and cause agglutination and destruction of red blood cells. Transfer of antibody across the placenta increases as gestation advances and is minimal before about 16 weeks’ gestation. In late pregnancy, there is a surge of antibody transfer to equip the neonate with antibodies to fight infection. The breakdown of fetal erythrocytes has two consequences. First, bilirubin is a breakdown product of haemoglobin and while not a problem in utero (as the mother will clear the bilirubin from the fetus), accumulation of unconjugated bilirubin in the neonatal period can have serious consequences for the neonate, with the possible development of ‘kernicterus’ (see Ch 68). Where the amount of haemolysis is great, the accelerated erythropoiesis will not be able to keep up with the rate of haemolysis and anaemia will occur. Where anaemia is severe, the fetus will develop congestive cardiac failure with widespread accumulation of fluid subcutaneously and in the peritoneal, pleural and pericardial cavities—fetal hydrops. Further haemolysis will produce fetal death. Maternal white cell

ABO incompatibility ABO incompatibility is numerically three to four times more common than rhesus incompatibility. It is very rarely (if ever) responsible for fetal deaths or even severe anaemia; the usual clinical problem is early jaundice which may require phototherapy or possibly exchange transfusion. This condition is further characterised by fetal involvement in first pregnancies and unpredictable severity in future pregnancies.

PREVENTION OF RED CELL ISOIMMUNISATION Blood transfusion compatibility When a woman needs a blood transfusion, it is impractical to transfuse only blood that is antigenically fully compatible with the woman for all possible red-cell antigens. In practice, no D-negative person should receive D-positive blood. Kell-positive blood is generally only given to males or women beyond childbearing age. No specific efforts are generally made to avoid blood transfusion causing a primary immune response to other antigens (e.g. c, E, Duffy, M).

Passive administration of anti-D To prevent the development of anti-D antibodies, passive administration of anti-D was introduced in the late 1960s. As illustrated in Figure 22.2, passively administered anti-D binds to the D antigen on the fetal red cell and prevents recognition by the maternal immune system, therefore preventing primary immunisation as a consequence of fetomaternal haemorrhage. It should be noted that there is no similar process for preventing anti-c, anti-Kell or any other red cell isoimmunisation. This is simply because the high frequency of anti-D isoimmunisation makes the passive anti-D program cost-effective, whereas a program to prevent immunisation to other antigens would not be costeffective. Note that the passive administration of anti-D

Maternal red cells

anti-D

Fetal red cell

Passive antibody

FIGURE 22.2

Mechanism of action of passive anti-D. Administration of passive anti-D blocks the D-antigenic sites on the fetal red cells and prevents the primary immune response. 181

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is only effective to prevent primary immunisation and has no impact in preventing a fetomaternal haemorrhageinduced titre increase in a woman who is already immunised with anti-D.

When to administer anti-D Anti-D is generally administered at times of likely fetomaternal haemorrhage. There are broadly four such occasions: 1. bleeding in pregnancy (miscarriage, abortion, ectopic pregnancy, antepartum haemorrhage); 2. trauma (amniocentesis, chorionic villus sampling (CVS), external cephalic version, major fall or motor vehicle accident); 3. third-trimester administration (at 28 and 34 weeks’); and 4. following birth. In the latter circumstance, there is the opportunity to test the neonate to determine if the neonate is D-positive. In the event that the neonate is D-negative, unnecessary wastage of anti-D can be avoided by withholding passive anti-D.

Testing the partner This issue is obviously complex; in a small number of cases, there will be paternal uncertainty or even a desire to obscure the identity of the father of the child. Practically, it is best to assume that any fetus might be positive until it can be tested at birth. One possible exception is where the mother, without prompting, volunteers that her partner is also D-negative. Some clinicians are content to take this as evidence of undoubted paternity and withhold anti-D during pregnancy to a D-negative woman. The same would obviously not apply if the woman was asked to determine the D-status of her partner. It also needs to be noted at this point that in cases of immunisation being present (i.e. the presence of circulating maternal antibodies), the partner is tested. This is because invasive testing is likely during the pregnancy which could not be justified if the partner was negative, so asking for detailed grouping of the father of the child is therefore justifiable.

Amount of passive anti-D There are a number of different formulations of anti-D currently available. For sensitising events prior to 12 weeks’, 250 IU would commonly be administered. After 12 weeks’, prophylaxis occurs with 625 IU of anti-D. In some countries, a single dose of 1500 IU of anti-D will be given at 28 weeks’ instead of two doses of 625 IU at 28 and 34 weeks’. Kleihauer testing of maternal blood is able to detect the presence and amount of fetal erythrocytes and permits a more scientific approach to prophylaxis. A Kleihauer should be performed in the presence of a sensitising event in late pregnancy to see if more than one ampoule of anti-D is required to neutralise the amount of fetally derived D-antigen in maternal blood. In the case of a massive fetomaternal haemorrhage, a large amount of passive anti-D will be needed.

anti-D from approximately 10% of pregnancies to only 1% of pregnancies with a D-positive fetus and D-negative mother. With passive anti-D also being administered prophylactically at 28 and 34 weeks’ gestation, the number developing anti-D antibodies may drop to as low as 0.1%. These persisting cases may result from spontaneous fetomaternal haemorrhage before the prophylactic anti-D is administered at 28 weeks’, an unusually large fetomaternal haemorrhage that has not been administered sufficient anti-D or failure to appropriately administer anti-D globulin (due to blood group error, oversight, refusal by the woman). Some will question whether the passively administered anti-D can cause problems in the fetus. In fact, the anti-D does cross the placenta and bind to fetal red cells but the amount of anti-D is very small and the amount of haemolysis occurring clinically insignificant.

DETECTION OF ANTI-RED BLOOD CELL ANTIBODIES Apart from seeing that anti-D prophylaxis is appropriately carried out in D-negative women, the other major task of the obstetric attendant is to ensure that maternal antibodies, if present, are detected by routine antenatal testing. All women are screened at the first antenatal visit for the presence of anti-red blood cell antibodies. If no antibodies are present at the first visit, further checks are made in D-negative women at 28 weeks’, prior to the administration of passive anti-D. Some units will do repeat screening on all women at 28 weeks’ but the costeffectiveness is less in those women that are D-positive as the proportion that become immunised during pregnancy (e.g. with ‘c’, ‘E’ or Kell) will be less than that of D-negative women with ‘D’. If antibodies are present at any time, the woman must be referred to a specialist or special centre dealing with this problem. A number of complex decisions and therapeutic measures will be required if moderate or severe haemolysis is occurring in the fetus (next section).

MANAGEMENT OF A PREGNANCY WITH ANTI-RED BLOOD CELL ANTIBODIES Allocation of risk at the first antenatal visit Approximately 1% of women will be found to have anti-red blood cell antibodies at the first antenatal visit. They have become immunised as a consequence of a previous pregnancy or blood transfusion. As a first step, it is then necessary to determine the likely risk of this antibody to the fetus.

Effectiveness of passive anti-D

Determining the partner’s antigen status

The introduction of anti-D in the late 1960s reduced the incidence of the mother becoming immunised with

The partner’s genotype needs to be determined with respect to the offending antigen. He may be homozygous

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positive (e.g. DD, all children will be affected), heterozygous (e.g. Dd, 50% of offspring will be affected) or homozygous negative (e.g. dd, no children affected). For Fya/ Fyb C/c, K/k, E/e and so on, zygosity may be determined precisely. It is very important to realise that if the partner is negative for the relevant antigen, the fetus will have no problem whatsoever and any concerns of the parents or healthcare provider can be dismissed very early in the pregnancy.

Quantifying the amount of antibody in maternal plasma The likelihood of significant problems for the fetus can be estimated from the antibody level in the maternal plasma (Table 22.3).

Does the specific antigen affect risk? The management of an affected pregnancy is largely dependent on the amount of antibody, rather than which particular antibody is present. The exception is anti-Kell, which may be more serious than others at the same antibody level because the Kell antigen is particularly expressed on the erythroblast.

Management of the low-risk immunised pregnancy Maternal isoantibody levels should be estimated every 4 weeks until 28 weeks’ and fortnightly thereafter until birth. While the antibody level remains in the low-risk range, antenatal management can generally remain with the chosen model of care. If the titre were to rise, the woman should be managed as for moderate or high risk and referred appropriately. If the antibody is anti-D, there is no value in administering prophylactic passive anti-D; however, anti-D would still be administered to Rh-negative women with another isoantibody. At birth, the cord blood should be sent for grouping, bilirubin and haemoglobin determination. The baby should be managed by a doctor with experience in the management of immunised neonates. Early severe jaundice is possible and may follow a quite different course from that of physiological jaundice.

Management of the moderate- or high-risk immunised pregnancy Women with antibody levels in the moderate or high range (Table 22.3) should be referred to a unit with experience in the management of isoimmunised pregnancies. In most situations, this will be under the direction of a fetomaternal medicine subspecialist. Where the partner is heterozygous, it is pertinent to know whether the fetus inherited the relevant antigen. CVS should be avoided as this may provoke fetomaternal haemorrhage and an increase in antibody level. Amniocentesis is less likely to produce a rise in titre but it is increasingly possible to isolate free fetal DNA from the maternal bloodstream and type the fetus on the basis of that DNA. Fetal anaemia can be anticipated on the basis of peak systolic velocity (PSV) in the middle cerebral artery (MCA) of the fetus. In severe cases, this may be commenced as early as 17 weeks’ gestation and would commonly be performed weekly. It may be less reliable after 34 weeks’ gestation and would then be complemented by weekly or twice-weekly cardiotocography. Cardiotocography may be initially non-reactive in fetal anaemia, with a sinusoidal pattern only developing as a late sign (Fig 22.3). If anaemia is thought probable on the basis of the MCA PSV, fetal blood sampling may be performed under ultrasound control into either the umbilical cord or the ductus venosus. Fetal anaemia can be corrected with the infusion of donor blood into the fetal vessel. The blood infused will be negative for whichever antigen the maternal antibody is directed against. Fetal transfusions are commonly needed frequently at first (e.g. twice weekly) but with reducing frequency (e.g. even four-weekly) as the fetal blood type ‘changes’ to that of the donor blood and is no longer being destroyed by the maternal antibody. Delivery will be indicated when the risks of fetal transfusion exceed the risks of prematurity. It would be uncommon to continue to transfuse after 35 weeks’ gestation. The neonate needs to be carefully watched for both severe jaundice and anaemia. If transfusions have

TABLE 22.3  FETAL RISK AND MATERNAL ANTIBODY LEVEL. Risk level

Likelihood of fetal anaemia if titre remains unchanged

Likelihood of clinically significant neonatal jaundice

Titre level

Quantified antibody level

Low

Negligible

Moderate

≤ 16

< 4 IU/L

Moderate

Low

High

32–256

4–10 IU/L

High

High

Very high

≥ 512

> 10 IU/L 183

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FIGURE 22.3

Sinusoidal cardiotocograph due to severe fetal anaemia.

Source: Martin R, Fanaroff AA, Walsh MC. Fanaroff and Martin’s Neonatal-Perinatal Medicine. 9th edn. St Louis, Mosby, 2010. Copyright © 2010 Mosby, An Imprint of Elsevier.

not occurred, severe jaundice should be anticipated. In contrast, the fetus that has had many transfusions may not have jaundice at all but may suffer from later anaemia as the transfusions have suppressed fetal erythropoiesis, which needs to re-establish in the neonatal period.

WHITE CELL AND PLATELET ISOIMMUNE DISEASE IN PREGNANCY NEONATAL ALLOIMMUNE THROMBOCYTOPENIA Pathophysiology In neonatal alloimmune thrombocytopenia (NAIT), the isoantibody is directed against an antigen on the fetal platelets that the mother does not possess. This is most commonly anti-HPA-1a. Approximately 2% of mothers are HPA-1a negative and therefore capable of developing anti-HPA-1a antibodies, but clinically significant NAIT occurs only in about 1 in 2000 pregnancies.

Clinical sequelae NAIT is inappropriately named as the antibody crosses the placenta and may produce a profound fetal thrombocytopenia (i.e. not just neonatal). Spontaneous fetal haemorrhage may occur as early as 18 weeks’ gestation, particularly intracranial or gastrointestinal. The former

184

may present clinically with a porencephalic cyst or asymmetric enlargement of the cerebral ventricles. Gastrointestinal haemorrhage may be evidenced by increased intestinal opacity on ultrasound. Other cases will not present until birth with extensive petechiae or bruising that may be wrongly attributed to a traumatic delivery.

Management NAIT is a rare condition and all suspected cases should be referred to a major centre. In general, most cases will be managed with weekly immunoglobulin infusion from early pregnancy. However, severe cases may require more aggressive therapy, including such modalities as corticosteroids, plasmapheresis or even fetal platelet transfusion prior to birth of a persistently severely thrombocytopenic fetus.

NEONATAL ALLOIMMUNE NEUTROPENIA In this condition, the isoantibody is directed against an antigen on the fetal neutrophil that the mother does not possess. As a result, the fetus and neonate are severely neutropenic. This is generally not a problem in utero but the neonate is at risk of overwhelming bacterial sepsis and requires immunoglobulin infusion and antibiotic prophylaxis. Recovery may take weeks as the antibody affects the bone marrow production of white cells and not just the circulating neutrophils.

Chapter 23  DIABETES MELLITUS Peter Wein

KEY POINTS Diabetes mellitus is relatively common in pregnancy and, if not diagnosed and managed skilfully, has the potential for serious complications to both mother and baby. Pregnancy represents a stress on islet-cell function because of the effect of pregnancy hormones on carbohydrate metabolism. This leads to an increase in insulin requirement in prepregnancy diabetics or may lead to the onset of a diabetic condition in pregnancy (gestational diabetes). Although it usually resolves after delivery, recognition of gestational diabetes is important in alerting the attendant to the possibilities of fetal macrosomia and, for the mother, the risk of subsequent development of permanent diabetes (approximately 30% develop diabetes mellitus over the following 15 years; 95% of these will have type 2 diabetes). There is a twofold increase in the risk of congenital malformations in women with prepregnancy diabetes. This risk can be significantly reduced by periconceptional close control of blood glucose values. The risk of fetal malformation is not increased in gestational diabetes since hyperglycaemia and associated metabolic derangements are not present at the time of organogenesis. Both prepregnancy and gestational diabetes may be complicated by a number of other important clinical sequelae including fetal macrosomia, intrauterine death, placental insufficiency, polyhydramnios and prematurity. In the neonate, hypoglycaemia and respiratory distress syndrome are more common. The latter may even occur in large infants born near full term. Perinatal mortality is increased to about 2% in prepregnancy diabetes. Screening for the development of gestational diabetes in pregnancy is necessary to enable appropriate surveillance and treatment. This is achieved by the performance of a glucose tolerance test in the late second trimester in all women. Recent trends emphasise the need for early diagnosis, preconceptional counselling and stabilisation, team management, close blood sugar monitoring, precise insulin dose regimen, careful fetal monitoring, optimal timing of delivery and good neonatal intensive care facilities. Reduced perinatal mortality related to the above has highlighted the residual problem of severe fetal malformation. Improvement in this area has been achieved with preconceptional counselling and better glycaemic control in the first 6 to 8 weeks of pregnancy. The increased risk of intrauterine death in late pregnancy in prepregnancy diabetes and the mechanical problems caused by macrosomia lead to a recommendation for delivery at 38 to 39 weeks’ gestation, depending on the glucose control and the degree of macrosomia. Close monitoring of fetal wellbeing is mandatory.

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PHYSIOLOGY In early pregnancy, glucose tolerance is largely unchanged or may even improve through consumption of glucose by the developing pregnancy. From the early second trimester, there is a progressive increase in insulin demand. This is largely due to the effect of the placental hormone human placental lactogen (hPL). This hormone structurally resembles growth hormone and shares the common property of promoting insulin resistance. Increased levels of corticosteroids may also contribute to the diabetogenic effect of pregnancy.

CLASSIFICATION OF DIABETES IN PREGNANCY BY AETIOLOGY Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of varying severity with onset or first recognition during pregnancy. The definition applies irrespective of whether or not insulin is used for treatment or if the condition persists after pregnancy. Prepregnancy diabetes may be type 1, type 2 or other. Type 1 diabetes is characterised by insulin dependence, the presence of circulating islet cell antibodies, an onset usually before the age of 35 years and a tendency to ketoacidosis. There is low or absent endogenous insulin production. Type 2 diabetes typically has non-insulin dependence, absence of islet cell antibodies, onset after the age of 35 years and obesity; ketoacidosis is uncommon. There is a tendency to high endogenous insulin production and insulin resistance. Other diabetes may occur as a consequence of pancreatic disease, pancreatectomy, contra-insulin hormonal

disturbances (acromegaly, Cushing syndrome), drugs and some rare genetic syndromes.

INCIDENCE Gestational diabetes occurs in about 10% of pregnancies. Prepregnancy diabetes is present in about 0.5% of the obstetric population but the incidence of type 2 diabetes is increasing due to the obesity epidemic.

DIAGNOSIS PREPREGNANCY DIABETES Where prepregnancy diabetes (of any type) is present, further confirmation during pregnancy is unnecessary. A glucose tolerance test (GTT) is usually necessary for the diagnosis of gestational diabetes, but if the condition is clinically florid (polyuria, polydipsia, weight loss, ketonuria), a single high random plasma glucose (≥ 11 mmol/L) is sufficient for the diagnosis.

SCREENING FOR GDM IN EARLY PREGNANCY The type of screening required for GDM in early pregnancy depends on the presence or absence of the risk factors shown in Table 23.1.

SCREENING FOR GDM AT 26 TO 28 WEEKS’ All women not known to have GDM should have a 75-g glucose tolerance test (GTT) at 26 to 28 weeks’ gestation. Two-step testing with an oral glucose challenge test and

TABLE 23.1  EARLY PREGNANCY SCREENING FOR GDM. Risk level

Risk factors

Screening test

Low

Nil

Random blood glucose in early pregnancy

Moderate

• • • •

High

186

• • • • • • •

Ethnicity: Asian, Aboriginal, Torres Strait Islander, Pacific Islander, Māori, Middle Eastern, non-white African BMI of 25 to 35 kg/m2 Family history of diabetes (first-degree relative with type 2 diabetes) Previous macrosomia (baby with birth weight > 4500 g or > 90th percentile)

Fasting blood glucose in early pregnancy

Abnormal random or fasting blood glucose Multiple ‘moderate’ risk factors Previous GDM Maternal age ≥ 40 years BMI > 35 kg/m2 Polycystic ovarian syndrome Medications: corticosteroids, antipsychotics

GTT in early pregnancy

Chapter 23  Diabetes Mellitus

50

55

proceeding to a POGTT if abnormal is no longer recommended as it misses approximately 30% of GDM and delays diagnosis in many other women.

45

DIAGNOSTIC CRITERIA

Congenital malformations are twice as common in women with prepregnancy diabetes compared with the normal population. The most common malformations are of the central nervous system (particularly neural tube defects) but cardiovascular (transposition of the great vessels, ventricular septal defects, coarctation of the aorta), genitourinary and gastrointestinal malformations may also occur. The caudal regression syndrome (sacral agenesis) is very rare but it is almost pathognomonic of the infant of a diabetic mother. Congenital malformations appear to be related to glycaemic control around the time of organogenesis. They are therefore not increased in women with gestational diabetes. Spontaneous abortion is increased if there is poorly controlled disease. Problems that may occur later in pregnancy include: 1. preeclampsia; 2. polyhydramnios; 3. preterm labour; 4. placental insufficiency; 5. unexplained intrauterine death; 6. infections (e.g. urinary tract, vaginal candidiasis); and 7. macrosomia (large-for-dates fetus) (Figs 23.1 and 23.2). Macrosomia may result in cephalopelvic disproportion, prolonged or obstructed labour, and impacted shoulders during delivery. There is a tendency for the newborn to suffer from hypoglycaemia and respiratory distress in addition to the increased risk of congenital malformations, birth injury (from macrosomia) and prematurity. Perinatal mortality is considerably increased in the presence of poor glycaemic control, complications of longstanding diabetes (nephropathy, hypertension) and specific complications of pregnancy (congenital malformations, preeclampsia, prematurity, polyhydramnios, placental insufficiency, macrosomia). Unexplained intrauterine death is more common with macrosomia and poor glucose control. It is not a

35 30 25 20 15 10 5 cm

THE EFFECT OF DIABETES ON PREGNANCY

40

After a fasting plasma glucose sample has been taken, a glucose load of 75 g is given orally and the plasma glucose repeated at 1 and 2 hours after the glucose load. The woman must be fasted overnight. The definition of gestational diabetes, based on the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study and recommended by the International Association of Diabetes in Pregnancy Study Groups (IADPSG) and endorsed by the World Health Organisation (WHO), the Australasian Diabetes in Pregnancy Society (ADIPS) and RANZCOG, requires either a fasting glucose value of ≥ 5.1 mmol/L or a 1-hour value of ≥ 10 mmol/L or a 2-hour value of ≥ 8.5 mmol/L after a 75-g oral glucose load.

FIGURE 23.1

This fetus from a diabetic mother weighed 6420 g when stillborn at 35 weeks’ gestation.

Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

FIGURE 23.2

The 6700-g infant of a diabetic mother delivered by caesarean section after a failed attempt at forceps delivery. Source: Courtesy of Prof. Norman Beischer.

feature of women with well-controlled gestational diabetes and no macrosomia. Findings at autopsy in these babies are usually indicative of hypoxia, but the precise pathogenesis is uncertain. The effect of diabetes on pregnancy depends largely on its severity. For example, early diabetes is characterised 187

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by effects of the elevated maternal blood sugar resulting in macrosomia, polyhydramnios and preeclampsia. With increasing instability, there is a greater likelihood of congenital malformations and perinatal morbidity/mortality. Finally, at the stage of maternal vascular disease, the predominant effect on the fetus is one of growth restriction and fetal death due to uteroplacental insufficiency.

THE EFFECT OF PREGNANCY ON DIABETES In the first trimester of pregnancy, there is an improvement in glucose tolerance partly as a result of fetal demands and partly because of diminished appetite. Insulin requirements may therefore slightly decrease during early pregnancy. Hyperemesis gravidarum may affect carbohydrate intake and require careful insulin adjustment to avoid hypoglycaemia. In the second half of pregnancy, the above tendency is counteracted by the anti-insulin effect of placental hormones (particularly hPL) and to a lesser extent an increase in glucocorticoids, resulting in higher insulin requirements. After delivery, the situation is reversed and the insulin requirement is rapidly reduced, usually to that existing before the pregnancy began. If glycaemic control is poor, there may be more rapid progression of microangiopathy (retinopathy and nephropathy). With changing insulin requirements and often superimposed illness, hypoglycaemic attacks and ketoacidosis are more common than in the non-pregnant diabetic woman.

MANAGEMENT PREPREGNANCY Preconceptional advice is important in women with known diabetes. One of the most useful measures is the minimisation of spontaneous miscarriage and birth defects by ensuring optimum control during the period of fetal organogenesis. As with any prepregnancy counselling visit, a general assessment should be made with a complete history, physical examination, rubella and varicella status and cervical cytology. As there is some crossover with other autoimmune diseases, these women should be screened for hypothyroidism and coeliac disease. Preconceptual folic acid is recommended at a dose of 5 mg daily. The diabetes needs to be fully assessed with respect to glucose control (home blood glucose monitoring, Hb A1c), renal function and retinopathy. Appropriate treatment should be instituted, aiming for tight control of the blood sugar using dietary manipulation and insulin. Advice should be given regarding anticipated problems in pregnancy, particularly if there is evidence of micro­ angiopathy or a history of previous perinatal death. The danger of smoking should be emphasised, since there is a compounding ill-effect on blood flow in smaller blood vessels. 188

FIRST ANTENATAL VISIT As with any high-risk pregnancy, accurate assessment of gestational age is important. An early ultrasound is recommended. A full screening assessment for coincident problems should not be overlooked. The usual first visit management for all women must not be forgotten, and screening for hypothyroidism and coeliac disease should be performed if not already done.

DIABETIC MANAGEMENT Surveillance Assessment of diabetes should be instituted with home blood glucose monitoring. This is a vital part of glucose control throughout the pregnancy. Blood glucose measurements should be performed fasting and 2 hours after every meal. The aim should be to maintain fasting blood glucose levels in the range 4.5 to 5.5 mmol/L, with 2-hour postprandial levels 6.0 to 7.0 mmol/L. More information about very short-term and overnight fluctuations in glucose levels can be obtained using continuous monitoring of interstitial fluid glucose levels (CBGM). A sudden drop in insulin requirements should raise the suspicion of fetal compromise and should be reported promptly. A general idea of blood sugar control over the preceding weeks is obtained by measurement of glycosylated haemoglobin (Hb A1c). A satisfactory value is < 8%, optimally near 6%. Renal function and eye disease should be reassessed.

Treatment Diet and exercise are important components of diabetes management, whether insulin is being taken or not. The keynotes are regular and more frequent meals, 130 kJ/kg/ day for non-obese women, with an extra 120 kJ/kg/day for each kilogram of weight gain in pregnancy with 50% of this as carbohydrate (mostly complex). In type 1 diabetes, the woman is often not overweight and quality rather than quantity of food is important. In type 2 diabetes, an attempt should be made to achieve ideal weight for height (by calorie reduction); with the decrease in obesity, insulin sensitivity usually improves. In both conditions, the aim is to maintain blood glucose levels in the normal range, prevent ketonuria and allow for a normal weight gain through the pregnancy. Obese women need only 105 kJ/kg/day. The following are suggested daily intakes at the beginning of pregnancy for the ‘standard’ 58-kg woman: protein 70 g, carbohydrate 270 g and fat 50 g; this should make up 7500 kJ per day. Complex carbohydrates or starches (low glycaemic index [GI]) are much preferred to concentrated sucrose-type sweets (high GI). Brown and/or basmati rice is preferred to white jasmine rice, and wholemeal bread should be recommended rather than white bread. Insulin regimens differ from centre to centre. There is increasing evidence from diabetes outside pregnancy that tight glycaemic control has benefits in terms of

Chapter 23  Diabetes Mellitus

reduction in the long-term complications of diabetes (nephropathy, retinopathy, vascular disease). Many women will therefore enter pregnancy using the ‘basalbolus’ insulin regimen, and many centres are advising all pregnant women with insulin-dependent diabetes to use this regimen. It involves using a small dose of medium- or long-acting (isophane, detemir or glargine) insulin in the evening to provide constant basal insulin levels, and bolus doses of short-acting insulin analogue (lispro, aspart or glulisine) before each meal in an attempt to mimic physiological patterns of insulin secretion.

Planning care for the pregnancy The pregnant woman with diabetes should be managed jointly by a team with a special interest in this problem: obstetrician and internist/endocrinologist, consulting with diabetic educator, dietician and, later, a neonatal paediatrician.

SUBSEQUENT ANTENATAL CARE Diabetic management Home blood sugar monitoring, repeat Hb A1c (e.g. 4-weekly), diet, exercise and insulin form the fundamentals of care. Regular ophthalmological examination should be carried out to assess retinal vascular changes. An important distinction should be made between starvation ketosis (normoglycaemia) and diabetic ketosis (hyperglycaemia); the former requires glucose, the latter insulin. Women with gestational diabetes should perform home blood glucose monitoring four times per day as for women with prepregnancy diabetes. The targets are fasting glucose < 5.1 mmol/L and 2-hour postprandial glucose levels < 6.7 mmol/L. If these targets are persistently exceeded despite dietary modification and exercise, insulin should be used. Control can sometimes be achieved with once- or twice-daily injection of isophane insulin, but some women require basal-bolus insulin. About 50% of women with gestational diabetes will need insulin. Recent studies have shown that metformin can achieve glycaemic control in about 50% of women who would otherwise need insulin.

Early diagnosis of complications More frequent antenatal visits are necessary. Congenital abnormalities should be sought on an 18-week ultrasound. Fetal surveillance in the third trimester is necessary in order to detect placental insufficiency. The frequency of testing (e.g. cardiotocography, ultrasound) depends on the period of gestation, severity of the disease and the presence of other factors likely to influence fetal wellbeing (e.g. hypertension, renal insufficiency). Ultrasonography should generally be carried out at 28 and 34 weeks’ in prepregnancy diabetes to assess fetal growth (macrosomia or placental insufficiency). In gestational diabetes, fetal surveillance may be clinical only if sugar control is very good and clinical parameters

satisfactory. The clinician should have a low threshold for ultrasound assessment for either placental insufficiency or macrosomia.

MANAGEMENT OF BIRTH Timing of birth Complications such as fetal compromise or preeclampsia may necessitate preterm delivery. Otherwise delivery should take place at 38 to 39 weeks’ gestation in women with prepregnancy diabetes. In women with gestational diabetes and no evidence of fetal macrosomia, delivery at 40 weeks’ is reasonable, but allowing the pregnancy to proceed significantly beyond the due date would mostly not be recommended on the basis of increasing risks of stillbirth and macrosomia. This data is observational as there has not been a sufficiently powered randomised controlled trial to assess the outcomes in gestational diabetes at postdates gestations.

Mode of birth Elective caesarean section will usually be preferred to induction of labour where there is malpresentation or a previous caesarean section. The incidence of caesarean section is about 50% in large reported series for prepregnancy diabetes and about 25% for women with gestational diabetes. As diabetes in pregnancy is an independent risk factor for shoulder dystocia, elective caesarean section is also recommended for severe fetal macrosomia (e.g. estimated fetal weight > 4250 g). If an elective caesarean section is planned, it should be performed as the first case of the morning. On the day of operation, the morning dose of insulin is withheld, and insulin and dextrose infusions are administered. These will need to be continued postoperatively until bowel function returns and the woman is able to tolerate oral nutrition.

Intrapartum care Where insulin has been used antenatally, a plan should be made antenatally regarding management of the woman’s insulin requirements in labour. In labour, the woman should be able to maintain sufficient energy intake orally. All urine should be tested for the presence of ketones. If ketonuria is present, the energy intake should be increased, if necessary by intravenous dextrose infusion. Blood glucose levels during labour are most readily controlled by a sliding scale of subcutaneous insulin. Routine intravenous dextrose infusion is not necessary for most women. Vigilant assessment of the progress of labour is indicated in anticipation of dystocia. Continuous electronic fetal monitoring is indicated. Epidural analgesia may be recommended in anticipation of a long labour. In addition, an epidural may also aid in blood glucose control, by reducing the level of circulating catecholamines. The delivery should be performed in the lithotomy position by an experienced accoucheur in anticipation of 189

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possible shoulder dystocia. Pushing in the second stage is contraindicated in the presence of diabetic proliferative retinopathy. The umbilical cord should be clamped early to decrease the risk of neonatal polycythaemia.

MANAGEMENT IN THE PUERPERIUM Diabetes management Immediately after vaginal delivery, the insulin infusion should be ceased. In a woman with prepregnancy diabetes, it is simplest to revert to her prepregnancy dose of insulin the following day and await the establishment of lactation to fine tune glycaemic control. Lactation necessitates an additional 50 g of carbohydrate per day. Women with gestational diabetes requiring insulin therapy can cease insulin after delivery. They should then be monitored with blood glucose levels for 48 hours. Levels > 10 mmol/L will require further treatment, and should be reported to the endocrinologist.

Neonatal management The baby of a diabetic mother is often macrosomic (excess fat and fluid), flabby, sleepy and difficult to feed. Because of immature behaviour, the baby is usually treated in a similar manner to the premature baby. In addition, a close watch is kept on blood glucose levels (tendency to hypoglycaemia) and respiratory function (atelectasis, respiratory distress syndrome). A careful check for congenital malformations should be made as well as for birth trauma. With more advanced disease, the baby often shows the features of intrauterine growth retardation, with attendant complications of wasting, asphyxia and meconium aspiration. Breastfeeding is not contraindicated, although this may be more difficult initially. The parents should be counselled regarding the inheritance risks of type 1 diabetes, which is 2% if the mother has diabetes but 6% if the father has diabetes, and 30% if both have type 1 diabetes mellitus.

FOLLOW-UP OF GESTATIONAL DIABETES All women with GDM should have a GTT at approximately 6 weeks postpartum to ensure resolution of the

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diabetes. Long-term follow-up of gestational diabetics has shown incidences of diabetes requiring specific therapy at approximately 25% by 15 years. Predictive factors in development of overt diabetes are: 1. persistence of abnormal glucose tolerance in the puerperium; 2. recurrence of gestational diabetes in a subsequent pregnancy; and 3. persistent obesity. From the mother’s viewpoint, the major advantage of the diagnosis of gestational diabetes is that follow-up offers the possibility of early diagnosis and prevention of the vascular complications of overt diabetes. All women with former gestational diabetes should be encouraged to continue the diet and exercise regimen adopted during pregnancy. Ongoing surveillance for the development of diabetes can most conveniently performed by annual measurement of Hb A1c. Levels > 6.5% are diagnostic of diabetes mellitus. FURTHER READINGS Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. New Eng J Med 2005;352:2477–86. HAPO Collaborative Research Group. Hyperglycemia and adverse pregnancy outcomes. New Eng J Med 2008;358:1991–2002. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International Association of Diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82. Landon M, Spong C, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. New Eng J Med 2009;361:1339–48. Lee AJ, Hiscock RJ, Wein P, et al. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care 2007;30(4):878–83. Moses RG, SanGil F, Morris G, et al. Impact of the potential new diagnostic criteria on the prevalence of gestational diabetes mellitus in Australia. Med J Aust 2011;194:338–40.

Chapter 24  NEUROLOGICAL DISEASE Susan Walker

KEY POINTS There are a wide range of neurological conditions predating pregnancy that require obstetric management in partnership with the woman’s neurologist. Prepregnancy counselling is invaluable in optimising the maternal outcome in conditions such as epilepsy, multiple sclerosis and spinal cord injury, Care of women with epilepsy includes provision of reliable contraception, optimisation of antiepileptic drug regime, prepregnancy folate, surveillance for congenital abnormalities in pregnancy and attention to times of increased seizure risk, particularly intrapartum and postpartum. Conditions such as myasthenia gravis and myotonic dystrophy may have important fetal implications which need to be considered prior to, and during, pregnancy. Migraines tend to improve during pregnancy. Ergotamine is contraindicated in pregnancy, and triptans are not recommended. Pregnancy is a risk factor for both ischaemic and haemorrhagic stroke. Peripheral neuropathies such as carpal tunnel syndrome and Bell’s palsy are more common in pregnancy but are mostly self-limiting.

MULTIPLE SCLEROSIS Multiple sclerosis (MS) is a chronic degenerative condition caused by autoimmune-mediated demyelination of the brain and spinal cord. MS is more common in women than men, and the diagnosis is most commonly made between 15 and 50 years of age. Accordingly, a typical patient will be a woman of childbearing age.

PREPREGNANCY PLANNING The major issue facing women with MS planning a pregnancy is making a decision regarding disease-modifying drugs (DMDs). Beta interferon is the most commonly used agent and this is not recommended periconceptually, or during pregnancy and lactation. Nevertheless, for women who have conceived unknowingly on interferon,

the available data is reassuring, and would not generally be considered grounds for recommending abortion. The best prognosis is for women with well-controlled disease, as pregnancy and postpartum relapses are more common among women who have had a relapse in the 12 months prior to pregnancy. Reliable contraception is recommended to optimise pregnancy timing, with regard to both disease stability and to ensure women and their families are able to plan adequate support for the pregnancy, depending on both the physical and psychological needs of the woman during pregnancy and postnatally with her new baby.

MULTIPLE SCLEROSIS IN PREGNANCY In common with other autoimmune conditions, MS disease activity decreases during pregnancy. This may be

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due to the relative immune-tolerant state of pregnancy. This decrease is offset by an increased rate of relapse in the first 12 weeks postpartum, with up to 30% of women with relapsing MS having a postpartum relapse, presumably due to the return of immunocompetence. When the protective effects of pregnancy and the increased postpartum risks are combined, the overall effect of pregnancy is for no increase in the risk of MS exacerbations. Women who experience a relapse in pregnancy should be managed as usual, with the mainstay of therapy pulsed corticosteroid therapy. MS has little or no effect on important pregnancy outcomes such as preterm birth or fetal growth restriction.

LABOUR AND DELIVERY Most women with MS can expect to have a normal vaginal delivery. Spinal or epidural anaesthesia is not contraindicated, although a predelivery anaesthetic consult is recommended to discuss pain relief in labour and document any preexisting neurological deficit.

Postpartum Breastfeeding is not contraindicated in women with MS, and more stable disease has been reported in association with lactation, presumably due to the stable hormonal state induced by lactational amenorrhoea. The benefits of breastfeeding need to be weighed against the need to remain off DMDs during lactation. The importance of good psychosocial support in the postpartum period cannot be overemphasised.

EPILEPSY PREPREGNANCY PLANNING Women of reproductive age with epilepsy should avoid unplanned pregnancy with reliable contraception. The efficacy of hormonal contraception may be reduced by enzyme inducing antiepileptic drugs (AEDs), such as phenobarbitone, primidone, phenytoin, carbamazepine, oxcarbazepine and topiramate. When pregnancy is planned, AED medication should be optimised and adequate folic acid supplementation instituted.

PREGNANCY CARE First seizure In women who present during pregnancy with their first seizure, consideration should also be given to alternative diagnoses, such as eclampsia, a primary neurological event, metabolic disturbance or drug toxicity or a seizure complicating a vaso-vagal faint.

Seizure frequency Most studies suggest that pregnancy has little or no impact on seizure frequency. If seizure control deteriorates in pregnancy, potential contributors that should be 192

considered include: decreased medication compliance because of concern about teratogenesis; decreased drug absorption because of nausea and vomiting; impaired sleep; and decreased drug levels because of the increased volume of distribution in pregnancy.

The impact of seizures on pregnancy outcomes While the fetus is relatively resistant to short hypoxic episodes, prolonged convulsive seizures may result in sustained fetal hypoxia. While there are legitimate concerns about teratogenicity of AEDs, the potential benefit of ceasing or changing medication must be weighed against a risk of increased seizure frequency, with the attendant risk to the patient, her fetus and possibly other children.

Congenital malformations The risk of congenital malformation is higher among women with epilepsy (WWE), higher among treated compared to untreated women and highest among those using polytherapy rather than monotherapy. The risk of major congenital malformation associated with individual AEDs as monotherapy are estimated at approximately 3% for lamotrigine, 5% for carbamazepine and phenobarbitone, 7% for phenytoin and more than 10% for valproate. There is limited data on newer anticonvulsants such as levetiracetam, topiramate and gabapentin. As a single agent, valproate (particularly in doses > 1100 mg/ day) appears to be associated with the highest risk and this is further amplified when combined with other AEDs.

Surveillance for birth defects In WWE, especially those taking AEDs, an ultrasound examination should be offered at 11 to 13 weeks’. Acrania (the precursor of anencephaly) should be recognised at this gestation, and an increased nuchal translucency is also a useful screening test for cardiac and other structural defects. At second trimester, an expert morphological assessment should be performed.

LABOUR AND DELIVERY Labour and delivery is a relatively high-risk time for seizure recurrence. The reasons for this are multifactorial including poor bioavailability and compliance with AEDs, sleep deprivation, anxiety and hyperventilation in labour. Key management issues for managing women with epilepsy in labour are summarised in Box 24.1.

POSTPARTUM CARE Most AEDs are compatible with breastfeeding. WWE and all their maternity care providers should be aware of the risk of postpartum seizures, particularly in the setting of sleep deprivation. Upon discharge, WWE will be anxious about the prospect of having a seizure while caring for a

Chapter 24  Neurological Disease

BOX 24.1  Intrapartum care of women with epilepsy. Intravenous access should be secured in labour in anticipation of a seizure. Women should continue to take their usual AEDs in labour. Hyperventilation and maternal exhaustion should be avoided. Labouring in water is not recommended for women with epilepsy. Generalised tonic–clonic seizures are associated with hypoxia, and continuous CTG tracing is recommended in the event of a seizure. An intravenous benzodiazepine (e.g. diazepam and midazolam) is recommended to terminate the seizure. In the event of benzodiazepine (e.g. diazepam and midazolam) being used to terminate the seizure, loss of baseline variability of the fetal heart rate tracing can be expected to follow for approximately 1 hour. Women should deliver in a centre with adequate facilities for neonatal resuscitation.

triggers are the mainstay of treatment in pregnancy. The triptans are also not recommended for use in pregnancy although registry data for sumatriptan is largely reassuring following exposure in pregnancy.

SECONDARY HEADACHES Secondary headaches are those due to an underlying cause such as space-occupying lesions, vascular disorders, infections or other systemic illness. ‘Red flag’ symptoms such as postural headache, headache provoked by Valsalva or exertion, ‘thunderclap’ headache or headache accompanied with neurological signs warrant further investigation.

CEREBROVASCULAR DISEASE IN PREGNANCY Stroke in pregnancy may be haemorrhagic or nonhaemorrhagic. Pregnancy and the postpartum period are recognised risk factors for both haemorrhagic and ischaemic stroke, due to the increase in cardiac output, and changes in vessel tone, coagulation factors and endothelial function. Preeclampsia/eclampsia is an important independent risk factor for both haemorrhagic and ischaemic stroke. Haemorrhagic causes of stroke include subarachnoid haemorrhage or intracerebral haemorrhage. Con­ tributors to intracerebral haemorrhage include preeclampsia/eclampsia, arteriovenous malformations and aneurysmal rupture. Non-haemorrhagic stroke includes arterial ischaemic stroke and cerebral vein thrombosis.

• baby at home alone. To minimise the risk of harm if a seizure occurs, changing or feeding the baby on the floor is recommended, the use of baby slings should be avoided, stair climbing should be minimised where possible and bathing the baby should be avoided when alone. The importance of adequate postnatal social supports cannot be overemphasised.

HEADACHE IN PREGNANCY TENSION HEADACHES Tension headaches are the most common form of headache and there does not appear to be any change in headache frequency or character during pregnancy. Tension headaches may be difficult to differentiate from pregnancy-specific disorders, such as preeclampsia. As a general rule, any patient over 20 weeks’ with a headache not resolved with simple analgesics should be evaluated for preeclampsia.

MIGRAINES Migraines may be triggered by hormonal fluctuations associated with menstruation, puberty and menopause. The stable hormonal environment in pregnancy may be the reason that many migraine sufferers experience an improvement in symptoms during pregnancy. Simple analgesics and avoiding known dietary and lifestyle

•

INTRACRANIAL HAEMORRHAGE Subarachnoid haemorrhage and intracerebral haemorrhage have clinical features similar to those seen in nonpregnant populations. The causative aneurysm or vascular malformation can be managed by surgical clipping or embolisation. Women with a known vascular malformation should undergo treatment prior to attempting pregnancy; these women can undergo normal labour and delivery. If women with untreated vascular malformations are considering vaginal delivery, regional anaesthetic and instrumental delivery to minimise pushing in the second stage is recommended.

CEREBRAL VENOUS THROMBOSIS Cerebral venous thrombosis (CVT) is most common in the postpartum period. Risk factors include dehydration, infection and hypercoagulable states. CVT usually presents with a diffuse severe headache, followed by vomiting, seizures, confusion, focal neurological deficits and impaired conscious state. Management involves anticoagulation, initially with intravenous heparin or 193

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subcutaneous low molecular weight heparin, followed by warfarin for at least 6 months.

supports during pregnancy and following delivery of the baby.

NEUROIMAGING IN PREGNANCY

MYOTONIC DYSTROPHY

Neuroimaging may involve CT scan or MRI. CT scanning is useful for diagnosing intracranial bleeding, trauma and cerebral oedema, while MRI may provide further information on vascular malformations, tumours, small infarcts, cerebral vein thrombosis and inflammatory processes. MRI has the advantage of not using ionising radiation. The MRI contrast agent gadolinium crosses the placenta and is generally withheld during pregnancy.

SPINAL CORD INJURY Fertility is usually preserved in women with spinal cord injury. Important considerations in pregnancy include managing anaemia and avoiding upper tract urinary sepsis. The need for thromboprophylaxis should be individualised, weighing the increased in venous thromboembolism risk in pregnancy against the increased risk of preterm—and possibly silent—labour. Women with lesions between T5 and T10 may have painless labours and delivery. Serial cervical examinations or fetal fibronectin testing may be used to assist with detecting silent uterine activity, and hospitalisation may be necessary close to term. A serious complication among women with lesions above T6 is autonomic dysreflexia (ADR). ADR is caused by sympathetic hyperactivity below the level of the spinal lesion in response to stimuli such as distended bowel or bladder, urinary infection or labour. Uncontrolled sympathetic discharge results in severe hypertension, headache and cardiac arrhythmia. ADR may be complicated by intracranial haemorrhage or myocardial infarction in the mother, and uteroplacental vasoconstriction can result in acute fetal compromise. Management involves removing the noxious stimulus, sitting the patient upright to lower blood pressure and aggressive antihypertensive treatment.

Myotonic dystrophy (MD) does not generally worsen in pregnancy and is not associated an increased rate of pregnancy complications. Its importance lies in that the inheritance is autosomal dominant. The phenotype of MD can be extremely variable, and congenital myotonic dystrophy, associated with polyhydramnios, neonatal hypotonia, feeding and breathing difficulties, can occur in infants of mothers with relatively mild symptoms. Prenatal diagnosis is possible, although predicting prognosis may be difficult. Genetic counselling is recommended for families where either parent is known to have myotonic dystrophy.

MYASTHENIA GRAVIS Myasthenia gravis is an immune-mediated disorder with antibodies directed against the acetylcholine receptor on the neuromuscular endplate of skeletal muscle. Maternal myasthenia may run a variable course in pregnancy. It is important that women with myasthenia gravis receive specialised care, since transplacental passage of the ACh receptor antibodies may cause congenital myasthenia, a potentially life-threatening condition in the newborn.

PERIPHERAL NEUROPATHIES CARPAL TUNNEL SYNDROME Carpal tunnel syndrome is characterised by numbness and tingling in the distribution of the median nerve as a result of median nerve compression as it travels in the carpal tunnel, exacerbated by the weight gain and fluid retention of pregnancy. Wrist splints may provide symptomatic relief. Steroid injections or surgical release is not usually necessary as most resolve spontaneously over the weeks to months following delivery.

CEREBRAL PALSY

BELL’S PALSY

Cerebral palsy (CP) describes a group of non-progressive motor disorders characteristically appearing in infancy or early childhood. The degree of postural and motor dysfunction will vary according to the CP subtype, but intelligence is often normal. Along with motor disability, common comorbidities with CP include epilepsy, hypertension and bladder dysfunction. Management of women with CP in pregnancy will need to address potential problems with: 1. increased seizures and muscle spasticity, particularly bladder dysfunction; 2. attention to skin care; 3. surveillance for urinary sepsis; 4. managing the relevant comorbidities of hypertension and epilepsy; and 5. addressing any additional mobility aids and social

Bell’s palsy is also more common in pregnancy. Corticosteroids, as prescribed in non-pregnant patients, can be given in pregnancy.

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FURTHER READING Algra AM, Klijn CJ, Helmerhorst FM, et al. Female risk factors for subarachnoid hemorrhage: a systematic review. Neurology 2012;79(12):1230–6. Coyle PK. Pregnancy and multiple sclerosis. Neurol Clin 2012;30(3):877–88. Lu E, Wang BW, Guimond C, et al. Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review. Neurology 2012;79(11):1130–5.

Chapter 24  Neurological Disease

MacGregor EA. Headache in pregnancy. Neurol Clin 2012;30(3):835–66. Pearce CF, Hansen WF. Headache and neurological disease in pregnancy. Clin Obstet Gynecol 2012;55(3):810–28. Scott CA, Bewley S, Rudd A, et al. Incidence, risk factors, management, and outcomes of stroke in pregnancy. Obstet Gynecol 2012;120(2 Pt 1): 318–24.

Semere LG, McElrath TF, Klein AM. Neuroimaging in pregnancy: A review of clinical indications and obstetric outcomes. J Matern Fetal Neonatal Med 2013;26(14):1371–9. Walker S, Permezel M, Berkovic S. The management of epilepsy in pregnancy. BJOG 2009;116:758–67. Wlodarczyk BJ, Palacios AM, George TM, et al. Antiepileptic drugs and pregnancy outcomes. Am J Med Genet 2012;Part A 158A:2071–90.

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Chapter 25  MENTAL HEALTH DISORDERS DURING THE PERINATAL PERIOD Megan Galbally and Martien Snellen

KEY POINTS Identifying and treating mental illness is an integral component of quality maternal care and essential for the delivery of best outcomes for mother and baby. Assessment of mental illness in pregnancy is important to ensure better outcomes for mothers and babies. However, the form that psychosocial assessment ideally takes is open to debate. Use of psychopharmacological treatments for mental illness in pregnancy and lactation must weigh the risks and benefits for both mother and child. Postpartum blues affect at least 50% of women, most commonly approximately 3 to 5 days postpartum. Postnatal depression affects approximately 10% of women and requires consideration of pharmacological therapy if of moderate severity. Puerperal psychosis is a rare condition (0.1% of pregnancies) but a psychiatric emergency.

INTRODUCTION Mental illness has been one of the leading indirect causes of maternal mortality in Australia1 and, in particular, postnatal depression is one of the most common complications of childbirth, with prevalence rates of between 10 to 20%.2,3 Yet a study of obstetric-gynaecology outpatients in the United States found that while 20% met the criteria for mental illness, only 23% of these women had been recognised within the service,4 and a more recent study in Australia of midwives, GPs and maternal and child health nurses (MCHNs) found all practitioners were more likely to identify depression during the postpartum rather than in pregnancy.5 It is now accepted that identifying and treating women with mental illness is an integral component of quality maternity care, whether this is best through universal or targeted screening or through other forms of psychosocial assessment is still unclear. This arises out of the recognition that untreated mental illness during pregnancy impacts not just women but also their developing babies. Mental illness has been associated with an

increased risk of pregnancy complications such as prematurity, low birth weight and preeclampsia.6,7 Untreated mental illness in pregnancy and the postpartum has also been associated with poorer long-term developmental outcomes for children.8 Therefore, early detection and effective management are crucial to ensuring best outcomes for mothers and their children.

EMOTIONAL WELLBEING IN PREGNANCY The birth of a child represents a major life event that demands psychological, emotional, practical and relational adjustment. Early work in the area suggested that this transition should be considered to be a crisis moment for the family unit due to the dramatic need for change and reorganisation. However, more recent conceptualisations of the entry into parenthood offer the view that this transition is associated with the experience of stress as well as the satisfactions and rewards of parenting. Frequently, there are discrepancies between women’s and

Chapter 25  Mental Health Disorders during the Perinatal Period

men’s expectations about how parenting would affect their lives and how they would fare in their parenting role, and their actual experiences. Adjustment has been found to be more difficult when parenting expectations exceeded experiences in the following domains: relationship with spouse, physical wellbeing, maternal competence and maternal satisfaction. The recent focus has been on how the transition into parenthood affects the marital relationship and it has revealed a tendency towards a decline in marital satisfaction. Common areas of dispute and dissatisfaction relate to differing expectations regarding household duties, childcare, finances and sex. An Australian study of first-time fathers found that pregnancy was a time of greater emotional stress for men than the postnatal period and this was associated with changes in the marital relationship.9 Most studies find that sexual interest and frequency of sexual activity remain below prepregnancy levels for up to a year after delivery.10 The majority of couples have resumed sexual intercourse by the time their baby is 3 months old, and it isn’t uncommon for a couple to delay resumption until the 6-week check-up where reassurances are required and permission sought. While most couples successfully negotiate the transition into parenthood, many continue to struggle. During the postnatal period, simple questions that enquire into a woman’s experience of her transition into parenthood can easily identify those who are struggling and allow the activation of pathways to appropriate care.

IDENTIFICATION AND ASSESSMENT OF MENTAL ILLNESS IN PREGNANCY Whether or not to screen for antenatal and postnatal depression has been the subject of an international debate.11,12 The apprehensions regarding screening have focused on the choice of measures, with concerns that the most commonly used tool, the Edinburgh Postnatal Depression Scale (EPDS) (Box 25.1), has been reported to display a wide-ranging sensitivity and specificity.12 There has also been concerns about whether this results in a reduction in morbidity, the cost-effectiveness, whether women will take up treatment following screening and whether as a result of the high falsepositive rate we potentially risk overpathologising women.13 While many maternity services and maternal child health centres in Australia have taken up routine antenatal and postnatal screening with the EPDS, other services internationally have not, with the 2014 NICE guidelines in the United Kingdom recommending the EPDS be considered only for targeted use, not universal use, and as part of a full assessment.14 In addition, a recent Cochrane review that focused on the role of antenatal psychosocial screening found that screening did not lead to a reduction of maternal morbidity and better outcomes.15

BOX 25.1  The ten questions of the Edinburgh Postnatal Depression Scale. 1. I have been able to laugh and see the funny side of things. 2. I have looked forward with enjoyment to things. 3. I have blamed myself unnecessarily when things went wrong. 4. I have been anxious or worried for no good reason. 5. I have felt scared or panicky for no very good reason. 6. Things have been getting on top of me. 7. I have been so unhappy that I have had difficulty sleeping. 8. I have felt sad or miserable. 9. I have been so unhappy that I have been crying. 10. The thought of harming myself has occurred to me. Source: Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 1987;150:782–6. Wisner KL, Parry BL, Piontek CM. Postpartum Depression. N Engl J Med 2002 July 18;347(3):194–9.

Regardless of depression screening, it is important for maternity services to recognise that this is not the only mental illness that needs to be considered as part of good obstetric care. Schizophrenia and bipolar disorder, for instance, also carry risks in pregnancy from the illnesses themselves, as well as the medications used to treat them.16 Therefore, clinical assessment of past and present symptoms of mental illness, as an addition to screening measures in antenatal care, is critical for the identification of women who may be at risk of perinatal mental illness. While the focus of the debate around screening and psychosocial assessment in pregnancy and the postpartum revolves around maternal mental health, an ideal assessment should be broader and contain three key elements: 1. a focus on a woman’s emotional wellbeing; 2. her relationship and bonding with her fetus/baby; and 3. a wider focus on her relationship with her partner or key supports. This can be done simply through enquiry at relevant points during pregnancy and potentially integrated within routine antenatal care appointments.

SPECIFIC DISORDERS OF THE PERINATAL PERIOD MATERNITY BLUES The maternity blues are thought to occur in at least 50% of women. The disorder generally coincides with days 3 197

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to 5, which is often the time of onset of lactation, and is regarded as a self-limiting condition which remits within days with reassurance alone. It is characterised by lowered mood, anxiety, tearfulness, indecisiveness and insomnia. However, it is important that clinicians distinguish this from emerging depression or anxiety disorders.

showed a reduction in relapse in women with a past history of puerperal psychosis by commencing lithium at delivery.21

ANTENATAL AND   POSTNATAL DEPRESSION

Despite schizophrenia and bipolar disorder being lowprevalence mental illnesses (1% and 2.5% respectively), they have the potential to be high-impact disorders within the perinatal setting. Both the illnesses themselves and their pharmacological treatment significantly elevate the risk of poor outcomes for both mother and child. Unplanned and unwanted pregnancies are common and relapse rates of both disorders are significantly elevated when pharmacological treatment is suspended (i.e. 37% for patients with bipolar disorder who continue mood stabiliser medication versus 85% for those who cease treatment).22 Poor nutrition, lack of social supports, decreased attendance for antenatal obstetric review, substance abuse and single motherhood frequently complicate the scenario further. It is becoming increasingly clear that these disorders elevate obstetric and neonatal risks with significantly higher rates of low birth weight, intrauterine growth retardation, preterm delivery, gestational diabetes, preeclampsia, instrumental delivery, lower Apgar scores, stillbirth, infant malformation, need for neonatal resuscitation, admission to the neonatal intensive care unit and infant death. Active psychotic symptoms, in particular, have been found to increase these risks. In addition, the medications used to treat these illnesses (anti­ psychotics and mood stabilisers) may be associated with complications such as teratogenicity, pregnancy complications, neonatal complications and concerns about effects on longer-term adverse neurodevelopmental. Pregnancy-related changes in pharmacokinetics may also decrease medication serum levels to the point of being subtherapeutic. A range of other mental illnesses such as borderline personality disorder, eating disorders and anxiety disorders have also been associated with particular risks across pregnancy and the early postpartum.

Depression across the perinatal period affects approximately 10% of women.2,3 The risk factors that have been identified include depression/anxiety during pregnancy, stressful life events during pregnancy, low level of social support and past history of depression. Depressive illness can be difficult to distinguish from a normal increase in emotional lability often associated with pregnancy and the postpartum. Key distinguishing symptoms include: anhedonia (loss of enjoyment and pleasure); depressive cognitions that involve a sense of worthlessness, inadequacy and hopelessness; and suicidal ideation. Common symptoms of depression such as insomnia, lethargy and appetite disturbance are less pathognomonic of depression in pregnancy, as pregnancy itself can also affect these functions. Untreated maternal depression has been associated with a range of pregnancy complications and poorer child developmental outcomes. These include gestational hypertension, preeclampsia, prematurity, low fetal growth and poorer child development.7,8 There is some evidence that ceasing antidepressant treatment during pregnancy in women who are stable increases their risk of relapse,17 although this remains controversial.18 While specific studies of efficacy for depression treatments in pregnancy are limited, the general research findings recommend that for mild depression, psychological and pharmacological treatment are equally efficacious. However, moderate to severe depression often requires consideration of pharmacotherapy. The difference in pregnancy is that careful consideration needs to be given to the risks and benefits for both mother and child should she be either treated or untreated.

PUERPERAL PSYCHOSIS Puerperal psychosis occurs in approximately 0.1% of women, and most who develop this condition do so within the first 4 weeks following delivery.19 The condition is regarded as a psychiatric emergency as it usually develops rapidly with psychotic symptoms, disorganised behaviour and cognitive impairment, and is associated with infanticide and suicide.20 Both lithium carbonate and electroconvulsive therapy (ECT) have been demonstrated to be effective treatments.20 Women with a history of puerperal psychosis have a high risk of relapse after subsequent deliveries.20 However, Bergink et al. 198

SCHIZOPHRENIA AND   BIPOLAR DISORDER

MANAGEMENT OF MENTAL ILLNESS IN PREGNANCY Management of mental illness, regardless of diagnosis, is typically conceptualised as having a biopsychosocial approach. In pregnancy and the postpartum, it is also important to consider the fetus/infant and the wider family unit as an essential part of effectively managing mental illness across this period. Comorbidities such as smoking, alcohol and substance abuse, and commonly occurring risk factors such as inadequate nutrition and obesity, should always be addressed and systems established that encourage attendance at antenatal

Chapter 25  Mental Health Disorders during the Perinatal Period

appointments. Co-existing domestic violence can be present and must be addressed. Perinatal mental healthcare plans developed in pregnancy for management across delivery and the early postpartum are effective tools for multidisciplinary communication. The important components are contained in Box 25.2.

PHARMACOLOGY Pharmacological treatments of mental illness include antidepressants, antipsychotics (typical and atypical), mood stabilisers (anticonvulsants and lithium carbonate), anxiolytics and hypnotics. Although coverage of the pharmacological treatment of mental illness and the evidence of risks in pregnancy is beyond the scope of this chapter, it is important for all clinicians to understand the principles of weighing benefits and risks in pregnancy and to ensure that where medication is prescribed, there is adequate monitoring and care and that informed consent is sought.23 The aim should always be to seek the minimal effective dose; however, the emphasis should be on effective rather than minimal, and polypharmacy avoided wherever possible. Pharmacological treatment in pregnancy involves balancing both the risks associated with untreated mental illness for both mother and unborn child against the relatively unknown effects that pharmacological treatment of mental illness may pose for the child. In particular, there is a paucity of long-term developmental studies that examine for effects beyond pregnancy from exposure to psychopharmacological treatments. For many medications, any comfort we may have prescribing them in pregnancy and breastfeeding comes from the relative

BOX 25.2  Perinatal mental health plan. Patient name, expected date of delivery, treatment team, consideration of setting of delivery depending on risks Pharmacological and other treatments; monitoring and dosage requirements/changes Recommendations for lactation (related to risks with any pharmacological treatments and/or extra supports if appropriate), supports and rest in the early postpartum Length of stay; will be determined by clinical need, in particular related to observation and risks for the neonate and ensuring adequate support and monitoring of mental state for the mother Discharge planning that includes partner and family or other key supports in postpartum care; consideration of supports for early parenting skills and identification of pathways to care should relapse occur

absence of negative data rather than the presence of positive data. However, for many women pharmacological treatment is essential for them to maintain mental health. For depression, this was recognised with joint guidelines for the treatment of depression in pregnancy developed and published by the American College of Obstetricians and Gynaecologists in collaboration with the American Psychiatric Association. Likewise, women with schizophrenia and bipolar disorder often cannot cease or alter their treatments as the risks of relapse are high with serious health implications. The medications used to treat these conditions (antipsychotics and mood stabilisers) do have implications for antenatal monitoring and care.16 A summary is contained in Table 25.1. Again, it needs to be remembered that pregnancyrelated physiological and pharmacokinetic changes frequently decrease the effectiveness of medications, particularly in the third trimester, and dose adjustments may need to be made.

PSYCHOLOGICAL THERAPIES Psychological therapies have been found to be equally as effective as medications for mild depression and for anxiety disorders. Both the United Kingdom’s NICE guidelines and the Australian beyondblue/NHMRC guidelines support a range of psychological treatments for depression and anxiety. A recent Cochrane review also found preliminary evidence to support specific psychological interventions for the prevention of postnatal depression. A cautionary note is their role in prevention of the deleterious effects of maternal depression on child development with a Cochrane review failing to find any beneficial effect for child outcomes.24 There are a wide range of psychological models for addressing the parent–infant relationship25 and new research into better understanding the underlying mechanisms.26 Interestingly, a review of psychological interventions for women with schizophrenia that focused on the mother– infant relationship identified that no specific models of care have been published. Regardless of this, pharmacological treatment of mental illness should always be accompanied by psychotherapy, whether it is supportive, psycho-educational, focused on cognitive behaviour or psychodynamic, in order to both maintain mental health and negotiate the patient’s transition into motherhood.

ELECTROCONVULSIVE THERAPY Where women present with severe or life-threatening depressive illness, where other treatments have failed and where the mother may pose a risk to herself and her unborn infant, consideration may be given to treatment with electroconvulsive therapy (ECT) during pregnancy. The risks that have been associated with such treatment in pregnancy include fetal bradycardia, fetal distress, placental abruption, onset of premature labour, maternal 199

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TABLE 25.1  PREGNANCY MONITORING FOR ANTIPSYCHOTICS AND MOOD STABILISERS (AEDS AND LITHIUM CARBONATE). Stage

Antipsychotic

Lithium carbonate

AEDs

First trimester

FBE; U&E; TFT; LFT; B12/ folate; vitamin D; iron studies; Ca; fasting glucose and lipids; BMI; BP; ECG high-resolution ultrasound; early GTT

FBE; U&E; TFT; LFT; B12/folate; vitamin D; iron studies; lithium levels every 4 weeks; highresolution ultrasound and Doppler flow studies

FBE; U&E; TFT; LFT; B12/folate; vitamin D; iron studies; drug level; high-resolution ultrasound for NT assessment (if inadequate maternal/ amniotic fluid); alpha-fetoprotein

Second trimester

Weight; BP; high-resolution ultrasound

Lithium level every 4 weeks; U&E; TFT; growth monitoring; morphological scan and fetal echo

Drug level; FBE; LFT; highresolution ultrasound; growth monitoring

Third trimester

Weight; BP; high-resolution ultrasound

Lithium level weekly; U&E; TFT

Drug level; FBE; LFT

After delivery

Observe baby for withdrawal, toxicity, sedation; postpartum GTT if indicated

Maternal lithium level; U&E; TFT; cord blood: lithium; TFT; U&E

Drug level; observe baby for adverse effects and careful morphological examination

Abbreviations: AEDs = antiepileptics; BP = blood pressure; Ca = calcium; ECG = electrocardiography; FBE = full blood examination; GTT = glucose tolerance test; LFT = liver function test; NT = nuchal translucency; TFT = thyroid function tests; U&E = urea and electrolytes. Source: Adapted from Galbally M, Snellen M, Walker S, Permezel M. Management of antipsychotic and mood stabilizer medication in pregnancy: recommendations for antenatal care. Aust N Z J Psychiatry 2010 Feb;44(2):99–108.

status epilepticus and maternal aspiration if she is not intubated. To ensure safety, consultation with experts in anaesthesia of pregnancy, perinatal psychiatrists and recommendations and monitoring by obstetrics is recommended before proceeding. REFERENCES 1) Austin MP, Kildea S, Sullivan E. Maternal mortality and psychiatric morbidity in the perinatal period: challenges and opportunities for prevention in the Australian setting. Med J Aust 2007;186(7):364–7. 2) Buist AE, Austin MP, Hayes BA, et al. Postnatal mental health of women giving birth in Australia 2002–2004: findings from the beyondblue National Postnatal Depression Program. Aust N Z J Psychiatry 2008;42(1):66–73. 3) Bennett HA, Einarson A, Taddio A, et al. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol 2004;103(4):698–709. 4) Spitzer RL, Williams JBW, Kroenke K, et al. Validity and utility of the PRIME-MD patient health questionnaire in assessment of 3000 obstetric-gynecologic patients: the PRIME-MD Patient Health Questionnaire ObstetricsGynecology Study. Am J Obstet Gynecol 2000;183(3):759–69. 5) Buist A, Bilszta J, Milgrom J, et al. Health professional’s knowledge and awareness of 200

6)

7)

8) 9)

10) 11)

12)

perinatal depression: results of a national survey. Women Birth 2006;19(1):11–16. Jablensky AV, Morgan V, Zubrick SR, et al. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am J Psychiatry 2005;162(1):79–91. Kurki T, Hiilesmaa V, Raitasalo R, et al. Depression and anxiety in early pregnancy and risk of pre-eclampsia. Obstet Gynecol 2000; 95:487–90. Deave T, Heron J, Evans J, et al. The impact of maternal depression in pregnancy on early child development. BJOG 2008;115:1043–51. Condon JT, Boyce P, Corkindale CJ. The First Time Fathers Study: a prospective study of the mental health and wellbeing of men during the transition to parenthood. Aust N Z J Psychiatry 2004;38(1):56–64. Snellen M. Rekindling: your relationship after childbirth. Melbourne: Text Publishing; 2010. Buist AE, Barnett BE, Milgrom J, et al. To screen or not to screen—that is the question in perinatal depression. Med J Aust 2002;177(Suppl.): S101–5. Gibson J, McKenzie-McHarg K, et al. A systematic review of studies validating the Edinburgh Postnatal Depression Scale in antepartum and postpartum women. Acta Psychiatr Scand 2009;119(5):350–64.

Chapter 25  Mental Health Disorders during the Perinatal Period

13) Matthey S. Are we overpathologising motherhood? J Affect Disord 2010;120(1–3):263–6. 14) NICE. Identifying and assessing mental health problems in pregnancy and the postnatal period. Manchester, UK: National Institute for health and Care Excellence; 2014. 15) Austin MP, Priest SR, Sullivan EA. Antenatal psychosocial assessment for reducing perinatal mental health morbidity. Cochrane Database Syst Rev 2008;(4):CD005124. 16) Galbally M, Snellen M, Walker S, et al. Management of antipsychotic and mood stabilizer medication in pregnancy: recommendations for antenatal care. Aust N Z J Psychiatry 2010;44(2):99–108. 17) Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006;295(5):499–507. 18) Yonkers KA, Gotman N, Smith MV, et al. Does antidepressant use attenuate the risk of a major depressive episode in pregnancy? Epidemiology 2011;22(6):848–54. 19) Kendell R, Chalmers J, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry 1987;150(5):662–73. 20) Sit D, Rothschild AJ, Wisner KL. A review of postpartum psychosis. J Womens Health 2006;15(4):352–68.

21) Bergink V, Bouvy PF, Vervoort JS, et al. Prevention of postpartum psychosis and mania in women at high risk. Am J Psychiatry 2012;169(6):609–15. 22) Viguera AC, Whitfield T, Baldessarini RJ, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry 2007;164(12):1817–24, quiz 923. 23) Galbally M, Snellen M, Lewis AJ. A review of the use of psychotropic medication in pregnancy. Curr Opin Obstet Gynecol 2011;23(6):408–14. 24) Dennis CL, Dowswell T. Psychosocial and psychological interventions for preventing postpartum depression. Cochrane Database Syst Rev 2013;2. 25) Galbally M, Lewis AJ, Ijzendoorn M, et al. The role of oxytocin in mother-infant relations: a systematic review of human studies. Harv Rev Psychiatry 2010;19(1):1–14. 26) Anderson EL, Reti IM. ECT in pregnancy: a review of the literature from 1941 to 2007. Psychosom Med 2009;71(2):235–42. FURTHER READING Galbally M, Snellen M, Lewis A. Psychopharmacology and pregnancy: treatment efficacy, risks and guidelines. Heidelberg, Germany: Springer; 2014.

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Section 2.6 COMMON CLINICAL SCENARIOS AND PRESENTING PROBLEMS IN PREGNANCY Chapter 26

Common problems in pregnancy

Chapter 26  COMMON PROBLEMS IN PREGNANCY Michael Permezel and Megan Di Quinzio

KEY POINTS Pregnancy is associated with substantive physiological changes, consequent on the physical presence of the pregnancy itself but also the consequential haemodynamic changes and the large amounts of hormones emanating from the placenta. While all these changes have important roles in facilitating a healthy pregnancy, they can also have undesirable consequences for maternal comfort and sometimes serious sequelae for the mother and/or developing fetus. Whether minor or serious, it is imperative that all care providers are attentive to maternal symptomatology, are able to distinguish the normal from the abnormal, take pains to alleviate symptoms where possible and provide ongoing maternal support where difficulties persist. Oesophageal reflux is particularly common and responds to antacids, H2-antagonists or proton pump inhibitors for the more severe cases. Constipation should be avoided with appropriate dietary advice but mild laxatives can and should be used if needed. Abdominal pains of varying sorts are extremely common in pregnancy but usually ‘fleeting’ if not of clinical consequence. More substantive abdominal pain requires clinical evaluation to exclude potentially serious causes that might impact adversely on pregnancy.

OESOPHAGEAL REFLUX (HEARTBURN) PATHOPHYSIOLOGY This is a very common symptom of pregnancy and arises from relaxation of the gastro-oesophageal sphincter under the influence of progesterone and is further exacerbated in late pregnancy with pressure of the gravid uterus on the stomach. Vomiting in pregnancy will aggravate the condition but is sometimes also a consequence of severe reflux.

MANAGEMENT The following measures can help minimise heartburn. 1. Meals should be light and avoid those foods found to be most likely to provoke heartburn. 2. The bed should be raised at the head some 15 to 20 cm, and an extra pillow used if this is compatible with a good sleep. Even though the reflux may be more symptomatic during the day, less reflux at night may help daytime symptomatology. 3. Drug therapy involves antacid preparations (e.g. aluminium hydroxide/magnesium hydroxide, Mylanta),

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which can be taken liberally according to the manufacturer’s recommendations. The H2-antagonist, ranitidine, can also be used in pregnancy. There is less experience with proton pump inhibitors in early pregnancy but they are commonly prescribed in late pregnancy for refractory cases not responding to other medication.

CONSTIPATION PATHOPHYSIOLOGY Constipation is a common feature of pregnancy and presumably relates to the relaxant effect of progesterone on the gastrointestinal smooth muscle. It may be aggravated by dehydration with excessive vomiting in early pregnancy, iron supplementation and any relative immobility.

CLINICAL CONSEQUENCES Constipation commonly causes general abdominal discomfort and is rarely severe. Excessive straining may aggravate haemorrhoids and is intuitively unwise if there is any reason to suspect cervical insufficiency.

MANAGEMENT Constipation should be alleviated with the following strategies. 1. Increase of dietary fibre (bran, green vegetables, dried fruit) should be the focus of therapy. The woman troubled with constipation should become familiar with the fibre content of specific foods and also what is effective for her. 2. Fluid and exercise may assist. 3. Laxatives are indicated if diet, fluid and exercise are insufficient. Suitable agents would include bulkproducing compounds (Fybogel, Metamucil, Normacol), magnesium hydroxide (milk of magnesia) and lactulose (e.g. Duphalac). Stimulant laxatives such as senna (Senokot) are also safe in pregnancy and may be appropriate.

ABDOMINAL PAIN IN PREGNANCY DIFFERENTIAL DIAGNOSIS There are conditions specific to pregnancy in addition to those that are possible in any woman. It is best to think of the differential diagnosis in terms of the likely organ involved and then secondarily what might cause pain at that location. A framework for this is as follows. Uterine. Round ligament pain, miscarriage or labour, red degeneration of a fibromyoma, placental abruption, chorioamnionitis.

•

204

• • • • • • •

Urinary tract. Urinary tract infection, urinary calculus. Ovary. Complication of an ovarian cyst (THIN-RIM: torsion, haemorrhage, infection, necrosis, rupture, incarceration, malignancy). Tube. Ectopic pregnancy. Hepatobiliary. Preeclampsia, cholecystitis, cholelithiasis. Peritoneum. Endometriosis, haemoperitoneum from any cause (uterine rupture, splenic artery aneurysm rupture, hepatic rupture). Gastrointestinal. Gastroenteritis, appendicitis, Crohn’s disease, bowel obstruction. Pancreatic. Pancreatitis.

ROUND LIGAMENT PAIN Clinical features Pregnant women often report lower abdominal pain and tenderness in the second trimester, at approximately 15 to 20 weeks’ gestation. The pain is usually lateral to the uterus, in the groin and overlying the round ligament, which can be palpated as a tender cord. The pain is usually unilateral and is more often left-sided, perhaps associated with dextrorotation of the uterus bringing the left ligament into apposition with the peritoneum of the left anterior abdominal wall. The pain is often initiated or accentuated by sudden movement (standing up, bending, coughing, sneezing).

Treatment Treatment is to rest in a position of comfort and take analgesia with paracetamol. Occasionally the pain necessitates absence from work. Usually the condition abates completely within 2 to 3 weeks, although hypertrophy and stretching of the ligaments continue.

RED DEGENERATION OF A UTERINE FIBROMYOMA Clinical features This is usually an acute presentation with severe localised abdominal pain that can be readily confused with appendicitis or a placental abruption. Known presence of a fibromyoma is extremely helpful in making the diagnosis, as is point tenderness over an area of the uterus in the context of an obviously healthy fetus.

Treatment After exclusion of more sinister causes, treatment is conservative with simple analgesia. Resolution of pain occurs over a few days.

UTERINE CONTRACTIONS OF LATE PREGNANCY Differential diagnosis Braxton Hicks contractions are contractions in late pregnancy that do not culminate in labour. They are most

Chapter 26  Common Problems in Pregnancy

commonly completely asymptomatic but the woman may recognise a palpable tightness of the uterus that may be associated with mild discomfort. Sometimes Braxton Hicks contractions are more significant and the woman needs to briefly stop what she was doing. When that discomfort is more severe but still does not result in labour, the contractions may be termed threatened preterm labour when before 37 weeks’ and spurious labour when they occur at term.

Management Braxton Hicks contractions require only an explanation and a reminder of the signs of labour. Threatened preterm labour and spurious labour are, by definition, retrospective diagnoses and will not generally be distinguishable from genuine labour until they are observed over time and labour is found not to eventuate. Recurrent spurious labour at term is a risk factor for adverse perinatal outcome and should be managed with increased fetal surveillance and consideration given to induction of labour.

UPPER RESPIRATORY TRACT INFECTION

FIGURE 26.1

Varicose veins of the leg in pregnancy. Source: Courtesy of Prof. Norman Beischer.

This is as common in pregnancy as at other times but may be more severe and of longer duration in view of the general immunosuppression of pregnancy. For example, bronchitis is probably more common, which may have implications for women who suffer from bronchial asthma (see Ch 17).

EPISTAXIS This is often related to oestrogen-induced engorgement of the profuse network of veins lining the nasal passages. Usual measures, such as pressure and ice packs, will be sufficient. Only very rarely is cautery of specific vessels is needed.

VARICOSE VEINS PATHOPHYSIOLOGY The prime cause of varicose veins in pregnancy is probably a relaxant effect of progesterone on vascular smooth muscle, added to by increased pressure within the venous system as a consequence of the arteriovenous shunting effect of the placenta and direct pressure of the uterus on the pelvic veins. Incompetence of the valves in the upper leg occurs, causing further aggravation. Although there is a strong hereditary tendency, each pregnancy makes the condition worse. Some 10 to 20% of women suffer varicose veins of the legs, with higher figures occurring in multiparas and those over 30 years (Fig 26.1). Varicosities of the vulva occur in about 2% of pregnancies and are also more common with increasing parity (Fig 26.2).

FIGURE 26.2

Severe varicose veins of the vulva.

Source: Reproduced with permission from the Royal Women’s Hospital, Parkville Victoria.

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CLINICAL CONSEQUENCES

HAEMORRHOIDS

The main complaint is of aching, tiredness or pain in the legs, night cramps and fullness/oedema. The fullness related to vulval varicosities may create alarm in the patient but a strong postural dependence (only apparent on standing) makes diagnosis relatively easy and the woman can be reassured that complete resolution is extremely likely in the puerperium. Thrombophlebitis (thrombosis) occurs in 5% of women with varicose veins, usually in the puerperium. Haemorrhage will occur if the vein is damaged and bleeding can be profuse but, being of low pressure, is readily controlled by direct pressure. If a varix in the leg is bleeding, the woman must lie down, elevate the leg and have pressure applied to the bleeding site. Significant bleeding may eventuate during delivery if an episiotomy incision or tear involves vulval or vaginal varicose veins.

PATHOPHYSIOLOGY

MANAGEMENT Antenatal

If prolapse has occurred, replacement is carried out with the aid of a rectal lubricant. If prolapse is immediately recurrent, repeated replacement is obviously unhelpful. Bleeding from haemorrhoids is common during pregnancy and the puerperium. It is important that a rectal

Reassurance is the hallmark of management of varicose veins in pregnancy. The veins will improve after pregnancy but this can take several months and not usually right back to the pre-pregnancy state. The following strategies may minimise worsening of lower limb varicose veins in pregnancy. 1. Weight-bearing exercise should be minimised. An understanding of the incompetence of the perforating veins will make it obvious that exercise will aggravate the condition. Similarly, long periods of standing will aggravate the condition. Swimming will not have the same effect as the lower limb venous pressure will be less and therefore becomes the preferred mode of exercise for these women. 2. Support stockings may be helpful but a tight roll occluding veins at the top of the stocking should be avoided. 3. Surgical management is virtually never needed in relation to pregnancy.

This term describes varicose enlargement of the veins of the anal canal (inferior haemorrhoidal plexus). The aetiology and behaviour during pregnancy are the same as described above. The main aggravating factors are constipation (see above) and prolonged pushing down during the second stage of labour.

CLINICAL CONSEQUENCES Bleeding may occur as well as thrombosis. The former is usually associated with the passage of a hard motion, and is rarely severe. Haemorrhoids are often particularly painful in the postnatal period but usually rapidly resolve during the puerperium (Fig 26.3).

MANAGEMENT

Intrapartum Care should be taken at the time of delivery to minimise laceration to varicosities. In extreme cases, a midline episiotomy may be considered, recognising the atten­ dant risk of sphincter damage. Any haemorrhage from damaged vulval varices should be controlled by simple pressure until medical assistance is obtained.

Puerperium Superficial thrombophlebitis is both common and painful. A low-molecular-weight heparin may speed resolution, as may anti-inflammatory drugs. 206

FIGURE 26.3

Haemorrhoids. Oedematous painful haemorrhoids in association with a sutured episiotomy that has probably been sutured too tight, leading to oedema of the suture line. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville Victoria.

Chapter 26  Common Problems in Pregnancy

examination is performed when the woman reports bleeding and if bleeding persists after pregnancy, further investigation with sigmoidoscopy is indicated to exclude other bowel pathology.

BREAST SORENESS

MANAGEMENT Oedema usually subsides after resting at night and is aggravated by prolonged standing. The condition is managed largely by increasing the rest periods, with the legs well elevated; diuretics are contraindicated.

PATHOPHYSIOLOGY

COMPRESSION NEUROPATHIES

As a result of the stimulatory effects of oestrogen and progesterone on the breast parenchyma, as well as a general increase in vascularity, the woman often experiences fullness, discomfort and tenderness in the breasts.

PATHOPHYSIOLOGY

MANAGEMENT The main aspects of management are reassurance regarding the cause of the symptoms and their temporary nature. Symptomatic relief is obtained by adequate breast support and local warmth.

OEDEMA PATHOPHYSIOLOGY This is a very common finding, especially in hot weather. It is due to the increased venous pressure consequent on both the arteriovenous shunt through the placenta and extrinsic compression of the great veins by the uterus. It is more common in preeclampsia but in that condition the oedema is usually generalised, involving fingers and face as well as the lower limbs (Fig 26.4).

The most troublesome of these is the carpal tunnel syndrome, so called because the median nerve (which supplies the ‘thumb half’ of the hand) passes through the bony-aponeurotic tunnel at the wrist and becomes compressed if there is swelling, which often occurs in pregnancy. A similar phenomenon can occur with the lateral cutaneous nerve of the thigh and is known as meralgia paraesthetica.

CLINICAL FEATURES The usual symptoms are numbness, tingling and a burning sensation.

MANAGEMENT With median nerve compression, rest of the wrist during the day will alleviate nocturnal numbness, tingling and pain. Splinting of the wrist is often helpful in ensuring the wrist is rested. Only very rarely is surgery needed during pregnancy to relieve the pressure by incising the fibrous roof of the tunnel.

HEADACHE PATHOPHYSIOLOGY This is a common complaint, and must be attributed to intracranial vascular changes related to oestrogen and progesterone.

CLINICAL FEATURES Headache tends to be most troublesome in the second trimester but in some women persists throughout pregnancy.

MANAGEMENT FIGURE 26.4

Gross pitting oedema in a 34-year-old para 7 at 38 weeks’ gestation. She had iron deficiency anaemia with haemoglobin of 7.8 g/dL.

Analgesics can be used as needed—most commonly paracetamol but with codeine or even morphine if necessary. Metoclopramide 10 mg is useful if there is associated nausea and vomiting. Investigation is required if the attacks are frequent, severe or persistent or are associated with localising neurological symptoms or signs. 207

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FAINTING PATHOPHYSIOLOGY Progesterone-induced vasodilatation of pregnancy, with or without varicose veins, leads to venous pooling in the lower limbs with reduced venous return and consequent risk of a hypotensive syncope. In late pregnancy, syncope can be induced by pressure on the inferior vena cava by the gravid uterus, the supine hypotensive syndrome.

CLINICAL FEATURES The effect is compounded by heat (vasodilatation) and standing (failure of muscles to pump venous blood back to the heart). Although a relationship between fainting and fetal sequelae is not established, anaphylaxis and other examples demonstrate that the fetus is exquisitely sensitive to sustained maternal hypotension.

MANAGEMENT Although syncope is not unusual in pregnancy, strategies are needed to reduce the occurrence and promptly minimise the duration of hypotension should a faint occur. 1. Avoidance of predisposing factors. It is important that the woman recognises potential predisposing factors (e.g. standing in a queue at the checkout in a supermarket) and takes steps to avoid these situations (e.g. dad does the shopping). 2. First aid treatment consists of lying down, preferably with the legs elevated. Such action should be initiated at the first sign of giddiness. 3. Supine hypotension is avoided by advising women and their carers of the inadvisability of lying supine (on the back) for any length of time during the third trimester. Much fuss is made in the common press regarding the ‘dangers’ of sleeping supine in pregnancy. While this could be true, it would appear more likely that sleep apnoea poses the greater risk and the woman that develops supine hypotension during sleep is most likely to experience discomfort and instinctively move to a more suitable position.

FATIGUE PATHOPHYSIOLOGY Fatigue during pregnancy is exceedingly common, particularly in the first and third trimesters, with a window of greater energy between. The mechanism is unclear but there is good evidence that excessive exertion results in lower birth weights and occupational physical labour is associated with a higher incidence of preterm birth.

MANAGEMENT Although the precise evidence is lacking, the overwhelming view is that fatigue is an evolved mechanism to 208

reduce activity in the interests of the pregnancy. Resting would therefore seem to be the appropriate response.

SACROILIAC PAIN PATHOPHYSIOLOGY The hormones of pregnancy soften the three key joints of the pelvis (two sacroiliac and the symphysis pubis) in order to enable some ‘give’ in these joints during parturition. Therefore, it is not surprising that a majority of pregnant women complain of a backache or sense of strain in the lower back, most commonly to one side or the other. During weight-bearing exercise, the entire upper body is supported through this joint that is normally ‘fixed’ but has been ‘loosened’ by the hormones of pregnancy.

CLINICAL FEATURES Sacroiliac joint strain can be confirmed by elicitation of tenderness over the posterior aspect of the joint. Often this is maximal around mid-pregnancy, implying a hormonal basis as much as a mechanical one.

MANAGEMENT Assessment is indicated, as in rare cases the back pain is related to a vertebral apophyseal joint or an intervertebral disc. 1. Rest is the most important form of treatment, particularly avoiding activities that aggravate the condition. Very often the pain is worse at night, following increased activity during the day. Every patient with the condition must be made aware of the mechanism and the obvious imperative of avoiding weightbearing exercise. Swimming is good to enable exercise that does not strain the joint. 2. Analgesia in the form of paracetamol can be used if necessary but as the condition is likely to be long standing during pregnancy, management by avoidance of causative factors is key. 3. Maternity belts or corsets are commonly advocated by physiotherapists and may benefit some women. 4. While massage, manipulation or exercises sometimes provide short-term relief, they are unlikely to be helpful in the longer term.

MUSCLE CRAMPS PATHOPHYSIOLOGY Muscle cramps, particularly in the calf muscles, are very common in pregnancy, affecting approximately 33% of women; they are severe in 5% of women. The exact cause is not known, but must be related either to a temporary shunt of blood away from the muscle (ischaemic cramp) or to a change in the pH or electrolyte milieu (tetanic cramp).

Chapter 26  Common Problems in Pregnancy

CLINICAL FEATURES Cramps usually occur late in pregnancy and are worse at night. The attacks are often precipitated by ‘stretching’ in the early morning.

MANAGEMENT Placing a pillow at the foot of the bed to remind the woman not to ‘stretch’ the legs (i.e. plantar flex the ankle joints). Many find that magnesium or vitamin B complex supplementation is helpful.

SKIN CONDITIONS IN PREGNANCY These may be related to a specific condition, such as drugs, jaundice, malignant disease, infestations or bites. Often, no cause can be found and the condition must be assumed to be related to other metabolic products, skin stretching or altered neurovascular sensitivity. Three conditions specific to pregnancy should be remembered.

ISOLATED ABDOMINAL PRURITUS This is common in the second half of pregnancy and is not associated with a rash. It may or may not be associated with abdominal striae (stretch marks).

3. Delivery is indicated at 37 to 38 weeks’ but earlier if there is deteriorating hepatic function. Delivery is indicated even if biochemistry has normalised on ursodeoxycholic acid.

PRURITIC URTICARIAL PAPULES AND PLAQUES OF PREGNANCY Pathogenesis The pathogenesis of pruritic urticarial papules and plaques of pregnancy (PUPPP) is poorly understood. Preponderance in first pregnancies is suggestive of an immune aetiology.

Clinical features PUPPP is the most common rash in pregnant women. It normally occurs in first pregnancies during the third trimester, with an average onset of 35 weeks’. The rash commonly begins on the abdomen but spreads to breasts, thighs and arms (Fig 26.5). Just as the name suggests, it is very itchy, red and raised and is rarely vesicular. Unlike cholestasis, there is no risk to the mother or baby and the condition resolves in the early puerperium.

Management

This is an effect of the pregnancy steroid hormones on the liver. Raised circulating bile salts cause generalised pruritus.

PUPPP can be extremely itchy and a caring approach is needed, with more frequent antenatal visits to provide general patient support. 1. Symptomatic relief is all that is required for milder cases: lukewarm shower and dab dry, and oral antihistamines. 2. Corticosteroids can also be used: betamethasone cream for moderate severity, oral prednisolone for the more severe cases.

Diagnosis

HERPES GESTATIONIS

The serum levels of the hepatocellular enzymes (e.g. AST, ALT) are commonly elevated along with the bile salts.

This extremely rare but serious condition occurs mainly in the second and third trimesters. Crops of papillae become bullous, initially on the trunk and spreading to the limbs (Fig 26.6). Treatment is by oral steroids.

CHOLESTASIS OF PREGNANCY Pathophysiology

Clinical features The pruritus is generalised but often worst on the palms and soles. Jaundice is rare. Most importantly, there is an increased risk of still birth—the mechanism of which is uncertain but is more likely be through placental insufficiency than a direct effect on the fetal heart.

Management The following need to be considered with cholestasis in pregnancy. 1. Ursodeoxycholic acid alleviates symptoms and restores biochemistry. However, the risk of stillbirth may remain increased. 2. Fetal surveillance should be intensified through increased maternal vigilance with respect to fetal movements, ultrasound and cardiotocography (e.g. weekly).

PRURITUS VULVAE DIFFERENTIAL DIAGNOSIS Pruritus vulvae in pregnancy may be due to: infections, particularly Candida, which are increased in pregnancy chemical irritation (e.g. soaps, detergents) dermatological conditions such as lichen sclerosus, lichen planus.

• • •

MANAGEMENT Assessment through clinical examination is essential as well as the vulval swab for culture if the diagnosis is 209

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A

B

C

D

FIGURE 26.5

Pruritic urticarial papules and plaques of pregnancy (PUPPP). A Typical periumbilical sparing and distribution of the lesions along the abdominal striae. B Early PUPPP shows urticarial lesions in the abdominal striae. C Lesions with microvesiculated appearance on the forearm in PUPPP. D Widespread PUPPP may resemble a toxic erythema.

Source: James D, Steer PJ, Weiner CP, Gonik B. High Risk Pregnancy. 4th ed. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 51.16A–D. Photographs courtesy of Helen Raynham, MD.

uncertain. Treatment will depend on aetiology but all women should be given advice to avoid chemical irritation from soaps, inappropriate creams and, most importantly, perspiration.

VAGINAL DISCHARGE DIFFERENTIAL DIAGNOSIS Increased vaginal discharge is a common condition in pregnancy and the following should be considered in the differential diagnosis. 1. Leucorrhoea is a normal increase in the vaginal discharge as a consequence of the impact of oestrogen on the lower genital tract. It is commonly white 210

(hence the name) and non-offensive. There is no specific treatment other than maternal reassurance. 2. Infections may produce vaginal discharge of which Candida is most likely. 3. Premature rupture of the membranes is an important differential diagnosis. 4. Discharge of the cervical mucus plug or ‘show’ is common in late pregnancy. It may be only mucoid or blood-stained.

ASSESSMENT A careful history and clinical examination (including speculum examination) is essential. Sometimes it will become apparent that it is not a vaginal discharge at all but an

Chapter 26  Common Problems in Pregnancy

of the enlarging uterus. Typically, it is most apparent in early pregnancy when the uterus has a pelvic location, and again in late pregnancy when the head enters the pelvis and presses on the bladder. Nocturia may also be due to nocturnal return of increased tissue fluid (oedema) to the vascular system. This will improve with measures that reduce lower limb oedema in pregnancy, mainly avoiding prolonged standing.

ASSESSMENT All women should have a urine microscopy and culture requested at the first antenatal visit to exclude asymptomatic bacteriuria. If urinary frequency is troublesome, particularly if combined with other features suggestive of infection (e.g. dysuria, scalding, more than a trace of protein on dipstick), the urine culture should be repeated.

INSOMNIA IN PREGNANCY FIGURE 26.6

Herpes gestationis. Rash at 32 weeks’. Commenced on soles of feet at 26 weeks’. Spread generally with vesicles on legs and feet. Responded to oral then topical steroids and delivered at term. Source: Courtesy of Monash Health.

episode of urinary stress incontinence, which is extremely common in late pregnancy. History features that would suggest membrane rupture are discussed elsewhere but include a profuse watery discharge that is ongoing and may be associated with predisposing factors in the pregnancy. Sterile speculum examination reveals a ‘washed-out appearance’. A vaginal swab for microscopy and culture should be taken from all women with a vaginal discharge but if there is doubt about rupture of the membranes, specific biochemical tests can be performed on the discharge, including placental alpha microglobulin-1 (e.g. AmniSure). Tests relying on the higher pH (more alkaline) of amniotic fluid are less reliable as serum extravasate from an extra-amniotic blood clot and semen will also both be alkaline.

URINARY FREQUENCY AND NOCTURIA DIFFERENTIAL DIAGNOSIS Urinary tract infections are more common in pregnancy and it is important to exclude them; however, urinary frequency is a common symptom of pregnancy even in the absence of an infection. It probably is simply a consequence of reduced bladder capacity through pressure

DIFFERENTIAL DIAGNOSIS Pathophysiology Disturbances to the sleep rhythm may be a direct hormonal effect on sleep rhythm. Other contributing factors will be nocturia (see above) and the sheer physical size of the uterus later in pregnancy (Fig 26.7). Sleeping in the afternoon as a consequence of general fatigue may lead to insomnia at night, which in turn creates greater need for the afternoon nap. Backache, nocturia, nocturnal cramps and heartburn are all common and may aggravate the sleep disturbance. Less commonly, insomnia may be a presentation of depression in pregnancy (see Ch 25).

Clinical features Physiological insomnia is particularly apparent in the third trimester and very common.

Management Women are often distressed by insomnia in late pregnancy. It is important that the clinician takes the matter seriously and works with the woman to manage the problem as follows. 1. Reassurance regarding the normality of the condition is often all that is required. 2. Avoidance of the afternoon nap can certainly aid sleeping at night and break a cycle of daytime sleep and nocturnal wakefulness. 3. Symptomatic alleviation of heartburn, nocturnal cramps and so on as discussed elsewhere may also assist. 4. Experiment with dietary changes (e.g. avoiding a late meal) or an exercise regimen (e.g. an evening walk) may assist some women. 5. Sleeping tablets are generally used only as a last resort as other measures are preferred and are mostly 211

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reasonably effective. Doxylamine is safe in pregnancy. Temazepam is sometimes used sparingly in late pregnancy for refractory insomnia not responding to other measures.

FIGURE 26.7

Triplets at 35 weeks’ gestation in a 25-year-old para 2. The midline scar was from a previous ovarian cystectomy. She delivered 4 days later of babies weighing 2601 g, 2195 g and 2140 g. The placenta tissue weighed 1340 g.

212

FURTHER READING Centers for Disease Control and Prevention. Prevention of perinatal Group B streptococcal disease. Revised Guidelines from CDC; 2010. International Association of Diabetes and Pregnancy Study Groups. Recommendations on the diagnosis and classification of hyperglycaemia in pregnancy. Diabetes Care 2010;33(3):676–82. Katzberg HD, Khan AH, So YT. Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2010;74(8):691–6.

Section 2.7 LABOUR AND BIRTH Section 2.7.1 Normal labour and birth Chapter 27

The physiology of parturition

Chapter 28

Management of normal labour

Section 2.7.2 Induction of labour, instrumental delivery and casearean section Chapter 29

Induction of labour, including cervical ripening

Chapter 30

Episiotomy and vaginal outlet tears

Chapter 31

Instrumental delivery

Chapter 32

Caesarean section and trial of labour after caesarean

Section 2.7.3 Intrapartum clinical problems Chapter 33

Intrapartum fetal compromise

Chapter 34

Failure to progress in labour

Chapter 35

Malpresentation and malposition

Chapter 36

Postpartum haemorrhage

Chapter 37

Maternal collapse

Chapter 38

Obstetric analgesia and anaesthesia

Section 2.7.4 The puerperium and lactation Chapter 39

The physiology of the puerperium and lactation

Chapter 40

Normal postpartum care

Chapter 41

Puerperal disorders

Chapter 42

Maternal and perinatal mortality and morbidity and global reproductive health

Chapter 43

Australian Indigenous women’s health in pregnancy

Section 2.7.1 NORMAL LABOUR AND BIRTH

Chapter 27  THE PHYSIOLOGY OF PARTURITION Michael Permezel and Megan Di Quinzio

KEY POINTS Labour (or parturition) is defined as the process in which the fetus, placenta and secundines are expelled from the birth canal after a minimum period of 20 weeks. Before this, the term ‘miscarriage’ or ‘abortion’ is applied. From early in the third trimester, the uterus progressively delineates into a thick upper segment and a thin lower segment. By the time labour commences, there has been a general softening of the connective tissues of the pelvis: joint ligaments, cervix and other pelvic connective tissue. The increase in elasticity facilitates dilatation of the cervix and the passage of the baby through the birth canal. The onset of labour is the consequence of dominance of factors promoting uterine activity over contrasting factors promoting uterine quiescence. Having reached this threshold, a series of positive feedbacks further expand factors promoting activity and suppress those causing quiescence. Labour is described in three stages. The first stage comprises the slower latent phase when the cervix is effacing and beginning to dilate, and the more rapid active phase up until full cervical dilatation. The second stage concludes with birth of the fetus and the third stage with delivery of the placenta and membranes.

ANATOMICAL AND PHYSIOLOGICAL CHANGES IN LATE PREGNANCY STRUCTURAL CHANGES OF THE UTERUS At the end of pregnancy the uterus fills most of the abdominal cavity. Its length has increased from around 7.5 cm to 40 cm and its weight from around 60 g to 900 g. There is usually some rotation of the uterus to the right side, so that at caesarean section the left round liga­ ment is seen more readily than the right. There is general thickening of the ligaments supporting the uterus and the blood vessels are greatly enlarged, especially the veins (Fig 27.1).

The upper and lower uterine segments In early pregnancy, the uterus has two distinct compo­ nents: the uterine body and the cervix. As indicated in Chapter 1, the uterine body is predominantly muscular but the cervix is only 20% muscle and 80% connective tissue. From approximately 26 to 28 weeks’ gestation, there is progressive development of a lower uterine segment (LUS) by stretching of the uterine tissues between the histological and anatomical internal os of the cervix. Like the cervix, the LUS has a fibromuscular composition and is easily recognised as it is covered by loose peritoneum. In contrast, the upper uterine segment (UUS) is thicker, muscular and covered by a serosal layer that is firmly adherent to the underlying muscularis (Fig 27.2). At term, before labour has commenced, the LUS will commonly measure around 6 cm in length. In normal

Chapter 27  The Physiology of Parturition

labour, there is progressive stretching of the LUS making it both broader and thinner. The junction of the LUS and UUS is commonly around the level of the symphysis pubis prior to labour but rises during labour as the LUS is stretched. In obstructed labour, the junction of UUS and LUS may be as high as the umbilicus as the LUS becomes very broad and thin and may even rupture if the obstruction is not alleviated. This is more common in an obstructed multiparous labour than a nulliparous labour. In obstructed labour, the thin LUS may ‘balloon’ outwards, sometimes making the junction of UUS and LUS visible on abdominal examination—a ‘retraction ring’ (see Chapter 34).

The cervix FIGURE 27.1 

Distended ovarian and uterine veins lateral to the left round ligament. This is a common finding at caesarean section. This woman was undergoing repeat elective caesarean section. Source: Courtesy of Prof. Norman Beischer.

The cervix is approximately at the level of the ischial spines and begins to shorten and dilate prior to labour. The cervical canal shortens from above down, until only the external os remains as a thin rim (Fig 27.3). This sequence is classically seen in the nullipara; in the multipara, effacement and dilatation may occur simultaneously.

INITIATION OF LABOUR Factors favouring uterine activity and uterine quiescence Rather than there being a single cause for the onset of labour, labour ensues when the factors favouring uterine activity overcome those factors favouring uterine quiescence. The factors are listed in Table 27.1. Most important would appear to be rises in corticotrophin releasing factor and oestrogen efficacy (through changes in the oestriol:oestradiol ratio) and a reduction in pro­ gesterone efficacy (through changes in the progesterone receptors).

Positive feedback loops

FIGURE 27.2 

The retractor in the midline subumbilical incision exposes the juntion of the upper and lower uterine segments. The loose peritoneum over the lower uterine segments abuts the firmly adherent serosa over the upper segment. Source: Courtesy of Prof. Norman Beischer.

Once the balance favours onset of labour, positive feed­ back loops rapidly amplify the factors promoting labour. Positive feedback is a powerful means to rapidly convert quiescence to labour so that, once it starts, it usually con­ tinues ‘full steam ahead’. Two examples of positive feed­ back at a biochemical level are given in Figures 27.4 and 27.5. At a mechanical level, Ferguson’s reflex is also positive feedback. Distension of the cervix and upper vagina cause increased release of oxytocin, which in turn triggers more contractions and more cervical and vaginal distension.

Biochemical changes in the myometrium, cervix and membranes prior to and in early labour The above mechanisms then act through the key organs responsible for successful parturition: the myometrium, 217

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A

B

C

D

FIGURE 27.3 

Changes in the cervix during the first stage of labour. A Cervix at term—no dilatation or effacement. B Cervical effacement (‘taking up’ to become part of the lower uterine segment) has commenced. C The endocervical canal has disappeared as effacement of the cervix is complete. The external os is 2 to 3 cm dilated. D The cervix is almost fully dilated and the intact bag of forewaters bulges into the vagina.

TABLE 27.1  ONSET OF LABOUR VERSUS UTERINE QUIESCENCE. Factor

Favouring onset of labour

Favouring uterine quiescence

Stress

Biological stress through bacterial colonisation

Antibacterial defences: vaginal pH, cervical mucus

Physical stress through mechanical stretch

Hormones

Oxidative stress

Antioxidants: thioredoxin, superoxide dismutase

Oestrogen

Progesterone

Corticotrophin-releasing factor (CRF) Cytokines

Pro-inflammatory cytokines: IL-1β, IL-6, IL-8, TNFα, MCP-1

Anti-inflammatory cytokines: IL-10

Transcription factors

Pro-inflammatory transcription factors: NFκB, MAPK, FOX-01

Anti-inflammatory transcription factors: SIRTs, PPARs

Prostaglandins

PGE2, PGF2α

PGHs

Proteases

Matrix metalloproteinases (MMPs)

Tissue inhibitors of MMPs (TIMPs)

218

Chapter 27  The Physiology of Parturition

Progesterone Placental CRH Oestrogen

Fetal and maternal pituitary ACTH

Fetal and maternal adrenal cortisol

FIGURE 27.4 

Placental corticotrophin-releasing hormone (CRH), adrenal cortisol and pituitary ACTH: a positive feedback loop.

in late pregnancy and early labour in parallel with the changes in the uterine muscle and the cervix. Through a process of apoptosis (programmed cell death) and release of connective tissue degradation enzymes (matrix metal­ loproteinases [MMPs]), the membranes progressively weaken. Interestingly, the process occurs almost exclu­ sively in the supracervical membranes and hardly at all at the sites distant from the cervix. The membranes may rupture prior to the onset of labour, during the first stage or in the second stage. Where an extreme preterm baby may be born with membranes still intact (‘born in a caul’), this is extremely uncommon at term due to the changes that occur in the supracervical membranes in late preg­ nancy and labour. Occasionally, the outer chorion may rupture before the amnion, creating a significant fluid leak (transudation across the amnion) suggestive of rup­ tured membranes but still clinically with membranes intact, as evidenced by bulging forewaters or a further ‘gush’ when the amnion ruptures.

The vagina, perineum and ligaments

NFKB, MAPK

SIRT

Pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8

FIGURE 27.5 

Pro-inflammatory and anti-inflammatory transcription factors and cytokines interacting, producing positive feedback.

the cervix, the fetal membranes and the connective tissue of the birth canal.

The uterine muscle The uterine muscle exhibits an increase in oxytocin receptors and an increase in gap junctions (with an increase in collectively connexon proteins), which enhance the transmission of the contraction impulse through the myometrium.

The cervix Dissolution of collagen and elastin fibres and an increase in interstitial fluid produces a softening of the cervical substance so that it more readily shortens and dilates, progressively losing its ability to function as a mechanical sphincter retaining the fetus in utero.

The amniotic and chorionic membranes The fused amniotic and chorionic membranes line the cavity of the uterus and are attached to the endometrium except over the cervix. Changes occur in the membranes

The vagina and perineum share with the uterus a general increase in vascularity and markedly increased elasticity to allow passage of the fetus, mostly with only a minor degree of distension injury. The ligaments of the pelvic joints also soften to allow some increase in pelvic capacity.

Labour onset The strength and frequency of contractions are usually greater during the night and the peak incidence of labour onset is soon after midnight; nocturnal labours are usually shorter than day labours. The criteria used for the onset of true labour are: 1. rhythmic, regular contractions that show a progressive increase in amplitude and frequency, and are discomforting to the woman (unlike Braxton Hicks contractions); and 2. a ‘show’ of blood and mucus, which indicates that the cervical canal is opening (Figs 27.6 and 27.7). These features will usually distin­ guish true labour from false (spurious) labour.

Uterine contraction strength, duration and frequency The uterus has a baseline tone of approximately 5 mmHg. During the active phase of labour, uterine contractions will result in an increase in pressure of 25 to 60 mmHg. Contraction frequency in active labour is commonly 3 to 5 in 10 minutes and contraction duration of 40 to 60 seconds. The contractions exhibit ‘fundal dominance’ which causes a peristaltic wave forcing the contents of the uterus downwards. The contractions begin in pacemakers which are situated in the region of one or other uterine horn (near the attachment of the tubes).

The pain of uterine contractions Pain is not usually perceived until the contraction pres­ sure reaches approximately 25 mmHg. While some pain 219

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FIGURE 27.6 

At the onset of labour, dilatation of the cervix begins and the plug of mucus (operculum) which occluded the endocervical canal is shed (Fig 27.7). The show of blood at this time is due to the membranes being stripped off the uterine wall.

FIGURE 27.7 

An unusually long, thick, intact cervical mucus plug passed by a 26-year-old primigravida immediately before the head came on view. It is uncommon for an intact mucus plug to be passed in this way. Source: Courtesy of Prof. Norman Beischer.

undoubtedly arises from the uterine contraction itself, much of the pain of the first stage of labour arises from the forceful dilatation of the cervix. Clinical estimates of the duration of contractions are usually shorter than the real duration, since the beginning and end of the contrac­ tion are below the pain threshold.

How do uterine contractions produce cervical dilatation and presenting part descent? The uterus causes the cervix to dilate basically because the muscle of the UUS pulls the LUS and cervix up over the presenting part, stretching the LUS and cervix and forcing the presenting part downward (Fig 27.8). For this to occur, it is necessary for the uterus to be fixed in 220

A

B

FIGURE 27.8 

Changes in the uterus during the first stage of labour. The arrows mark the site of Bandl’s physiological ring between the upper and lower uterine segments. In obstructed labour, this ring rises and becomes visible as a pathological retraction ring. A At the onset of labour, there is neither taking up nor dilatation of the cervix. B On completion of the first stage, the vagina, cervix and lower uterine segment form a continuous surface; the cervix no longer acts as a ledge preventing descent of the presenting part.

position in relation to the pelvis. If the uterus was floating free within the abdominal cavity, the uterus would rise up as the muscle fibres shorten rather than the presenting part go down. Fixation of the uterus within the abdominal cavity is provided by the supports which are attached in the region of the cervix: the transverse cervical ligaments laterally, the uterosacral ligaments posteriorly and the pubocervi­ cal ligaments anteriorly. It is with these ligaments to pull against that the uterus can push the baby through the soft tissues (pelvic and perineal floors) and hard structures (bony pelvis) that constitute the birth canal. Descent occurs in an oscillatory fashion, as anyone familiar with the terminal phases of labour has observed. With each contraction the baby descends, but because of the resistance of the birth canal structures, it loses some of this ground during the relaxation phase. However, with each contraction some descent is maintained, however small, and this gain is secured by retraction of the uterine muscle. With retraction of the UUS myome­ trium, the muscle does not relax to its original length, but stays at a new shorter length.

THE STAGES OF LABOUR Three stages of labour are traditionally described: first, from the onset of regular contractions to full dilatation of the cervix; second, from full dilatation to delivery of the baby; and third, from birth of the baby until delivery of the placenta.

Chapter 27  The Physiology of Parturition

THE FIRST STAGE OF LABOUR

Duration of the first stage of labour

The latent phase The latent phase is usually defined as being from the onset of labour until both contractions are established and the cervix is 3 cm dilated and effaced. The latent phase varies greatly in duration, more so in the nullipara than a multipara. It may be almost non-existent when contractions quickly establish in the presence of a cervix that has ripened (anterior, soft, dilated and effaced with a low presenting part) in late pregnancy. In contrast, the latent phase may last many hours or days when labour begins with irregular contractions or episodes of spurious labour and an unripe cervix (posterior, firm, long and closed with a high presenting part).

The active phase Once active contractions occur and the cervix is 3 cm dilated and effaced, labour characteristically proceeds quickly until full dilatation (Fig 27.9). The 90th percentile for rate of dilatation is at least 0.9 cm/hr in the nullipa­ rous woman and 1.2 cm/hr in the multipara. This rapid progress can be attributed to some of the positive feed­ back mechanisms referred to earlier where the estab­ lished labour enhances both the release and responsiveness to prostaglandins and oxytocin. Prior to rupture of the membranes, there is a ten­ dency for the force of uterine contractions to be dispersed equally on all points of the uterine cavity. Following rupture of the membranes, the presenting part is directed forcefully against the cervix.

The major problem in determining an average duration of the first stage of labour is defining the point of labour onset in those women in whom the latent phase is very prolonged and merges with the latter stage of pregnancy. A median first stage duration is much easier to deter­ mine. Approximate values are 8 hours in a nullipara and 4 hours in a multipara.

THE SECOND STAGE OF LABOUR The mechanism of a normal birth Figure 27.10 diagrammatically illustrates the progress of the head through the birth canal through successive steps of descent, internal rotation, extension and external rota­ tion (restitution).

Descent Descent of the fetal head into the pelvis has already occurred in most nulliparas in the later weeks of preg­ nancy. In parous women, significant descent usually occurs only after labour commences. Descent occurs because of the contractions of the uterus, which push the fetus down and at the same time stretch and draw up the muscle fibres of the lower uterine segment. Descent is continuous throughout labour unless an insuperable obstruction is present. After the membranes rupture, the uterus acts more directly on the fetus (fetal axis pressure), driving the head down more efficiently through the lower birth canal.

Cervical dilatation (cm)

10

8

Active phase of labour

6

4

2 Latent phase of labour

2

4

6

8 Hours

10

12

14

16

FIGURE 27.9 

The latent phase of labour, where a slow rate of cervical dilatation is followed by an active phase from about 3 cm of cervical dilatation with more rapid cervical dilatation. 221

FIGURE 27.10 

A

A

B

B

C

C

D

D

E

E

F

F

G

G

H

H

The mechanism of delivery from the left occipitolateral position. This is an explanation of the steps or movements the fetus undergoes to negotiate the birth canal. Each step is illustrated by paired diagrams of the pelvis viewed laterally and of the head as palpated from below during vaginal examination. A The head enters the pelvic brim with the posterior parietal bone presenting. Both fontanelles are shown at the same station, as would be the case if flexion was incomplete. B Lateral flexion of the head on the neck enables the head to descend and engagement has occurred. The head is now synclitic. C Further lateral flexion allows descent of the head past the pubic symphysis. Internal (anterior) rotation of the occiput by 90° is required. D The occiput has rotated 45° towards the front. The shoulders have rotated with the head, which is not always the case. The sagittal suture lies in the right oblique diameter of the pelvis. E Internal (anterior) rotation of the occiput is complete. Further descent has occurred with the head now distending the lower vagina and stretching the muscles of the pelvic floor (Fig 27.11). The sagittal suture lies in the anteroposterior diameter of the outlet. The head now begins to extend. F Birth of the head is due to extension, with the pubic symphysis acting as fulcrum. Restitution of 45° will now occur. G Restitution of the head is due to the twist on the neck (due to internal rotation) being undone. Had the shoulders not rotated 45° with the head (see D above) restitution would have been through 90°; 45° external rotation will now occur. H External rotation of the head is due to internal (anterior) rotation of the shoulders. This movement does not occur if the internal rotation of the head is unaccompanied by the movement of the trunk, as the shoulders are already in the anteroposterior diameter of the pelvis. Traction on the head directed posteriorly releases the anterior shoulder from beneath the pubic symphysis. 222

Chapter 27  The Physiology of Parturition

External urinary meatus

Vagina Ischiocavernosus

Levator ani

Bulbocavernosus

Central point of perineum

Superficial transverse perineal muscle Anal sphincter

FIGURE 27.11 

During delivery, the muscles of the pelvic diaphragm are pushed downwards and the aperture between the origins of the levatores ani muscles (from the back of the pubic bones) is greatly increased. The perineum bulges downwards and the tissues between vagina and anus are stretched to approximately double their previous length.

Engagement is defined as the station at which the maximum diameter of the presenting part has passed through the pelvic inlet. Although the maximum diame­ ter of the presenting part has not yet passed through the ischial spines (the narrowest part), engagement is of great importance as it suggests that a vaginal birth is highly likely (although not certain). Flexion of the head will be maintained and even increased during head descent as pressure on the vertex will lead a flexion rotation around the atlanto-occipital joint. With full flexion and a vertex presentation, the most favourable diameter presents (suboccipitobregmatic).

Internal rotation This means rotation of the head inside the pelvis prior to birth, most often to occipitoanterior from a previously occipitotransverse or even occipitoposterior position (Fig 27.12). Internal rotation is probably effected by the angulation of the pelvic floor through the shape of the levator ani muscles. It is also aided by the fact that the more angular shape of the anterior pelvis is a better fit for the angular occiput and the posterior pelvis is more suited to the flatter forehead (sinciput).

Extension The head remains flexed until the leading part reaches the perineum. As the head is crowned it follows the natural forward inclination of the birth canal and extends, the lower border of the symphysis pubis acting as a fulcrum (Fig 27.13). It follows that the occiput will appear initially, and as the process of extension continues, the vertex, forehead and finally the face will appear from beneath the posterior part of the vulval ring.

External rotation (restitution) The phase of external rotation of the head is also called restitution. It is simply the undoing or reversal of the

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FIGURE 27.12 

Restitution and external rotation from the left occipitoanterior position. A The head is born by extension and restitutes 45° to undo the twist on the neck. B The head externally rotates a further 45° in the same direction as restitution, due to internal violation of the shoulders through 45°. External rotation, although named for the head, is due to the shoulders and if prevented by the accoucheur, can result in impacted shoulders. C The face is directed laterally and the shoulders now lie in the anteroposterior diameter of the pelvic outlet.

head twisting which had taken place as described under internal rotation. The head will almost always birth occip­ itoanterior but the shoulders will pass through the pelvis in the anterior-posterior plane. That means, the head, once free on the perineum, will rotate to either left or right occipitotransverse, depending on which side the back is on. Restitution should happen spontaneously and does not need to be effected by the accoucheur.

Trunk delivery Because of the curve of the birth canal, the anterior shoul­ der appears first, and with further downward fetal axis pressure exerted by the uterus, the posterior shoulder follows the forward sweep of the canal and appears at the 223

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120 mmHg with the addition of 60 mmHg from mater­ nal effort.

Fetal compromise in the second stage of labour

FIGURE 27.13 

The position of the fontanelles and sagittal suture before birth of the head by extension of the neck. The posterior fontanelle is readily palpable anteriorly, but because the head is well flexed, the anterior fontanelle is situated out of easy reach in the hollow of the sacrum at a higher station. The bones and ligaments of the pelvic outlet are shown. Source: Courtesy of Prof. Norman Beischer.

fourchette. The remainder of the trunk is born by the process of lateral flexion or sideways bending of the spine. The initial movement, freeing the anterior shoul­ der, is usually assisted by downward and backward pres­ sure on the head by the accoucheur (Fig 27.10H). This means that the full bisacromial diameter (12.5 cm) does not transverse the vulval ring, the shorter acromio­ humeral diameter (10 cm) presenting. This is important in reducing the incidence of posterior vulval tears.

Secondary powers and the bearing-down reflex When the cervix is fully dilated, the second stage of labour is entered. The contractions are usually stronger, but may occur less frequently. With the cervix no longer offering resistance, the head has less resistance and descends more readily than in the first stage. A strong bearing-down reflex coincides when the presenting part is low enough to exert pressure on the rectum. This bearing down sensation can of course sometimes occur prior to full cervical dilatation. If bearing down occurs in this circumstance, it risks a cervical tear and may lengthen the ligaments supporting the cervix as it is pushed infe­ riorly by the added forces of maternal effort. The woman is therefore encouraged not to bear down until the cervix is fully dilated; if in doubt, full dilatation can be verified by vaginal examination. Bearing down uses both the diaphragm and abdomi­ nal wall muscles (‘secondary powers’). Peak intrauterine pressures of 60 mmHg may be further increased to 224

It is not uncommon for fetal compromise to develop in the second stage of labour. A reduction in uteroplacental blood flow with the increased intrauterine pressures may be compounded by compression of the umbilical cord as the presenting part descends through the pelvis. This makes the second stage of labour the most dangerous hour of almost every person’s life. Few will undertake activities during their lifetime associated with greater mortality and long-term consequences. During each uterine contraction, the high intra­ uterine pressures reduce uteroplacental blood flow. With the secondary powers also operative, the higher pressures lead to even greater reductions in uteroplacental blood flow and more fetal compromise than would oth­ erwise occur. The umbilical cord encircles the neck in around 25% of labours. Cord prolapse occurs in about 0.5% and true knots in around 1% of labours. Other cases have the cord trapped between the lower segment and the presenting part. In each case, there will be cord compression with each contraction that may become cord occlusion when the presenting part descends. The second stage is usually short (especially in a multipara) and the fetus is adapted to be able to tolerate short periods of reduced oxygenation. Fortuitously, in those cases where the second stage is not short, rapid instrumental delivery can usually be effected as soon as any fetal compromise is detected.

Duration of the second stage of labour The median duration of the second stage ranges from around 40 minutes in the nullipara to around 20 minutes in the multipara. Factors influencing the duration include the strength and coordination of uterine contractions, the strength of the mother’s secondary powers (ability to push), the resistance of the lower birth canal (high in the nullipara because it has not been distended previously) and the size, presentation and position of the presenting part. Epidural analgesia may prolong the second stage by removing the sensation to bear down.

Damage to the tissues of the pelvic floor During the second stage, the neuromuscular tissues, fascia and ligaments of the pelvic floor will inevitably undergo a combination of traction injury (particularly ligaments and muscles) and compression injury (particu­ larly nerves). Together, these injuries may leave a legacy of prolapse and varying degrees of urinary and faecal incontinence. The likelihood of long-term compression (nerve) injury will increase with the duration of the second stage and sustained compression. In contrast, traction injury will largely be a consequence of a

Chapter 27  The Physiology of Parturition

relatively large fetus and aggravated by a rapid forceful delivery as may occur either spontaneously or with instrumental birth.

THE THIRD STAGE OF LABOUR The third stage of labour is the period from the birth of the baby to the delivery of the placenta and membranes. Separation of the placenta usually occurs quickly after the birth of the baby because the marked reduction in size of the uterus produces a shearing force between the maintained surface area of the placenta and the reduced surface area of the uterine wall to which it is attached. Descent of the placenta then occurs, first into the lower segment and then into the vagina. The maternal circulation provides around 750 mL/ min to the placental bed. Following placental separation, in the absence of any haemostatic mechanism, there is the possibility of haemorrhage at this rate into the uterine cavity. As the maternal blood volume is only around 7 L, the woman would rapidly exsanguinate. It is therefore small wonder that in resource-poor settings maternal mortality approaches 1% of all births, and postpartum haemorrhage is paramount in causing this terrible statistic. Therefore, haemostasis is truly vital and effected in two ways: 1. compression of the uteroplacental blood

vessels by the retracted uterine muscle fibres; and 2. through normal vascular haemostasis through vasospasm, platelet aggregation and clot formation. The latter is enhanced by having specialised vessels that are particu­ larly able to effectively occlude in this manner, and the release of thromboplastins into the intervillous space on fracturing of the anchoring villi during placental separa­ tion. The positive pressure in the intervillous space with the sustained postdelivery uterine contraction will lead to thromboplastins refluxing back into the uteroplacental vessels and effecting haemostasis by interacting with the vascular endothelium.

Uterine atony in the third stage of labour The uterus contracts less well if there has been a pro­ longed labour with decreasing uterine contractions and ‘uterine exhaustion’. Other factors contributing to atony in the third stage of labour include uterine overdisten­ sion (polyhydramnios, multiple pregnancy, macrosomia) and high parity, particularly grand multiparity where the woman has been delivered of five or more children previ­ ously. Unfortunately, failure to provide family planning in resource-poor settings is frequently responsible for high parity and consequential maternal deaths from atonic postpartum haemorrhage in pregnancies that women might not have chosen to have, had family plan­ ning been available.

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Chapter 28  MANAGEMENT OF NORMAL LABOUR Michael Permezel

KEY POINTS The diagnosis of labour is not straightforward, as the spurious labour (that which does not establish) may mimic early labour in every respect. Women are usually able to telephone birth suite staff at the hospital to obtain advice on when they should come to hospital. On admission of a woman who presents in possible or probable labour, a detailed assessment should be made, aided by a copy of the woman’s antenatal obstetric record. Many centres recommend an admission cardiotocograph (CTG), recognising that it is wrong to conclude from the randomised controlled trials that an admission CTG confers no benefit. The place of birth is a personal choice based largely on two things: how risk averse or tolerant a woman is for perinatal risk and the priority a woman places on birth in a home-like setting. The vast majority of women are very risk averse and hospital is most appropriate. For a few less risk-averse women looking for a homelike birth experience, an alternative birth centre is often chosen. Only a very small number of women are so risk tolerant that homebirth is an acceptable option. Management of the first stage of labour should consider psychological support, assessment of the mother, assessment of fetal wellbeing, progress of the labour, fluid and nutrition, position and mobility, analgesia and any extra requirements such as antibiotics for women who are colonised with Group B streptococci (GBS). Where there are no risk factors, fetal surveillance may be by auscultation or continuous cardiotocography according to guidelines. Indications for an obligatory recommendation for continuous cardiotocography are generally agreed. Semirecumbent is the most common position for normal birth in Western hospitals. Assistance in the birth by an accoucheur has the primary objective of reducing perineal trauma. Active third-stage management focuses on the administration of an oxytocic, awaiting placental separation and then assisting delivery of the placenta. A ‘non-actively’ managed third stage has double the rate of postpartum haemorrhage.

Chapter 28  Management of Normal Labour

THE ASSESSMENT OF A WOMAN WHO MAY BE IN LABOUR There are several key issues that must be addressed when a woman presents in labour or possibly in labour. As in all clinical medicine, each question is resolved through history, examination and investigations.

ISSUES TO BE ADDRESSED BY THE ADMISSION ASSESSMENT Is the woman in labour? Labour is defined as progressive painful uterine contractions resulting in the expulsion of the products of conception after 20 weeks’ gestation. As discussed in the previous chapter, the latent phase of labour may blend in with the last days of prelabour such that in some women, there may be no clear point where the antenatal period ended and labour began.

Spurious labour As the definition is dependent on a result, at the time of admission it may be unclear whether the painful contractions are going to progressively increase in strength, duration and frequency (true labour) or subside before the active phase of labour establishes (spurious labour). While some associated features make true labour more likely, in many cases there is no way of being certain whether the current episode of painful contractions is the real thing or not. Happily, in most cases this is not a critical diagnosis and a period of observation will determine whether the labour is ‘establishing’ or not.

What is the gestational age? Determining gestational age is important for a number of reasons, including for deciding whether continuous cardiotocography (CTG) is to be recommended (< 37 weeks’ or ≥ 41 to 42 weeks’ gestation). Prolonged pregnancy is associated with an increase in many complications (see Ch 13). Gestational age will be determined by reference to the expected date of delivery as calculated in early pregnancy based on obstetric ultrasound and/or menstrual dates.

Are there any complications of relevance? These may be from the current pregnancy or from past obstetric, gynaecological, medical or surgical history. Most often the information can be obtained from the medical record or a referral letter if the patient has come from antenatal care elsewhere.

How is fetal wellbeing? This should have been assessed at each antenatal visit but requires further evaluation on admission in labour. The key objective at this point is whether continuous CTG is to be recommended in labour.

THE CLINICAL ASSESSMENT The precise admission procedure differs from hospital to hospital. If the woman is in significant discomfort from strong contractions, the admission procedures should be expedited, and finalised when she has become settled.

History The woman should be asked about all features of the contractions: frequency, duration and intensity. In general, contractions that the woman can still talk through or continue performing a task through are unlikely to be labour pains. The presence of a show or rupture of the membranes increases the likelihood that labour has begun. Fetal movements should be specifically inquired about. Most relevant history of the current pregnancy and past history can be reliably obtained from the antenatal record.

Examination A general examination is carried out, with attention being paid to the abdomen. The blood pressure is recorded, as are the temperature, pulse rate and respiratory rate. The abdomen should be examined systematically, determining the fundal height and the lie, presentation and station of the fetus (Fig 28.1). The station is particularly important as it will act as a baseline for the assessment of progress and a low station assists in the diagnosis of true rather than spurious labour. The strength, duration and frequency of contractions are observed. The perineal pad should be inspected to determine if there is any evidence of amniotic fluid and, if so, whether meconium is present. A vaginal examination should be performed in the absence of any contraindications such as an undiagnosed antepartum haemorrhage (risk of causing haemorrhage from a placenta praevia) or ruptured membranes with a plan to manage conservatively (risk of introducing infection). The introitus is first examined and any abnormalities noted such as vulval varices. The labia are parted and a digital vaginal examination performed. Attention should be paid to the following: excessive discomfort that maybe suggestive of vaginismus any abnormalities such as a vaginal septum, vaginal cyst (e.g. Gartner’s) or cervical anomalies (rarely, cervical cancer may be first diagnosed in labour) the cervical consistency, position, dilatation, effacement and how well it is applied to the presenting part (Fig 28.2) the nature, station and position of the presenting part (Fig 28.3) the degree of caput and moulding; the latter can be scored from 0 (nil) to +++ depending on the degree of apposition/overlap of the fetal skull bones

• • • • •

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A

B

C

D

E FIGURE 28.1

Examination of the abdomen. A The height of the fundus is noted. B The fetal pole occupying the fundus (usually the breech) is palpated. C Lateral palpation (‘umbilical grip’) detects the fetal back on one side and flexed limbs on the other. D The presenting part is identified and its station noted. This fetus is large and there is a retraction ring visible below the umbilicus and above the distended lower uterine segment. E Pelvic palpation is useful in labour to follow descent of the presenting part. Source: Courtesy of Prof. Norman Beischer.

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Chapter 28  Management of Normal Labour

•

the abnormality of the bony pelvis such as undue prominence of the ischial spines, the sacral promontory or an unusually narrow pubic arch (Fig 28.4). After the vaginal examination has concluded, a sterile perineal pad should be applied and the woman allowed to adopt whichever position gives her most comfort: walking, sitting, squatting on all fours, resting in bed and so on.

Investigations In the uncomplicated pregnancy, no specific investigations are indicated other than possibly an admission cardiotocograph.

A

The admission cardiotocograph The question of whether to perform an admission cardiotocograph (CTG) is a fraught with controversy. Only a very small number of women will benefit by virtue of detecting serious fetal compromise not otherwise evident. If performed routinely, it is an inconvenience to a large number of women and inevitably leads to a proportion of women having continuous CTG throughout their labour when they would not otherwise have had it. Opponents of the admission CTG point to these disadvantages and the failure of randomised controlled trials to show benefit. Advocates of the admission CTG point to a small number of unequivocal ‘saves’ detected

B

C

FIGURE 28.2

Assessment of the cervix. A Primigravida prior to labour with an unfavourable cervix; the cervix is long, undilated and not effaced. B Primigravida in early labour. In most primigravidas the cervix is well effaced before cervical dilatation begins. C Multipara in early labour. The cervix typically begins to dilate before it is completely effaced.

Not engaged

Engaged

Narrow pelvic plane

Past narrow pelvic plane

FIGURE 28.3

Station of the head. The fetal scalp is on view when the maximum diameters of the head (biparietal and suboccipitobregmatic) reach the narrow pelvic plane and this is the level of a low-forceps delivery.

FIGURE 28.4

Palpation of the right ischial spine.

Source: Courtesy of Prof. Norman Beischer.

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on admission CTG and the deficiencies of randomised controlled trials in the assessment of clinically important but rare outcomes.

MANAGEMENT OF THE FIRST STAGE OF LABOUR WHERE SHOULD THE WOMAN BE LOCATED? When should the woman come in to hospital in labour? If a hospital birth is planned, the woman in early labour will commonly ring the hospital, relate her particular circumstances and seek advice as to when she should come to hospital. In very early labour and in the absence of risk factors, there is no immediate rush to come to hospital. Issues to be considered in advising when to come in include the: 1. presence of any risk factors; 2. strength, frequency and duration of contractions; 3. ability of the woman to cope and potential need for pain relief; and 4. time from the hospital in the event that labour suddenly accelerates. Although perinatal death in the latent phase of the first stage of labour is very uncommon, there are good reasons why it is more likely than at any time antenatally for the following reasons. First, a placenta that is only just maintaining fetal oxygenation will have a further reduction in uteroplacental blood flow with the onset of contractions. Second, early labour may be associated with significant descent of the presenting part, which in turn may produce serious cord compression in the event that the cord had already been tight around the neck prior to any descent. Third, the precipitating factor for labour initiation is sometimes an event that is associated with fetal compromise such as fetal hypoxia, chorioamnionitis or a placental abruption. For these reasons, and also for reassurance, the very risk-averse woman in early labour merits a timely assessment.

The place of birth Homebirth Homebirth lacks the immediate availability of potentially life-saving therapeutic procedures, should they be needed. Unfortunately, serious obstetric complications such as acute fetal compromise and postpartum haemorrhage may occur both profoundly and without warning. A small increase in maternal and perinatal morbidity and mortality would therefore be expected. As a randomised controlled trial of sufficient size is unachievable, perinatal outcome with homebirth can only be assessed in case-control and population studies. Unfortunately such studies are easily manipulated by each side of the homebirth debate and it is difficult to obtain accurate estimations on how often the place of birth causes mortality or long-term morbidity of either mother or infant. A figure of an additional 1 in 1000 230

for perinatal death would appear likely for homebirth, a risk that would appear to be acceptable for some women in order to have a better birth experience.1,2 If homebirth is undertaken, there should be counselling regarding the attendant risks, strict guidelines should be followed and a clear contingency put in place for rapid transfer to an adequately resourced hospital should complications develop.

Alternative birthing centres Alternative birthing centres (ABCs) offer many women birthing in a home-like environment but with closer proximity to emergency care than would be available to a homebirth. Women are screened for the presence of risk factors and transferred to conventional care according to agreed guidelines in the event that complications occur. Transfer rates vary among centres, but approximately one-third of women booking in an ABC might expect to be transferred antenatally and a further one-third of the remainder transferred in labour. This means that often only a little over half of all women booking in an ABC will actually remain there. Population studies of births in ABCs suggest that perinatal mortality is not significantly higher than the conventional birth centre, but these are not randomised studies and matching for equivalent risk is very difficult (Figures 28.5 and 28.6).

WHO SHOULD CARE FOR THE WOMAN IN LABOUR? Obstetricians and midwives Women are generally cared for by a midwife or obstetric nurse, overseen to varying extents by an obstetrician. In many labours there is no need for the obstetrician to attend at all but in most countries, only an obstetrician will perform caesarean sections or any instrumental delivery other than the most straightforward. If a midwife is caring for a woman in labour, an obstetrician will need to be consulted in the event of complications according to agreed guidelines.

Unregulated birth attendants A number of perinatal deaths under the care of unregulated birth attendants led South Australia to legislate in 2013 that only a medical practitioner or midwife can provide healthcare to a woman in labour in that Australian state. At the time of writing, other states have not yet followed, but somewhat controversial legislation does emphasise the need for knowledge, skills and attitudes in the care of a woman and her fetus in labour.

Partner, family and friends A supportive partner giving psychological support has been shown to reduce the analgesic requirements of women in labour. The partner can help with relaxation, psychoprophylactic techniques and timing of contractions. Extension to a broader circle of family and friends is most often unhelpful. Some women will want a second

Chapter 28  Management of Normal Labour

FIGURE 28.5

Birth centre in a major teaching hospital. Note the absence of the usual hospital equipment. Source: Courtesy of Prof. Norman Beischer.

or third person present but it is uncommon to want more. If children are to be present, this needs to be a considered decision with significant antenatal preparation.

ASPECTS OF CARE IN THE FIRST STAGE OF LABOUR Psychological support Psychological support is very important in labour. The needs of every woman are different and a perceptive carer will be responsive to the woman’s psychological needs. As discussed in the previous section, the partner (and possibly others) will contribute to the psychological support.

Assessment of the mother The following observations are routinely performed (more frequently if abnormal). Temperature is recorded 4-hourly. A rise in temperature is common in a long labour but a significant pyrexia mandates continuous CTG and antibiotic administration. Blood pressure and pulse rate are taken hourly. Respiratory rate is recorded 4-hourly.

• • •

Assessment of the labour Uterine contractions The intensity, duration and frequency of uterine contractions are recorded every 30 minutes in the first stage of labour and every 10 minutes in the second stage. The intensity of contractions can be measured using an intrauterine pressure catheter as a research tool but in practice, the intensity of contractions is assessed subjectively by abdominal palpation of the uterus by the midwife. With weak contractions, the uterus can readily be indented, whereas with strong contractions, the uterus feels rigid. Long duration (e.g. 60 secs) and high frequency (e.g. 4 to 5 in 10 mins) usually (but not always) parallel high intensity.

Abdominal station A formal assessment of the descent of the presenting part by abdominal examination should be made every 1 to 2 hours, according to circumstances.

Vaginal examination Vaginal examination is commonly performed about every 4 hours in the active phase of the first stage of labour. In the latent phase of labour, this may be less often but 231

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FIGURE 28.6

A father holds his newborn daughter whom he has delivered in a birth centre. The mother is witnessing the birth and receiving support and encouragement from friends.

approaching second stage, it is common to re-examine to confirm full dilatation of the cervix, say, 2 hours after a cervical dilatation of 8 or 9 cm has been diagnosed. The rate of cervical dilatation is the benchmark of adequate progress in labour. Other important features include the station of the presenting part, rotation of the presenting part (if not occipitoanterior) and any signs of obstructed labour including caput, moulding and cervical oedema.

Fetal membranes The state of membranes and nature of the liquor should be recorded along with the time of membrane rupture. The presence of meconium in the liquor should be reported immediately.

Assessment of fetal wellbeing Clinical assessment of fetal condition in labour is performed by observation of the amniotic fluid (oligohydramnios, meconium staining), as already mentioned, 232

and auscultation of the fetal heart rate. Some practitioners favour amniotomy in labour when cervical dilatation has reached 4 to 6 cm or more, to exclude the passage of meconium and also because the process of labour may thus be accelerated and its duration lessened.

Auscultation of the fetal heart Auscultation of the fetal heart rate should be performed every 15 to 30 minutes in the first stage of labour and after every contraction in the second stage of labour. Auscultation optimally occurs with a hand-held Doppler device, begins before the end of the contraction and continues for at least 60 seconds. The landmark randomised controlled trial upon which a policy of allowing auscultation as an alternative to continuous CTG is based used 15-minutely auscultation in the first stage, and this is preferred in some jurisdictions. When there is slowing of the heart rate during a contraction or delay in return to the normal rate (120 to

Chapter 28  Management of Normal Labour

160 bpm) after it has ceased, then CTG is indicated (Figs 28.7, 28.8 and 28.9) unless delivery is imminent.

Continuous cardiotocography Continuous electronic fetal heart rate monitoring (CTG) is indicated where there are risk factors for fetal compromise—either apparent antenatally or having occurred in labour. The indications for continuous CTG are listed in Box 28.1. Particularly risk-averse women without any complications may still choose continuous CTG to monitor their fetus in labour. They should be

informed that this may increase the likelihood of instrumental birth, particularly in units where fetal blood sampling is not available or not commonly used in labour.

Ambulation and position There is some evidence that ambulation in early labour will shorten the duration of labour. When mothers are given free choice, they will usually sit up or ambulate until the cervix is 5 to 6 cm dilated, and thereafter will often recline on their side in bed. Squatting positions,

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FIGURE 28.7

A Normal baseline and variability. In this case, the absence of accelerations could be due to early fetal hypoxia or fetal sleep, or it may be due to the use of morphine, pethidine or other pain relief in labour. B Absent variability of the fetal heart rate in labour. This is almost always due to near-terminal fetal hypoxia but may also be seen with fetal tachyarrhythmias or fetal brain death. 200

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FIGURE 28.8

A Baseline tachycardia with accelerations and normal variability. The tachycardia could be due to maternal fever, which in turn may be a consequence of either infection or obstructing labour. B Baseline bradycardia with normal variability. This is not uncommon with prolonged gestations (e.g. 41+ weeks’) and is likely to be a normal variation if there are no other features suggesting fetal hypoxia. 233

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FIGURE 28.9

A Variable decelerations. These are due to cord compression in labour. The abrupt onset and rapid recovery distinguish variable decelerations from early decelerations. B Late decelerations with tachycardia and reduced variability. This unequivocally suggests fetal hypoxia. The sharp spikes may be fetal ectopic beats.

BOX 28.1  Indications for continuous CTG in labour. Antenatal risk factors ✚ Abnormal antenatal CTG ✚ Abnormal Doppler umbilical artery velocimetry ✚ Suspected or confirmed intrauterine growth restriction ✚ Oligohydramnios or polyhydramnios ✚ Prolonged pregnancy ≥ 42 weeks’ ✚ Multiple pregnancy ✚ Breech presentation ✚ Antepartum haemorrhage ✚ Prolonged rupture of membranes (≥ 24 hours) ✚ Known fetal abnormality which requires monitoring ✚ Uterine scar (e.g. previous caesarean section) ✚ Essential hypertension or preeclampsia ✚ Diabetes where medication is indicated or poorly controlled, or with fetal macrosomia ✚ Other current or previous obstetric or medical conditions which constitute a significant risk of fetal compromise (e.g. cholestasis, isoimmunisation, substance abuse) ✚ Decreased fetal movements ✚ Morbid obesity (BMI ≥ 40) ✚ Maternal age ≥ 42 ✚ Abnormalities of maternal serum screening associated with an increased risk of poor perinatal outcomes (e.g. low PAPP-A < 0.4MoM) Intrapartum risk factors ✚ Induction of labour with prostaglandin/oxytocin ✚ Abnormal auscultation or CTG ✚ Oxytocin augmentation 234



Regional anaesthesia (e.g. epidural or spinal) and paracervical block ✚ Abnormal vaginal bleeding in labour ✚ Maternal pyrexia: recommend ≥ 38°C ✚ Meconium or blood-stained liquor ✚ Absent liquor following amniotomy ✚ Prolonged first stage of labour ✚ Prolonged second stage as defined by referral guidelines ✚ Preterm labour < 37 completed weeks’ ✚ Tachysystole (more than five active labour contractions in 10 minutes without fetal heart rate abnormalities), ✚ Uterine hypertonus (contractions lasting more than 2 minutes in duration or contractions occurring within 60 seconds of each other, without fetal heart rate abnormalities) ✚ Uterine hyperstimulation (either tachysystole or uterine hypertonus with fetal heart rate abnormalities) Other conditions where a recommendation for continuous cardiotography should be considered, particularly if multiple conditions are present ✚ Pregnancy gestation 41.0 to 41.6 weeks’ gestation ✚ Gestational hypertension ✚ Gestational diabetes mellitus without complicating factors ✚ Obesity (BMI 30–40) ✚ Maternal age ≥ 40 and < 42 ✚ Maternal pyrexia ≥ 37.8°C and < 38°C ✚

Chapter 28  Management of Normal Labour

unless practised, are usually too tiring to maintain for any length of time. Many women like to have a shower during labour but water immersion is controversial for two reasons. First, there are increased difficulties delivering care during the first stage (see below). Second, rapid birth may ensue, resulting in a location where there will be considerable difficulty in the management of complications such as unexpected shoulder dystocia, maternal collapse or haemorrhage.

Nutrition and fluid intake An intravenous infusion should be considered in any long labour (e.g. more than 12 hours). The woman may eat in early labour but this is usually not encouraged in established labour due to gastric slowing, a tendency to experience nausea and vomiting late in labour, and the risk of inhalation of stomach contents in the unlikely event that the woman suffers a grand mal convulsion or requires general anaesthesia.

Analgesia The subject of pain relief is addressed in Chapter 38.

Antibiotics These maybe indicated prophylactically for any of the following indications: Group B streptococcal colonisation on vaginal/ perianal swab in late pregnancy prolonged rupture of the membranes (≥ 18 hours) suspected chorioamnionitis (temperature ≥ 37.8°C in labour) perceived risk of infective endocarditis (e.g. cardiac valve disease).

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Bladder and bowels Although the days of the routine enema on admission are thankfully long gone, attention to urinary tract and bowel activity remains a necessary component of intrapartum care. 1. Bladder. The bladder should be emptied every 2 hours. Each specimen of urine should be assessed for volume, glucose, ketones and protein. If urine retention develops, a urinary catheter should be passed. This is almost inevitable with epidural analgesia and many units will have a policy of routine urinary cauterisation whenever epidural analgesia is used. 2. Bowels. All bowel actions are recorded. If the rectum is obviously loaded on admission, a low volume enema or glycerine suppositories are recommended.

MANAGEMENT OF THE SECOND STAGE OF LABOUR The same principles that were applied to the first stage of labour should continue in the second stage, including

attention to maternal surveillance, labour progress assessment, fetal surveillance, maternal positioning, fluid intake, analgesia, antibiotics (if indicated) and bladder care. The posture usually adopted is one of semi­ recumbency. Squatting is not easy to maintain unless practised.

THE SECOND STAGE PRIOR TO BIRTHING Recognising the onset of the second stage of labour At or near the end of the first stage, the woman may exhibit one or more of the following: shivering, hiccups, vomiting, flushing and a small amount of vaginal bleeding. As the presenting part descends to the pelvic floor, the woman will experience a desire to ‘bear down’ or ‘push’. At this point, no head should be palpable abdominally. If there is doubt regarding whether there is full cervical dilatation, a vaginal examination should be performed to confirm that there is no cervix palpable.

Management of the normal second stage of labour prior to the actual birth If progress is satisfactory, it is probably unnecessary to exhort the woman to push, until the presenting part has reached the pelvic floor. This is particularly so if she has had an epidural anaesthetic. It is probably safer for the woman to push naturally, not close her glottis, and not push continuously for more than 6 to 8 seconds. The actual pushing is best effected by the woman partially sitting and grasping the backs of the thighs, the legs being well separated. After pushing, the woman is encouraged to exhale fully and take another deep breath to take advantage of the contraction. Confusion as to the true amount of progress may arise in breech presentations if a limb (or limbs) presents; it may have slipped through the not fully dilated cervix. In multiparas, strong pushing can sometimes cause the presenting part to descend to the level of the outlet, even though the cervix is not fully dilated. Finally, gross moulding and caput formation resulting from cephalopelvic disproportion can simulate deep descent of the head. The woman is much helped by sympathetic handling and encouragement, and wiping the face and neck with a cool wet sponge is soothing. If pressure on the presenting part of the rectum causes the expulsion of faecal material, this should be removed with a pad and the perineum swabbed. Towards the end of the second stage, the presenting part will reach the perineum and begin to distend it. The woman is now ready for delivery. If continuous CTG is not being used for fetal surveillance, auscultation should be carried out after each contraction as described above. There is much debate as to a reasonable duration of the second stage before recommending instrumental 235

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birth. In a multipara, there is a small risk of uterine rupture with prolonged pushing and an upper limit of pushing for 1 hour is generally recommended. In a nullipara, 2 hours of pushing is generally accepted, providing fetal surveillance is instituted after the first hour. The nullipara may be permitted an hour or more in second stage without pushing for the head to descend to the pelvic floor, particularly if there is effective epidural analgesia.

CONDUCT OF A NORMAL DELIVERY Preparation for birth Universal precautions The risk of exposure to blood-borne viruses during birth has potentially serious consequences for staff attending the birth. Precautions will include the use of gloves for procedures such as venepuncture or changing bedpans, with sterile gloves, aprons or gowns and eye protection routinely used for birth.

Instruments Instruments and surgical drapes should be placed in readiness for birth when the woman enters the second stage. Minimum instrumentation should include clamps for the umbilical cord and scissors to cut the cord.

Position of the woman There are a number of positions that may be recommended to the woman at this stage of labour. Squatting. This is more physiological than the other positions and allows better pushing by the mother. It is associated with a widening of the pelvic outlet through hyperflexion and abduction of the hip joint, causing movement at the sacroiliac joint. Many women find the position difficult to sustain for any length of time. Semirecumbent (modified dorsal). This is the most common position for a woman to birth in hospital. The woman lies on her back in a semi-sitting position, the knees and hips are flexed, and the legs are widely separated. This combines the pelvic advantages of hyperflexion and abduction of the hip joint but without necessitating the muscular strength needed for squatting. Lithotomy. Although less popular and less comfortable, this position is more likely to be used for instrumental birth since assessment of position and required manipulations are facilitated. When shoulder dystocia (impacted shoulders) is anticipated, the dorsal position is unfavourable because downward traction, which is required to free the anterior shoulder from beneath the symphysis pubis, is prevented by the bed. The lithotomy position permits easy downward traction towards the floor. On all fours. This position has a number of disadvantages. In general, there is poor access of the accoucheur

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to the perineum, meaning little control over the birthing process and an increased risk of damaging tears. Auscultation of the fetal heart can be more difficult and various manoeuvres in the management of shoulder dystocia impossible. Most relevant is that the fetus is being pushed ‘uphill’ (against gravity) and without the pelvic advantages of hyperflexion of the hip joint. All this adds up to temporarily delaying pressure on the perineum (supporters say that the woman is more comfortable) and prolongation of the second stage, which is undesirable from both maternal and fetal perspectives. Standing or sitting. These positions may be used but some support to the back is usually required.

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Antisepsis Cotton wool or gauze swabs soaked in antiseptic solution are used to clean the perineum prior to birth. Aqueous chlorhexidine 0.1% is commonly used for this purpose.

The birth The role of the accoucheur at the time of birth is illustrated in Figure 28.10. There is a series of steps that ensure safe delivery of the neonate with minimisation of trauma to the pelvic floor.

Delivery of the head The position of the accoucheur will depend on the position of the woman. The following description applies to birth in the semirecumbent (dorsal) position. The left hand is placed so that the fingers are spread over the vertex, usually with the base of the hand applied to the back of the occiput and the fingers spread forwards over the parietal bones. The purpose of this manoeuvre is not to exert backward pressure on the head (which will delay birth), but rather to prevent sudden expulsion of the head, which will produce increased perineal damage. The hand should also act as a barometer of progress that enables the accoucheur to inform the woman of optimum ‘bearing-down force’ to achieve a steady, controlled birth of the head and thereby minimising perineal trauma. As the occiput descends under the symphysis pubis, extension occurs and progressively the forehead, nose, mouth and finally chin emerge from beneath the posterior ring of the vulval opening. If the perineum is tight, the chin may need freeing by slipping the index finger under the baby’s mandible and elevating it. Blood and mucus maybe wiped from the baby’s mouth and nose.

Cord around the neck A finger of the right hand is run up past the occiput to ascertain whether the cord is looped around the neck (approximately 25% of fetuses). If the cord is present, it is drawn down over the head; other loops are treated similarly. If there is undue tension, two clamps are placed on the cord approximately 2 cm apart and the cord is cut between them. The release of additional loops can be achieved quite easily by unwinding the clamped ends around the neck.

Chapter 28  Management of Normal Labour

A

B

FIGURE 28.10

A The posterior shoulder is delivered by lateral flexion of the trunk in an anterior direction. Note that the overemphasis of external rotation is no longer applied and so the head faces laterally. B The baby is born and held head downwards. He is covered with vernix and is very slippery; it is necessary to hold his head as shown since his weight could cause his feet to slip from the grasp of the other hand. Source: Courtesy of Prof. Norman Beischer.

Delivery of the shoulders and trunk Following external rotation (restitution) of the fetal head, the shoulders should be delivered. Delivery of the shoulders can traumatise the perineum, so care is needed. Usually the anterior shoulder slips from under the symphysis pubis aided by downward and backward traction of the head. This can be firm but not strong traction, because of the risk to the brachial nerve plexus (Erb’s) palsy. If difficulty is experienced, the woman should be positioned over the edge of the bed so that traction can occur towards the floor in a manner that will release the anterior shoulder from behind the symphysis pubis. If further difficulty is experienced, the birth should be managed as shoulder dystocia (see Ch 34). After the anterior shoulder is freed, the direction of traction is more in the line of the lower birth canal— upwards and forwards. Further gentle and steady trac­ tion allows the posterior shoulder to emerge over the perineum. The latter structure should be watched carefully during this time. The rest of the birth follows easily. It is usually best, when the shoulders are delivered, to change the hold on the baby’s head, the right hand securing it behind the neck while the left hand grasps the feet at the ankles. Some babies are thickly covered with vernix and are quite slippery. They should never be held with only one hand and should always be placed so that a fall would be harmless if the grip is lost.

‘Hands-off’ management of birth In this technique, the baby is delivered ‘naturally’ with little in the way of assistance from an accoucheur. Of course, this will commonly occur without great incident but there is an expectation that uncontrolled birthing will be associated with increased rates of perineal injury. As yet, trials of sufficient size have not been undertaken to quantify any additional adverse outcomes in association with a ‘hands-off’ technique.

MANAGEMENT OF THE THIRD STAGE OF LABOUR Management of the third stage is of vital importance in minimising postpartum haemorrhage, retained placenta, maternal morbidity and maternal death. As indicated in Chapter 27, postpartum haemorrhage is the major cause of maternal death worldwide, particularly so in resourcepoor settings where women lack access to family planning and achieve a high parity with associated increased risk of atonic postpartum haemorrhage.

CLAMPING OF THE CORD After the baby has been delivered and attended to, the cord is doubly clamped and divided. If the baby is held below the level of the placenta, blood will transfuse from 237

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the placental circulation into the fetus. This has benefits for the fetus in terms of improved iron stores but it will aggravate the level of jaundice commonly seen in the first few days of life. Both early and delayed clamping are therefore acceptable strategies. In either event, issues around cord clamping should not delay active management of the third stage of labour.

CORD BLOOD Specific tests on cord blood Cord blood will be collected into appropriate tubes if there are conditions where tests are indicated. The most common reason is the Rh-negative mother where a cord blood group will reveal whether or not the mother requires the administration of prophylactic anti-D. A direct Comb’s test is also commonly performed in this situation to determine whether there are anti-red cell antibodies adherent to the fetal red cells. Cord blood may also be required in certain maternal disorders (e.g. maternal immune thrombocytopenic purpura).

Donation for stem cell storage Cord blood is particularly rich in stem cells. The blood is usually collected by needling of the cord with the placenta still in situ. Approximately 80 mL of cord blood rich in stem cells can be obtained. Two sorts of cord stem cell donations are possible. First, there is a public cord blood bank that can be accessed by a suitably ‘antigenically matched’ member of the community in need of a stem cell transfusion (e.g. in the management of leukaemia). This has universal support. There is also a facility for private donation; that is, an individual pays quite a large sum to have the cord blood stored specifically for their own future use or a nominated family member. This is more controversial because of an uncertain likelihood of future need for the cord stem cells. At the time of writing, there are a number of possible future uses but none as yet in established clinical practice. Each woman must weigh the cost and inconvenience against an uncertain future benefit.3

There are essentially four alternatives for oxytocic in third-stage management. Oxytocin (5 or 10 units administered intravenously or intramuscularly) has a more rapid onset of action (approximately 30 seconds after intramuscular administration) but shorter duration of action (approximately 20 minutes). The only significant adverse effect is a tendency to hypotension in a few women. This is thought to be an anti-vasopressin effect, oxytocin obviously being structurally similar. Ergometrine (0.5 mg intramuscularly) has a slower onset of action than oxytocin (approximately 2 minutes) but it lasts longer (approximately 60 minutes). Side effects include nausea, vomiting and hypertension. It is therefore contraindicated if there is preexisting hypertension. It is also contraindicated if there is diminished cardiac reserve as the intense arteriolar spasm increases afterload and both the venular spasm and profound uterine contraction increases preload. Ergometrine is now uncommonly used in third stage management other than in combination with oxytocin (below). Oxytocin-ergometrine in combination intramuscularly (e.g. Syntometrine: oxytocin 5 units, ergometrine 0.5 mg) combines the early onset of oxytocin and the longer duration of action of ergometrine. A Cochrane review has shown oxytocin-ergometrine in combination to be superior to oxytocin alone in the prevention of postpartum haemorrhage greater than 500 mL, but not better in the prevention of PPH greater than 1000 mL.4 However, it has all the adverse effects of ergometrine and the same contraindications. Misoprostol (400 mcg rectally) has been shown to be less effective than oxytocin or ergometrine but in resource-poor settings, misoprostol can be given orally or rectally and is likely to save many lives as it is progressively introduced to areas where injections of oxytocin or ergometrine are not feasible.

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ACTIVE MANAGEMENT OF THE THIRD STAGE OF LABOUR

Await uterine contraction, placental separation and descent

There are three aspects to active management of the third stage of labour: 1. administer an oxytocic; 2. await uterine contraction, placental separation and descent; and 3. assist delivery of the placenta and membranes.

The uterus is not massaged or prodded unless there is excessive bleeding. A sterile basin or bedpan is placed against the perineum which serves to contain the umbilical cord and to enable blood loss to be assessed. The cord is drawn down until resistance is felt. If there is a perineal wound, it should be compressed with a gauze pad if it is obviously bleeding. The signs of placental separation and descent are classically as follows: 1. show of blood; 2. lengthening of the cord; and 3. the uterus assumes a more globular shape and greater mobility. These signs may occur with partial separation and may not all be present when complete separation has occurred.

Oxytocic administration Immediately after the birth of the child, it is customary to palpate the uterus to exclude a second twin, although this will be an extremely unlikely occurrence if the woman has had multiple ultrasound examinations during pregnancy. Administration of a bolus oxytocic with a fetus still in utero will produce profound fetal anoxia and possibly uterine rupture. 238

Chapter 28  Management of Normal Labour

Assist delivery of the placenta and membranes Controlled cord traction After separation and descent, delivery of the placenta is most physiologically and painlessly effected by controlled cord traction. The essentials of this method are as follows. The cord is reclamped near to the vulva and steadied with one hand while the other hand is used to push the uterine fundus upwards (Fig 28.11). This will confirm that the placenta has separated, since the cord will not then follow the upward movement of the uterus. If separation has occurred, a combined movement is made of downward and backward traction on the cord and upward displacement of the uterus, provided that the latter is firmly

contracted. The abdominal hand is the controlling factor since it holds the fundus and prevents the possibility of inversion of the uterus; this only occurs when cord traction is performed with an uncontracted uterus. If the placenta does not advance, there are two possibilities: it is still attached to the uterus (perhaps only partially) or it has become trapped in a tightly contracted uterus. In such cases, the accoucheur must be patient and repeat the procedure at intervals of some minutes, resisting the temptation to massage the uterus if bleeding is not excessive. If the umbilical cord vessels are congested, the clamp can be removed and the blood drained out. This reduces the size of the trapped placenta. If there is a delay in delivery of the placenta, urethral catheterisation may be performed, although it is doubtful whether this actually makes a difference. Usually, the membranes readily follow the placenta. If they begin to tear, the placenta should be rotated to cause a bunching up of the membranes near the vulva; a wide clamp is then applied and a steady traction exerted (Fig 28.12). Experienced assistance must be sought if the placenta is not delivered within 10 minutes, or earlier if bleeding is excessive. The further management of these complications is considered later.

A

B FIGURE 28.11

Delivery of the placenta by controlled cord traction. A The contracted uterus is pushed upwards as traction is exerted on the cord in the direction of the curve of the birth canal. B The abdominal hand ‘palms’ the fundus as the folded placenta appears fetal-surface first. Another method of holding cord and clamp is shown. Source: Courtesy of Prof. Norman Beischer.

FIGURE 28.12

The trailing membranes are detached from the uterine wall and delivered complete by careful traction with a seesaw action. Source: Courtesy of Prof. Norman Beischer.

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Fundal expression of the placenta If the cord has snapped, an alternative method of placental delivery is fundal expression. Here, fundal pressure on the contracted uterus is used as a piston to push the placenta downwards from the lower segment or upper vagina. Too much force will cause pain to the mother and stretching of the supports of the uterus.

PASSIVE MANAGEMENT OF THE THIRD STAGE OF LABOUR A few women will choose not to have active management of the third stage of labour. They should be informed that this is associated with a twofold increase in the risk of postpartum haemorrhage (8% instead of 4%).

INSPECTION OF THE PLACENTA AFTER DELIVERY The placenta is examined carefully and methodically. 1. The maternal surface is inspected to see if there are any missing cotyledons (Fig 28.13). 2. The fetal surface is examined to determine if there could be a missing section of the placenta. That is, if a vessel runs to the edge of the placenta and the membranes there are ragged or absent, the presence of a succenturiate lobe should be suspected (Fig 28.14). Whitish areas are common in the subchorial region and these usually represent fibrin deposition, not infarcts. The weight of the placenta is

recorded, together with the time of its delivery and any significant anomaly. 3. The membranes are inspected for completeness. Ideally, there is a circular hole where the fetus emerged and the membranes are otherwise complete. The distance of the hole from the edge of the placenta indicates how close the placenta was to the internal os; if less than the length of the lower uterine segment, then the placenta was partially praevia. Often the membranes are ‘ragged’; that is, incomplete. In such cases, an estimate should be made of how much of the membranes remains in the uterus. The membranes may insert on the surface of the placenta rather than at its edge (circumvallate placenta) and this should be recorded (Fig 28.15); in this condition the placenta is unusually thick but has a reduced diameter, as though excessive regression of chorionic villi had occurred, with later extension of the remainder beyond the original edge of the placental disc. Placenta membranacea is the converse and much less common condition, where the chorionic villi persist over most or all of the circumference of the chorion, the placenta being wide but thin (Fig 28.16).

Management of an incomplete placenta If part of the placenta is missing (Fig 28.13) or a succenturiate lobe is suspected, exploration of the uterus should be made (Fig 28.14). If this is not done, there is a risk of later secondary postpartum haemorrhage in relation to infection of retained products of conception.

FIGURE 28.13

A missing placental cotyledon was noted at routine inspection of the placenta. Although there was not excessive postpartum blood loss, manual exploration of the uterine cavity was performed under anaesthesia and the missing cotyledon removed. Source: Courtesy of Monash Health.

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FIGURE 28.14

Fetal surface of a placenta succenturiata. Several large vessels pass across the membranes to the succenturiate lobe. The condition is termed vasa praevia when such vessels pass over the region of the internal os. Source: Courtesy of Prof. Norman Beischer.

Chapter 28  Management of Normal Labour

INSPECTION OF THE VULVA, VAGINA AND PERINEUM AFTER BIRTH A gentle but thorough inspection is made for injuries to the vulva and vagina, especially tears in the region of the vulval ring. Occasionally, the epithelium may be intact but a haematoma may have developed in the deeper tissues. After operative vaginal deliveries, or if bleeding is abnormal, the whole length of the vagina and the cervix must be inspected. Any episiotomy or birth canal injury should be repaired in a timely manner (see Ch 30).

FURTHER CARE IN THE EARLY POSTNATAL PERIOD Maternal observations and investigations FIGURE 28.15

Circumvallate placenta; the amnion forms a double fold as it attaches to the placenta and obscures the vessels at the outer rim of the fetal surface. A mild accidental haemorrhage occurred at 38 weeks’ gestation. Source: Courtesy of Monash Health.

Routine observations of temperature, pulse rate and blood pressure are made, the frequency depending on whether the preceding labour was normal or complicated. Palpation of the uterine fundus for atony and inspection of the perineal pad should be made every 15 minutes for at least 2 hours after birth. If there is voiding difficulty or the bladder is palpable after voiding, a urinary catheter should be passed. If the woman is Rh-negative, her blood will be sent for a blood group antibody screen in order to confirm that she has not developed anti-D antibodies in late pregnancy. REFERENCES 1) Wax JR, Lucas FL, Lamont M, et al. Maternal and newborn outcomes in planned home birth vs planned hospital births: a metaanalysis. Am J Obstet Gynecol 2010;203: 243.e1–8. 2) Walker SP, McCarthy EA, Ugoni A, et al. Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds. Obstet Gynecol 2007;109(1):67–72. 3) RANZCOG. Statement on provision of routine intrapartum care in the absence of pregnancy complications. July 2014. Online. Available: ; [17 Dec 2014]. 4) McDonald SJ, Abbott JM, Higgins SP. Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour. Cochrane Database Syst Rev 2004;(1):CD000201.

FIGURE 28.16

Placenta membranacea; the chorionic villi have persisted over the entire surface of the gestation sac. Source: Courtesy of the Estate of Dr. Ian MacIsaac.

FURTHER READING RANZCOG. Statement on umbilical cord blood banking. May 2013. Online. Available: ; [17 Dec 2014]. 241

Section 2.7.2 INDUCTION OF LABOUR, INSTRUMENTAL DELIVERY AND CASEAREAN SECTION

Chapter 29  INDUCTION OF LABOUR, INCLUDING CERVICAL RIPENING Michael Permezel and Gillian Paulsen

KEY POINTS In approximately 25% of pregnancies, the clinical circumstances reach a position where the risk–benefit equation of induction versus remaining in utero favours the former. Elective caesarean section should be considered as an alternative to induction of labour where the situation is such that vaginal birth is contraindicated or where the likelihood of achieving a vaginal birth is low. The suitability of the cervix for induction should be assessed with a cervical score. The cervical score may influence the decision as to whether induction of labour is recommended in a particular clinical situation. If induction is still recommended with an unfavourable cervix, mechanical or pharmacological cervical ripening agents will increase the likelihood of vaginal birth. Each technique for induction of labour has its own side effect profile. Of particular concern is the possibility of excessive uterine muscular activity with the use of oxytocic drugs, particularly prostaglandins.

BACKGROUND INCIDENCE Induction of labour takes place in approximately 25% of pregnancies but can vary considerably in different health services and care models.

THE RISK–BENEFIT EQUATION WITH INDUCTION OF LABOUR The decision regarding a recommendation for induction of labour will depend on the following factors that need to be carefully assessed in each individual: indication for induction of labour gestational age suitability for induction of labour maternal tolerance of risk in order to avoid medical procedures around childbirth.

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Indication for induction of labour The indication for induction should be a circumstance or condition that may benefit from delivery before spontaneous labour. A list of all the conditions that might benefit from early birth is extensive and could include almost every obstetric or medical (including psychological) condition (Box 29.1). Other benefits might be legitimately social where, for example, the partner has only a specific window of leave before returning to a military service position overseas. Almost regardless of the indication, the perceived benefit needs to be balanced against the risks (potential adverse consequences) of labour.

Risks of birth occurring earlier than it would have occurred spontaneously The risks of birth occurring earlier than it would have without induction are the common problems of prematurity, particularly respiratory distress, poor feeding and so on (see Ch 12).

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

BOX 29.1  Common indications for induction of labour. Prolonged pregnancy Hypertensive disorders ✚ Essential hypertension, gestational hypertension, preeclampsia Diabetes mellitus ✚ Gestational diabetes mellitus, prepregnancy diabetes mellitus Other medical conditions ✚ Renal disease, liver disease, cholestasis of pregnancy, red cell isoimmunisation, thrombophilia, anticoagulation in pregnancy, substance abuse, neurological (e.g. myotonic dystrophy) Placental insufficiency suspected or likely ✚ Fundus less than dates, poor late fetal growth, ultrasound suggesting placental insufficiency, oligohydramnios, fetal movements decreased, previous placental insufficiency, low PAPP-A in first trimester Prelabour rupture of the membranes Multiple pregnancy Antepartum haemorrhage with normally sited placenta Gynaecological ✚ Long-standing infertility, may be particularly risk averse Musculoskeletal conditions ✚ Disabling ligamentous pain in late pregnancy Psychological or mental health issues may sometimes benefit from labour induction Social ✚ Most commonly partner availability

Risks related to the method of induction of labour These will be discussed with each method but include, for example, cord prolapse after artificial rupture of the membranes and excessive uterine muscular activity after administration of oxytocics such as prostaglandins or oxytocin.

compared to awaiting spontaneous labour. Repeated randomised clinical trials have shown either no increase in caesarean section or actually a reduction in caesarean section. Examples include the Hannah randomised controlled trial of induction versus observation of the post41 weeks’ pregnancy and the HYPITAT trial of the management of hypertension in late pregnancy.1,2

Assessment of gestational age Accurate ultrasound dating is important because of not only the risks of prematurity complications but also because the hazards of remaining in utero in many conditions escalate exponentially in late pregnancy.

Assessment of suitability for induction of labour If the head is high and mobile, induction of labour is relatively contraindicated due to the small risk of a cord prolapse with rupture of the fetal membranes. A caesarean section may be a wiser option if delivery is needed. Most attention is usually paid to the state of the cervix through assessment of the cervical (Bishop’s) score (see Ch 13). A ‘ripe’ cervix increases the likelihood of an uncomplicated vaginal birth following induction of labour. If the cervix is ‘unripe’, various methods may be used to improve the cervical score (mechanical or pharmacological) but these have some morbidity attached and an unfavourable cervix affects the risk–benefit of induction of labour.

Assessment of maternal factors: how much fetal risk is the woman prepared to take in order to avoid induction of labour? Most women are relatively intolerant of fetal risk and prepared to accept obstetric procedures such as caesarean section or induction of labour in order to minimise fetal risk. There is, however, a small group of women who are particularly averse to ‘medicalisation’ of birth and more tolerant of fetal risk in order to avoid induction of labour.3 This should also be considered in the risk–benefit model when recommending induction of labour.

Risk of caesarean section after attempted (‘failed’) induction of labour

CONTRAINDICATIONS TO INDUCTION OF LABOUR

The term ‘failed’ should probably be eliminated from obstetric terminology as it has the connotation that either the woman or her carers have somehow not met expectations. In truth, it is perfectly reasonable to attempt induction of labour in the knowledge that caesarean section is a possibility or even a probability. It is a persisting misconception that induction of labour makes a caesarean section more likely when

It is self-explanatory that those conditions unsuitable for vaginal birth will also be unsuitable for induction of labour. Examples include malpresentation, placenta praevia, previous classical caesarean section, vasa praevia and active genital herpes simplex infection.

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Chapter 29  Induction of Labour, Including Cervical Ripening

CONTRAINDICATIONS TO ADMINISTRATION OF AN OXYTOCIC (OXYTOCIN OR PROSTAGLANDINS) Conditions that predispose to uterine rupture are relative contraindications to oxytocic administration (particularly prostaglandins). Examples include grand multiparity and a previous uterine scar.

CONTRAINDICATIONS TO ARTIFICIAL RUPTURE OF THE MEMBRANES A high mobile presenting part risks a cord prolapse with artificial rupture of the membranes (ARM).

TECHNIQUES FOR LABOUR INDUCTION ASSESSMENT PRIOR TO INDUCTION OF LABOUR A detailed history should already have been taken paying particular attention to those factors that will most impact on the risk–benefit equation with respect to labour induction. Abdominal examination will reveal whether the presenting part is fixed. A vaginal examination to assess the cervical score is paramount in determining the most appropriate method and whether cervical ripening is advisable.

The cervical (Bishop’s) score The cervical score gives an idea of the likelihood of induction being successful in achieving labour; that is, painful regular uterine contractions associated with progressive dilatation of the cervix. There are several variants of the cervical score but an example is given in Table 29.1. The cervical score is calculated by summing the score in each of the five categories as determined on vaginal examination prior to induction of labour. Where the cervical score is ≤ 5, cervical ripening with either prostaglandin or a transcervical catheter is recommended to increase the likelihood of a successful induction.

Assessment of fetal wellbeing The fetus will be assessed clinically and may already have had some investigations antenatally (depending on the clinical circumstances). Regardless of prior assessments, a (further) cardiotocograph should be performed prior to cervical ripening or labour induction as each of the techniques may further compromise the fetus at risk.

CERVICAL RIPENING As indicated already, some form of cervical ripening is preferred where the cervix is ‘unripe’ (cervical score ≤ 5) in order to increase the probability of a vaginal birth. The two common techniques for cervical ripening are pharmacological (prostaglandin therapy) or mechanical (transcervical catheter, e.g. Foley). Where the cervix is ‘favourable’ (ripe) (cervical score > 5), neither of these agents is required and they will unnecessarily delay birth. In addition, the administration of prostaglandins in the presence of a favourable cervix will further increase the likelihood of a precipitate (rapid) labour and/or uterine hyperstimulation (excessive uterine activity associated with fetal compromise). Sometimes, a cervical ripening agent alone has caused labour to begin but ‘augmentation’ (Ch 34) with ARM and/or oxytocin may still be required as the effect of the ripening agent may wear off before labour is established. If the cervix is favourable (whether cervical ripening agents have been used or not) and labour not yet established in a woman scheduled for induction, labour is commonly induced with ARM followed by an oxytocin infusion. It is normal practice not to administer an oxytocin infusion until after the ARM. This is because there may be a relatively sudden increase in sensitivity to oxytocin after rupture of the membranes, with all the potential consequences of uterine hyperstimulation.

FETAL SURVEILLANCE FOLLOWING CERVICAL RIPENING OR INDUCTION OF LABOUR Regardless of which agent is selected, even if the indication for induction of labour does not mandate a

TABLE 29.1  CERVICAL SCORE. 0

1

2

3

Cervical dilatation

0 cm

1–2 cm

3–4 cm

> 5 cm

Cervical effacement

0–30%

31–50%

51–80%

> 80%

Cervical position

Posterior

Intermediate

Anterior

Cervical consistency

Firm

Intermediate

Soft

Presenting part station

–3

–2

–1, 0

+1, +2 245

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recommendation for continuous cardiotocography, continuous cardiotocography is indicated when labour begins. All agents used to induce labour can have direct or indirect effects on fetal wellbeing.

SPECIFIC AGENTS Prostaglandins Which prostaglandin? There are four structural groups of prostaglandins (A, B, E and F). Each of these is further subdivided into 1 or 2, depending on the number of saturated bonds between the carbon atoms, and alpha or beta, depending on their spatial arrangement. Only the E1, E2 and F2 compounds are of obstetric therapeutic interest. The routes of administration can be oral, intravenous, extra-amniotic, intraamniotic, intracervical or high vaginal but for cervical ripening at term, the intravaginal route is most commonly used. Dinoprostone (prostaglandin E2 gel) Intravaginal dinoprostone (prostaglandin E2) gel is commonly used to ripen the unfavourable cervix on the day prior to planned induction of labour. A dose of 1 mg would be recommended initially and 1 or 2 mg (depending on response) 6 hours later as long as the cervix remains unfavourable, uterine contractions have not established and fetal wellbeing is satisfactory. In some circumstances a third dose of dinoprostone may be required; however, the total dose should not normally exceed 5 mg. Dinoprostone slow-release pessary Controlled-release pessaries are designed to deliver approximately 4 mg of dinoprostone over a 12-hour period. A string attached to the pessary enables easy removal of the pessary in the event of hyperstimulation. A slow-release vaginal pessary containing misoprostol is also available. Misoprostol tablets These come in 200-mcg tablets formulated for the treatment of peptic ulcers. Misoprostol is highly effective in cervical ripening and induction of labour. The 200-mcg dose is commonly used orally or vaginally 4 hourly for second trimester induction of labour but almost inevitably causes hyperstimulation of the uterus at term, with consequent severe fetal compromise and sometimes even uterine rupture. A dose of 12.5 to 25 mcg can be obtained by dissolving the misoprostol in solution and administering only aliquots of 1/16 or 1/8 of the mixed solution.

excessively frequent (> 5 in 10 minutes) or of excessive duration (> approximately 70 seconds), placental oxygenation will fall and the fetus will become first hypoxic and then acidotic. Excessively frequent contractions is termed uterine tachysystole. Where this results in fetal compromise, it is termed uterine hyperstimulation. The other consequence of excessive uterine muscular activity is the possibility of excessive thinning of the lower uterine segment as the upper segment contracts (and retracts) vigorously around the fetus. This can result in uterine rupture, most commonly from a tear within the lower uterine segment. A less than full thickness tear can result in a uterine vein being torn, with intrauterine pressure forcing amniotic fluid into the maternal blood stream. The catastrophic consequences of amniotic fluid embolism are covered in Chapter 36. Management of excessive uterine muscular activity Uterine tachysystole mandates continuous cardiotocography and consideration of any oxytocic cessation. If the contractions are relatively low intensity and with some interval between, some clinicians will refrain from immediately withdrawing the oxytocic and opt for vigilant observation of the fetal wellbeing. Where there is any evidence of fetal compromise (uterine hyperstimulation), any oxytocic must be discontinued (e.g. cessation of any oxytocin infusion, removal of a dinoprostone pessary or attempted removal of dinoprostone gel from the vagina) and consideration given to the administration of a tocolytic in order to suppress the excessive uterine activity. Alternative tocolytic regimens are given in Table 29.2.

Contraindications to prostaglandin administration The following are relative contraindications to administering prostaglandins for cervical ripening or induction of labour. Conditions that predispose to uterine rupture. Grand multiparity and previous uterine scar are predisposing factors for uterine rupture and are relative contraindications to prostaglandin administration.

•

TABLE 29.2  ACUTE TOCOLYSIS FOR UTERINE HYPERSTIMULATION. Drug

Dose

Salbutamol

50 mcg slowly intravenously; repeated if necessary up to 250 mcg, but one or two doses usually sufficient

Terbutaline

250 mcg subcutaneously

Glyceryl trinitrate

400 mcg sublingual or buccal spray; may be repeated once if necessary

Adverse effects of prostaglandins

Excessive uterine muscular activity The principle concern with prostaglandin administration is the risk of excessive uterine muscular activity. The clinical consequences are twofold. First, there is a reduction in uteroplacental blood flow with every uterine contraction. If the sufficiently intensive contractions are 246

Chapter 29  Induction of Labour, Including Cervical Ripening

•

Any situation where there is concern that fetal compromise will develop in the presence of increased uterine muscular activity. An unfavourable cervix in the presence of suspected placental insufficiency is probably best managed with a transcervical balloon catheter rather than prostaglandins as the likelihood of sudden severe fetal compromise with uterine tachysystole will be reduced.

Pre- and post-prostaglandin fetal surveillance A reactive antenatal cardiotocograph should immediately precede the administration of prostaglandins, both the first dose and any subsequent doses. Some units have protocols that recommend repeat cardiotocographs approximately 6 hours after the administration of prostaglandins to detect fetal compromise related to uterine activity that is not otherwise apparent. All women need continuous cardiotocography in any labour subsequent to prostaglandin administration.

Transcervical balloon catheter In women in whom the cervix is unfavourable, a 30-mL Foley balloon catheter is passed through the cervix. The balloon is then insufflated with saline in the lower segment of the uterus. This is most often done on the evening before planned induction of labour in the presence of an unfavourable cervix. The Foley balloon is usually expelled from the lower uterine segment through the cervix overnight, leaving a cervix ripe for induction of labour the next morning.

Adverse effects of a transcervical balloon catheter Infection The main concern when using a catheter for cervical ripening is that infection may be introduced and chorioamnionitis may result. In practice, this does not appear to be a significant problem. However, given that even a very small number of cases of chorioamnionitis would be clinically important, those employing this technique should be vigilant in their aseptic technique and be alert to any increase in incidence of chorioamnionitis.

Artificial rupture of the membranes Mechanism of action Artificial rupture of the membranes (ARM) probably works in two ways. First, there is likely to be an increase in endogenous prostaglandin release which both directly augments uterine muscular activity and also increases receptivity to endogenous or exogenous oxytocin. Second, prior to ARM intrauterine pressure is directed evenly in all directions as per any fluid-filled cavity. Following ARM, contraction will exert a more direct pressure on the fundal pole of the fetus, forcing the presenting part down against the cervix, which will assist mechanically with cervical dilation and, via the Fergus reflex (Ch 27), will promote endogenous oxytocin release.

Technique An aseptic technique should be performed, first swabbing the vulva and vagina with aqueous chlorhexidine and then using chlorhexidine lubricant, sterile gloves and sterile implements. The instrument used for the procedure depends on the preference of the operator. Most commonly, the specially designed AmniHook is used but alligator forceps are an alternative, particularly if the procedure is difficult in the presence of a cervical score that is lower than usual. After the procedure, a check for cord prolapse is made, and the fetal heart is auscultated. If the amount of liquor is greater than normal, the hand should be kept in the vagina and the liquor released slowly. It is preferable not to perform an ARM when the head is mobile. Sometimes, however, it is necessary and wise to make sure the presenting part remains over the pelvic brim and the liquor drains away. Early use of an oxytocin and vertical posturing will make it less likely that the presenting part drifts into one or other iliac fossa.

Adverse effects of ARM

Cord prolapse This will be most likely when ARM is performed with a high mobile presenting part, a malpresentation or polyhydramnios. Infection ARM should be performed aseptically, as indicated.

Oxytocin infusion for induction of labour Regimen This should almost always be preceded by spontaneous or artificial rupture of the membranes, as indicated. The concentration and infusion rate will be dictated by local preference. A widely used regimen places 10 units per 1000 mL normal saline or Hartmann solution (10 units/L). An infusion pump line is usually inserted into the routine intravenous drip line. Beginning with an infusion rate of approximately 12 mL/hr (0.12 units/hr, 2 milliunits per minute), the infusion rate is increased by 12 units at intervals until regular contractions of moderate intensity are occurring at a rate of approximately four in 10 minutes. If there is good progress of labour (cervical dilatation of at least 1 cm/hr) or more than four contractions in 10 minutes, the oxytocin infusion rate should not be increased. It is wise to increase the oxytocin dose only every 30 minutes, since it takes this time for plasma levels of oxytocin to reach a steady state. During the infusion, the frequency and nature of contractions should be assessed every 15 minutes.

Adverse effects of an oxytocin infusion

Excessive uterine muscular activity This may result from overdosage or unusual sensitivity to oxytocin. The latter is particularly prevalent when 247

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prostaglandins have been used for cervical ripening. As a consequence, the oxytocin infusion rate should be commenced at a lower rate after prostaglandin use. Hypotension Oxytocin has a mostly mildly hypotensive effect but some women exhibit greater sensitivity to this side effect. This side effect presumably relates to the fact that the structure of oxytocin is analogous to the vasoconstrictor vasopressin. Water intoxication In contrast to an apparent antagonism of the vasoconstrictor effect of vasopressin, oxytocin has an agonistic effect with respect to water retention. Where high doses of oxytocin are used, hyponatraemia can be a problem. This is now very uncommon; however, prior to the availability of prostaglandins very high doses and prolonged use of oxytocin frequently caused serious water intoxication. Postpartum haemorrhage Oxytocin, like other hypothalamo-pituitary peptides, down-regulates its own receptor. This means that there will be reduced sensitivity to endogenous oxytocin if the high levels of infused oxytocin are ceased. This can

248

be particularly important after birth. The oxytocin infusion used for induction or augmentation should be continued for at least an hour after birth to assist in maintaining uterine tone and preventing postpartum haemorrhage. REFERENCES 1) Koopmans CM, Bijlenga D, Groen H, et al.; HYPITAT study group: Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009;374(9694):979–88. 2) Hannah ME, Hannah WJ, Hellmann J, et al. Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group. N Engl J Med 1992;326(24):1587–92. 3) Walker SP, McCarthy EA, Ugoni A, et al. Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds. Obstet Gynecol 2007;109(1): 67–72.

Chapter 30  EPISIOTOMY AND VAGINAL OUTLET TEARS Michael Permezel and Gillian Paulsen

KEY POINTS An episiotomy is a valuable adjunct to the management of a vaginal birth but should only be used when clearly indicated. Indications for episiotomy include to avoid a major perineal tear, expedite birth, reduce traction needed during instrumental birth and improve access for manipulative deliveries. Midline episiotomies have only a very limited place in clinical practice as there is a higher likelihood of extension into the anal sphincter. Third- and fourth-degree perineal tears require an experienced surgeon with good lighting and adequate analgesia. A cervical tear should be expected if there is brisk bleeding immediately after delivery of the baby and before the placenta has separated. A vulvovaginal haematoma usually requires a urinary catheter and conservative management is generally preferred.

EPISIOTOMY An episiotomy is an incision made in the perineum and vagina that enlarges the introitus and lessens the curve of the birth canal to facilitate the birth of the fetus.

INDICATIONS The liberal rather than the restricted use of episiotomy for normal delivery does not appear to offer any benefits. However, judicious use can avoid serious complications of vaginal birth. The potential benefits are as follows.

Avoidance of major perineal tear Perineal tear already occurring early with head crowning; instrumental birth A small perineal tear is clearly associated with less discomfort than an episiotomy. However, an episiotomy may

avoid a large tear, a ragged tear that does not heal well or a tear in areas of particular disadvantage such as in the anterior compartment around the urethra or clitoris and involving the anal sphincter (see the section on third- and fourth-degree tears later in this chapter). There is little doubt that enlarging the posterior compartment with an episiotomy will reduce anterior tears (Fig 30.1). The evidence for avoiding third- and fourth-degree tears is less clear.

Expedite birth Fetal compromise and/or inadequate progress with the head on the perineum; vaginal breech delivery It is common, especially in a nulliparous woman, that an inelastic perineum will considerably delay birth, with possible consequences in terms of fetal compromise and compression injury to the nerves of the pelvic floor.

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Traction force reduction

involved. Analgesia can be provided with local infiltration in the absence of a regional or pudendal block.

Instrumental birth; breech extraction A tight perineum can add considerably to the traction forces necessary to effect an instrumental birth or even a breech extraction. An episiotomy will reduce the traction required, with obvious benefits for the fetus. If the perineum is not particularly ‘tight’, an episiotomy may not be necessary.

Improve access for manipulative delivery Shoulder dystocia; vaginal breech delivery Occasionally, a tight perineum may make manipulative birth more difficult. Examples of this include delivery of the posterior arm in a case of shoulder dystocia (Ch 34) or delivery of the after coming head of a breech (Ch 15).

THE PROCEDURE Prior to the episiotomy Before episiotomy is carried out, it is important to explain to the woman the reason for the procedure and what is

Clitoris

External urinary meatus

Technique of the surgical incision Mediolateral episiotomy A finger should be inserted into the vagina to guard the fetal head during local anaesthetic infiltration of the perineum when the perineum bulges downwards during a contraction (Fig 30.2). The incision is made when the head bulges the perineum because it is easier to judge the proper length, the anal sphincter is displaced and blood loss is less. One blade of the scissors is inserted inside the vagina with the cutting angle resting on the fourchette. The incision is made posterolaterally at a 45° angle (at a position equivalent to 7.30 on the clock). Make a single cut during a contraction (Fig 30.3). It is important not to begin the incision away from the midline as Bartholin’s duct may be inadvertently damaged. If delivery is not immediate, bleeding from the cut edges can be controlled by firm pressure with a gauze swab while awaiting the next contraction.

Midline episiotomy A midline episiotomy has the major disadvantage that extension through the anal sphincter is significantly more common. The advantages of this technique are less bleeding, greater ease of repair, less pain during healing and a lower incidence of subsequent dyspareunia. If vulval varicosities are particularly severe, a midline episiotomy will reduce blood loss compared to a mediolateral episiotomy. Median

Mediolateral J-shaped

Internal pudendal artery

Para-urethral tear due to failure to cut an episotomy

Inferior rectal artery

FIGURE 30.1 

Anterior vulval tear in the para-urethral region. An episiotomy may well have avoided this painful injury. The area near the urethral meatus and clitoris is very vascular and careful suturing is required. 250

FIGURE 30.2 

Types of episiotomy incision. If the incision extends past the anus, it enters the area innervated by the perforating cutaneous nerves which are not affected by a pudendal nerve block.

Chapter 30  Episiotomy and Vaginal Outlet Tears

A

B

C FIGURE 30.3 

Technique of episiotomy. A Local analgesia was provided by perineal infiltration (trickle of blood marks site of injection) when the head bulged the perineum. Note anal dilatation during a contraction. B The scissors are in position at the fourchette. C The incision being made during a contraction. Source: Courtesy of Prof. Norman Beischer.

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REPAIR AND MANAGEMENT OF AN EPISIOTOMY Prior to surgical closure The main principles in repair are to identify key structures and extent of the lesion, obtain haemostasis, align the edges anatomically and not suture too tightly. The woman is usually in the lithotomy position but a small lesion can be repaired in the dorsal position. There must be sufficient vision to be able not only to perform the surgical repair but also to clearly identify the structures involved, particularly whether the anal sphincter has been affected (see the section on third- and fourthdegree tears later in this chapter). The operative field is prepped, draped and well illuminated. Perineal infiltration with lignocaine 0.5 to 1% through the cut surface of the wound is performed if anaesthesia is inadequate. Synthetic absorbable sutures are used throughout. Catgut and chromic catgut have been shown to produce more pain in the early postnatal period.

A FIGURE 30.4 

Surgical closure Repair of the vaginal epithelium The first step is the repair of the vaginal epithelium, and for this a continuous suture is used (Fig 30.4A). A gauze pack may be introduced into the vagina to aid exposure. The structures to be sutured are identified and vaginal lacerations sought. Arterial bleeding is dealt with by clamping and ligating the vessel, but oozing from epithelial and skin edges is controlled by the pressure applied by the sutures. Haemostasis is imperative, otherwise extensive bruising and haematoma formation can occur with the subsequent complications of pain, infection and disruption of the wound. Sutures are placed at about 1-cm intervals and a good bite of epithelium and submucosa is taken to obliterate dead space. Vaginal lacerations are also repaired. Sutures should not be tied too tightly because of the swelling which occurs in the following 24 to 48 hours. Three markers should be used for accurate opposition: the vaginal apex, the hymen and the mucocutaneous junction.

B

Repair of episiotomy. A The vaginal incision has been sutured from apex down to the introitus. B Interrupted sutures have been inserted in the perineal muscles. Finally, the skin will be closed with a subcuticular continuous suture. Source: Courtesy of Prof. Norman Beischer.

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Occasionally, the episiotomy incision extends high up the vagina, usually due to difficulty with the delivery of the shoulders. If the upper limit of the vaginal incision cannot be seen, a stitch is inserted as high as possible and tied; traction upon this stitch then exposes the upper limit of the incision, which is sutured.

Approximation of the perineal muscles The second step is approximation of the perineal muscles. Interrupted sutures are used (Fig 30.4B) because they control bleeding and reduce dead space, thus preventing haematoma formation. Usually two to three sutures are sufficient. The anatomical distortion inevitable with the mediolateral incision should be allowed for as the lower elements of the levator ani muscle and the bulbocavernosus muscle are sutured. The ultimate strength of the repaired pelvic floor depends mainly upon this layer.

Closure of the perineal skin The third step is closure of the perineal skin, which is performed with a continuous subcuticular suture beginning posteriorly and working back towards the fourchette with absorbable suture material.

Immediately after surgical closure Once surgical closure is complete, a vaginal examination ensures that no pack remains and a rectal examination excludes stitches in the rectum or anal canal. If there is persistent oozing from an episiotomy wound and/or vaginal lacerations after repair, haemorrhage can usually be controlled by insertion of a gauze pack (10 cm × 2 m) into the vagina. This is removed 12 to 24 hours later. If a pack is used, an indwelling catheter is inserted because the pack will occlude the urethra and prevent voiding. If packing is required, an antibiotic should be prescribed.

Care in the early puerperium Analgesia is needed for the first 48 to 72 hours. Pain is greater with larger episiotomies and much external suturing, long second stage, operative delivery and perineal bruising. An icepack during the first 24 hours will reduce bruising and swelling. The wound should be kept clean and dabbed dry after showering. Non-steroidal antiinflammatory drugs (NSAIDs) are beneficial if discomfort is significant.

Complications of an episiotomy Infection Infection is relatively uncommon considering the nature of the area. It usually takes the form of a stitch abscess or infected haematoma, but occasionally infection of the ischiorectal fossa may occur.

Wound breakdown This is usually the result of poor suturing technique (e.g. knots too tight) or an infected haematoma. Management is usually to await healing without resuturing but with a

large wound some approximation of the wound edges is needed, which can be achieved with two or three large sutures with entry points well away from the wound edges.

PERINEAL TEARS CLASSIFICATION Perineal tears are classified in degrees from 1 to 4, as shown in Table 30.1.

PREDISPOSING FACTORS Rapid second stage of labour Instrumental birth; precipitate birth The connective tissue and muscles of the perineum have proportionately more tearing and less stretching, the more rapid the birth. Prevention In both the above situations, the accoucheur is responsible for effecting delivery in a controlled manner. This extends back to antenatal education and preparation of the woman for the second stage of labour.

Large presenting part or shoulders Large fetus; malpresentation with unfavourable diameter presenting (face to pubis) Occasionally the fetus may present with an arm alongside the head, leading to a sudden expansion of the perineum as the flexed elbow delivers. A ‘face to pubis’ birth is almost always associated with increased tearing in the absence of a large episiotomy. Prevention This can be prevented in two ways: 1. employ strategies to reduce macrosomia such as dietary advice and selected induction of labour; and 2. avoid ‘face to pubis’

TABLE 30.1  CLASSIFICATION OF PERINEAL TEARS. Degree

Structures involved in the perineal tear

1st

Skin, subcutaneous tissue and superficial fascia

2nd

Muscles of the perineum

3rd

Anal sphincter

  3A

  < 50% of the external anal sphincter

  3B

  ≥ 50% of the external anal sphincter

  3C

  internal anal sphincter involvement

4th

Anorectal mucosa 253

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instrumental delivery by either rotation before vaginal birth or caesarean section.

Perineum less elastic Nulliparity; scarring from a previous perineal tear or episiotomy Approximately 80% of women having their first baby will have a perineal tear. The major modifications to connective tissue during pregnancy are just sufficient in most women to allow passage of the fetus through the introitus with only minor perineal tears (first or seconddegree). Following the first birth, an increased ability of the perineum to ‘stretch’ is retained and perineal tears are much less common with a second or subsequent birth. There are also presumably inherent individual characteristics of connective tissue that make tearing more or less likely under the same stretch impulse. There are no known effective pharmacological techniques to make the perineum more elastic and therefore prevent tears. Devices that mechanically stretch the perineum in late pregnancy may have a role but studies examining long-term consequences with respect to prolapse are awaited. A timely episiotomy may avoid anterior tears (Fig 30.1) or major perineal tears by directing the stretch away from the sphincters. However, if performed too early and too small, all the stretch will be taken in that part of the perineum and an extension, possibly through the sphincter, becomes even more likely than if there was no episiotomy at all.

COMPLICATIONS Anorectal incontinence may occur if there is unrecognised disruption of the anal sphincter and therefore inadequate restoration of the normal anatomy. Transient incontinence is most often a result of neuropraxia and recovers after the first couple of weeks. An unrepaired anal sphincter injury will produce continuing symptoms with incontinence of flatus and possibly faeces. A rectovaginal fistula will occur with breakdown of a fourth-degree tear but can also occur if a repair suture is placed too deep so that the suture hole can form a fistulous track.

REPAIR AND MANAGEMENT OF FIRST- AND SECOND-DEGREE PERINEAL TEARS These are managed as for an episiotomy.

REPAIR AND MANAGEMENT OF THIRD- AND FOURTH-DEGREE PERINEAL TEARS Prior to surgical closure Third- and fourth-degree tears have a particularly significant risk of long-term sequelae related to anorectal 254

continence and it seems likely that such continence is affected by the quality of the repair. Therefore, the following special measures are usually undertaken for the repair of a third- or fourth-degree tear. Anaesthesia. The procedure is usually performed under regional or general anaesthesia. Local anaesthesia is inadequate. Positioning. The patient is placed in the lithotomy position. Lighting and exposure. Adequate lighting and exposure are used. This usually means that the procedure is performed in an operating theatre or a room in the birth suite that is equipped for such a purpose. Clinician expertise. The procedure should be either performed or supervised by an appropriately trained obstetrician.

• • • •

Surgical closure The external anal sphincter (EAS) and internal anal sphincter are best repaired with a monofilament suture such as polydiaxanone (PDS). Clear identification of the defect is critical. Approximation can occur either by a direct end-to-end apposition or an overlapping technique. The remainder of the repair is as for an episiotomy.

Care in the early puerperium The use of postoperative laxatives is recommended to reduce the incidence of postoperative wound dehiscence. Intraoperative and postoperative broad-spectrum antibiotics are recommended to reduce the risk of infection, which in turn may lead to anal incontinence and fistula formation. Inclusion of metronidazole is advisable to cover the possible anaerobic contamination from faecal matter.

Follow-up care Follow-up visits for assessment of second- and thirddegree tears and identification of continence problems should be recommended 3 to 6 months postpartum. Endo-anal ultrasound may be required. Counselling for future births should be considered for women with thirdand fourth-degree tears, with consideration of caesarean section for future births, especially in women with anal incontinence.

CERVICAL LACERATIONS CLINICAL FEATURES The characteristic feature of a cervical laceration is a steady loss of bright red blood, which commences soon after delivery of the baby. Unless the uterus is also damaged, it is firmly contracted. These features help to distinguish traumatic and placental-site bleeding.

Chapter 30  Episiotomy and Vaginal Outlet Tears

MANAGEMENT Control of blood loss before repair If the loss is heavy, bimanual compression should be employed (vaginal hand pressing firmly against the front of the cervix and lower segment, abdominal hand pressing the back of the uterus downwards and forwards against the vaginal hand). Packing may be used as an emergency, but must be properly performed; it often wastes time and blood, and bimanual compression is preferable.

Technique of repair The vaginal walls are well retracted by an assistant and a systematic inspection is made of the vagina and cervix. If the bleeding is from a vaginal laceration, it is closed with a continuous or interrupted chromic catgut suture. If the bleeding is from a cervical laceration, the cervix is grasped with two or more sponge forceps and drawn down until the apex of the tear is visible. A suture is placed just beyond this to secure haemostasis and the repair is completed with either a continuous or interrupted suture. Cervical lacerations are common during normal delivery (as seen in gynaecological practice when cervical cytology is performed), but seldom cause persistent haemorrhage requiring repair.

If the bleeding is coming from inside the cervical canal, it is likely that its origin is from the placental site or a tear in the uterus; exploration will determine this.

VULVAL OR VAGINAL HAEMATOMA The incidence of significant haematoma formation is approximately 1/1000 deliveries. The bleeding in this case is into the tissues, rather than external. It is caused by continued bleeding from vessels that have retracted into the deep paravaginal and vulval tissues (Fig 30.5). There may or may not be an overlying tear that has been repaired. Obviously, it is preferable to secure any deep bleeding point at the base of a tear or episiotomy to avoid haematoma formation. Rarely, the haematoma may be associated with uterine rupture, in which case the vaginal haematoma will usually extend up into the broad ligament. The degree of discomfort to the woman is proportional to the size of the haematoma; if large, severe pain is experienced (classically perirectal) and shock may result. Management is most often conservative as incision and draining may alleviate ‘tamponade’ of a deep-bleeding vessel and cause further bleeding which is difficult to control. The alternative is to attempt drainage of the

FIGURE 30.5 

Vulval haematoma seen 3 hours after a normal delivery due to failure to achieve haemostasis during repair of an episiotomy. An indwelling catheter was required because of urinary retention. The haematoma was evacuated and the woman was transfused with four units of packed cells. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

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haematoma with insertion of a vaginal pack to tamponade against further bleeding. A urinary catheter will be needed if a vaginal pack is inserted. FURTHER READING de Leeuw JW, de Wit C, Kuijken JP, et al. Mediolateral episiotomy reduces the risk for anal sphincter injury during operative vaginal delivery. BJOG 2008;115(1):104–8.

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Rezaei Z, Haghighi Z, Haeri G, Hekmatdoust A. A comparative study on relieving post-episiotomy pain with diclofenac and indomethacin suppositories or placebo. J Obstet Gynaecol 2014;34(4):293–6.

Chapter 31  INSTRUMENTAL DELIVERY Michael Permezel and Gillian Paulsen

KEY POINTS Approximately 12% of births are instrumental vaginal deliveries. Common indications include fetal compromise and delay in the second stage of labour. They are also used if the mother is not advised to ‘push’ and for the aftercoming head of a vaginal breech delivery. An instrumental birth can only be contemplated if the cervix is fully dilated and both the presentation and station are favourable. A favourable presentation is usually a vertex but can be a deflexed vertex (usually occipitoposterior) or a face in the mentoanterior position. The ‘station’ required is engagement, which means that the maximum diameter of the presenting part is through the pelvic inlet. Engagement is determined by both abdominal palpation and vaginal examination. With a vertex presentation at engagement, there is no head palpable abdominally and the vertex has reached the level of the ischial spines in the absence of caput or moulding. Prior to embarking on an instrumental birth, the membranes should be ruptured, uterine contractions present, the bladder emptied and appropriate anaesthesia in place. Perineal infiltration may be adequate for a vacuum but not for a forceps delivery. The choice between forceps and vacuum is often an individual one but each obstetrician should be able to do both types of instrumental birth. Simplistically, the vacuum is less traumatic for the mother as forceps need extra room beside the head. However (and importantly), the vacuum is associated with the very serious neonatal side effect of subaponeurotic (subgaleal) haemorrhage.

HISTORY The forceps, first brought into use in the 17th century by the Chamberlens, a Huguenot family, represent one of the milestones in obstetrical practice. The story of the invention is a fascinating one, in that it was hidden from general use for generations for personal profit by the family. James Young Simpson is credited with designing the first vacuum-like instrument in 1848, which he referred to as an ‘Air Tractor’. However, it was not until 1954 that

Tage Malmström in Sweden perfected and introduced the vacuum into clinical practice.

CHOICE BETWEEN INSTRUMENTS: FORCEPS OR VACUUM? In some centres, the vacuum extractor has almost entirely replaced the forceps; in others, it is hardly used at all. The correct situation is probably a balance between the two.

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The pros and cons of the two instruments are given in Table 31.1.

INCIDENCE There is a very wide range according to variations in the facilities available and different philosophies of practice. A common incidence would be approximately 12%. Centres with a high rate of epidural analgesia for pain relief in labour will generally have a higher rate due to a large number of ‘lift out’ instrumental births where the epidural has prevented the mother from being able to push the fetus over the perineum. Units that prefer a caesarean section to a rotational or mid-cavity instrumental delivery will have a lower instrumental rate but a higher caesarean section rate.

INDICATIONS The classical indications for instrumental birth are given below.

PROLONGED SECOND STAGE OF LABOUR This is the most common indication yet also the most contentious. The issue is discussed in more detail in Chapter 33 but, simplistically, a long second stage is undesirable because it increases the risk of fetal compromise and also increases the likelihood of compression injury to the structures (especially nerves) of the pelvic floor. The former can largely be averted by a policy of continuous cardiotography where second stage is prolonged but pelvic floor damage remains an issue. The usual time limits for the ‘active’ second stage (i.e. ‘pushing’) are 2 hours for nulliparas and 1 hour for multiparas, although it should be remembered that these are merely guidelines and will depend on the condition of the mother and fetus as well as the nature and progress of the labour.

FETAL COMPROMISE The fetus is more prone to hypoxia in the second stage of labour for two reasons. First, as a result of the reduced maternal uteroplacental blood flow caused by the high intrauterine pressures during frequent, strong contractions with additional pressure rise from maternal pushing. Second, umbilical cord compression is very common in the second stage of labour with descent of the presenting part. This is rarely a consequence of cord prolapse and much more commonly the cord is tightened around the neck or shoulder or is between a fetal body part and the uterine wall.

MOTHER NOT ABLE TO BEAR DOWN (PUSH) Where the mother is not able to perform Valsalva manoeuvre (strain, push, bear down), an instrumental delivery will be necessary to effect birth. It is very uncommon for the lower birth canal and pelvic floor to allow birth with uterine contractions alone. Almost always some additional forces are required, either maternal effort from above or instrumental traction from below. Conditions where maternal straining is contra­ indicated include severe hypertension, preeclampsia/ eclampsia, cardiac disease, diabetic proliferative retinopathy, subarachnoid haemorrhage, Marfan’s syndrome (risk of aortic dissection) or a tumour or arteriovenous malformation that may haemorrhage under the added pressures of a maternal Valsalva.

AFTERCOMING HEAD OF A VAGINAL BREECH DELIVERY Forceps are often applied to the aftercoming head of the breech, to facilitate delivery (Fig 31.1). It should be noted that traction is being applied to the more brittle parietal

TABLE 31.1  FORCEPS VERSUS VACUUM. Forceps delivery

Vacuum delivery

More

Less

  skull fracture and intracranial haemorrhage

Rare

Extremely rare

  subgaleal haemorrhage

Rare

Uncommon

Analgesia requirement

Regional or general

Perineal infiltration mostly adequate

Contraindications

Those for vaginal birth

Face, preterm < 34 weeks’

Failure rate in the absence of cephalopelvic disproportion

Very low

Low

Maternal trauma Serious fetal injury

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bones in this circumstance rather than around the exceptional hard base of skull. At caesarean section, forceps may be used to deliver the baby’s head through the uterine incision (see Ch 32).

FIGURE 31.1

Forceps delivery of the aftercoming head of a vaginal breech delivery with the assistant holding the baby up by the legs. Source: Courtesy of Prof. Norman Beischer.

STATION PRIOR TO INSTRUMENTAL BIRTH The ‘station’ is the level of descent of the presenting part within the birth canal. The expected difficulty of instrumental birth can be to some extent anticipated by the station of the presenting part at the commencement of the procedure. (See Fig 31.2.) 1. Outlet station (or ‘lift-out’). The head has reached the pelvic floor, the position is anterior and the scalp can be seen at the introitus without parting the labia. 2. Low station. The maximum diameter of the head is through the narrowest plan of the pelvis—the bispinous diameter. Prior to a low-instrumental birth, in the case of a vertex presentation the presenting part will be at least 3 cm below the ischial spines in the absence of caput and moulding. 3. Mid-cavity station. The head is ‘engaged’; that is, the maximum diameter of the presenting part has passed through the pelvic inlet. No head will be palpable abdominally and the vertex has at least reached the level of the ischial spines in the absence of caput and moulding. It is extremely important to realise that in the case of a mid-cavity instrumental birth, the maximum diameter of the head is not yet through the narrowest part of the pelvis. It is still possible that the head may not fit through the pelvis and a caesarean section might be needed if instrumental birth is not easily effected. 4. High station. The head is not engaged.

1 2

A

3

B

C

FIGURE 31.2

Types of forceps delivery and direction of traction. A Station of the head for mid-forceps (1), low forceps (2) and outlet forceps (3) deliveries. The arrows show how the direction of traction must change as the head descends, in order to follow the curve of the birth canal. B The usual type of mid-forceps delivery: the lowest part of the presenting part (vertex) is past the level of the ischial spines and the maximum diameter of the head is through the pelvic inlet. C Outlet forceps: the greatest diameter of the head is past the narrow pelvic plane. Delivery is completed by extension of the head around the symphysis pubis. 259

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DESCRIPTION OF THE INSTRUMENTS OBSTETRIC FORCEPS The obstetric forceps consists of two pieces, joined together by a locking mechanism. Each piece has a handle and this

is connected to the blade by the shank (Fig 31.3). The lock is usually situated at the junction of the handle and shank; it is usually of fixed type but may be sliding, as in Kielland forceps. There is often a projection at the lower end of the handle called the shoulder, which is used for assisting traction and/or rotation of the baby’s head. The blades of the forceps, which are applied to each side of the head, are

A

B FIGURE 31.3

A Barnes forceps are shown on the left and Kielland forceps on the right. The cephalic curve of the blades is similar in each. The different locking mechanisms are shown. B Lateral view showing that Barnes forceps have a much larger pelvic curve than Kielland forceps. Source: Courtesy of Prof. Norman Beischer.

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usually open (fenestrated). In all forceps there is a cephalic curve which fits the contour of the baby’s head, and a pelvic curve, which allows for the concave shape of the sacrum. In forceps primarily designed for rotation of the head (e.g. Kielland forceps), the pelvic curve is minimal. By means of the cephalic and pelvic curves, each forceps blade can be designated as left or right, according to which side of the maternal pelvis it is applied.

VACUUM EXTRACTION DEVICE (‘VENTOUSE’) The principle of use is that a suitably sized plastic or metal cup is applied as near the occiput as possible (to maintain flexion during traction) and a vacuum is created inside the cup by means of a hand or electric pump. Ideally the cup should be placed over the posterior fontanelle symmetrically (i.e. the sagittal suture is evenly overlapped on either side by the cup). The suction draws the loose scalp of the fetus into the cup in the form of a ‘chignon’. Traction is then applied by means of a chain or cord attached to the cup with a handle on the other end. Pressure tubing passes from (or along) the traction handle to the source of suction. A pressure gauge indicates the pressure developed in the system.

THE PROCEDURE OF INSTRUMENTAL DELIVERY PREREQUISITES The traditional description is FORCEP, as follows. 1. Favourable presentation, position and station. Position: the vertex should be occipitoanterior unless using Kielland or similar forceps. If the station is low, it is possible to perform a forceps delivery ‘face to pubes’ with the occiput remaining posterior. In the rare event that a forceps delivery is performed with a face presentation, the necessary position is mentoanterior. Station: the head must be ‘engaged’. This is defined elsewhere in the chapter. 2. Os (cervical) fully dilated. 3. Ruptured membranes. 4. Contractions present: the absence of contractions after a long labour and uterine exhaustion increases the likelihood of an atonic postpartum haemorrhage; in this situation, an oxytocin infusion should be commenced before beginning the instrumental birth 5. Empty bladder. 6. Pelvic and perineal analgesia. It is apparent that steps 3 to 6 can be accomplished with therapeutic procedures but 1 and 2 need to be present. That is, the decision as to whether an instrumental birth

can be contemplated requires FO: a favourable presentation and station with the cervix fully dilated.

PRIOR TO COMMENCING AN INSTRUMENTAL BIRTH The woman should be fully informed of the reason for the procedure and what is involved, but a specific written consent form is not required in most centres. The indication should be clear and also that the basic requirements are met in terms of station, presentation and full dilatation of the cervix.

TECHNIQUE The woman is usually in the lithotomy position and full antiseptic preparations and draping are carried out; precaution against the supine hypotensive syndrome (pelvic tilt) may be indicated as for caesarean birth. Anaesthesia may be local (perineal infiltration), regional (pudendal nerve block, epidural or spinal) or general (Chapter 38) depending on the station and position of the head, and the anticipated difficulty of the procedure. Perineal infiltrate may be adequate for a low vacuum birth but not for a forceps delivery. The bladder is catheterised and then emptied. A careful examination is made to determine the state of the membranes, dilatation of the cervix, presentation, station and position of the head, presence of caput and moulding and the tightness of fit of the head in the pelvis. The forceps are applied left blade first into the hollow of the sacrum and wandered over to the left side of the fetal head. The same on the opposite side occurs with the right blade, followed by locking the two together (Figs 31.4 and 31.5).

Outlet and low forceps delivery Here the blades are applied to the sides of the baby’s head, the left blade being inserted first. A check is made that the forceps are applied correctly and symmetrically. If this is the case, the two blades come together and lock easily (Fig 31.5); the sagittal suture lies midway between the blades and parallel to them. Minor rotation may be necessary to bring the sagittal suture to the anteroposterior position. Traction is applied at the time of contractions and with the mother bearing down. The direction of traction follows the direction of the birth canal. The fetal heart should be auscultated between contractions. As the head distends the perineum, the direction of traction moves horizontally and then upwards in line with the birth canal. An episiotomy is preformed unless there is little perineal resistance and no sign of tearing. The blades are carefully removed as the head is about to pass through the expanded vulva, and the rest of the procedure is carried out as for a normal delivery.

Mid-cavity forceps delivery The general procedure is similar to that outlined in the outlet forceps, the main difference being in the rotation of the fetal head. The first essential is an accurate appraisal 261

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A

B

C

D

E

F

G FIGURE 31.4

Technique of forceps application.  Note that forceps are held with the handle in the palm of the hand when being applied; in these pictures the instrument is held by the shank to show the movements of the handle. A Introduction of the left blade. The handle is rotated through a wide circle to avoid trauma by the blade as it rotates into position around the head. B The handle is lowered and the blade passes the fetal cheek and temple. C The blade in position when applied to the head with its pelvic curve coinciding with that of the birth canal. D Introduction of the right blade which is inserted in the midline. E The blade passing fetal cheek and temple. F The forceps in position and locked. G The biparietal diameter of the fetal head is enclosed within the widest diameter of the forceps and the tips overlie the fetal cheeks. The head is well flexed (posterior fontanelle readily palpable). Source: Courtesy of Prof. Norman Beischer.

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A

B

C

D

FIGURE 31.5

Forceps application and delivery. A This primigravida had delay in the second stage of labour with the head on view. An outlet forceps was performed. The left forcep blade is first inserted between the fetal head and the hollow of the sacrum. Note lubrication of the forceps and the fingers of the left hand protecting the vaginal wall. B The right forcep blade is then inserted into the same position and wandered 90° to the right in the same way as the left. C The forceps have been locked into position and a right mediolateral episiotomy is performed, commencing at the fourchette in the midline. D Delivery of the head by traction. Source: Courtesy of Prof. Norman Beischer.

of station, flexion and position. This is aided by the usual measures of palpation of sutures and fontanelles. If there is any uncertainty, additional palpation of the ear and occipital ridge is essential (Fig 31.6). Ultrasound may be used to confirm fetal position but will rarely be needed by an experienced accoucheur. If the position is not occipitoanterior, rotation of the head is achieved either manually or by means of forceps. If manual rotation is performed, the head is held in the anterior position and the forceps blades are applied. Great care is necessary to ensure that they are symmetrically placed on the baby’s head, since this is the key to successful delivery and a baby in good condition. Traction is often much greater than that required for outlet forceps. Because of the higher station in the pelvis, the correct direction of pull is aided by exerting downward pressure on the shanks of the forceps with traction (Pajot’s manoeuvre) or applying the axis traction apparatus.

If forceps rotation is to be attempted, a larger episiotomy is usually made and the Kielland forceps employed. The blades are applied to the fetal head in the posterior or occipitolateral (transverse) position, usually by ‘wandering’ the anterior blade over the baby’s face (the sinciput being smoother than the occiput offers less resistance to the forceps blade as it is rotated into position), and directly applying the posterior blade. The handles of the instrument are pushed downwards against the perineum and the occiput is rotated to the front by means of a rotational force applied to the shoulders on the blades. While traction forces are applied to the very hard bones at the base of skull, rotational forces are applied over the softer parietal bones. Fetal damage (skull fracture and/or intracranial haemorrhage) may be the consequences, and rotational forceps should only be undertaken with caution and under the direction of an experienced obstetrician. 263

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A

B

FIGURE 31.6

Diagnosis of position of the fetal head. A The anterior fontanelle is readily palpated when the head is deflexed (unless there is considerable caput). B When the position is occipitolateral, the ear may be palpated below the pubic symphysis. The root of the ear indicates whether the occiput is to the left or right.

Vacuum birth The cup, lubricated with obstetric cream, is inserted into the vagina—preferably at the time of a contraction. Perhaps the single most important factor in safety and success is placement of the cup in the proper area of the fetal skull. The application of the vacuum cup is at the flexion point, which is 3 cm anterior to the posterior fontanelle. The edge of the cup should abut the edge of the posterior fontanelle. After a negative pressure of 0.1 to 0.2 kg/cm2 is reached, a check is made that there is no interposed maternal tissue under the cup edge. Traction is applied coincident with uterine contractions and maternal effort. If the position of the fetal head is not occipitoanterior, the direction of pull is the same but the occiput should rotate to the front spontaneously during descent. The vacuum should not be applied for more than 15 minutes and should also be ceased if there is no progress with active pulling with three contractions. If birth has not been achieved, either caesarean section or forceps delivery should be performed. Vacuum birth followed by forceps delivery has the highest complication rates but becomes the only option if the head has reached a low station but the vacuum has been unsuccessful.

NON-VERTEX PRESENTATIONS Face presentation The same principles apply as with vertex presentations; however, greater care is necessary to avoid damage to the facial structures during placement of the blades. Obviously, a vacuum cannot be used with a face presentation.

Brow presentation In most cases of brow presentation at full dilatation, a caesarean section is still the preferred option. However, some brows will descend deeply into the pelvis and behave 264

more as a particularly deflexed occipitoposterior position. In these cases, rotation with Kielland’s through 180° may lead to flexion of the fetal head and a relatively easy delivery of a vertex in the occipitoanterior position.

TRIAL OF INSTRUMENTAL DELIVERY A trial of instrumental delivery is done in the operating theatre, with everything ready for caesarean section should the instrumental delivery not succeed. There are several advantages to being in the operating theatre for what may be either a difficult instrumental birth or a failed instrumental birth and caesarean section. Fetal condition is commonly compromised by a trial of instrumental birth. This is thought to be a consequence of a vagal reaction to the application of either vacuum or forceps. The consequent bradycardia can cause hypoxia and acidosis as a consequence or reduced fetal placental blood flow. If a difficult instrumental vaginal delivery is successfully accomplished, both shoulder dystocia and lower genital tract tears are common. Both these conditions benefit from the superior anaesthesia, lighting and assistance available in the operating theatre.

•

•

FAILED INSTRUMENTAL BIRTH ‘Failed instrumental birth’ is an undesirable term as it implies some deficiency in management when in fact the opposite is more likely. The astute clinician is aware that it is very difficult to predict which mid-cavity instrumental birth can be effected easily with minimal risk to mother and fetus and which cannot. The wise course of action in these circumstances is obviously to attempt an instrumental birth but if unexpected difficulty is encountered at any step (application, rotation or traction), abandon the procedure and move to prompt caesarean section.

Chapter 31  Instrumental Delivery

Forceps delivery after failure of vacuum A particular situation is where the vacuum fails to obtain an airtight seal and traction keeps resulting in the seal being broken and the cup falling off. Many clinicians will then appropriately apply the forceps, particularly if the station is low. Criticism that a caesarean section should have been performed would appear ridiculous if the station is low and the forceps performed without difficulty.

ADVERSE EFFECT OF INSTRUMENTAL BIRTH MATERNAL High vaginal and cervical tears, third- and fourth-degree perineal tears Even with a meticulous technique, tears are to some extent unpreventable. Every effort should be made to perform procedures slowly to enable tissues to stretch rather than tear.

Postpartum haemorrhage This may be from genital tract trauma (at any level) but also from an atonic postpartum haemorrhage. It is not uncommon to perform an instrumental birth for delay in the second stage related to uterine exhaustion. Having delivered the baby with forceps or vacuum, the uterus remains atonic in the third stage of labour. For this reason, contractions should be reinstated with an oxytocin infusion prior to embarking on an instrumental birth.

FETAL Skull fracture and/or intracranial haemorrhage Incorrect application of the forceps may cause abnormal distortions of the skull architecture with potential rupture of large intracranial veins. Mostly this is inadvertent and a consequence of excessive moulding of the fetal head, rather than incorrect technique. It happens that with the unmoulded fetal head in the occipitoanterior position, the tips of the forceps (where traction is applied) serendipitously come to lie on the extremely hard mastoid and petrous temporal bones at the base of the skull. However, with a posterior position or excessive moulding, traction may be exerted over the softer occipital bones with resulting risk to the integrity of the skull and the underlying intracranial vessels. Also, during rotation, there are forces applied to the parietal and frontal bones that are less able to take these stresses (Fig 31.7). Damage to the cervical spine and/or vertebral arteries may occur with rotational births. Complete uterine relaxation (often assisted pharmacologically) is essential before embarking on a rotational forceps. Direct damage to structures such as the eye, nose and ear is more likely (Fig 31.8). Occasionally, pressure

FIGURE 31.7

Depressed fracture of the left frontal bone in a 1-day-old 3100 g male infant born after a Kielland forceps rotation. The fracture was elevated after four days and the outcome was (surprisingly) good. Source: Courtesy of Prof. Norman Beischer.

of the forceps blade on the facial nerve as it passes forwards in front of the ear causes temporary paralysis of that side of the face. Abrasions are not uncommon, but these heal quickly.

Sub-aponeurotic haematoma (subgaleal haemorrhage) The scalp is an aponeurosis that slips easily over the underlying skull. This property reduces the risks of abrasive injury with bumps to the head. The absence of any firm attachment between scalp and underlying skull means that there is a large potential space into which bleeding can occur. The volume can be more than 500 mL and result in fatal hypovolaemia in a neonate with total blood volume not much more than a litre. This most commonly occurs with vacuum birth when the scalp is lifted from the skull, potentially tearing veins. Early diagnosis is essential and there are recommended guidelines for close neonatal surveillance after anything other than very straightforward vacuum births.

Soft tissue injury The vacuum causes a large oedematous lump on the scalp (chignon). This disappears in the first 24 hours. Of longer duration is a cephalhaematoma which is due to subperiosteal bruising (Fig 31.9). This can last many weeks but eventually resolves. It is particularly common after forceps delivery but also may occur after vacuum birth or even spontaneous vaginal birth.

Shoulder dystocia While not strictly a consequence of the instrumental birth, if the head just makes it through the pelvis it is 265

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A FIGURE 31.9

Bilateral cephalhaematoma in a 4-day-old infant of birth weight 4170 g born by mid-cavity forceps from the occipitoanterior position. These can be expected to resolve spontaneously without long-term sequelae. Source: Courtesy of Prof. Norman Beischer.

possible that the shoulders may not. Anticipation of possible shoulder dystocia should accompany every mid-cavity instrumental birth undertaken for failure to progress. This is particularly so if the position is occipitoanterior, as it is genuine cephalopelvic disproportion causing the slow progress rather than an unfavourable presenting diameter as occurs with a posterior position. B FIGURE 31.8

A Periorbital haematoma in a 4-kg male infant aged 4 days. He was born by rotational forceps. B Corneal opacity beneath the orbital haematoma, related to a corneal abrasion. Two weeks later the corneal opacity had resolved but vision was impaired in that eye at follow-up. Source: Courtesy of Prof. Norman Beischer.

266

FURTHER READING RANZCOG. College statement: instrumental vaginal delivery (C-Obs 16); Nov 2012. Online. Available: . RANZCOG. College statement: rotational forceps (C-Obs 13); Nov 2012. Online. Available: . RANZCOG. College statement: prevention detection and management of subgaleal haemorrhage in the newborn (C-Obs 28); July 2012. Online. Available: .

Chapter 32  CAESAREAN SECTION AND TRIAL OF LABOUR AFTER CAESAREAN Michael Permezel

KEY POINTS Caesarean section is the mode of birth in approximately 30% of pregnancies. The overall rate is surprisingly uniform across Western countries, with the Scandinavian countries having notably lower rates than others. The rise in the caesarean section rate over the last 50 years has generated much political debate. There are essentially two reasons for this rise. The first is an increasing incidence of conditions more likely to lead to caesarean section such as advanced maternal age and increasing maternal obesity. The second and more important reason is the evolution of a more risk-averse population. In the past, a less risk-averse maternity sector would attempt vaginal birth with conditions that had a ‘low’ incidence of poor outcome that could have been averted by caesarean section. For most women now, unless the likelihood of an adverse outcome as a consequence of vaginal birth is ‘extremely low’, caesarean section will be preferred. The most common reason for a caesarean section is that the woman has had one previously. The first caesarean section most commonly had been performed for obstructed labour, poor progress in labour and/ or fetal compromise or a malpresentation. Approximately 99% of caesarean sections are performed through a transverse incision in the lower uterine segment. The classical incision is a vertical incision in the upper uterine segment and the consequent uterine scar is 20 times more likely to rupture in the next pregnancy in comparison to the lower-segment incision. Overall, a woman who has had a single transverse lower uterine segment caesarean section has a 1 in 200 risk of uterine rupture if she tries to birth vaginally in her next pregnancy and approximately 1 in 5 of these will be associated with a perinatal death. The improved perinatal outcome with repeat caesarean section is partly due to avoiding uterine rupture but even more attributable to the lower perinatal mortality if born at 39 weeks’ gestation rather than awaiting spontaneous labour beyond that date. If labour is occurring after a previous caesarean section, assessment of both fetus and progress should be vigilant, with early recourse to caesarean section if progress is inadequate or there is acute fetal compromise.

DEFINITION Caesarean section is the surgical technique whereby the fetus is delivered through an incision in the uterus.

INCIDENCE There is considerable variation in the incidence of caesarean section between types of hospitals, with higher rates

in the tertiary centres and private sector. The overall caesarean section rate in most OECD countries is in the 28 to 32% range; Australia is fairly typical. Much has been made of the continuing rise in caesarean section rate. Clearly, it is not unique to Australia. There are essentially two reasons for this rise. First, there is a change in profile of the pregnant population that makes them more likely to need a caesarean section. The most obvious changes are increases in maternal age,

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maternal obesity and gestational diabetes mellitus (in part linked to the first two). The other and more important reason for the worldwide increase in caesarean section is that women are becoming more ‘risk averse’. That is, most women are relatively intolerant of even small risks to their fetus in order to achieve a vaginal birth.1 This means that where previously most women would be accepting of the very small added risks of, say, vaginal breech delivery, most women now will opt for a caesarean section in that circumstance. Other obstetric conditions carry similar small risks with vaginal birth (e.g. previous caesarean section) and many women now choose caesarean section over attempted vaginal birth in such situations.

TYPES OF OPERATION UTERINE INCISION Lower uterine segment caesarean section The lower uterine segment caesarean section (LUSCS) is by far the most common technique (98%). The approach is nearly always a transverse one through the lower uterine segment after opening the peritoneal cavity and then the loose peritoneum over the lower uterine segment. Rarely, an extraperitoneal approach is used.

Classical caesarean section This was the only type of operation used for several centuries, hence the term ‘classical section’ but is now performed in only approximately 1% of caesarean sections. A vertical incision is made in the upper part (i.e. body) of the uterus (Fig 32.1). Common indications include a transverse lie with the back down and extreme prematurity where there the lower uterine segment is not as yet formed. Classical caesarean section has a much higher rate of uterine rupture in subsequent pregnancy, both antenatally

A FIGURE 32.1

and in labour. If vaginal birth is attempted after a classical caesarean section, uterine rupture can be expected in about 10% of cases (compared to only 0.5% after a transverse lower uterine segment caesarean section).

Vertical lower uterine segment caesarean section This is a ‘compromise’ technique where the lower segment is not yet fully formed but is long enough to deliver a preterm infant. Rupture rates in a subsequent pregnancy are probably less than for a classical incision.

ELECTIVE/EMERGENCY CAESAREAN SECTION An elective caesarean section is both planned antenatally and performed before the onset of labour. An emergency caesarean section is either performed in labour or unplanned in the antenatal period. A repeat elective caesarean section at 39 weeks’ on a routine operating list would be elective, but a caesarean section performed for fetal compromise or obstructed labour would be an emergency. The distinction is not always clear as a woman with a previous caesarean section may develop preeclampsia and the following day have a previously unscheduled caesarean section—this could be classified either as emergency or elective.

INDICATIONS There are few more contentious issues in medicine than the decision to have a caesarean section rather than a vaginal birth. Passions run high on both sides of the decision equation. As indicated earlier, this is not a unique situation in any geographic location and not confined to the developed world. China and Brazil both have relatively high caesarean section rates while the rates in Scandinavian countries are relatively low compared to others in Europe.

B

A The lower uterine segment incision. Note the thin uterine muscle and incision in the lower uterus just above the retractor. B The classical caesarean section incision. The skin is still incised transversely above the symphysis but the uterine incision is vertically through the thick muscle of the upper uterine segment. 268

Chapter 32  Caesarean Section and Trial of Labour after Caesarean

THE DECISION EQUATION FOR CAESAREAN SECTION VERSUS VAGINAL BIRTH Like all decisions in medicine, the decision for caesarean section is a balance of pros and cons. A model for the decision equation for caesarean section is given in Figure 32.2. In many cases, the maternal (e.g. major placenta praevia) or fetal (e.g. cord prolapse) advantage of caesarean section is so overwhelming that a maternal preference for vaginal birth does not materially affect the decision.

Maternal preference for a mode of birth and maternal risk tolerance There are many situations where the maternal or fetal advantages of caesarean section are much more subtle, and a maternal preference for vaginal birth in a relatively risk-tolerant woman appropriately becomes the determining factor in recommending attempted vaginal birth. Equally, in a similar clinical equation that is relatively evenly balanced and where the mother has no strong preference for vaginal birth but is particularly risk averse, it is appropriate for her preference to become the determining factor in favour of a caesarean section.

The influence of intended and likely future parity In a discretionary situation, where both attempted vaginal birth and caesarean section appear reasonable options, the likely and intended future parity are of great importance. Of all the adverse effects of caesarean section, the most grave is the possibility of placenta accreta in a subsequent pregnancy. The likelihood of such an outcome

increases almost exponentially as parity (and the further number of caesarean sections) increases. Recommendations in a 43 year old may therefore be quite different to those made to a 22 year old who is intent on having a large family.

COMMON INDICATIONS FOR CAESAREAN SECTION These conditions are covered in the various chapters as indicated.

Uterine scar Repeat elective caesarean section versus trial of vaginal birth after caesarean is addressed later in this chapter. There is less information regarding risks posed by other uterine scars but ruptures have certainly been recorded after myomectomy (especially if the scar is full myometrial thickness), uterine perforation at curettage and hysteroplasty for fusion abnormalities of the Müllerian system.

Obstructed labour (Ch 34) True obstructed labour is now relatively uncommon as most labours progress slowly before developing signs of obstruction and the caesarean section is performed for slow progress before all signs of obstruction have developed.

Inadequate progress in labour and/or fetal compromise (Ch 33) Inadequate progress in labour and fetal compromise commonly occur together. Typically, inadequate progress leads to an oxytocin infusion, which may not be tolerated if there is already borderline fetal compromise. The oxytocin has to be ceased in the interests of fetal wellbeing

Psychological Neonatal RDS Maternal risks of index pregnancy Maternal risks of subsequent pregnancy

Pelvic floor damage Perinatal moridity and mortality

Planned vaginal Birth

Elective caesarean section

FIGURE 32.2

The risk–benefit equation for planned delivery versus elective caesarean section. 269

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but then there are inadequate contractions to achieve progress. The result is commonly a caesarean section. Fetal compromise can, of course, occur in the absence of an oxytocin infusion for many reasons, as discussed in Chapter 33.

Malpresentation (Ch 15) A transverse or oblique lie in labour will almost always require a caesarean section. A breech presentation can be safely delivered vaginally, but only after a full and satisfactory assessment, including an ultrasound to exclude fetal abnormality or head extension (Ch 15). Most brow presentations will have a caesarean section, but some will effectively be a very deflexed posterior position and respond to rotation with full flexion and therefore deliver vaginally. Although a mentoanterior face presentation may deliver vaginally, a mentoposterior face presentation will almost invariably require caesarean section.

Antepartum haemorrhage (Ch 10) A major degree of placenta praevia requires caesarean section. If the lower placental edge impinges on the lower uterine segment but is more than 2 cm away from the internal cervical os, vaginal birth may still be possible. Where the placenta does not cover the os (grade 1 or 2) on a 32-week scan, a repeat ultrasound at around 36 weeks’ will establish whether expansion of the lower uterine segment has sufficiently displaced the placenta upwards to enable a vaginal birth. Minor degrees of placental abruption can usually deliver vaginally. A ‘moderate abruption’ (tense tender uterus or blood loss > 200 mL with a live fetus) may benefit from caesarean section on diagnosis, as rapid fetal deterioration can occur with further placental separation. A severe abruption is defined as sufficient placental separation to cause fetal death. Heavy blood loss is the rule and disseminated intravascular coagulation (DIC) will almost inevitably develop over the next few hours. There are two schools of thought. The first avoids caesarean section so that there is not a surgical wound in addition to the placental bed from which to bleed when the DIC develops. The second view is to perform an early caesarean section to avoid the development of DIC. Both strategies probably have a place, and a considered recommendation should be made given an understanding of the pathophysiology and the circumstances of the individual case.

Severe preeclampsia and eclampsia (Ch 16) Preeclampsia is not in itself an indication for caesarean section. However, when severe preeclampsia occurs at very or extreme preterm gestations, the cervix is commonly unripe and in the presence of preeclampsiaassociated placental insufficiency, induction of labour without fetal compromise is often unachievable and a caesarean section is the preferred option. 270

Multiple pregnancy (Ch 14) Multiple pregnancy does not mandate a recommendation for caesarean section. However, intrauterine manipulation (internal version and breech extraction) is reasonably likely to be needed between birth of the first and second twins. If this is contraindicated (e.g. previous caesarean section), elective caesarean section is usually preferred. Malpresentation of the first twin is also common in multiple pregnancy and a caesarean section is recommended. Note that malpresentation of the second twin does not usually affect the recommendation regarding mode of birth.

Probable cephalopelvic disproportion (Ch 33) It is almost axiomatic that it is not possible to predict cephalopelvic disproportion antenatally and attempted vaginal birth is the best approach, even if obstructed labour and an emergency caesarean section is a likely outcome. Certainly, there is little current credibility with attempts to predict outcome of labour with a combination of estimating fetal size on ultrasound and the maternal pelvis radiologically. There are, however, some situations where a successful vaginal birth is so unlikely that caesarean section is the appropriate recommendation. This will most often be where either mother or fetus is at the extremes of normality. An estimated fetal weight of ≥ 5 kg might lead to a recommendation for abdominal delivery unless the mother was obviously very tall with a likely large pelvis. Maternal height < 150 cm might similarly lead to a caesarean section recommendation unless the fetus was obviously small. Somewhere between is the primigravida with a high mobile head at 40 weeks’ or beyond. There is unequivocally a much higher rate of caesarean section in these cases and many clinicians will recommend elective caesarean section rather than a trial of labour, but both options are reasonable.

Caesarean section on maternal request Increasingly, some women are requesting caesarean section in the absence of a specific additional risk to mother or fetus. Most clinicians will respond favourably to such a request but have an obligation to ensure that the decision is a well-informed one. In particular, the woman should be apprised of the pros and cons of her request; of prime importance would be the future risk of placenta accreta if high parity is intended.

THE PROCEDURE PREPARATION FOR CAESAREAN SECTION Consent for an elective procedure is usually obtained at a late antenatal visit. The woman needs to be aware of two things: 1. what is going to happen prior to, during

Chapter 32  Caesarean Section and Trial of Labour after Caesarean

and after the procedure; and 2. any potential adverse consequences of the procedure. The gestation selected for a repeat elective caesarean section is usually at approximately 39 weeks, balancing the risk of neonatal respiratory distress against the undesirability of performing the procedure so late that the woman comes into labour and the operation then done as an emergency with increased attendant risks. Fasting is required before the procedure. For elective operations, the woman is admitted on the day of surgery. For morning surgery, the woman fasts overnight. If the operation is in the afternoon, she can have a light breakfast at least six hours before planned surgery. Blood tests are conducted prior to surgery. Two units of blood are cross-matched if an above-normal loss is expected (e.g. placenta praevia); otherwise, in many centres the blood is typed and screened for unexpected antibodies and cross-matched only if required (blood group and antibody screen). Only 1% of women will require a blood transfusion because of excessive haemorrhage at elective caesarean section; it is noteworthy that this rate is less than the rate of transfusion after vaginal delivery! Gastric acidity reduction is required for emergency caesarean section in labour. In active labour, gastric emptying is delayed, and so emergency caesarean section is always regarded as having a risk of aspiration of gastric contents. It is common to administer an H-1 selective antihistamine (e.g. ranitidine) or an antacid such as sodium citrate prior to emergency caesarean section. Regional analgesia, usually spinal, is the safest technique for mother and baby, and is used in the vast majority of elective procedures and in emergency procedures where possible if there is no existing epidural block. In emergency procedures, if there is an existing epidural block for labour this can be ‘topped up’ for the caesarean section. It is uncommon for general anaesthesia to be necessary, and it has many disadvantages (Ch 38). An intravenous infusion is commenced if it is not already running. Blood loss at caesarean section is often unpredictable, and can be heavy. In addition, the resulting haemoconcentration and trauma predispose to thromboembolism. Antibiotic prophylaxis at the time of caesarean section significantly reduces the incidence of endometritis and wound infection. There is some conflict regarding the timing of antibiotic administration. Early administration is most effective in preventing infection but risks anaphylaxis with the fetus in utero—with potentially disastrous consequences for the fetus. There is no evidence that combinations of antibiotics or more than one dose offer any advantage over a single dose of one antibiotic. The standard drug used is cephazolin 2 g prior to skin incision (2 g if the mother’s weight is > 80 kg, 3 g if maternal weight is > 120 kg). The instruments and drapes required are those for any abdominal operation, together with special requirements for caesarean section: abdominal retractor;

curved retractor; obstetric forceps; curved scissors; suturecutting scissors; Green–Armytage forceps (at least 4); tissue forceps (e.g. Allis); needle holders; sucker and tubing; diathermy; needles; sutures; sponge forceps; scalpel handles; scalpel blades; curved artery forceps; straight artery forceps; toothed dissecting forceps; swabs; and packs (should have a radio-opaque strip). Suction is required for the anaesthetist and operator and for neonatal resuscitation. A neonatal resuscitation table is set aside for the management of the infant after birth.

SURGICAL TECHNIQUE After the woman is anaesthetised, she is placed in partial Trendelenburg position and the right hip is elevated to relieve pressure of the uterus on the great vessels. The abdomen is prepared with a suitable antiseptic solution (e.g. alcoholic chlorhexidine solution) and drapes are applied. The Pfannenstiel incision (Fig 32.3) is used in 99% of caesarean operations. It is popular for cosmetic reasons

FIGURE 32.3

Pfannenstiel incision at the postnatal visit 7 weeks after caesarean section. The wound is well-healed. Source: Courtesy of Prof. Norman Beischer.

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and has the advantages of less postoperative pain (better convalescence) and lower risks of wound dehiscence and incisional hernia. The vertical subumbilical incision is indicated if hysterectomy is likely (e.g. known placenta accreta) since it provides better exposure. A transverse incision is made through the subcutaneous fat and rectus sheath. The bellies of the rectus muscle are then separated and the peritoneal cavity entered. The lower segment is exposed with the aid of a curved retractor and the loose peritoneum over it is cut with curved scissors. The peritoneum is reflected downwards, carrying the bladder with it. The muscle of the lower segment is incised with a scalpel in a transverse direction. The initial incision is extended either with scissors or by stretching with fingers at each angle. The retractor is removed and the baby is delivered either manually or with forceps. The cord is clamped and cut. A midwife or doctor will take the baby in a sterile wrap to the resuscitation table where, in the absence of a need for resuscitation, the baby can be quickly dried and wrapped before being given to the parents. Forceps, usually the Green–Armytage type, are sometimes applied to the edges of the uterine incision for traction and to control bleeding. After an oxytocic has been administered (e.g. oxytocin), the placenta is removed and the uterine cavity is explored. A finger or cervical dilator may be passed down through the internal os to ensure adequate patency. The uterus is closed in two layers with a synthetic absorbable suture (e.g. chromic catgut or polyglycolic acid) (Fig 32.4). Additional sutures may be required to control bleeding. At

this point an examination of the ovaries and uterine tubes is made to exclude such pathology (e.g. an ovarian cyst). The parietal peritoneum is usually closed but the visceral parietal peritoneum is left unsutured to reconstitute spontaneously. The rectus sheath is closed with a synthetic absorbable suture, as are the subcutaneous tissues and skin. Subcuticular suturing of the skin produces a superior cosmetic result to the use of staples or non-absorbable sutures. The skin is dressed with an occlusive waterproof dressing. The vagina is checked to ensure that there is no significant ongoing vaginal bleeding. The urinary catheter, if still indwelling, is usually left until the following day.

Difficulties that may be encountered at the time of caesarean section Adhesions from a previous caesarean section or pelvic surgery may render access difficult. A poorly formed lower uterine segment is more common early in the third trimester, and may necessitate a vertical incision. Difficulty with delivery of the fetal head from deep in the pelvis can be remedied by the administration of a tocolytic (e.g. glyceryl trinitrate or salbutamol) and upward pressure on the vertex from the vagina by an assistant. Occasionally, the skin incision has been too small and will need to be enlarged. Rarely, the breadth of the lower uterine segment proves inadequate for the aftercoming head of a breech presentation, and an ‘inverted T’ incision in the uterus is necessary to safely deliver the aftercoming fetal head. It is preferable in this situation to perform a vertical lower segment or classical incision from the start, as the junction of a ‘T’ becomes a point of future weakness and potential rupture.

Additional procedures that may be performed concurrently Hysterectomy Hysterectomy is required in about 1 in 150 women who have a caesarean section. The usual indications are an otherwise uncontrolled primary postpartum haemorrhage or a placenta accreta (Ch 36). The operative procedure differs in no way from that used in the non-pregnant woman except that haemorrhage is more likely and tissue planes are easier to identify.

Sterilisation To save an additional operation, tubal sterilisation can be performed after completion of the caesarean section. The Pomeroy technique is commonly performed (Fig. 32.5) but it is possible that salpingectomy may reduce the incidence of future ovarian cancer (Ch 63). FIGURE 32.4

Closing the uterus at caesarean section using running locking stitch.

Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 162.16.

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POSTOPERATIVE CARE Post-caesarean observations include pulse rate, blood pressure and respiratory rate and should be recorded as for any major surgical procedure: half-hourly for 4 hours, and thereafter 4 hourly for 24 hours. Additionally, the

Chapter 32  Caesarean Section and Trial of Labour after Caesarean

cases of an excessively narcotised mother falling asleep and inadvertently smothering the baby. If the bowels have not opened by the third day, an aperient is usually given night and morning until this is remedied. Other nursing measures are the same as for general puerperal and routine postoperative care. Silk tie

FIGURE 32.5

Pomeroy sterilisation. A knuckle of tube is ligated with absorbable suture, and a small segment is being excised. Source: Gabbe SG, Niebyl JR, Galan HL, et al. Obstetrics: Normal and Problem Pregnancies. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 20.23.

ADVERSE EFFECTS OF CAESAREAN SECTION Maternal and perinatal mortality are difficult to separate from the indication for the caesarean section. With purely uncomplicated repeat elective caesarean sections, maternal mortality appears to be no different from attempted vaginal births and perinatal mortality is almost certainly less. The main reason for avoiding caesarean sections is largely the risk of placenta accreta in subsequent pregnancies.

Immediate (at the time of the procedure) vaginal loss should be checked and abdominal palpation used to ensure that the uterus is not atonic. An intravenous infusion will be in place. Typically, the woman will receive 8-hourly saline or Hartman’s solution until tolerating oral fluids. The woman usually has nothing by mouth for 6 hours and then a light diet only until bowel sounds are heard and flatus passed. At this point, the intravenous infusion can be discontinued and a normal diet commenced. A urinary catheter is left in the bladder postoperatively, usually until the following morning. This avoids the woman having to mobilise immediately following surgery, when the epidural will make mobilisation difficult. Analgesia should be effective in the interests of maternal comfort and will assist with mobilisation, thus reducing the risk of thromboembolism. Most commonly administered is a combination of oral paracetamol, a nonsteroidal anti-inflammatory drug (NSAID) and opioids. If epidural or spinal analgesia has been used, there will be a pain-free period immediately after the operation. Mobilisation is important in the prophylaxis of postoperative complications such as thromboembolism and atelectasis/pneumonia. Leg movements, deep breathing and coughing are encouraged from 2 hours postoperatively and the mother will normally be encouraged to fully mobilise, shower and care for the baby from the morning immediately following surgery. Anticoagulation with a low-molecular-weight heparin is commonly administered routinely after caesarean section until discharge from hospital, to further minimise the risk of thromboembolism. Breastfeeding/nursing can commence in the recovery room and the mother should be allowed to feed and nurse the baby as desired on the first day. If the mother is taking narcotic analgesia on the day of surgery, she should be supervised at all times with the baby as there have been

For the mother, immediate complications include those related to the anaesthetic (drug overdose, hypoxia, apnoea, aspiration of gastric content), the operation (haemorrhage, damage to bladder or bowel) or the condition necessitating the operation (hypertensive disease, diabetes, uterine infection). Laceration to the fetus is uncommon but can occur if entry is difficult and if vision is impaired by excessive bleeding.

Early postoperative complications (in the week or so after surgery) Infection may occur in the abdominal wound, uterus, urinary tract or chest. Local infection is related to the duration of membrane rupture and labour, number of pelvic examinations and surgical technique (haemostasis and so on). Thromboembolism, ileus, secondary haemorrhage and wound dehiscence are less common early complications. The baby may be adversely affected by the operation itself; for example, hypoxia from the supine hypotensive syndrome if the mother is not positioned properly. If a general anaesthetic is used, the baby will usually be born under the influence of the anaesthetic. Respiratory distress is more common, which may be related to the fact that amniotic fluid is not squeezed out of the lung as in vaginal delivery (‘wet lung’).

Late sequelae Late complications relate principally to a subsequent pregnancy.

Uterine rupture This occurs consistently in about 1 in 200 pregnancies where a mother attempts to deliver vaginally after one previous caesarean section and no other vaginal births. The rate is higher if labour is induced and higher again if prostaglandins have been used for cervical 273

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ripening. More than one caesarean section is associated with a progressively increased risk of uterine rupture but probably only to approximately 1 in 70 pregnancies after two previous caesarean sections. The statement ‘you will rupture your uterus if you try and have a vaginal birth’ is most unwise as the vast majority will not rupture their uterus; it is just that sensible risk management means that a caesarean section should be strongly recommended.

Figure 32.2. Added to this is a component related to the likelihood of achieving vaginal birth. In those attempted VBACs where there is a much lower likelihood of vaginal birth (see below), the balance becomes tilted more towards elective caesarean section.

Placenta praevia and placenta accreta

This will occur in about 1 in 200 attempted VBACs but only approximately 1 in 5 of these will have a perinatal death. Serious morbidity is harder to estimate but may be a similar figure (a further 1 in 5), as is the number who will need a hysterectomy.2

Both placenta praevia and placenta praevia accreta increase with each caesarean section. Approximate rates are given in Table 32.1 and probably represent the single greatest argument against maternally requested caesarean section in a woman likely to have more than one future pregnancy.

TRIAL OF LABOUR AFTER A CAESAREAN SECTION THE DECISION EQUATION Trial of labour after a caesarean section (TOLAC) is also referred to as attempted vaginal birth after caesarean section (attempted VBAC). The following discussion refers largely to an attempted vaginal birth after a single lower uterine segment caesarean section. As stated already, the risks after more than one caesarean section or a single classical caesarean are much higher. Deciding between a repeat elective caesarean section and an attempt at vaginal birth after caesarean is an extension of the simple decision equation given in

TABLE 32.1  INCREASING LIKELIHOOD OF BOTH PLACENTA PRAEVIA AND PLACENTA ACCRETA WITH INCREASING NUMBERS OF PREVIOUS CAESAREAN SECTIONS. Number of previous caesarean sections

Praevia (%)

0

0.5

2

1

1

10

0.1

2

2

30

0.6

3

4

50

2

4

10

70

7

274

Accreta (% of those with praevia)

Accreta (% of all pregnancies) 0.01

Against an attempted VBAC Uterine rupture

Perinatal mortality and morbidity This is undoubtedly higher than for an elective caesarean section but the 1/1000 perinatal deaths consequent on uterine rupture is the lesser contributor. The added perinatal death rate from awaiting spontaneous labour is about 1 in 600,3 with a further significant morbidity related to awaiting vaginal birth and labour4.

Against a repeat elective caesarean section Placenta accreta in a subsequent pregnancy In a purely clinical sense, the greatest argument in favour of VBAC is the risk of accreta in subsequent pregnancies (see above). Therefore, expected future parity is an overwhelming consideration. If the current pregnancy is likely to be the last, the clinical balance strongly favours repeat caesarean section. If two or more further pregnancies are expected, the recommendation should mostly be for attempted vaginal birth. For those that perhaps will have one further pregnancy, the clinical equation is pretty balanced; there is a very small risk of accreta if the patient has a repeat elective caesarean, and a similar small risk of adverse perinatal outcome if VBAC is attempted.

Likelihood of achieving a vaginal birth if attempted after a previous caesarean section The overall success rate for attempted vaginal delivery ranges from 50 to 80% depending on local guidelines around the management of the labour (i.e. minimal accepted rates of progress, the use or non-use of oxytocin to induce or augment labour) and the selection of cases. Women with morbid obesity are not ideal candidates for caesarean section but the success rate with attempted VBAC is as low as 10%. Women who have had a previous vaginal delivery, either before or subsequent to a caesarean section, are more likely to have a successful outcome.

Chapter 32  Caesarean Section and Trial of Labour after Caesarean

MANAGEMENT OF LABOUR AFTER A PREVIOUS CAESAREAN SECTION Place of birth Trial of labour following caesarean section is a safe procedure only when conducted in an appropriate hospital setting that can perform an immediate caesarean section in the unlikely event of a uterine rupture.

First stage of labour management The first stage of labour management follows a standard regimen as outlined in Chapter 28. Key aspects are worth some emphasis. Assessment of progress of labour should be vigilant and at least 1 cm/hr in the active phase. Delivery should be achieved within 12 hours of the onset of labour. Slow progress would generally not be augmented with oxytocin. Maternal surveillance with respect to scar tenderness or pain is generally not helpful as both these clinical features are very common in the absence of rupture. A ‘ripping’ or ‘tearing’ sensation is more concerning and more likely to be a genuine rupture. Fetal surveillance with continuous cardiotocography is mandatory and a sudden deterioration in the fetal heart tracing is often the first sign of uterine rupture. A group and antibody screen should be performed and an intravenous line inserted. Epidural analgesia can be used.

REFERENCES 1) Walker SP, McCarthy EA, Ugoni A, et al. Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds. Obstet Gynecol 2007;109(1):67–72. 2) Appleton B, Targett C, Rasmussen M, et al. Vaginal birth after caesarean section: an Australian multicentre study. VBAC Study Group. Aust N Z J Obstet Gynaecol 2000;40(1):87–91. 3) Vashevnik S, Walker S, Permezel M. Stillbirths and neonatal deaths in appropriate, small and large birthweight for gestational age fetuses. Aust N Z J Obstet Gynaecol 2007;47(4):302–6. 4) Badawi N, Kurinczuk JJ, Keogh JM, et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998;317(7172):1554–8. FURTHER READING Crowther CA, Dodd JM, Hiller JE, et al; Birth After Caesarean Study Group. Planned vaginal birth or elective repeat caesarean: patient preference restricted cohort with nested randomised trial. PLoS Med 2012;9(3):e1001192.

Second stage of labour management There is concern with prolonged pushing in the second stage of labour. An upper limit of 1 hour of active pushing before instrumental delivery is wise.

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Section 2.7.3 INTRAPARTUM CLINICAL PROBLEMS

Chapter 33  INTRAPARTUM FETAL COMPROMISE Michael Permezel and Julia Francis

KEY POINTS Intrapartum fetal compromise may cause both perinatal death and permanent disability in the child. However, both are very rare outcomes (approximately 1 in 2000) of well-resourced intrapartum care. During each uterine contraction, there is a substantial impairment of uteroplacental blood flow. With a healthy placenta and normal uterine activity, this is well tolerated by the fetus. Causes of intrapartum fetal compromise include maternal hypoxia, maternal hypotension, excessive uterine muscular activity, placental abruption, placental insufficiency, cord complications and fetal conditions including haemorrhage from vasa praevia. The management of acute fetal compromise includes prompt intrauterine resuscitation, and assessment and treatment of any cause, then re-evaluation of the fetal condition and delivery if necessary. Where urgent delivery is indicated, instrumental birth may be attempted if there is a favourable presentation (vertex) and station (engaged) and the cervix is fully dilated. If these circumstances are not present, a caesarean section is required.

AETIOLOGY In the pathway from mother to fetus, there are essentially seven mechanisms which may impair fetal oxygenation (Fig 33.1).

seen in conditions such as fainting and the supine hypotensive syndrome (where it is usually transient; Fig 33.2), shock (where it may be prolonged) and epidural analgesia. Box 33.1 outlines the causes of maternal hypotension.

MATERNAL OXYGENATION

Fetal compromise after epidural anaesthesia

An inadequate oxygen content of the maternal blood may result from poor gas exchange in the lungs (poorly administered anaesthesia, lung pathology), cardiac failure or anaemia.

MATERNAL HYPOTENSION Placental gas exchange is dependent on adequate maternal blood flow through the placenta. A reduction in maternal blood pressure to deliver blood to the fetus is

Placental perfusion appears particularly sensitive to maternal hypotension and may participate in the vasoconstrictor response to reduced blood pressure. This means that even though the blood pressure may not be recorded as particularly low, the vasoconstriction that is maintaining the blood pressure is impairing uteroplacental blood flow. Once the spinal or epidural block is effective, the uteroplacental circulation will be within the field of block and therefore no longer participating in the vasoconstriction response.

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Maternal hypoxia

BOX 33.1  Causes of maternal hypotension.

Maternal hypotension Placental abruption

Placental insufficiency

Fetal conditions

Umbilical cord compression



Spinal or epidural anaesthesia Supine hypotension Vasovagal syncope Hypovolaemia Sepsis Cardiogenic (e.g. arrhythmia, valve disease) Anaphylaxis Pharmacological effect (e.g. antihypertensive, phenothiazine) Pulmonary embolism (thrombotic or amniotic)

FIGURE 33.1 

Mechanisms for the pathogenesis of impaired fetal oxygenation.

Placenta

PLACENTAL ABRUPTION

Fetus

Separation of the placenta from the decidual lining of the placental bed will diminish the area available for gas exchange. Placental abruption is more common in labour because: 1. the abruption may have caused the woman to labour; and 2. an intrapartum event that causes marked reduction in uterine size (e.g. rupture of membranes when there is polyhydramnios or following delivery of the first twin) predisposes to abruption (Ch 10).

CHRONIC PLACENTAL INSUFFICIENCY

Aorta L4

Inferior vena cava

FIGURE 33.2 

Postural (supine) hypotension syndrome. The inferior vena cava is compressed by the gravid uterus.

UTERINE HYPERSTIMULATION The pressure in the uterine wall (approximately 60 mmHg) during a contraction will impair uteroplacental blood flow. During pushing in second stage (approximately 120 mm Hg, depending on the maternal blood pressure) there may be cessation of uteroplacental and umbilical blood flow. If the contractions are of excessive frequency and/or duration, there will be inadequate time for gas exchange and the fetus will become hypoxic. When excessive uterine muscular activity (uterine tachysystole) is associated with fetal compromise, the situation is termed uterine hyperstimulation. 278

Placental insufficiency has multiple causes (Ch 11) but becomes almost inevitable in every pregnancy as the gestation advances beyond the due date. Serious placental insufficiency may begin early in the second half of pregnancy. In the best possible scenario, a pregnancy may not develop placental insufficiency until beyond 42, or even 43, weeks’ gestation. As elsewhere in the body, the arteries develop a disease process similar to atherosclerosis. The process is accelerated in the presence of such conditions as hypertension, preeclampsia, diabetes and chronic renal disease. The result is reduced blood flow and sometimes thrombosis of the vessel. Starved of oxygenation, the corresponding section of the fetal side of the placenta undergoes vasospasm and may infarct (Fig 33.3). Regardless of the aetiology, chronic placental insufficiency may lead to acute fetal compromise in labour. The reduction in uteroplacental blood flow with even normal uterine activity may not be tolerated by the fetus with a diseased placenta. As the uterine contractions progressively increase in frequency, duration and intensity during labour, there will be a point where the uteroplacental blood flow no longer maintains fetal oxygenation.

UMBILICAL CORD This is the final supply link to the fetus, and blood flow may be diminished or cut off by entanglements about the

Chapter 33  Intrapartum Fetal Compromise

BOX 33.2  Fetal causes of fetal compromise in labour. Fetal hypotension: acute fetal haemorrhage (vasa praevia bleeding) Fetal anaemia: for example fetomaternal haemorrhage, red cell isoimmunisation Fetal infection: for example bacterial chorioamnionitis, CMV Fetal cardiac disease

FIGURE 33.3 

Placenta from a case of placental insufficiency in a woman with essential hypertension and superimposed preeclampsia. The mother had an intrauterine death in her only previous pregnancy. Caesarean section was performed at 33 weeks’ gestation. The severely growthrestricted infant weighed only 1260 g, with the multiply infarcted placenta weighing only 280 g. Source: Courtesy of Prof. Norman Beischer.

body of the fetus, knotting, presentation or prolapse (Fig 33.4). The cord is looped around the fetal neck in at least 25% of deliveries and approximately 1% have a true knot. These seldom cause fetal death in utero before the onset of labour since the knot tightens only when contractions cause descent of the head (Fig 33.4). Cord compression when there is cord entanglement, oligohydramnios or compression between the presenting part and the uterine wall is a common cause of so-called ‘variable’ fetal heart rate decelerations seen on cardiotocography.

FETAL CONDITIONS Box 33.2 lists some fetal causes of acute fetal compromise in labour. Vasa praevia may be associated with acute bleeding at the time of membrane rupture and very rapid fetal deterioration as it exsanguinates from the torn vessels. Acute bacterial chorioamnionitis (e.g. Group B streptococcus) will produce villus oedema and impair placental gas exchange.

CONSEQUENCES OF INTRAPARTUM FETAL COMPROMISE The hypoxic fetus will become acidotic and develop ischaemic damage to vital organs including the brain, heart

and kidneys. Death will eventually ensue. A common compounding effect is the failure of the compromised neonate to establish respiration at birth. In the absence of skilled neonatal resuscitation, neonatal asphyxia will further contribute to the hypoxic damage prior to birth.

PERINATAL DEATH Perinatal death is a very uncommon result of labour at term. Where the fetus is alive at the onset of labour in a well-resourced setting, the perinatal mortality during labour is possibly only 1 per 2000 births. In home birth (less well resourced), the perinatal mortality is approximately doubled.1

CEREBRAL PALSY Much is made of the fact that most cerebral palsy is not the product of birth asphyxia. Studies have estimated that only approximately 10% of cerebral palsy has an intrapartum origin and only a proportion of that is potentially preventable with astute care. However, it is also noteworthy that cerebral palsy is much less common after elective caesarean section at term than after vaginal birth or emergency caesarean section.2 This leads to the hypothesis that at least some cerebral palsy at term would appear to be related to late pregnancy (after 39 weeks’) placental insufficiency but prior to the onset of labour.

MANAGEMENT OF ACUTE INTRAPARTUM FETAL COMPROMISE Acute intrapartum fetal compromise can be managed with a stepwise approach as follows. 1. Perform general intrauterine resuscitation. 2. Assess and treat the underlying cause. 3. Reassess. 4. If there is no response, prepare for immediate delivery. 279

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A

B

FIGURE 33.4 

Delivery of a face presentation by forceps in a case of fetal death after a 17-hour labour at 42 weeks’ gestation in a 17-year-old primigravida. The fetus weighed 3220 g and had three tight loops of cord around the neck. Labour was monitored by auscultation alone. Fetal death occurred 4 hours into the labour, presumably due to tightening of the loops of nuchal cord as the head descended. Source: Courtesy of Prof. Norman Beischer.

General intrauterine resuscitation The immediate response to acute intrapartum fetal compromise is to institute general measures to improve fetal oxygenation. These include the following. Reposition the woman with a view to minimising supine hypotension and also possibly reducing cord compression. Most commonly, the best position is left lateral but it may sometimes be better in right lateral. Oxygen can be administered by mask although evidence is lacking as to whether this has any fetal benefit, given that the mother’s haemoglobin would normally have 100% oxygen saturation. Intravenous fluid (e.g. normal saline) bolus of, say, 250 mL. This will reduce hypotension and improve cardiac output if there is some maternal dehydration (not uncommon in labour). Oxytocic withdrawal should occur, with any oxytocin infusion ceased and any prostaglandin that remains vaginally removed if possible. Tocolytic administration should be considered. Common regimens include salbutamol 100 mcg

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intravenously, terbutaline 250 mcg subcutaneously, and glyceryl trinitrate spray 400 mcg sublingually.

Assess and treat the underlying cause The causes of acute fetal compromise are listed earlier in this chapter. In an acute situation, the assessment requires a high level of clinical skill so as to be rigorous in establishing the most likely cause, while at the same time not delaying further treatment. Assessment must include some knowledge of the antenatal history as well as intrapartum progress. Vital signs and abdominal examination can be quickly established but often the most important step is the vaginal examination. This is because the most common cause of acute fetal compromise is cord compression as the head descends in the second stage of labour. What then is the most common finding on vaginal examination in the presence of acute severe fetal compromise in labour? Although it may rarely be a cord prolapse, the most common finding will be that the woman is in second stage and fortuitously suitable for instrumental birth if

Chapter 33  Intrapartum Fetal Compromise

the fetal compromise continues and spontaneous birth is not imminent. Maternal hypotension most often follows epidural anaesthesia and will respond to intravenous volume infusion. Excessive uterine muscular activity should respond to cessation of any oxytocic and administration of a tocolytic as described earlier.

Reassess the fetal condition Cardiotocography Has there been a dramatic response to treatment? A detailed discussion of cardiotocographs (CTGs) is given in Chapter 11. Intrapartum CTGs can be described as ‘reactive’ or ‘reassuring’ (fetal heart rate accelerations present with normal variability, normal baseline and no adverse decelerations). The intermediate level of concern is ‘non-reactive’. In these cases, there are no accelerations and often some reduced variability. This trace may be due to early fetal hypoxia but more commonly is a pharmacological effect of drugs administered in labour such as pethidine, morphine or even magnesium sulfate being administered for management of preeclampsia or neuroprophylaxis. Severe hypoxia is very unlikely in the absence of ominous features as the uterine contractions should lead to late decelerations. A CTG pattern with a higher probability of fetal hypoxia or acidosis is called ‘non-reassuring’ or ‘ominous’. The term chosen is a glass half-empty or half-full situation—an appropriate analogy given that late decelerations will commonly be associated with fetal acidosis in about half the cases. Units that use the term ‘nonreassuring’ place emphasis on the fact that half of these cases do not have significant fetal compromise. Those using the term ‘ominous’ are emphasising that half the fetuses are indeed acidotic. Apart from late decelerations, other patterns that have a high probability of acidosis are complicated variable decelerations, absent variability and sinusoidal traces.

Fetal blood sampling The degree of fetal acidosis can be measured reasonably accurately with the technique of fetal blood sampling. The fetal base deficit or lactate level can be assessed. Indications This procedure is indicated where there is significant uncertainty regarding fetal condition. Many units almost never perform fetal blood sampling in labour. A few units obligate fetal blood sampling prior to a caesarean section for fetal compromise. The right course of action is somewhere inbetween. If there is a high probability of severe fetal compromise, delivery should be expedited and not delayed by attempts at fetal blood sampling. The pros and cons of fetal blood sampling are listed in Box 33.3. Contraindications Fetal blood sampling is contraindicated if there is clear evidence of serious sustained fetal compromise on the CTG. It is also contraindicated if there is a known fetal

BOX 33.3  Pros and cons of fetal blood sampling. Pros ✚ Randomised controlled trials suggest that fetal blood sampling can reduce the caesarean section rate for fetal compromise as not all fetuses with CTGs suggestive of hypoxia are actually acidaemic. Cons

✚



✚



✚ ✚



✚

Delays during fetal blood sampling may aggravate fetal compromise. Requires use of equipment that may fail or not be available. Technically difficult if < 3 cm dilated. Blood-borne virus transmission may occur from mother to fetus. There is a risk of fetal haemorrhage from a scalp wound, particularly if there is unexpected fetal thrombocytopenia (e.g. NAIT, see Ch 22).

bleeding disorders, the gestational age is < 34 weeks’ or there is a non-vertex presentation or a risk of viral transmission from mother to fetus (HIV, hepatitis viruses, herpes simplex viruses). Technique After cleansing of the vagina, an appropriately sized amnioscope is inserted gently through the cervix until the presenting part comes into view. The area in view is wiped clean and sprayed with ethyl chloride. A sample of capillary blood is obtained by piercing the scalp with a small disposable blade and drawing the blood into a fine tube treated to prevent clotting. If a coincident acidosis is suspected in the mother, a sample of her blood should also be taken for analysis. The normal pH value is > 7.25; the more depressed the reading below this, the more likely the baby is to be suffering from hypoxia. A value below 7.20 is definitely pathological and calls for close review. A normal lactate is < 4.2 mmol/L. A level 4.2 to 4.8 is concerning and > 4.8 should mandate delivery.

Amniotic fluid quantity and meconium-staining Passage of meconium occurs because asphyxia stimulates the vagus nerve, which supplies the gut. This has occurred in approximately 20% of pregnancies prior to birth, most often during labour. In about half the cases, the meconium is not apparent until after delivery because the presenting part seals the vagina like a plug. Premature infants are less likely to pass meconium in the presence of asphyxia and post-term infants more likely to pass meconium without any evidence of asphyxia. Thick 281

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meconium implies an element of oligohydramnios combined with meconium passage and makes significant asphyxia more likely. Meconium not only makes fetal acidaemia more likely but also increases the possible consequences of fetal hypoxia. As gasping during hypoxic episodes may result in neonatal meconium aspiration syndrome, the threshold for delivery should be lowered by the presence of meconium liquor—particularly if thick meconium.

Other strategies for evaluating fetal condition Digital stimulation of the fetal scalp during a vaginal examination will commonly provoke an acceleration if the fetus is not acidaemic. Electrocardiography (ECG) requires the application of a fetal scalp electrode and may reveal ST segment and T-wave changes in the presence of hypoxia. A fetal pulse oximeter can be placed alongside the fetal cheek in labour for continuous measurement of the fetal oxygen level. Both the fetal ECG and pulse oximeter are yet to become established in clinical practice and remain areas for research.

Delivery or continued observation? The decision equation Factors to consider in deciding between delivery versus continued observation include: 1. likely severity of fetal compromise 2. likelihood that the fetal compromise will respond to measures put in place (e.g. supine hypotension, uterine hyperstimulation) or progressively worsen as labour progresses (e.g. cord compression, placental insufficiency) 3. adverse consequences of operative birth (e.g. outlet instrumental birth or episiotomy would be regarded as less adverse than caesarean section, whereas caesarean section in a high maternal age pregnancy would be regarded as a better outcome than the same procedure in a young woman with expected high future parity).

version and breech extraction is an alternative to be considered (Ch 14).

Urgency of birth Animal experiments have examined the effects of complete anoxia in the term primate fetus. Anoxia of up to 10 minutes’ duration appears to be well tolerated without apparent long-term neurological damage. More than 20 minutes is commonly fatal. These numbers are an approximate guide only to the human situation. Importantly, most situations will be hypoxia of varying degrees (rather than anoxia), suggesting that times may be a good deal longer. However, often the human fetus has already suffered some pre-morbid hypoxia, which the same experiments have shown reduces tolerance to acute insults.

UMBILICAL CORD ACCIDENTS PROLAPSE

Prolapse occurs where the cord lies beside the presenting part (occult prolapse) or below it (frank prolapse), the membranes having ruptured. The condition may or may not be preceded by cord presentation, where the cord is similarly placed but the membranes are still intact (Figs 33.5 and 33.6).

Incidence and predisposing factors Cord prolapse occurs in approximately 0.5% deliveries (cephalic presentations). It is more common in breech presentations (approximately 2%) and multiple pregnancy (approximately 4%). Other predisposing factors include transverse of oblique lie, polyhydramnios and artificial rupture of the membranes in the presence of a high mobile presenting part.

Diagnosis Cord presentation (Fig 33.5) may be diagnosed on antenatal ultrasound or very occasionally with a particularly

Mode of birth If delivery is urgent and the head is on the perineum, an episiotomy may rapidly effect birth. In other circumstances, the choice will lie between instrumental birth and caesarean section. Essentially, if there is a favourable presentation (vertex or deflexed vertex) and station (‘engaged’) and the cervix is fully dilated, an instrumental delivery can be performed. If the presentation is nonvertex, the head not engaged or the cervix not fully dilated, a caesarean section is required. The mid-cavity deflexed vertex with a posterior position is a special circumstance. Ideally, any attempt at instrumental birth should be performed in the operating theatre so that there is rapid access to caesarean section if the instrumental birth is not successful. In the event of fetal distress between the birth of twins, an internal 282

FIGURE 33.5 

Cord presentation; the membranes are intact.

Chapter 33  Intrapartum Fetal Compromise

6. Mode of birth is as described for acute fetal compromise: instrumental birth only if there is a favourable presentation and station and the cervix is fully dilated (breech extraction of the second twin being an obvious possible exception). If the fetus is already deceased, vaginal birth is preferred.

CORD ENTANGLEMENT AND TRUE KNOTS Incidence

FIGURE 33.6 

Prolapse of the cord in labour, with the cervix almost fully dilated.

Cord around the baby’s neck is relatively common. One loop of cord around the neck occurs in about 25% of pregnancies, two loops in 2.5%, three loops in 0.5% and more than three loops in 0.1%. Cord around the body is present in approximately 2% (Fig 33.7). True knots of the cord occur in approximately 1% of pregnancies but approximately 4% of stillbirths (Fig 33.8).

astute vaginal examination in labour. Cord prolapse (Fig 33.6) should be excluded by immediate vaginal examination when the membranes rupture in the presence of any of the aetiological factors listed previously (i.e. malpresentation, multiple pregnancy, high presenting part or polyhydramnios). Occasionally, the cord may pass through the introitus and its presence is reported by the woman. Cord compression typically results in variable decelerations of the fetal heart rate during a uterine con­traction with sustained bradycardia when the cord compression becomes continuous and causes complete occlusion.

Management An immediate assessment is made of the nature of the labour contractions, dilatation of the cervix, and pulsations of the cord (together with fetal cardiac activity). Treatment is immediate delivery when the fetus is alive and at a viable gestation (> 24 weeks’). If the cervix is not fully dilated, this will be by immediate caesarean section but, surprisingly often, the cord will be noticed first at full dilatation and an instrumental birth can be effected. The presence of a cord prolapse with a live fetus at a viable gestation should initiate the following. 1. Assistance should be summoned; it is likely that an anaesthetist and paediatrician will also be needed. 2. The knee–chest position will reduce pressure on the cord. 3. The presenting part is pushed upward via sterile gloved hand in the vagina to further reduce pressure on the cord. 4. The cord is replaced in the vagina if prolapse to the exterior has occurred. 5. Acute tocolysis (see earlier in the chapter) can be administered to reduce uterine contractions.

FIGURE 33.7 

Knotting of the umbilical cord around the ankle caused the death of this 3040 g infant. The mother had reported cessation of movements at 36 weeks’ gestation. A fetal death was confirmed and labour induced, delivering this fetus with some maceration 2 days after fetal movements had ceased. Source: Courtesy of Prof. Norman Beischer.

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Pathogenesis There is generally an excess of fluid and/or a long cord, and the occurrence is probably related to freedom of fetal movement. Tangling is common (20 to 25%) in monochorionic monoamniotic twins.

Complications There is often some compromise to umbilical blood flow if the cord is tight, and a variable deceleration pattern is seen if a CTG is being carried out in labour. Apgar scores are usually lower, and cord entanglement is occasionally a cause of stillbirth (Fig 33.4). The disposition of the fetus in utero can be disturbed by the effect of the cord traction (e.g. deflexion or malpresentation) or the head fails to descend in labour. Cord entanglement is more likely to cause intrauterine death before labour than the cord around the fetal neck, since the latter usually tightens only during descent in the second stage of labour.

SHORT CORD This has many of the features of cord entanglement. The shortening may be absolute (e.g. less than 30 cm) or relative, due to looping around the fetus. Features include fetal hypoxia, fetal death, placental abruption, breech presentation, delayed onset of labour and/or poor progress and occasionally cord rupture. FIGURE 33.8 

This healthy 3585 g male infant was delivered by forceps because of delay in the second stage of labour. There was no evidence of fetal compromise in labour but the cord was wrapped twice around the baby’s neck and contained two loose true knots. The cord was unusually long at 76 cm, which is associated with both an increase in nuchal encirclements and more true knots.

REFERENCES 1) Wax JR, Lucas FL, Lamont M, et al. Maternal and newborn outcomes in planned home birth vs planned hospital births: a meta-analysis. Am J Obstet Gynecol 2010;203:243.e1–8. 2) Badawi N, Kurinczuk JJ, Keogh JM, et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 1998;317(7172):1554–1558.

Source: Courtesy of Prof. Norman Beischer.

FURTHER READING RANZCOG. Intrapartum fetal surveillance guidelines. 3rd ed. East Melbourne: RANZCOG; 2014.

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Chapter 34  FAILURE TO PROGRESS IN LABOUR Michael Permezel and Julia Francis

KEY POINTS Prolonged labour is associated with a number of undesirable consequences including maternal and fetal infection, fetal traumatic injury, postpartum haemorrhage and damage to the maternal pelvic floor. Progress is carefully monitored in all labours. Where progress is inadequate, available options are: 1. ongoing observation; 2. augmentation of the labour with an oxytocin infusion; or 3. delivery. Where delivery is indicated, a caesarean section will be needed if there is not a favourable presentation (vertex) or station (engaged) or the cervix is not fully dilated. If all these criteria are met, an instrumental birth can be considered. Augmentation of labour with an oxytocin infusion is contraindicated by fetal compromise or conditions that predispose to uterine rupture such as high parity or a scar on the uterus. Shoulder dystocia should be anticipated, especially where there are predisposing factors such as maternal obesity, diabetes mellitus, prolonged pregnancy, fetal macrosomia or an extensively moulded fetal head. Management of shoulder dystocia consists of a series of steps undertaken sequentially until delivery is accomplished. Adverse consequences of shoulder dystocia include an upper brachial plexus palsy (Erb’s), birth asphyxia and maternal trauma.

DYSTOCIA Dystocia is abnormal or difficult labour and usually refers to slow progress in labour.

AETIOLOGY Traditionally, the causes of dystocia are the powers (uterine muscular activity), the passenger (fetus) and the passages (bony and soft tissues of the birth canal). However, in many cases all three combine to produce dystocia, the most obvious example being a large fetus in the posterior position in a small woman.

The powers This is also known as uterine muscle dysfunction. The major criteria for normal uterine activity during labour

are fundal dominance, synchronisation in the spread of the excitation wave, progressive increase in amplitude, duration and frequency of contractions, and, finally, relaxation between contractions. Uterine muscular dysfunction can be incoordinate or hypotonic. In the latter case, the uterine contractions are weak and/or occur infrequently; if tocographic measurements are being made, the pressures will be below 30 mmHg. The net result is that the work performed by the uterus is less than normal, the cervix fails to dilate and the presenting part fails to descend. In uterine inertia, the contractions are abnormal throughout labour and never establish properly. The condition is more common in nulliparas, but strangely, is also common in women of high parity (grand multipara). This dysfunction usually manifests as prolongation of the latent phase (cervical effacement) and presumably arises

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from inadequate development of the positive feedback loops that should see labour establish once it has begun (Ch 27). In some women, uterine overdistension or lack of a well-fitting presenting part contribute to uterine inertia. Uterine exhaustion is the term used when labour slows after being established. It is a protective action taken by the uterus against rupture (usually in the nullipara) and occurs when there is a serious relative or absolute obstruction to labour.

The passages Bony pelvis The different anatomical shapes and pelvic measurements are described in Chapter 2. Pelvic contraction will most commonly be diagnosed when associated with marked shortness of stature. Rarely, there may be a history of conditions that affect pelvic shape such as spina bifida, untreated congenital dislocation of the hip, rickets or severe pelvic trauma (Fig 34.1).

Soft tissues A uterine fibromyoma in the cervix or lower uterine segment may prevent descent of the presenting part, as may an ovarian mass in the hollow of the sacrum. The non-pregnant uterine horn of a uterus didelphys is a very rare example of a soft tissue mass that may obstruct labour (see Ch 21, Fig 21.2). Previous cervical surgery can leave cervical scar tissue which is resistant to cervical dilatation (cervical dystocia). A vaginal septum usually will run in the anteroposterior plane in the midline and commonly obstructs labour in the second stage, at which point it is easily divided. It is best divided antenatally as it can avulse during labour with major vaginal trauma.

The passenger The fetal causes of cephalopelvic disproportion are fetal macrosomia, malpresentation causing larger diameters to present (brow, deflexed vertex, shoulder) or fetal abnormalities (Fig 34.2).

OBSTRUCTED LABOUR Obstructed labour is the result of ‘cephalopelvic disproportion’. That is, the presenting part is unable to pass through the birth canal. Most commonly it is disproportion between bony skull of the fetus and the bony pelvis but, as indicated above, obstructed labour can be due to soft tissue obstruction or a fetal anomaly or malpresentation.

Natural consequences of obstructed labour Where the presenting part cannot negotiate the pelvis, two consequences are possible: 1. obstructed labour, sepsis, fetal death, genital tract fistula; and 2. obstructed labour, uterine rupture, maternal death and potential fetal death.

Obstructed labour, sepsis, fetal death, genital tract fistula

FIGURE 34.1 

Two years previously this woman was in a motor vehicle accident and suffered severe injury, including fractures of the pelvis (pubis, Ischium and iliac crest) and intraperitoneal and extraperitoneal rupture of the bladder. This film at 38 weeks’ shows distortion of the left side of the pelvis. A living infant (2950 g) was delivered by elective lower-segment caesarean section. The operation was difficult because of adhesions between the bladder, uterus and anterior abdominal wall. Source: Courtesy of Prof. Norman Beischer.

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This series of events is most common in primigravidae. The presenting part is forced against the pelvis, producing ischaemic necrosis of the soft tissues (vaginal or uterine wall, bladder, bowel) between the bony skull and pelvis. The uterus develops uterine exhaustion and the contractions wane in frequency and intensity. The necrotic tissues become infected. The ensuing sepsis leads to fetal death. With fetal death, the fetal skull collapses and the fetus is passed vaginally. Necrosis of the tissues of the pelvic brim may result in an obstetric fistula; this is most commonly vesicovaginal, but it can be rectovaginal or both. This sequence of events remains common in areas of the world with no access to medical care and caesarean section for obstructed labour. Medical practitioners applaud the work of those who are trying to provide care for these women, not only to treat their fistulae but also to put measures in place that reduce the likelihood of future women suffering these terrible consequences of obstructed labour.

Chapter 34  Failure to Progress in Labour

A

B

C

FIGURE 34.2 

A Dicephalic fetus. The incidence of this extremely rare congenital anomaly is 1 in 40 000 births. In this unusual case there were also two anuses separated by a tail, and the double heart was in the neck due to absence of the normal attachment of pericardium to diaphragm. B Sacrococcygeal teratoma associated with fetal and placental hydrops. The mother was a 23-year-old primipara. Labour was induced at 26 weeks’ gestation when she developed polyhydramnios and severe preeclampsia. The fetus weighed 1865 g and the placenta 1250 g. C Compound presentation (breech and hands) accounts for the extensive bruising and oedema shown by this 2320 g infant whose 24-year-old primigravid mother was admitted in premature labour at 32 weeks’ gestation. This photograph was taken shortly after birth by caesarean section. The next day a left Erb’s palsy was noted, which resolved as the bruising subsided. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

Obstructed labour, uterine rupture, maternal death This series of events is most common in a multigravida. The presenting part is forced against the pelvis but the uterus continues to contract strongly. The lower uterine segment gets thinner and thinner as the junction of the upper and lower uterine segments is drawn higher and higher by retraction of the muscle fibres of the upper segment. Eventually, the lower segment ruptures and the fetus is extruded into the maternal abdomen. The placenta separates with the reduction in intrauterine volume, and the woman exsanguinates from the uterine tear, with the fetus lies dead within the peritoneal cavity.

Signs of obstructed labour Neither of the scenarios just discussed is allowed to eventuate where obstetric care is provided. Poor progress in labour in conjunction with the signs of obstructed labour will lead to delivery of the fetus before rupture or fistula can develop. The signs of obstructed labour (Box 34.1) are largely the consequences of the pressure of the presenting part on the pelvic inlet. The maternal pyrexia, maternal tachycardia, fetal tachycardia and haematuria are consequences of pressure on the soft tissues at the pelvic brim. The retraction ring forms and rises as the upper segment retracts and pulls the ballooned lower segment upwards (Fig 34.3). The cervix becomes oedematous, as does the fetal scalp (caput formation), and the fetal bones 287

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BOX 34.1  Signs of obstructed labour. Lack of progress (contractions, cervical dilatation, station) in association with: Maternal tachycardia Fetal tachycardia Maternal pyrexia Macroscopic haematuria Retraction ring on abdominal examination Cervical oedema Caput Moulding

FIGURE 34.3 

overlap in an attempt to ‘mould’ the fetal head to the pelvis.

AUGMENTATION OF LABOUR Rationale It has proved extremely difficult with intrauterine pressure transducers to reliably quantify contraction intensity. As a result, it is generally assumed that lack of progress in a primigravida is due to inadequate uterine muscular activity. The response to poor progress in the primigravida is therefore to augment contractions, initially with artificial rupture of the membranes and then an oxytocin infusion. This assumption seems excessive when first encountered, but the practice has stood the test of time and almost certainly reduces problems related to slow progress in labour.

A 25-year-old primigravida seen before caesarean section, which was indicated by fetal distress (meconium in liquor, early decelerations, fetal tachycardia), incoordinate uterine action and obstructed labour due to an occipitoposterior position. Labour began spontaneously at 42.2 weeks’ gestation. The woman required epidural analgesia for pain relief; two top-ups were given during the 18 hours of labour. Note the subumbilical flattening immediately above the ballooned lower segment of the uterus. The urinary catheter was required because the woman had been unable to void. Note also the wedge under the mattress to tilt the woman, thus minimising the risk of vena cava occlusion. The infant was born in good condition, birth weight 3510 g. This is the most common clinical situation seen in women having primary (first) caesarean sections; the combination of posterior position, incoordinate and obstructed labour, often in association with evidence of fetal compromise on the cardiotocograph. Source: Courtesy of Prof. Norman Beischer.

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Adverse effects Increasing the frequency, duration and intensity of uterine contractions has potential adverse consequences as follows. 1. Fetal compromise. As indicated in Chapter 33, there is a reduction in uteroplacental blood flow consequent on the increase in intrauterine pressure during contractions. If that reduction exceeds the threshold for that feto-placental unit, there will be a failure of fetal oxygenation. Timely cessation or reduction of the oxytocin infusion is likely to restore fetal oxygenation. 2. Uterine rupture. This is an uncommon consequence of augmentation of labour and will be more common in the multigravida. A partial thickness tear may result in amniotic fluid embolism with often fatal consequences for both mother and baby.

Contraindications Augmentation is contraindicated where there is already fetal compromise or the risk of uterine rupture is increased such as in multiparity (especially grand multiparity) or a uterine scar (usually previous caesarean section).

Regimen An artificial rupture of the membranes (ARM) is almost always performed prior to commencement of the oxytocin infusion. First, ARM may direct the mechanical forces of uterine contractions against the cervix and better achieve cervical dilatation. Second, when the membranes do rupture, there may be a release of endogenous prostaglandins, which can lead to hyperstimulation if an oxytocin infusion is running. The oxytocin infusion regimen is usually as for induction of labour (Ch 29).

DEFINING INADEQUATE PROGRESS IN LABOUR Latent phase of labour As indicated in Chapter 27, it can be almost impossible to define when labour begins in late pregnancy. Augmentation during the latent phase of labour is more akin to induction than augmentation. However, recurrent presentations with early/spurious labour is a known risk factor for stillbirth and induction is a reasonable step at that point.

First stage of labour The 90th percentile for cervical dilation in the active phase of labour is 0.9 cm/hr in a primigravida and 1.2 cm/ hr in a multigravida. Instituting treatment for lack of progress should be tied to the risks of prolonged labour such as chorioamnionitis, compression injury to the tissues and nerves of the pelvic floor, uterine exhaustion with postpartum haemorrhage and, rarely, the consequences of neglected obstructed labour (discussed later).

A rate of cervical dilatation of less than 1 cm/hr in the active phase of labour would generally be regarded as ‘inadequate progress of labour’ and merit consideration of augmentation (primigravida) or delivery (multigravida).

Second stage of labour A primigravida will usually be allowed 2 hours in the second stage with 1 hour of active pushing before obstetric delivery is considered. Augmentation is a very reasonable alternative if the uterine contractions appear inadequate. Only 1 hour of second stage is recommended in a multigravida given the much higher risk of uterine rupture.

CONSEQUENCES OF A PROLONGED LABOUR Maternal complications Maternal complications of a prolonged labour may include the following. Chorioamnionitis. The barrier effect of the cervical plug of mucus and the fetal membranes is lost once active labour commences. Microorganisms, which are prevalent in the vagina, pass upwards into the amniotic cavity and cause an amnionitis, with later spread to the uterus and para-uterine tissues. Postpartum haemorrhage. This is more common because of uterine exhaustion and infection. Uterine rupture or vesicovaginal fistula. These are the ultimate consequences of neglected obstructed labour (as stated previously) and should not occur with appropriate obstetric care.

•

• •

Fetal complications Fetal complications of a prolonged labour are as follows. Fetal hypoxia. As indicated previously (Ch 33), there is a marked reduction of uteroplacental blood flow with each uterine contraction. Under normal circumstances, the fetus is adequately oxygenated during the time between contractions. However, in a prolonged labour, there may be a cumulative effect of the repeated mild hypoxia such that the reduction in uteroplacental blood flow with contractions is no longer tolerated and hypoxia develops. The other hypoxic impetus may be repeated cord compression. Again, mild degrees of cord compression that are well tolerated for short periods may be much less well tolerated in a long labour, and hypoxia may ensue. Fetal infection. The fetus may develop sepsis in association with maternal chorioamnionitis with inhalation of infected liquor. Pneumonitis, meningitis, pyelonephritis and so on may follow. Fetal trauma. A prolonged labour is more likely to be associated with a difficult birth. The head may be extensively moulded, enabling vaginal birth, but shoulder dystocia then becomes more common. The

•

• •

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extensively moulded head deep in the pelvis after prolonged obstructed labour may be difficult to deliver by either vaginal or abdominal routes.

MANAGEMENT OF INADEQUATE PROGRESS OF LABOUR General management This is similar to that outlined under the normal care of the woman in labour (Ch 28). Fetal surveillance with cardiotocographic monitoring should be considered if not indicated prior to this time. Intravenous fluid replacement is warranted if there are any signs of dehydration. A broad-spectrum antibiotic is indicated after the membranes have been ruptured for longer than 18 hours.

Assessment Objectives of assessment The following issues should be addressed. 1. Are there signs of obstructed labour? 2. Is obstruction of labour inevitable (e.g. massive fetus in a small woman, brow presentation)? 3. Is augmentation contraindicated by either fetal compromise or an increased risk of uterine rupture?

History and examination If the mother has had previous children, there will often be a history of prolonged labour and operative birth. Examination should be directed to maternal height, estimated fetal size and an assessment of fetal presentation. Careful assessment should be made of all facets of the labour—powers, passenger, passages—to determine whether any other abnormality, particularly disproportion, exists.

Treatment: first stage of labour 1. Obstructed labour present or inevitable caesarean section Delivery is indicated by the most appropriate means. In the first stage of labour, this will be a caesarean section.

2. Inadequate progress but augmentation contraindicated Observe then reassess. Labour would usually be observed for longer but with persistent failure to progress, delivery is indicated.

3. Inadequate progress and augmentation not contraindicated Augment then reassess. The assumption is made that powers are inadequate for the labour. Augmentation takes place with an oxytocin infusion in addition to an ARM. Many of these women will have minor disproportion, with or without malpositions (usually posterior position of the occiput), or minor deflexion attitudes (vertex or bregma presentations). Improved uterine activity is 290

often sufficient to produce normal anterior rotation and/ or flexion of the head, and thus oxytocin infusion is the treatment of choice (acceleration of labour) once significant disproportion has been excluded. Amniotomy alone is usually not effective. If satisfactory progress has not occurred in 2 hours (multigravida) or 4 hours (primigravida), a caesarean section is indicated. Note that if the woman is multiparous, particular caution is needed with the oxytocin infusion in that progress must quickly establish as normal, with reassessment after only 2 hours. Some clinicians will almost never use oxytocin to augment a multiparous labour but most obstetricians will do so with great caution where the contractions are infrequent and of short duration.

Treatment: second stage of labour In the second stage of labour, there may be four alternatives rather than just the three listed earlier: caesarean section; observation and reassess; augmentation and reassess; or instrumental birth. Note that just as an instrumental birth cannot be performed if the head is too high (not engaged), a caesarean birth is extremely difficult if the head is low. When an instrumental birth is possible in the second stage of labour, this is usually the preferred option. However, if a primigravida has a posterior position that is only just engaged, augmentation with oxytocin is probably the wisest recommendation, provided fetal well­ being is satisfactory. This will potentially allow for an easier instrumental birth or sometimes even a spontaneous birth if the oxytocin is particularly effective. In the situation of a posterior position that is only just engaged and needs delivery, obstetricians would be fairly evenly divided as to whether an attempt at instrumental delivery should be recommended or to proceed straight to caesarean section.

SHOULDER DYSTOCIA (IMPACTED SHOULDERS) Impaction of the shoulders is present when there is obstruction to the passage of the shoulders through the bony pelvis, the head having already been delivered. This complication is particularly important, since it can occur unexpectedly in cephalic presentations and there may be no time to summon help. The obstetric attendant should always be on guard for this emergency in any obese or diabetic woman, or one whose labour is prolonged despite good contractions. Impacted shoulders should not be confused with difficulty with the shoulders due to a small head passing through an incompletely dilated cervix; this can occur with anencephaly, microcephaly or fetal death with skull collapse. In this circumstance, the head is not delivered but is in the vagina. Treatment is to await full cervical dilatation when spontaneous delivery will occur; attempts to extract the fetus when the cervix is not fully dilated may result in rupture of the uterus.

Chapter 34  Failure to Progress in Labour

PATHOPHYSIOLOGY Shoulder dystocia is usually the result of large fetal shoulders in relation to the fetal head in a situation where the head just makes it through the birth canal, but the shoulders cannot. The fetal head delivers, often with difficulty, but the neck and shoulders fail to appear. The chin burrows into the maternal perineum. The posterior shoulder is usually in the hollow of the sacrum with the anterior shoulder trapped behind the symphysis pubis. Less commonly, both shoulders may be above the pelvic inlet.

ADVERSE CONSEQUENCES Facial purpuric rash The infant may develop a facial purpuric rash as a consequence of the intense venous congestion that follows delivery of the head with the body trapped in the birth canal.

Fractured clavicle Although this is more common with shoulder dystocia, a fractured clavicle may occur during a normal delivery and be unnoticed apart from a ‘click’ as the shoulders are delivered and a palpable lump over the mid-clavicle in the neonatal period. There are no long-term consequences.

Brachial plexus injury Excessive traction on the shoulders will lead to a traction injury of the upper segments (C5 to C7) of the brachial plexus—Erb’s palsy. The child cannot abduct the arm at the shoulder and has weakness of elbow flexion (Fig 34.4). Many cases of Erb’s palsy will undergo partial or complete resolution in the days and weeks after birth but severe brachial plexus palsy will produce permanent disability of the affected arm.

FIGURE 34.4 

Total brachial plexus palsy due to impacted shoulders in a 4-day-old baby following difficult mid-forceps delivery. His birth weight was 4950 g. Complete resolution did not occur. The more common nerve palsies (total incidence 2 per 1000 births) involve upper brachial plexus (Erb C5, 6, 50%) facial nerve (45%), total brachial plexus (3%) and lower brachial plexus (Klumpke C7, C8, T1, 2%). They are associated with impacted shoulders, breech extraction and difficult forceps delivery. More than 90% recover completely, usually within a few days. Source: Courtesy of Prof. Norman Beischer.

Birth asphyxia

PREDISPOSING FACTORS

Once the head has been delivered, there is increasing risk of fetal asphyxia as time elapses. This has commonly been ascribed to sustained compression of the umbilical cord within the birth canal, creating an anoxic situation for the fetus and a medical emergency. However, in many cases the cord is subsequently found to have been high above the pelvic brim and the reason for the asphyxia is unclear. Critical to fetal tolerance of transient asphyxia is the ‘pre-morbid’ fetal condition. If the fetus has been well throughout labour, the short period of hypoxia during management of shoulder dystocia is likely to be well tolerated. However, a fetus that has had a difficult labour will be much more likely to suffer long-term consequences of hypoxia at birth.

Conditions that predispose to shoulder dystocia are either associated with unusually large shoulders or unusually small head for the body size (Box 34.2). Anticipation of shoulder dystocia in the presence of one or more of the predisposing factors just discussed is key to the prevention of adverse sequelae. An experienced obstetrician and paediatrician should be present at delivery and the woman positioned such that the manoeuvres referred to in the next section can be accomplished without excessive difficulty.

Maternal traumatic injury Severe maternal trauma (including uterine rupture) can be caused during the various manipulations.

MANAGEMENT Shoulder dystocia is an obstetric emergency and all staff that may need to manage shoulder dystocia should know and rehearse the various manoeuvres. 1. Call for assistance. In anticipation of difficulty, an obstetrician or obstetric registrar experienced in the 291

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BOX 34.2  Conditions that predispose to shoulder dystocia. Relatively large shoulders ✚ Shoulder dystocia in previous pregnancies ✚ Maternal diabetes mellitus ✚ Maternal obesity and excessive weight gain in the pregnancy ✚ Macrosomia ✚ Prolonged pregnancy Relatively small head ✚ Moulded head with prolonged labour ✚ Microcephaly or anencephaly

management of shoulder dystocia should be summoned, along with a paediatrician. 2. Specific manoeuvres. Key to the prevention of brachial plexus injury is the avoidance of excessive downward traction on the fetal head. However, traction needs to be firm to effect timely delivery in order to minimise the risk of asphyxial damage.

1. Position the woman in McRobert’s position at the edge of the bed Marked flexion of the mother’s legs will decrease the inclination of the pelvis and some rotation at the sacroiliac joints may enlarge the pelvic outlet. Positioning on the edge of the bed to enables downward traction towards the floor. Traction in this direction has the greatest likelihood of releasing the shoulder from behind the symphysis pubis. Apply firm but not excessive downward traction. This should alleviate approximately 50% of cases of shoulder dystocia.

2. Apply suprapubic pressure and again apply firm downward traction This manoeuvre is shown in Figure 34.5.

3. Rotation of the shoulders Perform a vaginal examination to check alignment of the shoulders is in the AP diameter. The examining hand can rotate the shoulders if misaligned. If traction in the AP plane is not successful, traction after rotation to 45° may be attempted. Older books talk of rotating the shoulders 180° to make the posterior shoulder anterior but this is rarely attempted and more rarely successful. These manoeuvres may be referred to with eponyms such as Ruben’s 2, Woods’ screw and reverse Woods’ screw.

4. Delivery of the posterior arm An episiotomy is cut or extended and the accoucheur’s hand is passed into the hollow of the sacrum and grasps the humerus below the shoulder joint. The arm is swept 292

FIGURE 34.5 

Application of suprapubic pressure in association with downward traction in an attempt to release the anterior shoulder from behind the symphysis pubis.

across the fetal chest until the forearm can be grasped. This is then brought down and delivered posteriorly. An alternative technique is to pass a rubber tube (e.g. Foley catheter) into the posterior axilla and exert downward traction to deliver the posterior shoulder. Once the posterior arm is out, the anterior shoulder readily follows and delivery of the posterior arm is the most common successful manoeuvre in the management of severe shoulder dystocia. After delivery, the episiotomy must be repaired, together with any cervical or vaginal lacerations that may have occurred (these are common unless the episiotomy is extensive). Manual exploration of the uterus may be indicated to exclude uterine rupture; in any case, a careful check on the condition of the mother must be kept for postpartum bleeding and infection. The infant will usually require resuscitation, special observation and possibly treatment for brachial plexus and skeletal injury, particularly fractures of the clavicle and humerus (Figs 34.4 and 34.6).

5. Cleidotomy If all the preceding manoeuvres are unsuccessful, the situation is usually desperate. Cleidotomy will collapse the fetal shoulder girdle and can be effected with scissors but is very difficult to accomplish and carries a high risk of maternal trauma.

Chapter 34  Failure to Progress in Labour

6. Symphysiotomy Surgical division of the symphysis pubis is still practised in some resource-poor countries in the management of obstructed labour, as an alternative to caesarean section. It obviously carries a risk of surgical damage to the urethra and haemorrhage. However, in experienced hands, it has been successfully used in the management of severe shoulder dystocia.

7. Caesarean section Replacement of the head back into the vagina and performing a caesarean section will only be an alternative in those cases where there has been little cord compression and the head replaces easily. Both these circumstances

may apply in the situation where neither shoulder has entered the pelvis and both are firmly resting on the pelvic inlet. Note: Repositioning onto all fours has been recommended by some guidelines but in the author’s experience is unhelpful and often counterproductive in that the woman is positioned where further steps become extremely difficult. The acronym HELPERR has been popularised by the ALSO course and is given in Box 34.3. This acronym has received some criticism, including the early emphasis on episiotomy, failure to prompt movement of the patient to the edge of the bed and, finally, the recommendation of positioning on all fours.

BOX 34.3  Acronym for shoulder dystocia management (HELPERR). Help Evaluate for episiotomy Legs Pressure Enter Remove posterior arm Roll

Call for assistance McRobert’s: hyperflexion of hips; reposition over edge of bed Suprapubic pressure Vaginal examination to check alignment of shoulders and consider rotational manoeuvre(s) Most reliable technique when simple measures fail Position on all fours: doubtful benefit and can be counterproductive (see above)

FIGURE 34.6 

This clavicle was fractured during delivery of impacted shoulders; the newborn was otherwise unharmed. Source: Courtesy of Prof. Norman Beischer.

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Chapter 35  MALPRESENTATION AND MALPOSITION Julia Francis and Michael Permezel

KEY POINTS Axial pressure on the vertex within the birth canal results in rotation around the atlanto-occipital joint and a fully flexed vertex presentation in approximately 85% of pregnancies. This produces the smallest possible fetal diameters for birth. A deflexed vertex presentation complicates approximately 15% of labours and occurs almost always in association with a posterior position of the fetal occiput. Approximately 60% will rotate to anterior during labour; a very small number deliver ‘face to pubis’ but the remainder require some form of assistance to birth in the form of manual rotation, vacuum, forceps or caesarean section. Brow presentation is uncommon (about 1 in 500 deliveries), but should be recognised because obstructed labour is usual and caesarean section is usually necessary. Face presentation occurs in approximately 1 in 800 deliveries and may be due to increased extensor tone, a neck tumour or anencephaly. Because the presenting diameter (submentobregmatic) is similar to that in the fully flexed fetus (suboccipitobregmatic) there is a much greater likelihood of vaginal delivery than in brow presentation.

DEFLEXION OF THE FETAL HEAD PATHOPHYSIOLOGY The four cephalic presentations As the head starts to extend from fully flexed, through minor extension, partial extension and then fully extended, the presenting part will move forwards from the vertex, to deflexed vertex, brow and face. The presenting diameters and approximate measurements at term are given in Table 35.1 and Figure 35.1. Of greatest importance is the increase in presenting diameters as the head becomes progressively deflexed but then returns to 9.5 cm with complete extension (face presentation).

What causes flexion of the fetal head? When the fetus presents cephalically, there are two essential factors that maintain the flexed attitude of the head. The first, which acts throughout pregnancy and labour, is the normal predominance of flexor tone in the baby, which is seen not only in the relation of head to chest but also in relation to the limbs and trunk (Fig 35.2). Occasionally, this is reversed and a predominant extensor tone exists (‘flying fetus’, Figs 35.3 and 35.4). The second factor usually comes into operation in late pregnancy and especially in labour; it depends on the fact that the atlantooccipital joint, on which the head flexes and extends on the trunk, is not centrally placed at the base of the skull but rather more towards the back. As the vertex meets the pelvic floor, the pressure leads to flexion of the head at the atlanto-occipital joint. With a breech presentation,

Chapter 35  Malpresentation and Malposition

TABLE 35.1  PRESENTING DIAMETERS AND APPROXIMATE MEASUREMENTS AT TERM. Presentation

Presenting diameter

Approximate measurement at term (cm)

Prevalence

Vertex

Suboccipitobregmatic

9.5

85%

Deflexed vertex

Occipitofrontal

11.5

15%

Brow

Verticomental

13.5

1 in 500

Face

Submentobregmatic

9.5

1 in 800

Suboccipitobregmatic diameter (9.5 cm) Occipitofrontal diameter (11.5 cm)

Suboccipitobregmatic diameter (9.5 cm)

supraoccipital-mental diameter (13.5 cm)

FIGURE 35.1

Sagittal diameters of the fetal skull.

the same will occur but through pressure of the fundus on the vertex as the mother bears down with pushing in the second stage of labour.

DEFLEXED VERTEX PRESENTATION AND THE OCCIPITOPOSTERIOR POSITION The deflexed vertex presentation may also be called an anterior fontanelle presentation or military position. It is almost only ever seen in association with a posterior position, so these will be covered together. Extension of the fetal head in association with a posterior position may be more apparent than real. This is a consequence of the angle of inclination of the pelvis, placing a more anterior point on the head in the middle of the pelvis with a posterior position than an anterior position. The effect is the same as deflexion with the larger occipitofrontal diameter presenting (approximately 11.5 cm). This larger diameter has to negotiate the birth canal and is responsible for the majority of longer labours, with a higher incidence of forceps delivery and caesarean section.

FIGURE 35.2

The fetal attitude of universal flexion at term. In this case, the mother died undelivered from cardiac disease. Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

The occiput of the fetus lies posterior to the transverse diameter of the pelvic brim in about 15% of women at the onset of labour. In half it corrects to anterior but in the other half, there is persistence of a posterior or transverse position with its attendant deflexed vertex presentation and larger diameters of the fetal head that must negotiate the maternal pelvis.

AETIOLOGY The most likely and logical explanation for the posterior position is that of mutual configuration; that is, the larger posterior segment of the head fits better into the larger posterior segment of the maternal pelvis. This is particularly so where the heart shape of the pelvis is exaggerated through a marked sacral promontory. In addition, the normal anterior rotation may be impeded if 295

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FIGURE 35.3

Face presentation due to head extension (‘flying fetus’). Source: Courtesy of Prof. Norman Beischer.

fontanelle back towards the sacrum. The orbital ridges maybe just palpable under the symphysis pubis but if they are easily palpable, deflexion has occurred to a brow presentation.

SEQUELAE OF A POSTERIOR POSITION AT THE START OF LABOUR

FIGURE 35.4

Two neonates born on the same day. The infant on the left presented by the vertex and was born normally. The one on the right exhibited extension of the neck due to a brow presentation and required a caesarean section. Source: Courtesy of Prof. Norman Beischer.

the transverse diameter of the pelvis is reduced. If the placenta is situated anteriorly in the uterus, a posterior position of the baby is favoured, since there is more room for the prominent occiput posteriorly.

DIAGNOSIS On abdominal examination, fetal limbs are palpable anteriorly. The fetal shoulder (and loudest place for fetal heart auscultation) is out towards the flank, usually on the right (Fig 35.5). Vaginal examination reveals a prominent anterior fontanelle central within the pelvis with the posterior 296

There are several possible outcomes, depending on factors such as the size and shape of the pelvis and fetal head, and the strength and coordination of uterine contractions (Fig 35.6). 1. Anterior rotation occurs in about 60% of labours that are posterior positions at the start of labour. With this ‘self-correction’ during labour, the occiput rotates all the way to anterior as it descends through the pelvis. It is thought that the rotation is effected by the angulation of the pelvic floor as the head descends, deflecting the occiput towards the front. If there is failure of descent, there will also be failure of rotation. Where rotation does occur, there is usually a vaginal birth as having successfully descended the upper birth canal with large diameters of a posterior position, the smaller diameters of the now anterior position find a relatively comfortable passage through the lower pelvis. 2. Transverse arrest occurs in about 20% of posterior positions. 3. Posterior arrest occurs in about 15% of posterior positions. 4. ‘Face to pubis’ birth occurs in about 5% of posterior positions (i.e. approximately 0.75% of all births). In this circumstance, the larger diameters extend the perineum creating a high likelihood of extensive perineal trauma.

Chapter 35  Malpresentation and Malposition

Each of these strategies has complex pros and cons with respect to mother and fetus, which are covered in other chapters. The recommendation will be appropriately influenced by the expertise of the accoucheur and the particular circumstances of the labour (e.g. duration, station, position, fetal size, signs of obstruction). There may also be considerable differences between women in the relative priority of avoiding caesarean section (e.g. high parity anticipated, resource-poor settings, personal aversion to caesarean birth) versus risk minimisation (e.g. older woman, subfertility, particular aversion to perineal trauma and the consequences thereof).

THE OCCIPITOTRANSVERSE POSITION This is also termed the occipitolateral position and has two quite different situations. Normal labour. A lateral position is normal early in labour as the pelvic inlet is wider transversely than in the anterior–posterior diameter. It is actually uncommon for the head to engage directly occipitoanterior. With descent of the head through the pelvis, the shape of the pelvic floor against the occiput rotates it from lateral to anterior. It is very uncommon for this not to occur or for the rotation to be directed posteriorly. Partial rotation of a posterior position. Most occipitotransverse positions with inadequate progress began as posterior positions but failed to complete the rotation to anterior. Management is as for a posterior position but with a higher likelihood of successful spontaneous correction, manual rotation or vacuum rotation.

•

• FIGURE 35.5

In occipitoposterior positions, the anterior shoulder is palpated well out from the midline to the right. This contrasts with an occipitoanterior position where the anterior shoulder is usually palpated close to the midline on the left.

MANAGEMENT First stage of labour Anticipation of a longer labour will influence many of the recommended practices in the first stage of labour. Heightened vigilance is required in the assessment of mother, fetus and progress. Analgesia and food/fluid intake should consider the greater likelihood of both a prolonged labour and operative birth. Lack of adequate progress is managed along standard lines (see Ch 34).

Transverse or posterior position with inadequate progress in the second stage A number of options are available: 1. manual rotation; 2. instrumental rotation (Kielland forceps or vacuum); 3. instrumental birth ‘face to pubis’; 4. caesarean section; 5. oxytocin augmentation; or 6. continue to await progress.

BROW PRESENTATION In this complication, the brow (area between the anterior fontanelle and root of the nose) forms the presenting part. It is the most unfavourable of all of the deflexion attitudes since the large mentovertical diameter (13.5 cm) is presenting: in the mature fetus this usually prevents vaginal birth. However, as indicated below, rotation may occur with subsequent flexion, enabling a vaginal birth.

INCIDENCE Including transient situations, confirmed by vaginal examination in labour, brow presentation occurs about once in 500 pregnancies.

AETIOLOGY A failure of flexor tone in the fetus may lead to the brow presenting (Fig 35.7). In these cases, pressure from the pelvic floor on the presenting part will neither flex nor extend the head as the brow is positioned over the atlantooccipital joint. The head is therefore ‘stuck’ as a brow 297

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Right occipitoposterior

20% short (45°) t i rotation t ti posterior

20% transverse arrest aer 45° rotation

60% long (135°) anterior rotation

FIGURE 35.6

From a right occipitoposterior position in early labour, the incidence of rotation to other positions is approximately 60% anterior, 20% transverse and 20% posterior.

FIGURE 35.7

The neonate on the right presented occipitoanterior but the neonate on the left presented in labour as a brow. This photo is taken at 2 days of age and illustrates a persistence of the extensor attitude and prominence of the brow. Source: Courtesy of Prof. Norman Beischer.

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Chapter 35  Malpresentation and Malposition

presentation that is unable to fit through the pelvis because of the very large presenting diameter (13.5 cm).

DIAGNOSIS A brow presentation will rarely be diagnosed on abdominal palpation. On vaginal examination, a prominent anterior fontanelle gives the impression of a posterior position but further exploration (usually anteriorly under the symphysis) reveals the root of the nose in the midline and the orbital ridges laterally (Fig 35.8).

CLINICAL SEQULAE A brow presentation will almost always obstruct and be associated with signs of inadequate progress and then of obstructed labour. Unless extremely small (e.g. extreme prematurity), it will rarely deliver vaginally as a brow (Fig 35.9).

A

FIGURE 35.8

Brow presentation in labour.

B

FIGURE 35.9

A This neonate of birth weight 2960 g presented by the brow. The prominence of the brow is obvious. In this case, the fetus delivered vaginally as a brow, a rare outcome of brow presentation. B This contrasts with the elongation of a normally shaped head due to moulding in a term neonate that had presented by the vertex in an occipitoanterior position during labour and birth. Source: Courtesy of Prof. Norman Beischer.

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Rarely will a brow presentation spontaneously correct or deliver vaginally, almost always after rotating 180° from what was effectively a very deflexed posterior position to occipitoanterior.

MANAGEMENT With great caution, correction may be attempted in the second stage of labour by manual rotation with Kielland forceps rotation from a brow in the mentoanterior position that flexes to a vertex occipitoanterior during rotation. Much more commonly, a caesarean section will be performed to minimise risk to both mother and fetus.

FACE PRESENTATION This is maximal extension but paradoxically, a favourable diameter again presents to the pelvis (the submento­ bregmatic, 9.5 cm), which is the same as the most favourable diameter when the head is fully flexed (the suboccipitobregmatic).

INCIDENCE Excluding cases of anencephaly (which are now mostly diagnosed on ultrasound early in pregnancy), a face presentation only occurs about once in every 800 deliveries, so it is much less common than a brow presentation (Fig 35.10).

FIGURE 35.10

Maternal abdominal X-ray showing hyperextension of the fetal neck and a face presentation. Source: Courtesy of Normal Beischer.

AETIOLOGY Unless a distinctive cause such as anencephaly or tumour of the fetal neck is present, the usual cause will again be heightened extensor tone (Fig 35.11).

DIAGNOSIS As for brow presentation, diagnosis on antenatal abdominal examination is most unlikely but some will be diagnosed antenatally in the course of an ultrasound being performed for another reason. Most commonly, the face presentation will be diagnosed on vaginal examination in labour. A partly soft, partly firm, irregular contour will be noted which is easy to confuse with a breech presentation. The most useful landmarks are the orbital ridges, the nose, and the mouth and alveolar ridges. Unless a caput has formed, the general consistency is much firmer than in a breech presentation. If in doubt, prodding should not be vigorous because of possible damage to the baby’s eyes. Ultrasound may assist in early labour where diagnosis may be uncertain in the presence of minimal cervical dilatation.

CLINICAL SEQUELAE The labour is usually longer than normal, probably as a result of the poorer fit of the face in the lower uterine 300

FIGURE 35.11

Extension of the neck causing a face presentation in association with thyroid gland enlargement. The mother also had a goitre but was not on treatment. The condition resolved without treatment. Source: Courtesy of Monash Health.

Chapter 35  Malpresentation and Malposition

segment, poorer moulding and the fact that full extension is less easily achieved than full flexion. The face at birth is commonly bruised, blue, oedematous and quite disfigured but recovers very quickly over a few days in the absence of any direct trauma from an amniotomy, fetal electrode placement or fetal blood sampling.

MANAGEMENT Antenatal If a face presentation is suspected in pregnancy, an ultrasound should be performed to determine any predisposing factors such as anencephaly or a tumour of the neck. An elective caesarean section will usually be recommended because of the limitations on intrapartum care and the higher likelihood of needing an emergency caesarean section.

Intrapartum The progress of labour is followed by abdominal and, if necessary, vaginal examination. Application of a fetal scalp electrode or fetal blood sampling should be avoided. Otherwise, the management and labour is similar to that described for the woman with a normal vertex presentation. For birth, the chin rotates around under the symphysis pubis, and the brow, vertex and occiput will in turn sweep over the perineum. Unlike in the vertex presentation, there will be no chin to pick up below the coccyx, only the top of the baby’s head. After delivery of the head, the rest of the baby is managed as in a normal birth (Fig 35.12). A mentoposterior position will generally not correct during labour (Fig 35.13) and a caesarean section is recommended. Forceps or manual rotation of a face to mentoanterior is rarely performed. A vacuum is obviously absolutely contraindicated but a direct forceps delivery of a mentoanterior position may be appropriate for delayed second stage or usual maternal or fetal indications. However, it should be remembered that engagement will not have occurred until the face is at least 3 cm below the ischial spines.

FIGURE 35.12

Face presentation: mechanism of delivery. A The chin is anterior and has descended until the fetal hyoid bone is at the level of the symphysis pubis. B The head pivots on the symphysis pubis and is born by flexion. The chin appears first, followed by the nose, brow, vertex and occiput.

FIGURE 35.13

Persistent mentoposterior position: delivery cannot occur if the chin remains posterior. Delivery will only be effected vaginally if the chin rotates anteriorly.

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Chapter 36  POSTPARTUM HAEMORRHAGE Michael Permezel

KEY POINTS Postpartum haemorrhage (PPH) occurs in about 4% of pregnancies and accounts for about 10% of direct maternal deaths. The key to management is to act without delay in implementing the sequence of steps necessary to control the bleeding. The common causes are ‘tone’ (uterine atony), ‘tissue’ (retained placental tissue), ‘trauma’ (birth canal laceration) and ‘thrombin’ (coagulopathy). Active management of the third stage of labour (including the administration of an oxytocic), reduces the likelihood of uterine atony. Although most cases occur unexpectedly in women without risk factors, there are pregnancies where PPH should be anticipated: previous PPH, chorioamnionitis, placental abruption, placenta praevia, uterine overdistension (including multiple pregnancy), prolonged labour and instrumental birth. Initial management of a PPH in the birth suite will focus on summoning appropriate personnel, resuscitation, contracting the uterus (massage and oxytocics), emptying the uterus and excluding a lower traumatic site for the bleeding. If the PPH is persistent, the patient is taken to the operating theatre. Resuscitation continues with anaesthetic support monitoring volume, haemoglobin and clotting, and replacing as needed. Exploration of the uterus is performed to exclude retained products or high genital tract injury to the uterus, cervix or upper vagina. Ongoing bleeding is managed with further oxytocics and other measures as deemed necessary including balloon tamponade, compression sutures, vessel ligation and hysterectomy. Secondary PPH is almost always due to infection, often in combination with some retained products of conception. Microbiological assessment, ultrasound and antibiotics are required but only a minority of cases will need curettage.

PRIMARY POSTPARTUM HAEMORRHAGE Primary postpartum haemorrhage (PPH) is defined as bleeding of 500 mL or more from the birth canal in the first 24 hours after delivery of the baby. Major PPH is variously defined but most easily as blood loss of greater than 1000 mL. It remains the major cause of maternal death on a global basis—mostly in women of high parity who did not want to be pregnant. The consequences of

sustained haemorrhagic shock in a pregnant woman are discussed in Chapter 37 but include disseminated intravascular coagulation which will further add to the bleeding.

INCIDENCE There are many inaccuracies in the estimation of blood loss around the time of birth, but the best approximations would suggest 4% PPH with active management of the third stage and 8% if active management is omitted.

Chapter 36  Postpartum Haemorrhage

AETIOLOGY A PPH arises from either the placental site or a traumatic site. Possible aetiologies are in Box 36.1 and each is discussed later in this chapter.

MANAGEMENT OF ACUTE BLOOD LOSS AT BIRTH INITIAL MANAGEMENT IN THE   BIRTH SUITE 1.  Summon assistance Significant haemorrhage requires more than one pair of hands and experienced help can be lifesaving. The woman should never be left alone and a second person will be needed to obtain the necessary drugs, equipment and so on.

2.  Simultaneous resuscitation The resuscitation should take place simultaneously with manoeuvres to arrest the haemorrhage. An intravenous line is needed and blood should be taken for cross-match if not already done. Fluid infusion should be compatible with blood lost.

3.  Contract the uterus There is an old saying that ‘an empty contracted uterus will not bleed’. While this is not always true, achieving a strong uterine contraction should be the priority when faced with brisk bleeding after birth. a. Uterine massage (‘Rub up the fundus’). This is usually an effective means of contracting the uterus and at the same time, one gains an impression of whether the uterus is atonic. b. Oxytocic administration. What is used will depend on what has already been administered for the third stage of labour. A common regimen might be: ergometrine 0.25 mg slowly intravenously and

repeated after 5 minutes if necessary; oxytocin 40 units in 1 L over 4 hours and misoprostol 1000 mcg rectally. If atony is likely and bleeding persistent, dinoprost (prostaglandin F2α), 1 mg intramyometrial may be given with careful supervision. Note that asthma and hypertension are contraindications.

4.  Empty the uterus If the placenta is retained, a further attempt is made to deliver it by controlled cord traction (if the cord is still attached) or fundal pressure (if the cord has been avulsed). If the placenta has been delivered, it is rechecked carefully for completeness and the presence of a transected feeding vessel in the membranes, which might indicate a missing succenturiate lobe.

5.  Check the lower birth canal Check the lower birth canal, looking for an obvious traumatic bleeding site in the low vagina or perineum.

6.  Prepare for the operating theatre if the bleeding is continuing Bimanual compression will reduce blood loss while preparations are being made for theatre. Haematology should be investigated, including a full blood examination and clotting studies, as well as checking the availability of compatible blood products.

SUBSEQUENT MANAGEMENT   IN THE OPERATING THEATRE 1.  Summon further assistance if needed An anaesthetist will be needed in theatre to manage the resuscitation. Consideration should be given to the whereabouts of other personnel who may be needed, including experienced surgical assistance and haematology/blood bank expertise.

2.  Simultaneous resuscitation BOX 36.1  Causes of primary postpartum haemorrhage. 1. Placental site a. Uterine atony: grand multiparity, overdistension (e.g. twins), long labour b. Retained placenta c. Placenta praevia d. Placenta accreta e. Uterine inversion f. Bleeding tendency 2. Traumatic site a. Uterine rupture b. Cervical tear c. Vaginal or perineal laceration

The anaesthetist will be responsible for maintaining blood volume, coagulation and platelets. Resuscitation should take place simultaneously with manoeuvres to arrest the haemorrhage. An intravenous line is needed and blood should be taken for cross-match if not already done. Fluid infusion should be compatible with blood lost.

3.  Explore the uterus Look for either retained products of conception or a traumatic site of bleeding in the uterus (manual exploration), cervix or upper vagina (under vision). Good anaesthesia and good lighting are essential.

4.  Contract the uterus Contract the uterus as mentioned previously. The anaesthetist should be overseeing an oxytocin infusion. Up to 303

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1 mg of ergometrine may be given in 250-mcg aliquots. Misoprostol will have been administered rectally and up to a total of 3 mg of dinoprost (prostaglandin F2α) can be given intramyometrially in 1-mg aliquots at least 5 minutes apart.

it takes to perform these procedures does not irrevocably compromise the patient. It should not be attempted by a surgeon inexperienced in the technique.

5.  Balloon tamponade or packing

Hysterectomy is generally regarded as an operation of last resort but a timely hysterectomy can be lifesaving, while procrastination for too long with other approaches may increase the likelihood of a maternal death.

Balloon tamponade (Fig 36.1) or packing should next be considered if the bleeding appears to be from the placental site and is persistent. On rare occasions, there is uncontrollable bleeding from multiple vaginal tears that require packing for control of venous ooze after arterial bleeding has been arrested with sutures.

6.  Compression sutures (e.g. B-Lynch) Compression sutures can be lifesaving if the bleeding is from a placental site in the upper uterine segment (Fig 36.2). A B-Lynch will not be effective if the bleeding is from a low-lying placental site, but alternative styles of compression sutures have been suggested for that situation.

7.  Internal iliac ligation or placental site radiological embolisation

8.  Hysterectomy

PPH FROM THE PLACENTAL SITE UTERINE ATONY Contraction of the uterus after placental separation causes the vessels supplying the placental bed to occlude. Inadequate contraction and failure of this critically important mechanism is the most common cause of PPH. Uterine atony is less common with ‘active management of the third stage of labour’, comprising the Fallopian tube

These measures may be employed in an attempt to further control persistent bleeding and preserve the uterus. Specific expertise is needed and care taken so that the time

Round ligament Broad ligament

INSERTION OF SUTURES

SUTURE TIED

FIGURE 36.1 

The Bakri balloon tamponade for control of postpartum haemorrhage.

Source: Gabbe SG, Niebyl JR, Galan HL, et al. Obstetrics: Normal and Problem Pregnancies. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 19.10. Courtesy Cook Women’s Health.

304

FIGURE 36.2 

B-Lynch compression suture for control of massive PPH.

Source: James D, Steer PJ, Weiner CP, Gonik B. High Risk Pregnancy. 4th ed. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 75.12. From B-Lynch C, Coker A, Lawal AH, et al. The B-Lynch surgical technique for the control of massive postpartum hemorrhage: An alternative to hysterectomy? Five cases reported. Br J Obstet Gynaecol 1997;104:372–5.

Chapter 36  Postpartum Haemorrhage

administration of oxytocic drugs and then assistance with the delivery of the placenta. Women choosing to have a ‘natural third stage’ are about twice as likely to have an atonic PPH. A number of factors may interfere with normal uterine retraction after birth: chorioamnionitis, uterine ‘exhaustion’ after a prolonged labour, high parity and overdistension of the uterus prior to birth. Overdistension may be the result of a large baby, multiple pregnancy or polyhydramnios, and in the first two cases will also be associated with an increased placental blood flow. Management is as described for an acute primary PPH. It is important not to assume atony without pursuing the possibility of other causes of placental site bleeding or a traumatic site.

RETAINED PRODUCTS OF CONCEPTION Non-separation and retention of part or whole of the placenta is also a common cause of PPH. Arteries and venous sinuses in the placental bed are inhibited from occluding even by relatively small amounts of placenta tissue (e.g. a cotyledon). This may be partly an effect on uterine contraction but may also be a failure of constriction of the arterioles and venous sinuses in the placental bed. Where the whole placenta, or a large portion, is retained, the diagnosis is obvious. Difficulty arises, however, if there is a small cotyledon retained (especially if the placenta is ragged) or if there is an additional (succenturiate) lobe (Fig 36.3). On occasions, large segments of retained membrane may act in the same way as

a cotyledon. In all women with significant ongoing bleeding, it is to be assumed that there ‘may’ be retained placental fragment and uterine exploration with adequate anaesthesia is indicated.

PLACENTA PRAEVIA AS A CAUSE   OF PPH With a placenta praevia, there is less muscle in the lower uterine segment and therefore less efficient contraction of the uterine wall around the vessels supplying the placental bed. This results in higher than usual blood loss from the placental bed if the placenta is located in the lower uterine segment. Fortuitously, this is usually at caesarean section where surgical measures can be instituted promptly. Sometimes sutures are directed specifically at bleeding points in the lower uterine segment but also a balloon catheter may be employed. Compression sutures are more difficult and those of the B-Lynch type are not suitable. Hysterectomy is necessary in about 1% of first caesarean sections for placenta praevia but the risk increases greatly where there are previous caesarean sections (see placenta accreta).

PLACENTA ACCRETA Pathology Placenta accreta implies morbid adherence of the placenta to the uterine wall. It is sometimes termed ‘percreta’ if the placenta completely traverses the uterine wall (often into the bladder).

FIGURE 36.3 

Missing placental cotyledon that was noted at routine inspection of the placenta after birth. Although there was no postpartum haemorrhage, a manual removal was performed and the missing cotyledon retrieved from the uterine cavity. Source: Courtesy of Monash Health.

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Predisposing factors This condition is usually associated with previous caesarean section (especially repeated) and may be tested for by estimation of serum alpha-fetoprotein (elevation) or by ultrasonography.

Clinical presentation The condition should be suspected clinically where there is a low-lying anterior placenta and a previous caesarean section. With placenta praevia and one prior caesarean section, the risk of accreta is about 25% but increases to 60% after two caesarean sections. Antenatal bleeding may be minimal or absent but separation of the placenta is difficult at caesarean section followed by heavy and persistent bleeding from the placental bed.

Management Placenta accreta is a life-threatening condition and all resources must be available to minimise maternal risk. Unless unavoidable by virtue of emergency substantial haemorrhage, a caesarean section for possible placenta accreta should only occur in a hospital equipped to manage massive haemorrhage and with the necessary surgical, anaesthetic, haematological and maybe radiological expertise available. Surgical approaches are varied and will depend on the specific circumstances and preference of the experienced obstetricians undertaking the procedure. Options include: 1. attempting to remove the placenta and control the bleeding, or 2. performing a high classical caesarean section and leaving the placenta in situ in the lower uterine segment. A hysterectomy may then be performed at that time. Alternatively, there may be attempted conservative management, waiting for the placenta to pass vaginally—which can take many weeks. The latter approach may be effective but a small number present with sudden haemorrhage days or weeks after the birth and this may be fatal.

inversion is a submucous fibromyoma projecting through the external os; this can be confused with partial inversion where the fundus may still be palpable abdominally. Bleeding may or may not be excessive, but shock is common if the uterus is not quickly replaced. Neurogenic shock usually ensues due to a massive parasympathetic output (vasovagal attack) consequent on traction on the infundibulopelvic ligaments as the ovaries are drawn down with the fundus of the uterus.

Management If recognised at the moment it occurs, immediate replacement can usually be effected. Otherwise, after shock has been corrected by intravenous therapy, an attempt is made to replace the uterus manually: with the fundus in the palm of the hand, strong upward pressure is exerted to place the uterine ligaments on the stretch; if this is maintained for 3 to 5 minutes the fundus will usually recede upwards as the ring widens. It is then pushed upwards with the clenched fist. The placenta, if still attached to the fundus, is manually removed after the inversion has been replaced; it provides a firmer base to press upon and lessens the risk of uterine rupture. Alternatively, O’Sullivan’s hydrostatic method may be used: here, sterile saline at body temperature is run into the upper vagina while the forearm occludes its egress below; the vagina balloons, the ring stretches and the fundus returns to its normal position. If the constricting ring feels tight, it may be relaxed with a slow intravenous bolus of 2 g of magnesium sulfate. Rarely, abdominal surgery may be necessary.

UTERINE INVERSION Pathophysiology The fundus of the uterus descends through the cervix and lies either in the vagina or outside the introitus. The placenta is usually still adherent, either totally or partially. This condition is extremely rare with active management of the third stage of labour including the routine administration of an oxytocic. Uterine inversion usually occurs in the presence of a fundal placenta with cord traction applied to an uncontracted uterus (Fig 36.4). It may also occur during a manual removal and at caesarean section.

Clinical features A large mass is felt or seen and there is no uterus palpable in the abdomen. The only condition which simulates 306

A FIGURE 36.4 

B

Uterine inversion. Traction on the cord when the uterus is atonic and the placenta not separated produces initial dimpling of the fundus A and then inversion of the uterus through the cervix B.

Chapter 36  Postpartum Haemorrhage

COAGULATION DEFECT The impact of coagulopathy on peripartum blood loss highlights the fact that uterine contraction alone is not responsible for cessation of placental site bleeding after separation. Activation of the endothelium with vasospasm, platelet aggregation and clot formation are all important as well. In obstetric practice, disseminated intravascular coagulation is easily the most common cause of failure of blood clotting. The clinical conditions predisposing to this complication are placental abruption, fetal death in utero (more than 4 weeks), severe preeclampsia, amniotic fluid embolism, chorioamnionitis and sustained hypotension with poor tissue perfusion for any reason (Ch 20). All of these conditions act by massive release of thromboplastin into the circulation. Occasionally, other conditions such as severe thrombocytopenia or hereditary disorders of coagulation (e.g. von Willebrand’s) may present with postpartum haemorrhage. In all of these conditions, correction of the underlying haematological disturbance will be key to controlling the blood loss.

PPH FROM A TRAUMATIC SITE Any disruption of the birth canal may cause excessive bleeding, because of the increased vascularity in pregnancy. In general, tears of the uterus, cervix and upper vagina are more serious, because of the larger vessels that may be torn and the difficulty in gaining access to them. More common and usually more manageable are tears of the lower vagina, introitus and perineum. A high tear should be suspected if bleeding is coming down from the upper vagina immediately after birth and before any separation of the placenta.

FIGURE 36.5 

Uterine rupture at the site of a previous classical caesarean section scar (subtotal hysterectomy specimen). Source: Reproduced with permission from the Royal Women’s Hospital, Parkville, Victoria.

UTERINE RUPTURE Predisposing factors Uterine scar Upper uterine segment scars (classical caesarean section, hysterotomy) are more likely to rupture (Fig 36.5) than the transverse scar from a single lower uterine segment caesarean section (Fig 36.6). Management of labour after caesarean section is discussed in Chapter 32. Rupture may also occur after operation on the non-pregnant uterus, including myomectomy or perforation of the uterus at the time of curettage.

Obstructed labour Neglected obstructed labour may result in a uterine rupture, particularly as the parity increases. The lower uterine segment progressively thins as it is drawn up over the presenting part. Rupture may occur intraperitoneally or extend into the broad ligament.

FIGURE 36.6 

Intact fetal membranes bulging through a uterine scar dehiscence. Source: Courtesy of Prof. Norman Beischer.

Trauma A high-speed motor vehicle accident may cause uterine rupture, as may obstetric manipulation (e.g. internal version prior to breech extraction of a second twin). 307

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Clinical features The clinical picture depends on the extent of the haemorrhage. A dehiscence may be an incidental finding at the time of caesarean section. If there has been significant bleeding, fetal compromise may be evident. With a true ‘rupture’, if the fetus is alive it will rapidly show evidence of compromise and a hypoxic death will follow if the fetus or placenta are extruded into the peritoneal cavity through the tear. The mother will experience pain at the site of rupture followed by evidence of intraperitoneal bleeding (e.g. shoulder-tip pain) and subsequently hypovolaemic shock if the bleeding is not arrested. Rupture may present after a vaginal birth as persistent ongoing bleeding or unexpected maternal collapse.

Treatment Apart from the usual measures for haemorrhagic shock, a uterine rupture will usually require hysterectomy, although a small defect may be successfully repaired— albeit with a significant likelihood of rupture in a subsequent pregnancy.

CERVICAL LACERATIONS Predisposing factors for cervical lacerations include the following. Pushing on an undilated cervix. This can generally be avoided with patient instruction. If this is not effective, epidural anaesthesia will quell the desire to push against a cervix that is not fully dilated. A hypertonic labour. Rapid labour may have a similar effect but without necessarily being due to ‘pushing’. Traumatic tearing of the cervix. Instrumental vaginal birth (especially rotational forceps), internal podalic version (usually for a second twin) and treatment of impacted shoulders are all manipulations that may tear the cervix. The characteristic feature is a steady loss of bright red blood, which commences soon after delivery of the baby, but the diagnosis will not be confidently made until the cervix is carefully inspected under anaesthesia. With good exposure and lighting, ‘walking’ around the cervix with forceps will expose any cervical tear, which can then be repaired. It is difficult to effectively reduce haemorrhage from a cervical tear with packing but bimanual compression may be effective while awaiting access to an operating theatre.

• • •

HIGH VAGINAL WALL TEARS A high vaginal wall tear will have causes similar to cervical lacerations and they may occur together. Access to a tear high in the lateral fornix can be extremely difficult but may involve major vessels in the base of the broad ligament. Expert surgical repair, often followed by a need for tight packing of the vagina, is required. Packing can be very useful for emergency treatment of haemorrhage from vaginal lacerations as the pelvis is a bony basin that 308

has rigid walls to pack against. Two large ribbon gauze packs are tied together, moistened with obstetric cream and firmly packed, beginning high in the vagina. Since the packing occludes the urethra, an indwelling (Foley) catheter is required and a uterine balloon with catheter drainage may help reveal ongoing uterine bleeding. The pack is removed 12 to 24 hours later and healing of any unsutured vaginal lacerations is usually quite satisfactory.

Low vaginal, introital and perineal tears Tears may occur almost anywhere, including involving the anterior compartment of the perineum (around the urethra and clitoris) and posteriorly involving the sphincter and anal canal. Particularly heavy bleeding may result from an annular avulsion of the vulva from the lower vagina. Tears are more common where the fetus is large or the head extended, where delivery is rapid or instrumental (not allowing time for tissues to stretch) or where there is a need for difficult manipulations (e.g. delivery of the posterior arm with shoulder dystocia. While there is no place for ‘routine’ episiotomies, a timely incision to enlarge the introitus can save the woman tears causing considerable blood loss, significant perineal pain in the puerperium and sometimes followed by dyspareunia lasting months or years. Each layer should be carefully identified and sutured, and haemostasis secured. Where the anal sphincter is involved, this must be clearly identified and repaired in theatre with good lighting and adequate anaesthesia. Where there is persistent bleeding from deep in the perineum, packing is not possible because there is nothing to pack against. Pressure will be effective but difficult to maintain. A large ‘compression suture’ may be effective but needs to be removed within 12 to 24 hours.

VULVAL AND PARAVAGINAL HAEMATOMA In approximately 1 out of 1000 births there is extensive ‘concealed’ bleeding into the tissues of the perineum or vagina. It may or may not have been preceded by lacerations where a vessel has retracted or temporarily been hidden by vasospasm, only to open up after closure of the wound. If the haematoma is large, pain will be severe and may cause significant hypovolaemia. Treatment is usually conservative in the first instance as ‘tamponade’ by the tissues will generally arrest the bleeding. An indwelling urinary catheter is usually needed along with narcotic analgesia. Drainage after a few days may be needed for maternal comfort. If early drainage is performed, vaginal packing is usually needed to help tamponade a deep bleeding point that has not been readily identified.

THE RETAINED PLACENTA IN THE ABSENCE OF BLEEDING Sometimes the placenta has separated and is ‘trapped’ in the cervix. This can be readily palpated on vaginal

Chapter 36  Postpartum Haemorrhage

examination and if most of the placenta is in the vagina, it can be relatively easy to grasp and remove without significant maternal discomfort. If there is minimal bleeding, it is likely that the placenta has not separated and patience is required. The accoucheur should check for placental separation every 5 minutes of so as there is the risk of concealed haemorrhage when separation occurs and the placenta remains in situ. Where the placenta has been retained for more than 30 minutes, arrangements should be made for manual removal of the placenta, as retention longer than 60 minutes (approximately 2% of labours) carries a substantive risk of major PPH.

MANUAL REMOVAL OF THE PLACENTA Manual removal of the placenta will require either regional or general anaesthesia. Blood should have been taken for cross-match as a PPH is common at the time of manual removal, and can be severe if the placenta is particularly adherent. Fresh sterile gloves (preferably with a forearm extension), gown and drapes should be used. The fingers are brought into the shape of a cone and the hand follows the umbilical cord into the uterine cavity. An assessment is made of the degree of adherence of the placenta and the site of attachment. The fingers are then inserted at one edge of the placenta, with the external hand on the abdomen exerting firm counter-pressure. With sweeping movements, the placenta is stripped from the wall of the uterus (Fig 36.7). It is important that the procedure be carried out gently and methodically, the operator having a clear mental picture of the disposition and extent of the placenta on the uterine wall. Occasionally, the placenta may be morbidly adherent to the uterus (placenta accreta), either wholly or in part. In such cases, a plane of cleavage will not be found and bleeding is usually heavy (see above). Following manual removal, the uterine cavity should be carefully explored to exclude any retained fragments and to ensure the uterine wall was not torn during the procedure. An oxytocic is then administered along with prophylactic antibiotics. A check of the birth canal is undertaken and any tears repaired.

SECONDARY PPH A secondary PPH is defined as any bleeding in excess of normal lochial loss between 24 hours and 6 weeks postpartum. Most cases are due to infection that may be associated with retained fragments of placenta and/or membrane. Rarely, there may be other causes such as choriocarcinoma or a submucous fibroid. Bleeding is bright and can be heavy.

MANAGEMENT A full clinical assessment is needed to ascertain the degree of blood loss and whether any resuscitation is

FIGURE 36.7 

Manual removal of the placenta. The placenta is palmed as the fingers gently separate it from the uterine wall. The abdominal hand provides counter-pressure, which assists in finding the correct plane between placenta and uterine wall.

required. A haemoglobin check is needed and a vaginal swab is taken for microbiological study. Oxytocics (e.g. ergometrine, misoprostol) variably assist with controlling acute bleeding. Antibiotic therapy is commenced even if the woman is afebrile, since endometritis is likely. A serum hCG should be performed if the bleeding is unusual or persistent, suggesting trophoblastic disease. An ultrasound will be requested to exclude substantive retained products of conception that will require curettage for removal. Curettage carries a risk of perforation of the uterus softened by both involution and infection. In the longer term, there may be intrauterine adhesion formation, known as Asherman syndrome. FURTHER READING Angstmann T, Gard G, Harrington T, et al. Surgical management of placenta accreta; a cohort series and suggested approach. Am J Obstet Gynecol 2010;202:38.e1–9. Onwere C, Gurol-Urganci I, Cromwell DA, et al. Maternal morbidity associated with placenta praevia among women who had elective caesarean section. Eur J Obstet Gynecol Reprod Biol 2011;159(1):62–6. 309

Chapter 37  MATERNAL COLLAPSE Michael Permezel

KEY POINTS Maternal collapse is broadly classified into circulatory, respiratory and neurological. The first step will be to establish whether the patient is hypotensive: this immediately establishes whether the primary event is circulatory or respiratory/neurological. A raised jugular venous pressure (JVP) suggests pump failure or embolism, a low JVP is seen in hypovolaemia (blood loss) or circulatory collapse (anaphylaxis, sepsis, total spinal blockade). Important sites of concealed blood loss include rupture of the uterus, the liver or an upper abdominal aneurysm. Amniotic fluid embolism may be caused by a partial thickness tear in the uterine wall or at the time of placental separation at caesarean section (especially with an anterior placenta praevia). Consequences include immediate cardiorespiratory compromise with later disseminated intravascular coagulation. Cardiac arrest in pregnancy may benefit from immediate caesarean section in order to facilitate maternal resuscitation.

INTRODUCTION For the purposes of this section, maternal collapse means some unexpected disturbance of consciousness; that is, essentially a neuropsychological condition that may have circulatory origins through poor cerebral perfusion.

AETIOLOGY The aetiological classification is best thought of in terms of those causes associated with hypotension (shock, syncope or faint) and those cases of collapse with normal cerebral perfusion. Box 37.1 lists the causes of maternal collapse. In many cases, more than one factor is involved. Figure 37.1 presents a flow chart outlining the principal common diagnoses but the clinical picture is often complicated. For example, a woman with severe preeclampsia with an epidural in situ on magnesium sulfate may have a

postpartum haemorrhage or a woman with a vasovagal episode may have superimposed hysteria.

HYPOTENSIVE MATERNAL COLLAPSE HYPOVOLAEMIA Aetiology Haemorrhage in obstetrics will be the most important cause of hypovolaemia but may be aggravated by prior dehydration where the woman may have been taking little orally in labour, sometimes compounded by vomiting. The blood volume is decreased most rapidly and obviously by revealed haemorrhage (miscarriage, antepartum and postpartum haemorrhage). There are many possible sources of concealed haemorrhage that need to be considered such as rupture of the uterus, rupture of

Chapter 37  Maternal Collapse

BOX 37.1  Classification of maternal collapse. 1. Circulatory: hypotensive shock a. Hypovolaemic i. Revealed ii. Concealed (uterine rupture, splenic artery aneurysm) b. Acute vasodilatation i. Anaphylaxis ii. Sepsis iii. Inadvertent total spinal iv. Drugs • including antihypertensive drugs, MgSO4 v. Endocrine • Addisonian crisis, phaeochromocytoma rebound hypotension c. Cardiogenic i. Outflow obstruction • Thromboembolism, air embolism, amniotic fluid embolism • Aortic dissection, aortic stenosis ii. Pump failure • Vasovagal (including cervical shock, uterine inversion) • Peripartum cardiomyopathy, acute myocardial infarction (AMI), cardiomyopathy iii. Arrhythmias • Local anaesthetic toxicity, long QT syndrome

2. Respiratory a. Neurorespiratory i. Inadvertent total spinal ii. Narcotic overdose b. Airway obstruction i. Aspiration ii. Asthma c. Pulmonary oedema i. Especially beta-sympathomimetics, mitral stenosis d. Pneumothorax 3. Neurological a. Drugs i. Narcotic (prescribed or illicit), local anaesthetic toxicity, MgSO4 b. Metabolic i. Hypoglycaemia, ketoacidosis, hyponatraemia, hypernatraemia c. Intracranial haemorrhage i. Intracerebral haemorrhage ii. Subarachnoid haemorrhage iii. Subdural haemorrhage (may follow dural puncture and cerebrospinal fluid leak) d. Post-ictal i. Eclampsia, idiopathic epilepsy, local anaesthetic toxicity e. Hysteria

Maternal collapse BP

BP ok

Hypotensive shock JVP

Respiratory/neurological Conscious state okay

JVP

Pump failure, embolism

Hypovolaemia, vasodilatation

Warm Vasodilatation

Respiratory

Conscious state Neurological

Cold Hypovolaemia

FIGURE 37.1

Flow chart for diagnosis of maternal collapse.

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the liver or a hepatic/splenic/pancreatic artery aneurysm. These diagnoses are often made at caesarean section for severe fetal compromise in the presence of abdominal pain with a provisional diagnosis of placental abruption. On opening the peritoneum, the surgeon finds the blood to be intraperitoneal and prompts a search for the site of the haemorrhage.

Clinical features It is axiomatic in medicine that the young healthy patient copes with hypovolaemia extraordinary well until just before collapse. Markers of hypovolaemia such as tachycardia and hypotension are unreliable and the clinician should be alert to the fact that the patient can be near collapse even though she appears perfectly well and has relatively normal vital signs. A more subtle sign of hypovolaemia is the postural drop in blood pressure on standing up. This can be useful where intra-abdominal bleeding is suspected such as with an ectopic pregnancy. Sustained hypotension in pregnancy or the early puerperium may result in necrosis of the anterior lobe of the pituitary gland (Sheehan’s syndrome). The earliest clinical manifestation is failure of lactation, then amenorrhoea; gradual diminution in function of the thyroid and adrenal glands follows. Other rare consequences of sustained hypotension are acute tubular necrosis and, extremely rarely, acute bilateral renal cortical necrosis.

Management Regardless of the site of bleeding, sustained hypotension will lead to tissue hypoxia, release of tissue thromboplastins and the eventual development of disseminated intravascular coagulation, which in turn may exacerbate the bleeding in a vicious cycle that must be corrected by restoring tissue perfusion, correcting the coagulopathy and definitive action at the site of bleeding.

ACUTE VASODILATATION STATES Aetiology The following conditions are associated with acute dilatation of both arterioles and venules. Arterioles are the resistance vessels and lower blood pressure according to the formula: blood pressure = cardiac output × total peripheral resistance. Venules are the capacitance vessels so that dilatation produces effective hypovolaemia with lower central venous pressure and a fall in cardiac output as per Starling’s curve. In anaphylactic shock, liberated vasoactive substances (bradykinin, histamine) cause vasodilatation, increased capillary permeability and bronchospasm. Anaphylaxis is particularly severe on the uteroplacental circulation with the potential for long-term sequelae. Urgent therapy is indicated with volume replacement and adrenaline. In severe sepsis (septic abortion, chorioamnionitis, pyelonephritis, puerperal infection, gastrointestinal 312

perforation), bacterial endotoxins produce widespread vasodilatation. Management requires correction of the sepsis and circulatory support (e.g. noradrenaline infusion). Inadvertent total spinal anaesthesia occurs when the large dose of local anaesthetic destined for the epidural space is mistakenly injected into the subarachnoid space. The result is not only respiratory paralysis but also loss of sympathetic drive to the entire vascular system and heart. Acute management requires ventilation as well as circulatory support.

Clinical features With widespread vasodilatation, the periphery will generally be warm and the jugular venous pressure (JVP) will be low. The patient with sepsis will have a tachycardia. Total spinal anaesthetic blockade will result in respiratory paralysis and a bradycardia. Anaphylaxis is usually complicated by bronchospasm, urticaria and generalised oedema that may involve the laryngopharynx. Septicaemic shock of long duration may be associated with adrenal cortical necrosis (WaterhouseFriderichsen syndrome), which will lead to a further exacerbation of the hypotension if not treated with corticosteroid replacement.

Management Management requires an understanding of the pathogenesis and specific aetiology. Volume replacement will assist with the management of venular dilatation. Sympathomimetics will improve vasomotor tone and the choice will depend on the pathophysiology. In total spinal anaesthesia, the absence of sympathetic drive to the heart makes adrenaline a superior choice to noradrenaline. The same applies to anaphylaxis but for a different reason: the bronchospasm and mast cell degradation are both inhibited by the beta-adrenergic effect. In sepsis, there is often already a pronounced tachycardia and a noradrenaline infusion is preferred as a predominant alphaadrenergic effect is desired.

CARDIOGENIC Aetiology A cardiomyopathy, an acute coronary occlusion or myocarditis may result in acute cardiac pump failure. Aortic stenosis or dissection cause outflow obstruction. Although aortic stenosis is usually a chronic condition, there may be acute decompensation precipitated by suboptimal venous return (e.g. epidural anaesthesia, bleeding) that would not otherwise be so critical. A pulmonary embolus (thrombus, air or amniotic fluid) will have a similar effect on the right side of the heart with an acute obstruction of myocardial outflow. Arrhythmias may be induced by metabolic disturbance (e.g. hypokalaemia or hyperkalaemia) or drugs, including local anaesthetic toxicity. Also to be considered is the long QT syndrome, which may have arrhythmias precipitated by erythromycin.

Chapter 37  Maternal Collapse

In neurogenic shock (vasovagal), there is excessive efferent activity of the parasympathetic nervous system leading to depression of cardiac activity in the heart and blood vessels (vagus and other parasympathetic nerves) usually by an intense visual or painful stimulus. The condition of uterine inversion after delivery produces shock even if little blood has been lost, due to excessive parasympathetic activity precipitated by traction on the infundibulopelvic ligament. The same may happen when products of conception are trapped in the cervical os during a first-trimester miscarriage (cervical shock).

Clinical features In contrast to acute vasodilatation and hypovolaemia, the jugular venous pressure will usually be elevated in cardiogenic shock. A pronounced bradycardia will be present if there is excessive parasympathetic outflow.

Management Rapid establishment of the aetiology is important. An anticholinergic drug (e.g. atropine) will be effective for an acute vasovagal. A massive pulmonary embolus is a medical emergency and early confirmation of the diagnosis with appropriate imaging may allow radical but lifesaving measures such as fibrinolytic therapy or embolectomy.

Amniotic fluid embolism Aetiology Amniotic fluid can enter the maternal circulation through a small partial-thickness tear in the lower uterine segment. The predisposing factors are not unexpectedly similar to those of a full-thickness tear: hypertonic uterine action (whether spontaneous or oxytocic induced) and neglected obstructed labour. An alternative route for amniotic fluid to enter the bloodstream is through the placenta bed at caesarean section. This most commonly occurs where a low anterior placenta is separated before birth of the baby, enabling amniotic fluid to wash across the venous sinuses. These vessels are designed to ‘scoop up’ approximately 750 mL each minute of blood from the intervillous space. It is therefore no surprise that, given the opportunity, it is amniotic fluid and not blood that is drawn rapidly into the circulation.

Clinical features The entry of significant amounts of amniotic fluid into the pulmonary circulation cause an ‘after-load’ effect on the right side of the heart with acute pulmonary hypertension, which is further exacerbated by pulmonary capillary damage. The initial symptoms are dyspnoea and cyanosis, together with pallor, chills, restlessness and perhaps convulsions. Shock usually follows rapidly. If the woman survives the acute embolism, the thromboplastin contained in the amniotic fluid results in disseminated intravascular coagulation and a general bleeding tendency ensues.

Treatment This comprises full respiratory and circulatory support. Correction of clotting factor deficiencies may be necessary to control haemorrhage. Surgical control of bleeding is sometimes necessary but this is difficult in a cardiorespiratorily compromised patient with disseminated intravascular coagulation.

RESPIRATORY HYPOXIA AETIOLOGY Aspiration of gastric contents is particularly common in pregnancy due to pressure of the gravid uterus on the stomach in association with relaxation of the gastrooesophageal sphincter and slowed gastric emptying. Asthma may be precipitated by various medications including labetalol, PGF2α and anti-inflammatory drugs. Pulmonary oedema will eventuate if there is severe cardiac insufficiency (e.g. tight mitral stenosis) and the heart is further stressed by the haemodynamic shifts of blood volume around the time of birth, especially if ergometrine is used for the third stage of labour. A pneumothorax may occur with ‘straining’ (‘Valsalva’) in the second stage of labour.

CLINICAL FEATURES Acutely, the problem will be hypoxia with preservation of circulation. However, within minutes the heart will be compromised by the hypoxia.

MANAGEMENT The aetiology will usually be apparent, but a tension pneumothorax is critically important to diagnose early because it is eminently treatable when diagnosed. The author is aware of at least one maternal death due to a tension pneumothorax that was not diagnosed until autopsy.

NEUROLOGICAL CAUSES OF LOSS OF CONSCIOUSNESS AETIOLOGY Drugs commonly used in pregnancy that may lead to loss of consciousness include excessive magnesium sulfate (MgSO4) or narcotics. Hypoglycaemia will most often be seen in a diabetic patient on insulin and become more common in pregnancy (with vomiting being a common precipitating feature), but it may also be due to acute severe liver failure (e.g. acute fatty liver). Stroke may occur in hypertensive disorders and is most often occipital in severe preeclampsia. A subarachnoid haemorrhage is more likely in pregnancy due to the connective tissue softening 313

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that may be compounded by straining in the second stage of labour. Subdural haemorrhage is a rare complication of excessive cerebrospinal fluid leak from a dural tap. Convulsions are more common in pregnancy, labour and the puerperium, and if not observed, may cause diagnostic difficulty with an unexplained comatose or confused patient in a post-ictal state.

AETIOLOGY The causes are essentially those of hypotensive collapse and acute respiratory insufficiency, as given in Box 37.1.

DIAGNOSIS

In all of these situations, circulation is preserved and oxygenation is adequate as long as ventilation is maintained, thereby readily distinguishing the neuro­ logical causes from circulatory collapse and respiratory hypoxia.

Cardiac arrest will usually present with a sudden deterioration in the conscious state together with cyanosis and/ or pallor and absence of pulsation in a major vessel (e.g. femoral, carotid). Rapid diagnosis is crucial to survival without neurological damage. A flow chart of clinical signs to distinguish the major categories is given in Figure 37.1 but urgent investigations may be needed to establish the exact cause, which will guide treatment beyond the acute arrest.

MANAGEMENT

MANAGEMENT

Maintenance of oxygenation is critical if ventilation is compromised. Assessment should include a detailed clinical assessment, biochemical and toxin screen, and urgent neuroimaging if the diagnosis is not immediately apparent.

Management of a cardiac arrest in pregnancy follows the usual protocols of airway, breathing and circulation, but with measures to avoid caval compression by the gravid uterus. Lateral tilt should be initiated immediately but, in late pregnancy, caesarean section should be considered as part of the cardiac arrest procedure. Although it will undoubtedly give the fetus the best prospect of survival, the procedure is indicated to maximise the chances of maternal survival. The uteroplacental circulation impairs resuscitation in three ways: 1. mechanically through caval compression inhibiting venous return; 2. occupying approximately 15% of the cardiac output; and 3. acting as a venous reservoir. In the genuine cardiac arrest situation, no further anaesthesia is likely to be necessary and blood loss is minimal. Improved perfusion with cardiac massage is generally apparent as soon as the fetus is delivered and the uterus contracts down.

CLINICAL FEATURES

CARDIAC ARREST IN PREGNANCY DEFINITION This is defined as the cessation of effective myocardial contractions and cardiac output (e.g. no femoral pulse). It is associated with loss of consciousness, respiratory arrest, dilating pupils, cyanosis, pallor and finally death if the condition is not quickly relieved.

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Chapter 38  OBSTETRIC ANALGESIA AND ANAESTHESIA Richard Hiscock

KEY POINTS Maternal satisfaction with labour is largely unrelated to the type and quality of analgesia used and depends on the woman retaining a sense of control. Hence, education, preparation and support during labour are all important in achieving this objective. Labour is painful and most commonly used techniques, apart from neuraxial block, provide little or, at best, modest analgesia for women with moderate or more intense pain. Low-dose epidural analgesia for labour takes time to work (approximately 1 hour from request), is effective in over 75% of cases and is not associated with increased incidence of back pain or caesarean section. Regional anaesthesia for caesarean section is safe, effective and allows maternal and paternal participation in the birth and is preferred over general anaesthetic (GA). GA is now restricted largely to women with contraindications for regional techniques. All those caring for women in pregnancy must appreciate the risk of failed intubation and ventilation in obstetrics and ‘Can’t Intubate Can’t Ventilate’ (CICV) drills should be known and practiced.

OVERVIEW Labour is painful: over 60% of nulliparous and 45% of multiparous women describe labour pain as severe to intolerable.1 Its recall is modified by the passage of time, with pain described as severe to intolerable by 90% of women at 24 hours, by 65% at 6 weeks and by 10% at 12 weeks.2 For nearly all women, the choice, sequence and timing of analgesic options are an individual decision. It is important that they are provided with unbiased information about these options (efficacy, availability and delivery time) during the antenatal period and in the birthing suite. Maternal satisfaction with labour analgesia is not the same as maternal satisfaction with the childbirth experience. Irrespective of the analgesic used and it effectiveness, the vast majority of women are satisfied with their childbirth experience.3 Maintaining a sense of choice and achieving a normal vaginal delivery are associated with high maternal satisfaction.

PATHOPHYSIOLOGY OF LABOUR PAIN Pain of early labour results from lower uterine and endocervical stretching, transmitted by visceral afferents along sympathetic nerves to T10 to L1 spinal cord segments. It is poorly localised and referred to somatic dermatomes of the lower abdomen and upper thighs. In late first-stage and second-stage labour, pain arising from vaginal cervix, vagina and perineum is precisely localised, transmitted by the pudendal nerve to S2 to S4 segments of the spinal cord. Dilatation of the body of the uterus doesn’t produce pain. Caesarean section requires a dense block extending from S2 to T4.4 Labour pain elicits the same psychological and neurohormonal stress responses as severe pain of non-labour origin. Cardiovascular changes include increases in maternal heart rate, cardiac output, myocardial oxygen demand and systemic

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vascular resistance. In the majority of women these responses are not life-threatening, and if utero-placental perfusion is normal the fetus is not compromised. In women with obstructive cardiac lesions (stenotic valvular lesions, hypertrophic cardiomyopathies), untreated cerebral aneurysm or Marfan’s syndrome, effective analgesia is required to minimise these haemodynamic changes.

METHODS OF LABOUR ANALGESIA Analgesic options for managing labour pain can be classified by type (see Box 38.1), with the evidence base accessible through systematic reviews.5 The perception of and ability to tolerate labour pain is modified by the mothers’ physical and emotional status, previous labour experience and the current labour’s intensity and perceived duration. Information provided in the antenatal period, along with a supportive carer and midwife, provide a positive coping base. When a mother who is experiencing at least moderate pain requests relief, how effective are these analgesia options? Three broad functional categories based on efficacy are presented: 1. therapies with little or no evidence of effective relief of at least moderate pain 2. therapies that provide effective analgesia of moderate degree in some patients 3. therapies that provide effective analgesia in the majority of patients.

BOX 38.1  Methods of pain management used in labour.

Placebo/no treatment Hypnosis Biofeedback Intracutaneous or subcutaneous sterile water injection Immersion in water Aromatherapy Relaxation techniques (yoga, music, audio) Acupuncture or acupressure Massage, reflexology and other manual methods Transcutaneous electrical nerve stimulation (TENS) Inhaled analgesia Opioid drugs Non-opioid drugs Local anaesthetic nerve blocks Epidural (including combined spinal epidural)

Source: From Jones L et al, Pain Management for Woment in Labour: An overview of systematic reviews. Cochrane Pregnancy and Childbirth Group. Cochrane Database of Systematic Reviews, © 2013 John Wiley and Sons Ltd.

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THERAPIES WITH LITTLE   OR NO EVIDENCE OF   EFFECTIVE RELIEF OF AT   LEAST MODERATE PAIN Biofeedback, aromatherapy and relaxation techniques (including massage) are not effective in relieving moderate labour pain. TENS uses both continuous and demand electrical current delivered via gel electrode, placed on paravertebral skin (T10 to L1; S2 to S4), provides little analgesia even in early labour. Intracutaneous sterile water injected at four sites in the sacroiliac area provides relief of early labour back pain of short duration (45 to 90 mins) in some women. While commonly used, intramuscular opiates (100 mg pethidine) are poor labour analgesics that fail to provide adequate relief in over 75% of women (equivalent to TENS). Side effects include nausea, vomiting, sedation, increased gastric volume6 and a reduction in neonatal behaviour scores7.

THERAPIES THAT PROVIDE EFFECTIVE ANALGESIA OF MODERATE DEGREE IN SOME PATIENTS Self-hypnosis reduces the need for neuraxial analgesia in up to 25% of women. It requires a woman susceptible to hypnosis and training occurs over six 1-hour sessions in the last trimester. Acupuncture may provide some relief; however, the magnitude of effect is moderate and evidence is confined to a small number of studies. Nitrous oxide (30 to 50%) in oxygen can provide moderate analgesia in up to 50% of women, when inhalation is properly timed with contractions. This is widely used in Australian labour wards (60% women).8 Side effects include nausea (8 to 10%), emesis (2 to 3%), sedation (13%) and dizziness (20%). Rapid onset/offset is conferred by its low blood gas solubility with arterial and cerebral partial pressure rapidly approaching alveolar concentration. Gas delivery occurs when inspiration opens a demand valve; onset takes 20 seconds, with peak action 30 seconds later. To be effective, delivery needs to commence just prior to the onset of a contraction. Intravenous fentanyl or ultra-short-acting remifentanil, administered by a patient-controlled device (PCA), may provide adequate pain relief in 25% of women at the expense of sedation and hypoxaemia in some cases.9 Intravenous PCA techniques are often reserved for women where neuraxial techniques are contraindicated; the use of remifentanil requires skilled supervision. Local anaesthetic pudendal nerve block and paracervical block are options for first and second stages of labour respectively. Efficacy is equivalent to inhalational agents; however, major side effects include fetal bradycardia, fetal injection and maternal intravenous local anaesthetic toxicity.

Chapter 38  Obstetric Analgesia and Anaesthesia

THERAPIES THAT PROVIDE   EFFECTIVE ANALGESIA IN   THE MAJORITY OF PATIENTS

(secondary to opiates). Neonatal respiratory depression does not occur with standard narcotic doses. Major complications are listed in Table 38.1.10

Local anaesthetic/opiate drugs delivered by epidural or combined spinal epidural (CSE) routes provide effective analgesia in the majority of women, even those with severe pain. Satisfaction with epidural pain relief is higher than all other techniques,8 with over 80% of women achieving effective pain relief and many a painfree labour. Up to 70% of nulliparous and 40% of multiparous women receive epidural analgesia, with the incidence determined by midwife and obstetrician preferences along with availability of skilled anaesthetic services. The median time from request to effective analgesia is about 60 minutes; 75% of women will be comfortable at 90 minutes. Anaesthetic assessment is performed in all women requesting neuraxial analgesia and includes a focused history and examination, baseline observations, obstetric information (previous deliveries, assessment of the stage/progress of labour and fetal wellbeing). The labour ward should have both trained staff and resuscitation equipment that may be required to deal with lifethreatening complications (including respiratory and cardiac arrest). CSE is especially useful in advanced labour or second-stage labour where the rapid onset of block (especially vaginal and perineal) combined with the ability to extend the block if caesarean section is required.

TECHNIQUE

CONTRAINDICATIONS TO   NEURAXIAL BLOCKADE Contraindications to neuraxial blockade are: infection—local site, systemic (untreated) coagulopathy—platelet count less than 75 × 109 per litre, therapeutic dose low-molecular-weight heparin within 24 hours, inherited bleeding disorders untreated hypovolaemia epidural space obliterated by extensive lower thoracic lumbar spinal surgery allergy to local anaesthetic drugs.

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SIDE EFFECTS OF NEURAXIAL BLOCKADE The incidence of non-reassuring fetal heart rates may be increased after CSE. Central neuraxial block is associated with an increased duration of first-stage labour (approximately 20 minutes) and possible increases in the duration of second-stage (approximately 10 minutes) and the rate of instrumental delivery. The incidence of caesarean section and chronic back pain are not increased. Other side effects include maternal hyperthermia (usually < 38°C), mild hypotension (10%, treated by lateral positioning to remove aortocaval compression, intravenous crystalloid solutions and/or ephedrine) and pruritus

The insertion level is usually below termination of the spinal cord (L1 to L2), which is identified using a line across iliac crests (Tuffier’s line) that crosses the lumbar spine at L4 to L5 disc or L4 vertebral body. In pregnant patients, especially with increasing BMI, this clinical assessment can be up to three vertebral segments lower than the true level.11 For CSE, a site distal to L2 is chosen; if epidural technique alone is used placement above L2 is safe. In patients with difficult anatomy (morbid obesity and lumbar scoliosis), ultrasound is often used to delineate structures. Sterile technique (mask, gown, gloves and disinfection of skin with alcoholic chlorhexidine) is mandatory. The patient is positioned either in a sitting or lateral decubitus position, the skin prep applied and the area draped. The epidural space is identified using a loss of resistance (saline or air) when the Tuohy needle passes from non-compliant intra-spinous ligaments into the more compliant epidural space; depth varies from 3 to 9 cm and up to 15 cm in the morbidly obese. In CSE, a pencil point needle (26 G) is then passed into cerebrospinal fluid and intrathecal drug administered (Fig 38.1). In both techniques, a flexible multi-orifice side hole catheter is then inserted 4 to 5 cm into the epidural space (Figs 38.1 and 38.2).

ESTABLISHING AND MAINTAINING BLOCK Epidural blockade is established using a low-concentration local anaesthetic combined with a narcotic, solutions typically being ropivacaine (0.1 to 0.2%) or bupivacaine (0.0625 to 0.1%) plus fentanyl (2 mcg/mL). CSE analgesia uses a small dose of bupivacaine 2.5 mg plus fentanyl 15 to 25 mcg. Effective analgesia is usually achieved in 20 minutes with epidural technique and 10 minutes with CSE, often with minimal motor block. Analgesia is maintained using the same agents delivered by: 1. continuous infusion plus clinician bolus; 2. patient controlled epidural analgesia (PCEA); or 3. programmed intermittent epidural bolus (PIEB).12 Choice often depends on individual labour ward practices. Analgesia should be maintained until delivery and not ceased in the second stage of labour. Routine monitoring should include the mother’s heart rate, respiration rate, blood pressure, sensory spread of block (loss of cold sensation using ice) and density of motor block (Bromage score), and fetal cardiotocography. After delivery of the placenta, epidural catheter removal is painless and the mother is mobilised after return of sensory, motor and sympathetic function, usually within 1 to 4 hours. 317

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TABLE 38.1  ADVERSE EFFECTS OF EPIDURAL OR SPINAL ANAESTHESIA FOR INTRAPARTUM ANALGESIA Adverse effect

Approximate incidence

Intrapartum Hypotension

Around 10%

Total spinal blockade

Extremely rare

Instrumental birth through reduced maternal expulsive forces

Around 5% increase

Early postpartum Urinary retention

Common if no urinary catheter

Pruritus

Common if opiate used

Epidural abscess; meningitis

Extremely rare

Epidural haematoma

Extremely rare

Severe postpartum headache related to CSF leak

Around 1%

Nerve root damage (temporary; sensory or motor)

Around 0.1%

Long term Paralysis

Extremely rare

Fat in epidural space

Supraspinous lig. Interspinous lig. Ligamentum flavum

Subarachnoid space

Dura mater Subdural space

IC

SP

Arachnoid

A

B

FIGURE 38.1

Epidural anaesthesia. A Anatomy of the epidural space. B Performance of epidural block. Abbreviations: IC = iliac crest; SP = spinous process.

Source: A Brown DL. Atlas of Regional Anesthesia. Philadelphia, Philadelphia: Saunders, 1992;286. Copyright © 2011 Mosby, An Imprint of Elsevier. Figure 16.10A. B Davis PJ, Cladis FP, Motoyama EK. Smith’s Anesthesia for Infants and Children. 8th edn. St Louis: Mosby, 2011. Copyright © 2011 Mosby, An Imprint of Elsevier. Figure 16.10B.

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A

Spinal and epidural ‘needle through needle’ Luer slip-hubs

B

Needle

‘Back-eye’ Tuohy needle Tuohy needle

Ligamentum flavum

Dura

Cauda equina

‘Back eye’

Spinal needle

Epidural catheter

FIGURE 38.2

Combined spinal and epidural anaesthesia (CSE).

Source: Miller RD, Pardo M. Basics of Anesthesia. 6th edn. Philadelphia: Saunders, 2011. Copyright © 2011 Mosby, An Imprint of Elsevier. Figure 17.21. Modified from Veering BT, Cousins MJ. Epidural neural blockade. In: Cousins MJ, Bridenbaugh PO, Carr DB, Horlocker TT, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. Philadelphia: Lippincott-Raven, 2009:241–95.

ANAESTHESIA FOR CAESAREAN SECTION In Australia up to 40% of women deliver by caesarean section. The anaesthetic techniques used in caesarean section are: 1. spinal or subarachnoid block (SAB); 2. top-up of in situ epidural catheter; or 3. combined spinal epidural anaesthesia (CSE) and general anaesthesia (GA). These techniques are used in mothers undergoing elective, non-urgent (including labouring) and urgent caesarean section, when in the latter the time delay between GA and rapid SAB is about 5 minutes. The majority of both elective (approximately 95%) and non-elective (approximately 90% with over half having SAB) caesarean sections are now performed with the mother awake, allowing participation in the birth and presence of the partner. While anaesthetic-related mortality for caesarean section in developed countries is a very low (approximately 2:106 live births) the incidence is likely to be higher when performed under GA. The major reason is that after induction of GA an inability to

adequately ventilate the mother, combined with both increased oxygen consumption at term and ventilation perfusion mismatch, leads to rapid and severe hypoxaemia. Other benefits of awake caesarean section include maintenance of airway reflexes with decreased risk of pulmonary aspiration and venous thromboembolism, provision of postoperative analgesia using spinal morphine and avoidance of neonatal sedation. Perioperative anaesthetic evaluation is performed with special attention paid to the likelihood of difficult intubation, lumbar spinal anatomy and obstetric conditions associated with major intraoperative blood loss. Consent should be obtained; this may be verbal in timecritical cases. Increased gastric reflux is common, secondary to both hormonal and anatomical changes associated with pregnancy and antacid prophylaxis (0.3 M sodium citrate plus proton pump inhibitor or H2-receptor antagonists) is routine. In the late third trimester, when lying supine the uterus obstructs the inferior vena cava, resulting in reduced venous return and right heart filling pressures, 319

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cardiac output and mean arterial pressure. When awake, this is accompanied by dizziness and nausea leading to adoption of other postures. All patients undergoing caesarean section require a left lateral tilt (≥ 15 degrees) to shift the uterus, minimising inferior veno-caval compression and hypotension.

SPINAL ANAESTHESIA FOR ELECTIVE CAESAREAN SECTION Intrathecal single shot SAB or CSE (with epidural catheter used both to augment dermatome spread and prolong block) is performed using hyperbaric bupivacaine (10 to 12 mg) plus fentanyl (15 to 20 mcg). Additional agents used include morphine (0.1 to 0.2 mg) for prolonged postoperative analgesia and clonidine (20 to 30 mcg) to extend the duration of the spinal block. Onset of the block is rapid with spread to T4 at 10 minutes and usually provides an effective duration of 60 minutes above T8. Intraoperative pain requiring supplementation occurs in less than 5% and failure of block requiring conversion to GA occurs in less than 2%. Low-dose CSE is also used, a small intrathecal dose is administered and epidural volume extension (EVE), with saline or dilute local anaesthetic, is used to extend the block, minimising both the incidence of hypotension and duration of postoperative motor block, at the expense of increased incidence of intraoperative discomfort in some mothers. Routine oxygen supplementation is no longer used.

EPIDURAL TOP-UP FOR   CAESAREAN SECTION Epidural top-up, using 8 to 16 mL of 2% lignocaine in 1/200 000 adrenaline plus fentanyl 50 to 100 mcg, provides good quality anaesthesia in greater than 95% of labouring women, with surgery able to commence in 10 to 15 minutes.13 When labour analgesia has been imperfect, a CSE is often performed. Use of de novo epidural anaesthesia is usually restricted to patients when it has not been possible (extreme obesity) or is inadvisable to access the intrathecal space (cerebral space occupying lesion); onset time is 20 to 30 minutes. The use of the epidural route introduces two major maternal risks: 1. high or total spinal block; and 2. intravascular local anaesthetic toxicity.14 High block occurs when dermatome spread is above T2; if the level of motor block rises above C4 to C6, diaphragmatic function is impaired and respiratory arrest can occur. In total spinal blockade, loss of consciousness ensues. The mechanism is inadvertent placement of the epidural dose of local anaesthetic into the subarachnoid space directly or after initial placement into the subdural space complicated by pia mater rupture. Urgent treatment includes airway protection (intubation), ventilation and cardiovascular support (intravenous fluids and vasopressors) until the block recedes below T4 (60 to 75 mins), with caesarean section performed if there is severe fetal distress. 320

Unrecognised intravenous placement of the epidural catheter combined with doses used for epidural top-up can lead to local anaesthetic induced fitting and cardiovascular collapse and/or adrenaline induced severe hypertension and tachyarrhythmias. Resuscitation following advanced life support guidelines must be instituted.

GENERAL ANAESTHESIA FOR CAESAREAN SECTION Indications for a caesarean section under general anaesthetic include: 1. absolute contraindication to neuraxial blockade 2. failed regional technique 3. antepartum haemorrhage with uncorrected hypovolaemia or major intraoperative haemorrhage risk (placenta accrete, a percreta) especially in association with a difficult maternal airway 4. time-critical deliveries (vasa praevia, footling breech and pre-morbid fetal condition) 5. no consent for regional procedure. Fetal distress requiring emergent delivery demands rapid assessment of both the fetal condition and obstetric factors to determine if GA is required or neuraxial block possible. General anaesthesia for caesarean section includes: 1. patient positioning to optimise tracheal intubation 2. preoxygenation 100% oxygen 3. intravenous induction (propofol or thiopentone ± short acting opiate) 4. cricoid pressure to prevent passive gastric reflux 5. rapid-onset neuromuscular block (suxamethonium or high dose rocuronium) 6. maintenance using inhalational agents (sevoflurane ± nitrous oxide). The aim is to have an anaesthetised mother and a neonate delivered with adequate ventilator drive and airway tone who will rapidly regain consciousness. Intravenous oxytocics given after delivery are effective at volatile anaesthetic concentrations used. Postoperative multimodal analgesia with paracetamol, non-steroidal anti-inflammatories (NSAIDs) supplemented by oral or a parenteral opiate are effective and safe for breastfeeding mothers. Patient-controlled opiates and local anaesthetics blocks may also be used. Risks of GA for caesarean section are not different from that for other major procedures; however, of increased importance are the following. Difficult intubation and ventilation. In a mother who is difficult to intubate and ventilate, a critical hypoxaemic state rapidly develops. Overall, while the incidence of difficult intubation is 1 in 300 (10 times non-pregnant) the CICV scenario is very uncommon but constitutes the major cause of anaesthetic-related

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Chapter 38  Obstetric Analgesia and Anaesthesia

caesarean section death. All staff working in operating theatres must know the management protocol for a CICV scenario.15 Awareness. Caesarean section under GA is associated with a high risk of awareness, with an incidence of 0.26% (95%CI 0.03 to 0.9%).16 Use of appropriate concentrations of volatile anaesthetic agents and monitoring of conscious state using cerebral function monitors may further reduce this incidence. Aspiration pneumonitis. Gastric emptying is delayed in labour and current unrestricted dietary practices in labour wards increase aspiration risk should the mother require GA. Special circumstances. In severe preeclampsia, endogenous vasoconstrictors result in reduced intravascular volume; however, this vasoconstriction is independent of sympathetic function, and spinal anaesthesia for caesarean section is well tolerated with no increase in vasopressor requirements. Morbid obesity increases all risks so far discussed; in particular, establishing regional anaesthesia is often difficult and prolonged, and associated with higher failure rates requiring conversion to GA.

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REFERENCES 1) Melzack R, Taezner P, Feldman P, et al. Labour is still painful after prepared childbirth training. CMAJ 1981;125:357–63. 2) Morgan B, Bulpitt C, Clifton P, et al. Analgesia and satisfaction in childbirth. The Queen Charlotte’s 1000 mother survey. Lancet 1982;320:808–10. 3) Capogna G, Alahuhta S, Celleno D, et al. Maternal expectations and experiences of labour pain and analgesia: a multicentre study of nulliparous women. Int J Obstet Anesth 1996;5:229–35. 4) Russell R. Levels of anaesthesia and intraoperative pain at caesarean section under regional block. Int J Obstet Anesth 1995;4:71–7. 5) Jones L, Othman M, Dowswell T, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst Rev 2012.

6) Holdsworth J. Relationship between stomach contents and analgesia in labour. BJA 1978;50(11):1145–8. 7) Tsui M, Ngan Kee W, Ng F, et al. A double blind randomised placebo-controlled study of intramuscular pethidine for pain relief in labour. BJOG 2004;111:648–55. 8) Paech M. The King Edward Memorial Hospital 1000 mother survey of methods of pain relief in labour. Anaesth Intensive Care 1991;19(3): 393–9. 9) Volmanen P, Akural E, Raudaskoski T, et al. Remifentanil in obstetric analgesia: a dose finding study. Anesth Analg 2002;94:913–17. 10) Labour Pains.com. Pain relief in labour. 3rd ed. London: Obstetric Anaesthetists’ Association; 2008. p. 13. Online. Available: ; [27Nov 2012; 15 Dec 2014]. 11) Margarido C, Mikhael R, Arzola C, et al. The intercristal line determined by palpation is not a reliable landmark for neuraxial anesthesia. Can J Anaesth 2011;58:262–6. 12) Wong C, McCarthy R, Hewlett B. The effect of manipulation of the programmed intermittent bolus time interval and injection volume on total drug use for labor epidural analgesia. Anesth Analg 2011;112:904–11. 13) Halpern S, Soliman A, Yee J, et al. Conversion of epidural labour analgesia to anaesthesia for caesarean section: a prospective study of incidence and determinants of failure. BJA 2009;102(2):240–3. 14) Paech M, Godkin R, Webster S. Complications of obstetric epidural analgesia and anaesthesia: a prospective analysis of 10995 cases. Int J Obst Anesth 1998;7:5–11. 15) Nair A, Alderson J. Failed intubation drill in obstetrics. Int J Obstet Anesth 2006;172–4. 16) Paech M, Scott K, Clavisi O, et al. A prospective study of awareness and recall associated with general anaesthesia for caesarean section. Int J Obstet Anesth 2008;17(4):298–303.

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Section 2.7.4 THE PUERPERIUM AND LACTATION

Chapter 39  THE PHYSIOLOGY OF THE PUERPERIUM AND LACTATION Elizabeth Anne McCarthy

KEY POINTS The puerperium is the 6-week period following childbirth during which the anatomical and physiological changes of pregnancy reverse, the uterus undergoes involution and lactation commences. Recovery following vaginal birth generally involves management of perineal pain and pelvic floor exercises. Caesarean section is associated with reduced mobility and increased analgesic requirements for the abdominal wound. Postdelivery counselling includes management of pain, advice regarding pelvic floor exercises, relevant advice regarding future deliveries, and a discussion regarding contraception needs. Formal debriefing may be needed after a particularly difficult or complicated birth. Women should be also advised regarding symptoms of postnatal mood disorders, and provided with advice regarding clinicians from whom they can seek help. There are well-established benefits of breastfeeding; maternal benefits include reduced bleeding, faster return to prepregnancy weight and decreased risk of ovarian and breast cancer. Infant benefits include reduced risk of infection, atopy, childhood obesity and diabetes. Breastfeeding rates are optimised with early breastfeeding, rooming in, demand feeding, a clear breastfeeding policy within institutions, good social support and professional support available from midwives, doctors and lactation consultants.

THE PHYSIOLOGY OF THE PUERPERIUM AND LACTATION PHYSIOLOGICAL CHANGES IN THE PUERPERIUM The high blood flow perfusing the placental bed at term is controlled after expulsion of the placenta by myometrial retraction and thrombosis. Lochia is uterine discharge, mainly originating from the healing placental site. It may persist for 8 weeks with the colour changing from red (‘rubra’) to yellow (‘serosa’) to white (‘alba’). Endometrial atrophy and amenorrhoea occur due to low oestrogen levels during lactation, when prolactin inhibits ovarian function. However, ovulation and

fertility can occur as early as 4 weeks after childbirth, sometimes before menses recur, and this is particularly likely when lactation is suppressed. The myometrial hypertrophy of pregnancy reverses. Abdominal examination confirms involution, as shown in Figure 39.1; the uterus takes 12 weeks to emerge from the pelvis during pregnancy and 12 days to return to the pelvis during the puerperium. Low oestrogen associated with breastfeeding means that the vagina, cervix and endometrium tend to be atrophic during the puerperium. If colposcopy is indicated postnatally, this is more likely to be adequate if delayed until 8 to 10 weeks postpartum and if consideration is given to a 2-week course of topical oestrogen. The vagina and vulva are stretched during vaginal birth and are predisposed to tearing. Cooling measures

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Day 2 Day 4 Day 6 Day 8 Day 10

Intravenous fluids are required until oral volume intake is adequate. The urethral catheter is removed once the woman can use a toilet with or without assistance (e.g. 6 to 24 hours post-operation). Any non-absorbable sutures are removed by 5 days for Pfannenstiel and 7 to 10 days for vertical skin incision. Lochia, lactation, learning parenting skills and ‘bonding’ are essentially the same as following a vaginal birth. Breastfeeding can occur in a side-reclining or seated position. Maternal analgesia is safe for breastfed infants. Discharge home can be considered once intravenous and urethral catheters are removed and there is no longer a requirement for parenteral analgesia. Maternity hospitals may offer longer admissions to facilitate parent education, support breastfeeding and allow a smooth transition to community care. An important aspect of postnatal maternal education is to counsel the woman about the reasons for and consequences of caesarean section, especially if it was an upper segment (classical) uterine incision. Some women will need formal debriefing if a caesarean section was unexpected or particularly complicated. (See also Ch 32.)

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FIGURE 39.1

Clinical examination of the uterine fundus during the puerperium.

promote resolution of oedema and bruising and are soothing. Systemic analgesics, including paracetamol and non-steroidal anti-inflammatory agents with or without low doses of opiates, may be required for days to weeks. Vaginal dryness reflects lactation associated with low oestrogen and predisposes to superficial dyspareunia. See also Chapter 52 for methods to improve lubrication and allow normal sexual function. Pelvic floor muscles are stretched during pregnancy and birth. Physiotherapy expertise can guide women in promoting pelvic floor healing and when and how to recommence pelvic floor exercises. Pudendal nerve compression is associated with labour, particularly fetal head descent after 8-cm cervical dilatation, irrespective of the final mode of delivery. Some months may pass before normal nerve function is returned. Conservative management is usually appropriate, as most stretch injuries will resolve spontaneously.

Caesarean section recovery Delivery by caesarean section is common. Uncomplicated recovery after caesarean section includes the following. Mobility is reduced for 6 to 24 hours, due to regional and parenteral analgesia and anaesthesia. Sufficient analgesia is used to promote early mobility and parenting. Oral fluids within hours of surgery, increasing to a light diet later that day or the following day after passing flatus or faeces.

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PHYSIOLOGICAL CHANGES IN THE PUERPERIUM, OTHER THAN THE GENITAL TRACT Cardiovascular The immediate postpartum period (i.e. 10 to 120 minutes after birth) sees a rise in cardiac output and stroke volume by approximately 50%, due to an increase in systemic venous return, resulting from both autotransfusion of utero-placental blood and decompression of the vena cava. Women at risk of postpartum cardiovascular decompensation include those with preexisting and acquired ventricular dysfunction (e.g. in amniotic fluid embolus, stenotic valvular disease). By 2 weeks, there is a substantial reduction in left ventricular size and contractility but values may not return to the non-pregnant state until about 5 months postpartum.

Renal system and urinary tract Diuresis within days of birth reverses pregnancyassociated plasma volume expansion. Progesterone withdrawal reverses the tendency to renal tract smooth muscle relaxation. Minor bladder and urethra trauma is common during labour and birth (e.g. mucosal congestion, submucosal haemorrhage). Macroscopic haematuria usually clears within 6 to 24 hours of birth.

Chapter 39  The Physiology of the Puerperium and Lactation

Postpartum urinary retention is defined as the absence of spontaneous micturition within 6 hours of vaginal delivery or removal of an indwelling catheter. Risk factors include nulliparity, instrument-assisted delivery, prolonged first and second stages of labour, caesarean delivery and possibly epidural anaesthesia. If non-invasive measures do not work, then catheterisation should be continued for 24 hours or longer. Urinary retention is usually transient and resolved by 1 week postpartum.

Gastro-intestinal tract Constipation is common during the puerperium, particularly promoted by some or all of the following: perianal pain, opioid analgesia, low residue diet and/or dehydration.

Intermediary metabolism and nutrition Resolution of insulin resistance and gestational diabetes is discussed in Chapter 23. Regarding protein metabolism, postpartum uterine involution presents a proteolytic load of amino acids. Women with urea cycle disorders may decompensate with high levels of ammonia, typically between days 3 and 10 postpartum. The clinical picture may mimic postpartum psychosis. Lactation is partly supported by mobilising maternal lipid stores and, transiently, from calcium in bone. Lactation requires some additional dietary protein, vitamins, calcium and trace minerals. Milk production expends energy but a woman’s caloric output attributable to infant feeding and other parenting activities will vary from woman to woman, so a universal prescription of increased dietary calories will be too much for some new mothers and too little for others. Lactating mothers will usually benefit from the same dietary choices as apply to all adults, with particular attention to adequate iodine, iron and vitamin D. (See also Ch 6.)

Respiratory system The physiological changes described in Chapter 2 reverse. Progesterone withdrawal and emptying the uterus generally permit more effective ventilation. Breathlessness or hypoxia postpartum thus requires full assessment, especially for exclusion of pulmonary embolus, anaemia, asthma, left ventricular failure or other cardiorespiratory disease.

Immune system Cell-mediated immunity recovers after childbirth, presumably because immune tolerance is no longer required to protect the fetus from immune rejection. This likely explains puerperal ‘flares’ of certain immune conditions including multiple sclerosis, Graves’ disease and Hashimoto thyroiditis. (See also Ch 22.) Humoral immunity appears to be unaltered by pregnancy or the puerperium. Thus, maternal immunisation (e.g. against rubella and varicella zoster) is effective during the postpartum period.

Haematology The puerperium remains a hypercoagulable state. Pelvic veins are particularly at risk of thrombosis in the setting of local inflammation due to physical compression, stretch and infection. Venous thrombosis in pregnancy occurs in approximately 0.7 per 1000 women, and is three to four times higher in the puerperium than during pregnancy. (See also Ch 41.) Blood loss anaemia occurs after obstetric haemorrhage. Iron deficiency is a risk, particularly if there is poor dietary intake, chronic bleeding and/or closely spaced pregnancies. Supplements and dietary education optimise iron stores for new mothers at risk. Transfusion of packed red cells may also be required. (See also Ch 20.)

PHYSIOLOGY OF LACTATION AND BREASTFEEDING Breastfeeding includes infant suckling as well as variations such as bottle, cup, syringe or tube feeding using expressed or donated human milk or in combination with ‘formula’. Lactation and breastfeeding can usually succeed, even when aspects of physiological or anatomical set-up are not ‘perfect’. Some women suffer from perceived ‘conflicting advice’ about breastfeeding from peers and professionals. It may take different means to achieve the end of a healthy breastfed baby and a mother who can meet her infant’s nutritional and other requirements. The anatomical features of normal breastfeeding are shown in Figure 39.2. Maternal and infant benefits of breastfeeding are summarised in Box 39.1. Maternal sex steroid hormones during pregnancy prime the breast by elaborating ducts and exocrine glands. Placental expulsion withdraws sex steroid hormones and milk production begins. Colostrum is the first milk, sometimes expressible during pregnancy; it is low in volume (e.g. 0.5 to 5 mL) and rich in protein, including immunoglobulin A and fat. Colostrum is replaced by mature milk, which has a larger volume (e.g. tens to hundreds of millilitres) of white liquid with a balance of carbohydrate (lactose), fat, protein and micronutrients, growth factors and hormones which match human infants’ needs for growth and development. Lactogenesis II is the development of mature milk, often perceived by the mother as an increase in breast size and sense of fullness at 2 to 10 days after childbirth (commonly day 4). Milk production is similar whether birth occurred at term, post-term or preterm, by normal, assisted vaginal or caesarean birth. Stimulation of the breast, and especially the nipple, produces two major neurohormonal reflexes. The first is the production of oxytocin, which causes smooth muscle to contract along the breast ducts as well as in the myometrium. This ejects milk through sinuses and out of small holes around the nipple. A clinical correlation is that suckling a newborn may help promote uterine tone, 325

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Hard palate

Gum

Soft palate Milk glands Tongue Milk flow Lips creating air tight seal

Milk glands Areola Nipple Lactiferous sinus

Lactiferous duct

FIGURE 39.2

Anatomy of the breast and breastfeeding infant.

Source: Gabbe SG, Niebyl JR, Galan HL, et al. Obstetrics: Normal and Problem Pregnancies. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 23.3.

expel the placenta and staunch uterine blood flow in the first hour after birth. Suckling-stimulated uterine contractions are recognised by women as ‘afterpains’. These may require analgesia, especially for women of high parity. The second neurohormonal reflex is the production of prolactin, which promotes ongoing milk production. Thus, more frequent and vigorous suckling promotes greater milk volume, allowing supply to meet the demand of twins and triplets. If a baby’s suck is weak due to prematurity or illness or if maternal milk supply seems low, supply can be 326

increased by expressing breastmilk by hand or pump or by feeding more frequently. Minimising the baby’s use of infant pacifiers and bottle teats might help him or her suckle at the breast efficiently, thus supporting maternal prolactin levels. Dopaminergic antagonists (e.g. oral domperidone) raise serum prolactin and are sometimes administered as a short-term measure to increase milk supply. A typical regimen is domperidone 10 mg three times a day for 1 to 2 weeks, followed by a weaning dose, depending on response. A rare cause of lactation failure in the modern era is ‘pituitary apoplexy of Sheehan’ where postpartum

Chapter 39  The Physiology of the Puerperium and Lactation

BOX 39.1  Maternal and infant benefits of breastfeeding.

BOX 39.2  Ten steps to successful breastfeeding: World Health Organisation.

Infants ✚ Reduced infection risks, especially gastroenteritis, respiratory and ear infections ✚ Reduced childhood and later obesity and its complications, especially type 2 diabetes mellitus ✚ Reduced autoimmune disease such as type 1 diabetes mellitus ✚ Reduced atopy ✚ Possibly better neurological development associated with long-chain fatty acids, growth and endocrine factors present in human milk Maternal ✚ Reduced postpartum bleeding due to oxytocin-induced uterine contractions ✚ Lactational hormones, especially oxytocin, may reduce perceived stress ✚ Increased weight loss after pregnancy (if breastfeeding continues for at least 6 months) ✚ Decreased risk of breast and ovarian cancer

Every facility providing maternity services and care for newborn infants should: 1. have a written breastfeeding policy that is routinely communicated to all healthcare staff 2. train all healthcare staff in skills necessary to implement this policy 3. inform all pregnant women about the benefits and management of breastfeeding 4. help mothers initiate breastfeeding within half an hour of birth 5. show mothers how to breastfeed, and how to maintain lactation even if they should be separated from their infants 6. give newborn infants no food or drink other than breast milk, unless medically indicated 7. practise rooming-in—that is, allow mothers and infants to remain together—24 hours a day 8. encourage breastfeeding on demand 9. give no artificial teats or pacifiers (also called dummies or soothers) to breastfeeding infants 10. foster the establishment of breastfeeding support groups and refer mothers to them on discharge from the hospital or clinic.

haemorrhage and hypotension causes pituitary infarction and failure, hence prolactin insufficiency. Social factors that promote breastfeeding include support from: the partner and close family relatives, particularly the baby’s grandmothers peers, including mothers’ groups, Breastfeeding Australia groups and established friends and work colleagues maternity and paediatric hospitals (see Box 39.2 for ‘Baby friendly initiatives’ that are endorsed by the World Health Organisation for maternity hospitals) professional support (i.e. ready access to well-educated obstetric, paediatric, general practice, midwifery, nursing and dietetic professionals who will promote breastfeeding. Some women particularly benefit from lactation consultation before or soon after birth (see Box 39.3). A socioeconomic aspect that promotes breastfeeding is that it is usually more affordable for families than artificial infant formula. The highest rates of breastfeeding are seen in higher educated, older mothers in the developed world and in mothers in developing countries where infant formula is not promoted. It is prudent to monitor unreasonable advertising and promotion of artificial infant formula, which can interfere with women’s intentions to breastfeed. Lobby groups such as Breastfeeding Australia promote breastfeeding and/or expressing milk in all settings, including at home and

• • • •

Source: Protecting, Promoting and Supporting Breastfeeding: The Special Role of Maternity Services. A Joint WHO/UNICEF Statement. Geneva: WHO, 1989.

BOX 39.3  Clinical scenarios where referral to a lactation consultant during or after pregnancy should be considered. Maternal anatomical or surgical breast problems (e.g. inverted nipples) Maternal obesity Poor previous breastfeeding experience Maternal medical conditions (e.g. diabetes) Twin or triplet pregnancy Infant surgical problem (e.g. cleft lip or duodenal atresia) Expected birth of one or more premature infants

in the workplace and public places, as part of normal parenting. Information about breastfeeding is a useful part of parent education during the antenatal and postnatal periods. Many women are aware of some of the benefits 327

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for themselves and their babies but they, their partners and close relatives value more complete information. Others may find that specific reasons encourage them to persist with breastfeeding even if problems occur. For example, breastfeeding offers specific maternal benefits for those women trying to lose weight, those with a family history of breast cancer or those living in or travelling to areas where accessing safe formula and water is unreliable. Breastfeeding offers specific infant benefits for premature or sick infants and infants of diabetic mothers, in situations where the water supply makes artificial feeding hazardous and where there is a family history of atopy. Other women breastfeed happily and efficiently and their infants thrive in complete ignorance of the physiology or health benefits of breastfeeding, illustrating that detailed parent education is not mandatory! There are few absolute maternal or infant contraindications to breastfeeding. Infants of mothers using cannabis are at risk of neurodevelopmental problems related to cannabinoids concentrated in breastmilk, so artificial formula feeding may be preferable. Mothers with HIV infection are usually advised to suppress lactation in Australia and New Zealand. The risk versus benefit analysis for breastfeeding or artificial feeding with maternal HIV varies according to competing health risks such as infant risk of water-acquired gastroenteritis. Infants with specific metabolic disorders (e.g. phenylketonuria or urea

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cycle disorders) may have restricted breastmilk ingestion along with low-protein or amino-acid modified artificial formula under individual dietetic supervision. Hepatitis C infected mothers should avoid breastfeeding if the child could ingest blood (e.g. with nipple trauma). Expressing and discarding blood-stained milk may be a temporary measure, with breastfeeding re-established once the nipple has healed. There a very few maternal medications that are absolutely contraindicated for breastfeeding mothers; tertiary maternity hospital pharmacy departments are a good source of expert advice on medication safety. Women anticipating chemotherapy and/or radiotherapy postpartum will usually be advised to suppress lactation. Infants of women on immunosuppressant medication may be monitored for immunosuppressant ingestion in breastmilk or some mothers may choose artificial formula for infant feeding. Women with medical needs for uninterrupted sleep (e.g. those for whom epilepsy or psychiatric illness could become unstable with sleep deprivation) may find that milk supply alters to provide greater amounts during daylight hours and less at night when others may be able to provide baby care. FURTHER READING Australian Breastfeeding Association. .

Chapter 40  NORMAL POSTPARTUM CARE Elizabeth Anne McCarthy

KEY POINTS Routine postnatal care should include both maternal/infant vaccinations and anti-D administration where indicated. Women should be provided with education about: 1. normal physiological changes in the puerperal period; 2. how to maximise the chance of successfully initiating and maintaining breastfeeding; and 3. infant safety during discharge planning. Discharge planning should include liaison with community health personnel (i.e. general practitioner and maternal child health nurse), and ensuring the family can access healthcare in the event of an emergency.

INTRODUCTION Modern postnatal care saves women’s lives. In addition to this, postnatal care improves the quality of life for new mothers, their infant and the whole family, and provides a basis for a healthy family life in the future. The importance of routine postnatal care and health promotion is summarised in Box 40.1. Becoming a mother is an exciting but physically and emotionally challenging development for most women. Certain cultures prescribe traditional behaviour, food or rituals. Maternity staff, both hospital- and communitybased, are valuable sources of health education. When providing new mothers with realistic reassurance and monitoring for problems, midwives and doctors also need to identify women whose physical or psychological state is deteriorating and be ready to diagnose and treat a variety of complications in the puerperium.

0 TO 6 HOURS AFTER BIRTH In Australasia, some women will be discharged home as early as 6 hours after hospital birth. A small minority of women will have had a planned home birth and

midwifery presence will often cease within 6 hours after birth. Professional supervised postnatal care may need to be highly focused in the first few hours after birth, particularly concerning: prevention and detection of early puerperal complications planning for parent education and maternal and newborn care, which continues over the coming days and weeks. Close physical contact with their infant benefits most babies and mothers. Skin-to-skin contact immediately following birth promotes thermal stability for the infant and likely releases oxytocin in the mother and minimises impediments to the infant suckling colostrum. Midwives and doctors can particularly help promote mother and baby contact when the woman’s mobility is temporarily reduced by spinal/epidural anaesthesia and/or the need for her to be in lithotomy position or on an operating table to complete surgical procedures such as episiotomy repair or caesarean section. Provided steps are taken to minimise hypothermia by drying the baby’s skin and ensuring that bare skin not directly against the mother is covered, weighing and dressing the baby can usually be deferred until baby and

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BOX 40.1  Routine postnatal care and   health promotion irrespective of duration   of postnatal inpatient care. Educate about normal puerperal changes ✚ Lochia, breast changes, hormonal changes ✚ Maternal sleep, nutrition, exercise and restoring a healthy non-pregnant body weight ✚ Couple issues: communication, emotions, sexuality and family planning (see also Chs 52 and 53) Vaccinate against rubella and/or varicella if non-immune Prevent D immunisation by giving passive anti-D to Rh-negative mothers who have given birth to an Rh-positive infant Reinforce antenatal education about normal lactation ✚ Effective infant breast attachment ✚ Assess adequacy of infant intake ✚ Arrange scheduled midwifery/nursing review ✚ Confirm that the mother can access emergency support by telephone and in person Newborn examination and screening for congenital disease as per local protocol (see Ch 65) Parent education about infant safety ✚ Prevention of sudden infant death syndrome (Fig 40.1) ✚ Infant restraints in motor vehicles Discharge planning ✚ Liaise with community health personnel (e.g. discharge summary to general practitioner and maternal child health nurse) ✚ Confirm that the mother can access emergency health assessments by telephone and in person

mother have had some close physical contact and, ideally, a breastfeed. Maternal observations in the first 120 minutes are directed at assessing the degree to which the woman’s cardiovascular system copes with volume shifts, especially: 1. autotransfusion of blood from the placental bed back into her circulation, which increases systemic venous return; and 2. genital tract blood loss, which may reduce circulating blood volume. Routine oxytocic medications for management of the third stage of labour are superior to a placebo for preventing postpartum haemorrhage and its need for emergency treatment, but midwives and doctors need to be aware of their haemodynamic side effects. Ergometrine is a vasoconstrictor which can thereby increase systemic blood 330

FIGURE 40.1

Prevention of sudden infant death syndrome. Source: http://www.sidsandkids.org

pressure. Bolus oxytocin is a vasodilator, thereby reducing systemic blood pressure. A suggested schedule of haemodynamic observations is pulse and blood pressure checks every 15 minutes for the first hour after birth for most women. Routine maternal postnatal cardiovascular observations can usually be carried out without disturbing the baby on his or her mother’s chest. Cardiovascular observations should, however, be individualised. Postpartum haemorrhage of 500 mL or more warrants obstetric review, although the actual volume at which a woman becomes unstable will vary according to her pre-existing circulating volume and her ability to mount compensatory responses. (See also Ch 36.) If there are concerns about maternal cardiac function, haemodynamic observations need to be more frequent and continue beyond the usual first hour after birth; they usually include oximetry and respiratory rate. Infection prevention requires universal handwashing before handling food, before beginning a breastfeed or milk expression, and after personal hygiene: including using a toilet; changing sanitary pads, nappies and breast pads; or using a facial tissue to wipe nasolacrimal secretions. Visitors and staff should be encouraged to use the ‘five moments’ of hand hygiene (Fig 40.2).

Chapter 40  Normal Postpartum Care

2

4 3

AFTER TOUCHING A PATIENT

RE

BEFORE TOUCHING A PATIENT

AF E O TER A R PROC EX BO D Y F LU I D PO SU R E RIS K

DU

1

FORE A BE OCEDURE PR

5

AFTER TOUCHING A PATIENT’S SURROUNDINGS

FIGURE 40.2

Five moments of hand hygiene.

Source: Reproduced with permission of Hand Hygiene Australia. Based on World Health Organisation ©2009. All rights reserved. Online. Available http://www.who.int/gpsc/5may/background/5moments/en/index.html

In current Australasian maternity care, babies do not seem to benefit from specific antibacterial wiping or washing, for example, of eye secretions or the cord stump. Infection monitoring for the mother includes being alert to symptoms of genital tract, urinary tract, breast or other infections. (See also Ch 41.) Regarding maternal observations, a reasonable schedule of temperature, blood pressure, respiratory rate and pulse monitoring is at 1 and 5 hours postpartum, then daily if assessed as low risk for infection (e.g. afebrile in labour with ruptured membranes of less than 18 hours and a normal vaginal birth). If there is a higher risk for infection, more frequent pulse and temperature readings are reasonable (e.g. two to three times per day for the first 5 days after birth). (See also Ch 41.)

6 HOURS TO 7 DAYS AFTER BIRTH For many new mothers, this time is one of euphoria, pride and excitement in getting to know her new baby and her new role. Many women feel all of these positive feelings along with fatigue and physical discomfort. Immediate threats to maternal life and health are less

common than soon after birth. Nevertheless, physical and psychological risk can change quickly. It is dangerous to consider postpartum care ‘humdrum’. Open communication between postpartum women and health professionals is the key to successful and safe postnatal care. Any symptoms should be fully assessed. Routine observations can provide a point of contact for a new mother and her midwife. They also provide a safety net: altered physiology triggers escalation of medical attention. In one United Kingdom trust, all women (irrespective of prior risk) have a minimum frequency of 12-hourly observations while an inpatient after birth. This includes: respiratory rate heart rate blood pressure temperature. An example of an Australian maternal observations and response chart is given in Figure 40.3. Wounds, caesarean or perineal, should be inspected at least daily and more frequently if the mother has a concern. The frequency of observations should be increased in cases of identified risk (e.g. preeclampsia, risk of infection, maternal obesity, prior psychiatric disease).

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332 DOB:

First name:

OR AŸach Patient Label

White Yellow* Orange Red Purple –Acceptable observations –RN/RM intervention required –Medical intervention required –URGENT medical aŸendance –MET call (dial ext. 3333)

MHW MET CRITERIA

1 Respiratory Rate œ< 7 or œ> 30 2 Systolic BP œ< 70 or œ> 200 3 Heart Rate œ< 40 or œ> 130 4 Oxygen Saturation œ< 90% 5 Confusion or alteration in mental atate 6 Staff member is concerned

Carry out appropriate interventions as prescribed Manage fever, pain or distress Review O2 delivery Notify In-Charge Midwife/ Nuruse

Midwife/Nurse to Complete Doctor Notified Time

patient within 30 minutes Request medical review and note below in Response Notify In-Charge midwife/nurse Record observations at least once every 30 minutes If patient must leave ward area. Midwife/Nurse must accompany patient

•

•

•

patient within 10 minutes Request review and note below in Response Registrar to ensure Consultant is notified If patient must leave ward area. Registrar & Midwife/Nurse must accompany patient

Category 1 (Red) • Consider MET call • Medical Officer to review

Medical Officer to Complete Doctor Orders. Name and Signature

•

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•

Source: Mercy Public Hospitals, Inc.

Maternal observations and response chart.

FIGURE 40.3

Date

Response

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•

•

least once every hour including resp rate

Actions Required All observations in white zones, continue current management Category 2 (Orange) Category 3 (Yellow) • Record observations at • Medical Officer to review

*Three or more simultaneous yellow obs require an Orange (Category 2) Action

Assessment

Respiratory Rate O2 Saturation Blood Pressure Heart Rate Temperature

Modification to reportable observations New New New New New Date & Date & Date & Date & Date & Orange Orange Orange Orange Orange Initials Initials Initials Initials Initials Vital Sign Trigger Trigger Trigger Trigger Trigger

• This chart is to be completed in a step wise manner of documenting observations, assessment, actions required and response. • Any changes to reportable observations must be documented in the table below. Please record and changes to observation thresholds for this woman according to individual clinical need, e.g. Temp > 38.5 normally a Yellow response changed to Orange.

General Instructions

MATERNAL OBSERVATION AND RESPONSE CHART

Last name:

UR No:

200 190 180 170 160 150 140 130 120 110 100 90 80 70

If SBP > 200. 200 write value in box 190

write value in box

38.5 Temperature 38 37.5 (˚C) 37 (.) 36.5 If temp < 36. 36

If temp > 39. write value in box 39

120 110 100 90 Heart Rate 80 (breaths/min) 70 60 (.) 50 40

If HR > 130. write value in box 130

write value in box

180 170 160 150 Systolic Blood 140 Pressure (mmHg) 130 120 (v) 110 100 90 Diastolic Blood 80 Pressure 70 (mmHg)

39 38.5 38 37.5 37 36.5 36

130 120 110 100 90 80 70 60 50 40

100 95 90 85

O2 Saturation (%) (.)

100 95 90 85

OR AŸach Patient Label

35 30 25 20 15 10 5

DOB:

First name:

Last name:

35 30 25 Respiratory Rate 20 (breaths/min) 15 (.) 10 5

Time

Date Gestation

Observations

MATERNAL OBSERVATION AND RESPONSE CHART

UR No:

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MATERNAL OBSERVATION AND RESPONSE CHART MR 0552-0

Chapter 40  Normal Postpartum Care

Rooming-in of an infant with its mother is usual care in hospitals, benefiting mother and baby by: decreased risk of cross-infection opportunities for learning practical parenting skills (e.g. identifying infant hunger and satiety signals, matching maternal sleep cycles with infant feeding) reduced maternal anxieties generated by being separated from her baby increased maternal confidence minimal impediments to lactation and breastfeeding. Rooming-in is currently not standard practice for infants who are admitted to a neonatal medical or surgical unit but obstetricians and midwives should support the mother’s need to be with her baby/babies as much as possible. Early discharge of the mother with flexible domiciliary or outpatient monitoring is a practical solution, especially if the infant(s) is in another institution (e.g. for paediatric surgery). Women can be advised about normal and abnormal lochia flow (see Ch 39) and encouraged to change sanitary pads regularly. Keeping the perineum clean using water with ordinary soap can be done with a daily shower or bath and extra washing (e.g. over a bowl or bidet) following bowel actions. Paracetamol, non-steroidal antiinflammatory agents and local cooling relieve perineal pain and may hasten resolution of bruising and oedema. All of the educational, vaccination and newborn screening issues discussed in this chapter are continued into the later postnatal stay. (See Box 40.1.) Puerperal complications occurring within the days and weeks after childbirth are discussed in greater detail in other chapters. Knowledge of them guides routine care as follows. Thromboembolism. Routine postpartum care includes early ambulation and attention to symptoms and signs. Depending on an individual’s risk, prevention may also include compression stockings and low-molecular-weight heparin (e.g. following most caesarean births and for most women with BMI > 30). (See Ch 41.) Infections, including those associated with the genital tract, wound, cannula, and catheter. Routine postpartum care to prevent infection includes universal hand hygiene (Fig 40.2). Lines and catheters should be retained for the minimum time required and handled with appropriate antiseptic techniques. Infection control should guide social isolation of new mothers and babies from visitors or staff with respiratory or other infections. All pregnant women should have a current influenza vaccination, which also confers protection to them and their infants during the puerperium. (See Ch 41.) Urinary retention. Routine care includes providing sufficient analgesia and privacy to promote normal voiding. Urinary retention will not ‘go away’ if ignored, so appropriate help should be sought if

• •

•

• • •

•

•

•

•

•

•

•

initial measures do not rectify the problem. (See Ch 41.) Constipation. Routine care includes adequate fluids and fibre with ready recourse to stool softeners and stimulants if required. Again, analgesia and privacy will assist new mothers return to healthy bowel habits. (See Ch 41.) Haemorrhoids. Routine care which minimises constipation will usually prevent haemorrhoids. Treatment is discussed in Chapter 41. Incontinence of urine or faeces. Embarrassment may inhibit women from volunteering this symptom, so the major role of the postnatal midwife and doctor is to facilitate frank discussion so that comprehensive evaluation and treatment can begin. Incontinence is discussed in more detail in Chapters 41 and 56. Breastfeeding problems. Humans are mammals and breastfeeding is the default, normal form of infant feeding; however, women and their babies may experience some hurdles and need time to learn this skill. Routine care of the new mother and her young infant aims to instil maternal confidence and provide a range of feeding strategies without confusing the mother. (See Chs 39 and 67.) Abnormal mood. Low mood may be within the normal range of a new mother’s experience, especially a 24-hour ‘blues period’ experienced by about 80% of women, typically around day 4. Most women suffering blues are helped by knowing that these feelings are normal but transient. Midwives and doctors help women with ‘the blues’ to focus on simple goals (e.g. feed, eat, sleep and restrict visitors to a few support people). More sinister causes of low mood, especially with deranged cognition, include postnatal depression and psychoses. The differential diagnosis of blues includes organic psychosis, schizophrenia, bipolar or unipolar mood disorder. (See Chapter 25.)

THE FIRST WEEK Many women are at home by the end of the first week so discharge planning, including informing women about and often prescribing family planning options, is a priority. In current Australasian practice, it is common for primiparous women who have had a vaginal birth to go home after two nights and multiparous women who have had a vaginal birth to go home after one or two nights. It is common for women who have had a caesarean birth to go home after four nights. Generally, a maternal and child health nurse or other domiciliary nurse is able to visit the mother at home within the first 10 days after birth. Formal maternal observations are not commonly done after hospital discharge. If a woman presents problems to her midwife, nurse or general practitioner, 333

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assessment including observations of temperature, pulse, respiratory rate and blood pressure with or without referral for hospital assessment is reasonable.

1 TO 6 WEEKS POSTPARTUM Babies’ growth and development is usually monitored by a maternal child health nurse during the puerperium. These nurses also monitor maternal wellbeing and educate about normal puerperal changes. Many healthy women resume sexual intercourse well before the conventional 6-week postnatal check-up and should be aware that conception can occur again unless contraception is used.

CONTRACEPTION AND   FERTILITY CONTROL Contraceptive medications that contain oestrogen reduce breastmilk volume but non-hormonal or progestin-based methods are compatible with breastfeeding. (See also Ch 53.) At around 6 weeks postpartum, most women attend a general practitioner for review. Issues include recovery from the birth, debriefing, adjustment to motherhood, discussion about sexuality and family planning, review of pelvic floor health, continence, prolapse and pelvic floor exercises, and opportunistic health prevention screening, including cervical smear if due for this. It is important to confirm resolution of gestational diabetes with an oral glucose tolerance test and of gestational hypertension or preeclampsia by clinical review. Some women have the 6-week check with a community nurse.

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If the woman’s health or birth were particularly complex, she may have follow-up at the maternity hospital (e.g. with an obstetrician and/or general practitioner). Some women whose birth was unexpectedly complicated may benefit from specific debriefing with the midwives and doctors who were present. FURTHER READING Buppasiri P, Lumbiganon P, Thinkhamrop J, et al. Antibiotic prophylaxis for third- and fourth-degree perineal tear during vaginal birth. Cochrane Database Syst Rev 2010;11. Chou D, Abalos E, Gyte GML, et al. Paracetamol/ acetaminophen (single administration) for perineal pain in the early postpartum period. Cochrane Database of Syst Rev 2010;3. East CE, Begg L, Henshall NE, et al. Local cooling for relieving pain from perineal trauma sustained during childbirth. Cochrane Database Syst Rev 2012;5. Hedayati H, Parsons J, Crowther CA. Rectal analgesia for pain from perineal trauma following childbirth. Cochrane Database Syst Rev 2003;3. Moore ER, Anderson GC, Bergman N, et al. Early skin-toskin contact for mothers and their healthy newborn infants. Cochrane Database Syst Rev 2012;5. World Health Organisation/UNICEF. Ten steps to successful breastfeeding. Protecting, promoting and supporting breastfeeding: the special role of maternity services. In: A joint WHO/UNICEF statement. Geneva: WHO; 1989. Online. Available: ; [8 Dec 2014].

Chapter 41  PUERPERAL DISORDERS Elizabeth Anne McCarthy

KEY POINTS Thromboembolism is a leading cause of maternal death. Steps to minimise this risk include prophylaxis in high-risk women, early diagnosis and prompt treatment with anticoagulation of adequate duration. Puerperal infections are a re-emerging cause of maternal death. Potential sites to be considered in women presenting with puerperal sepsis include endometritis, mastitis, urinary sepsis, caesarean or perineal wound infection and influenza. Secondary postpartum haemorrhage is defined as excessive bleeding in the first 6 weeks after childbirth, after the first 24 hours. It is commonly due to endometritis, retained products of conception, or both. Bladder dysfunction following vaginal delivery is common; retention should be managed with adequate analgesia for perineal pain and, occasionally, short-term catheterisation. Constipation, haemorrhoids and anal fissure are relatively common following childbirth, and are best treated with advice, stool softeners and analgesia. Incontinence following childbirth always warrants urgent review to exclude fistula (which is rare) and to assess and treat neuromuscular damage (which is the most common cause). Common problems with breastfeeding include engorgement, inadequate supply, nipple trauma due to difficult attachment, blocked ducts and mastitis. While mood disorders are very common in the postnatal period, attention should always be given to a potential underlying organic cause.

INTRODUCTION Some women become critically ill during the puerperium although fortunately very few die (see Ch 42). The most important causes of maternal death and severe morbidity are thromboembolism, infection and psychiatric disease. Serious threats to quality of life include problems with defecation, urination and breastfeeding.

THROMBOEMBOLISM Because thromboembolism is a leading cause of maternal mortality, all new mothers should be assessed for this risk before and soon after delivery. Maternal mobility prevents venous stasis in leg and pelvic veins. The days of ‘confinement’ to bed are long past. Those at highest

risk of immobility (e.g. post general anaesthesia, laparotomy [caesarean section], obese or with comorbidities) need particular help to ‘get moving’ including adequate analgesia and physiotherapy. Compressive stockings with or without subcutaneous heparin from delivery help prevent venous thromboembolus and are now commonly routine after caesarean section. In the presence of an epidural cannula, the anaesthetist should be consulted about the optimal timing of anticoagulation to minimise the incidence of epidural space bleeding associated with cannula removal. The symptoms and signs of thromboembolus are summarised in Box 41.1. Investigations when pulmonary embolus is suspected can include: ECG, pulse oximetry; consider arterial blood gases, chest X-ray

•

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BOX 41.1  Symptoms and signs of thromboembolism. Pleuritic chest pain Cough, dyspnoea, haemoptysis fever (low grade) Collapse, tachycardia, tachypnoea, hypotension, right heart failure, cardiorespiratory arrest Requirement for oxygen supplementation to maintain percutaneous oxygen saturation, confusion, secondary to hypoxia Chest signs consistent with pleural effusion, chest signs consistent with pulmonary infarction Lower limb pain, oedema and discolouration, especially purple or white

•

diagnosis of pulmonary embolus by ■ CT pulmonary angiogram (CTPA); most informative if coexisting lung pathology is suspected on history or chest X-ray ■ radionuclide ventilation/perfusion scan (V/Q); more frequently useful in cases without prior pulmonary pathology, or ■ investigations seeking a venous thrombus origin to emboli, including Doppler of leg veins, pelvic MRI angiography or (rarely) contrast venography. Treatment of pulmonary embolus includes: anticoagulation, by weight and anti-Xa adjusted subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin consideration of thrombolysis if critically unwell and hazard of haemorrhage is considered acceptable; not strongly recommended within 10 days of childbirth or in the setting of hypertension cardiorespiratory support according to degree of decompensation; women may require critical care. Women requiring warfarin usually commence this soon after childbirth in the anticipation that the International Normalised Ratio (INR) will usually be therapeutic by about 3 days postpartum. Heparin is usually used for anticoagulation until full warfarinisation has been achieved. Infants can still be breastfed if their mothers are taking heparin and/or warfarin.

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Mastitis. This can be due to S. aureus sepsis of skin origin. Caesarean or episiotomy wound infections. These may be due to colorectal organisms, skin organisms or both. Intravenous, urethral and epidural catheters are all potential conduits of infection. Bacteraemia with or without urinary tract or neurological sepsis are serious complications. The mother’s altered immune state of pregnancy renders her particularly vulnerable to highly morbid influenza infection. This susceptibility persists into the first few weeks postpartum. Box 41.2 summarises monitoring and treatment for puerperal infection. Examination should include mental state, observations and systemic examination. In addition to site-specific microbiological testing for suspected bacteria or viruses, ill women may need assessment of haematology, biochemistry and medical imaging (e.g. chest X-ray, renal tract ultrasound). Supportive therapy and empiric antibiotic or antiviral treatment often need to be commenced prior to final diagnosis. Surgical treatments are rarely required, but may include drainage of abscesses and debridement of necrotising fasciitis. Referral to infection control and/or an infectious diseases physician can assist with minimising spread to other people, including newborn babies, and can assist with precise diagnosis and targeted treatment.

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SECONDARY POSTPARTUM HAEMORRHAGE

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Secondary postpartum haemorrhage is defined as bleeding that is of a volume larger than expected between 24 hours and 6 weeks postpartum and which is sufficient to derange maternal physiology. (See also Chapter 63.) The common causes are retained products of conception, endometritis or both, together with inflamed or infected decidual vessels whereby normal paracrine mechanisms to control uterine blood flow are deranged. Initial treatment includes high vaginal swabs and antibiotic therapy directed at the likelihood of ascending bowel flora, which can cause endometritis. An assessment of whether retained products of conception are present depends on history, examination and the prudent use of tests. Unless there has been a formal exploration of the uterine cavity at birth (e.g. at caesarean section or as part of an examination under regional or general anaesthesia), reports that the placenta was ‘complete’ are prone to error. If examination shows a larger than expected uterine fundus, it is prudent to be suspicious of retained products of conception. In the modern era, transvaginal ultrasound is better able to distinguish intrauterine tissue from blood than in previous times with transabdominal approaches. Intracavity blood usually transmits sound and so an ‘enhancement’ artefact is seen in the far field. Tissue absorbs ultrasound and therefore attenuates echoes from the far field.

•

INFECTION Puerperal infections remain among the leading causes of maternal death and maternal severe morbidity. Endometritis. Colorectal flora may colonise and cause sepsis in the genital tract, with endometritis the most common cause of puerperal fever. Group A streptococcus is another pathogen which can cause genital tract infection and generalised septicaemia. Urinary tract sepsis. Colorectal commensals can also cause serious urinary tract sepsis.

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Chapter 41  Puerperal Disorders

BOX 41.2  Monitoring and treatment for   puerperal infection. General impression of woman or her carers that she is ‘not right’ Chills, rigors, anorexia, confusion Localising symptoms, including increased lochia volume, offensive smell or purulent appearance of lochia, suprapubic pain, dysuria, haematuria, pyuria, localised breast tenderness, redness, swelling, wound pain, redness or discharge, sore throat, cough, chest pain, headache, photophobia or neck stiffness Routine temperature measurement: 1 hour, 5 hours postpartum then at least daily while an inpatient ✚ If temperature is > 37.4°C, recheck at 1 hour ✚ If temperature is > 37.9°C, medical review Routine pulse measurement at 1 hour and 5 hours postpartum then at least daily while an inpatient ✚ If pulse is > 100, recheck at 1 hour ✚ If pulse is > 100 on two occasions or > 110, medical review Test for site-specific infections and bacteraemia as indicated by clinical condition; for example blood culture, urine culture, wound swab, high vaginal or low vaginal swabs, throat swab, nasopharyngeal aspirate, sputum culture Treat with early, empiric antibiotic and/or antiviral until microbiological test results are available Support organ systems of mother; critical care is occasionally required Infection control to minimise infectious spread to infant, other patients and staff ✚ In most cases of puerperal infection, the baby will still benefit from breastmilk ✚ Most maternal antibiotic/antiviral treatments are not contraindicated to breastfeeding ✚ If the mother’s respiratory droplets are an infectious hazard for her baby, she can express milk and the infant can be fed by a healthy relative or staff members

If retained products are suspected, most practitioners proceed to evacuation (e.g. by dilatation and suction curettage) after about 24 to 48 hours of intravenous antibiotics. Intraoperative ultrasound may help reduce uterine perforation during dilatation and curettage. Supportive care, including blood transfusion and critical cardiorespiratory support, is occasionally necessary. Radiological methods for treating intractable secondary postpartum haemorrhage include embolisation of the uterine artery or its branches. Hysterectomy remains the definitive treatment in severe, intractable secondary postpartum haemorrhage.

URINARY AND BOWEL PROBLEMS DURING THE PUERPERIUM Urinary retention should mostly be preventable. If perineal pain is inhibiting urination, this should be overcome with adequate analgesia. If pudendal nerve neuropraxia or post-anaesthetic nerve dysfunction is suspected, then care must be taken not to complicate recovery further by superimposed bladder distension. Resting the bladder for 24 hours or longer with an indwelling urethral catheter may be required. Physiotherapy can assist by accurate assessment, specific exercises and educating the mother about pelvic floor strength and bladder control. Constipation is common after birth. Contributing factors include: opiate analgesia reduced oral intake around the time of birth anxiety and/or perineal pain inhibiting normal bowel habits. Education, avoiding dehydration and some use of fibre supplements and/or stimulant medication will usually see the return of normal bowel habits by about day 3. In the case of anal sphincter injury related to childbirth, it is particularly important to ensure that the woman can defecate without undue strain. Commonly, a stool softener such as lactulose is prescribed from day 1 so that constipation is prevented. Haemorrhoids are common. Prevention or treatment of constipation and the use of topical analgesic, antiinflammatory and/or anaesthetic medication usually mean that time, rather than surgery, resolves haemorrhoids. Third- and fourth-degree lacerations heal with the best functional result if there is no infection and no pressure on the wound (i.e. no constipation). Optimal sphincter muscle bulk is achieved with anatomical surgical repair and exercise-induced hypertrophy, which is best done under physiotherapy supervision. Optimal sphincter innervation is achieved with supervised physiotherapy. A course of antibiotics is routine. Anal fissure is treated expectantly in a similar manner to haemorrhoids, although occasionally medical treatment or a surgical opinion is warranted. Abdominal surgical emergencies can occur in the postpartum period (e.g. appendicitis, cholelithiasis, Ogilvie syndrome, intussusception). Appropriate referrals should be made if the practitioner is suspicious of these conditions. Incontinence of urine or faeces warrants serious attention. Fistula is uncommon in Australasia but can still occur. Pelvic neuromuscular damage is the more likely cause. Examination of the perineum and related neurology is necessary. Close follow-up by an obstetrician and physiotherapist, with or without colorectal or urological surgical expertise, is needed. Some hospitals have multidisciplinary ‘perineal clinics’ facilitating audit, education, research and clinical care.

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BREASTFEEDING PROBLEMS Breastfeeding problems sometimes occur. If the volume of milk does not seem to be meeting the infant’s needs, particularly if there is a relative delay in lactogenesis II (the conversion from colostrum to mature milk), then milk production can be augmented by using knowledge of the supply–demand endocrinology of lactation (see also Ch 40). Specifically, increasing breast stimulus by increasing the frequency of feeds and using a breast pump after the infant has suckled to obtain extra mother’s milk for ‘top-up’ feeds will usually increase supply. The mother–infant dyad is helped by a midwife or lactation consultant who can optimise both mother and baby factors to make breastfeeding most satisfying for both. Some individual manoeuvres include: optimising the mother’s comfort, especially by optimising the baby’s attachment to the breast (Ch 39); minimising maternal anxiety; building the mother’s confidence; and trying to help her see that there are many ways to achieve the same result of a healthy breastfed baby. Occasionally a good night’s sleep helps. Dopamine antagonists (e.g. domperidone) may also help. Other women and their infants experience hurdles to breastfeeding, which can usually be overcome. Engorgement, often at the time of lactogenesis II on day 3 to 6. Gentle expression of some milk before a feed makes the breast slightly softer and less domelike, so attachment is easier. Vigorous expressing is to be avoided because of the principle that more breast stimulation will increase milk production. A milk flow that is too fast for the baby to tolerate. This leads to spluttering and coughing. In the short term, feeding against gravity can slow the flow. In the longer term, older vigorous babies will cope with fastflowing milk. Milk stasis (e.g. blocked ducts). Look for and prevent obstacles to milk flow, such as wire or plastic shaping of underwear or the mother’s own hand. Massage and hot and cold packs before, during or after a feed or in the shower can keep milk flowing. Mastitis. This manifests as fever, rigors and a segment or quadrant of inflamed breast and may be caused by S. aureus. Milder forms may still have marked inflammation but lower bacterial counts. Physical measures to drain the breast are most important. Antiinflammatory agents give symptomatic relief. Oral or intravenous antibiotics directed at S. aureus (e.g. dicloxacillin) may be required. Because inflammation and infection will be helped by preventing stasis, mastitis is rarely a reason to suppress lactation. Breast abscess. This can evolve from mastitis. Ultrasound-guided drainage and measures to treat mastitis are usually required. Nipple sensitivity and discomfort. A degree of this is common when commencing breastfeeding, even for women who have successfully breastfed in the past. However, grazes and lacerations are not normal. Good

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338

attachment minimises nipple trauma. If the skin is broken, extra care should be taken about hygiene, including handwashing and regularly changing breast pads and bras so that the broken skin does not become a portal for skin flora to cause mastitis. A traumatised nipple may need to be ‘rested’ to heal. Hand expressing, the use of a nipple shield or a very gentle pump may be gentler than infant suckling in the short term. Hazards of prolonged ‘nipple rest’ include milk stasis, engorgement, blocked ducts and mastitis as well as insufficient nipple stimulus to maintain milk production. The latter is helped by maintaining as normal as possible infant feeding on the healthy breast while the damaged side heals. There are occasional situations where weaning is necessary. If at all possible, this should be done gradually to make the process least traumatic for mother and infant (e.g. exchanging one breastfeed per day for a bottle feed). The most serious medical reason for immediate weaning is the tragedy of perinatal loss. Physiological methods of lactation suppression include minimising nipple stimulation, using simple analgesia and a supportive brassiere. A dopamine agonist such as cabergoline can also be prescribed. Other medical reasons for rapid and complete weaning are where the mother will be commencing anticancer chemotherapy, is HIV infected or has a high intake of delta-9-tetrahydrocannabinol (THC) or other medications which are contraindications to breastfeeding.

PERINATAL MENTAL HEALTH Regarding women’s emotions and thought in the puerperium, midwives and doctors need to be aware of sinister but treatable causes of abnormal mood other than the blues. (See Ch 25.) Midwives and doctors are less likely to miss a serious diagnosis if they take a full set of observations and either know the woman or listen attentively to others who know the woman, such as her family or other healthcare providers. A detailed history, examination (including oximetry) and some pertinent blood tests (especially ammonia, glucose, renal function, electrolytes) and screens for infection (including a full blood count) will usually exclude the serious mimics of the blues. Untreated major psychiatric disease is associated with suicide and infanticide. Occasionally, the proteolysis that accompanies uterine involution unmasks inherited biochemical defects leading to critically elevated ammonia, which needs intensive physical care as well as psychological care to avert maternal mortality. FURTHER READING Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG 2011;118(1):1–203.

Section 2.7.5 GLOBAL WOMEN’S HEALTH AND INDIGENOUS WOMEN’S HEALTH

Chapter 42  MATERNAL AND PERINATAL MORTALITY AND MORBIDITY AND GLOBAL REPRODUCTIVE HEALTH Laurel Bennett

KEY POINTS Maternal mortality in developed countries is approximately 10 per 100 000 but can be as high as 500 per 100 000 in sub-Saharan Africa. The leading causes are haemorrhage, infection, eclampsia and obstructed labour. Important contributors include: ■ poor education and the social status of women ■ inadequate access to antenatal healthcare or a skilled birth attendant at delivery ■ delay in recognition of complications and receiving care ■ comorbidities such as anaemia, malaria and HIV. Prolonged obstructed labour causes pressure necrosis and results in obstetric fistulae; these fistulae commonly involve extensive tissue loss and are difficult to repair. Unplanned pregnancy results from unmet contraceptive needs. Denial of access to safe abortion services is increasingly regarded as a violation of human rights. Where there is no access to safe and legal abortion, unsafe abortions continue to be sought, claiming the lives of 68 000 women every year. Unmet contraceptive needs remains a leading contributor to maternal death worldwide. HIV infection is the leading cause of death in women of reproductive age in low to middle income countries; contributors to high rates of HIV include poor understanding of HIV prevention, partner sexual practices and the need to resort to sex work. Cervical cancer is the second most common female cancer, with the majority of deaths occurring in the developing world. Human papillomavirus (HPV) vaccination coverage remains poor in low to middle income countries. Female genital mutilation has four recognised subtypes; it is a harmful traditional practice which has now been recognised as a violation of human rights. The Millennium Development Goals have been instrumental in focusing the world’s attention on women’s reproductive rights and reducing maternal mortality; however, it will be important to maintain the momentum created to see sustained improvement.

INTRODUCTION In all regions of the world, women have a longer life expectancy than men. However, although women may live longer than men due to natural biological and behav­ ioural advantages, they are not necessarily healthier.1 In many areas a combination of social, cultural and economic

factors expose women to a number of health hazards, especially in their reproductive years. These include maternal mortality and morbidity, human immuno­ deficiency virus (HIV)/AIDS, cervical cancer, physical and/or sexual violence and female genital mutilation.2 The issues are most apparent in low to middle income countries where women’s rights are not always

Chapter 42  Maternal and Perinatal Mortality and Morbidity and Global Reproductive Health

recognised and resources are scarce. As such, global women’s health has been the focus of many international health agencies. The World Health Organisation’s Millen­ nium Development Goals, which were adopted by 189 heads of state in September 2000, have been vital in focusing the world’s attention. Specifically, Goal 5 calls for improving maternal health by reducing the maternal mortality ratio by three-quarters and by achieving univer­ sal access to reproductive health by 2015.3 Unfortunately, despite this, progress in reducing maternal mortality has been very slow.4

MATERNAL MORTALITY Pregnancy-related deaths … are often the ultimate tragic outcome of the cumulative denial of women’s human rights. Women are not dying of untreatable diseases. They are dying because societies have yet to make the decision that their lives are worth saving. United Nations General Secretary Ban Ki-moon 20105 In 2010, when last reported by the WHO, there were an estimated 287 000 women worldwide who died of complications during pregnancy, childbirth or in the 6 weeks following delivery.6 This rate has decreased from an estimated 543 000 in 1990, but is still insufficient to

fulfil targets set by the Millennium Development Goals.7 The developing world shoulders most of the burden of these deaths, with more than 99% occurring in low to middle income countries. Sub-Saharan Africa alone recorded 162 000 maternal deaths in 2010.6 The striking divide in health inequality between the developed and less developed world is highlighted by the maternal mortality rate (MMR, defined as the number of maternal deaths during a given time period per 100 000 live births during the same period). The estimated global maternal mortality rate published in 2010 was 210 per 100 000 live births. In more developed countries like Aus­ tralia, the MMR was as low as 9 per 100 000; however, in developing countries it averaged 240 per 100 000. In subSaharan Africa, the MMR was double the global average at 500 per 100 000 (Figure 42.1).6 In developing regions, not only is a higher mortality rate associated with each pregnancy but higher fertility rates mean that women have many more pregnancy exposures. Lifetime risk of dying from complications related to pregnancy or childbirth in developed countries is very low at 1 in 3800, whereas in low to middle income countries women have a 1 in 180 risk, and in sub-Saharan Africa a 1 in 39 risk of death.6 This differential is one of the widest among indicators of public health status.1,4 Unfortunately, the overwhelming majority of mater­ nal deaths are preventable and due in most part to inad­ equate access to healthcare and the low status of women in society. However, if given enough political focus,

Legend < 20

550999

2099

≥ 1000

100299

Population < 100 000 not included in assessment

300549

Not applicable

FIGURE 42.1

Map with countries by category according to their maternal mortality ratio (MMR, death per 100 000 live births), 2010. Source: Trends in Maternal Mortality: 1990 to 2010, World Health Organization, 2012, fig. 1, p. 23.

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adequate funding and the right approach, the tragedy of maternal death can be amended quickly. Countries like Romania, Malaysia, Sri Lanka, Thailand, Egypt, Mongolia and Bangladesh have achieved a 75% reduction in the maternal death rate in the past two decades and give hope for the future.3,8 Maternal deaths are most commonly due to obstetric complications such as postpartum haemorrhage, infec­ tions, eclampsia and prolonged or obstructed labour. There is also significant contribution from indirect causes that increase the risk of maternal death such as anaemia, iodine deficiency, malaria and HIV/AIDS.2 Cultural and societal factors also contribute to the maternal death toll. Women in developing countries have less freedom to act, less personal autonomy and less access to information than their male partners.2,3 As such, they often do not access antenatal care and, if complications arise in pregnancy or labour, there are often significant delays in receiving care. Delays occur for a number of reasons. If the woman has an untrained or no attendant during birth, the complication may not be initially recog­ nised. The poor social status of a woman, whose health may not be a priority, means she often would need to seek per­ mission from her husband or male relative prior to access­ ing expensive and distant health services. The cost of emergency obstetric care can be prohibitive, and enough to send families into poverty. Inadequate referral pathways and access to transport further exacerbates the problem. Access to antenatal care may help to identify prob­ lems early and to educate and engage women. However, programs to improve attendance have not effected a reduction in mortality.4 This is because the majority of obstetric complications cluster around delivery, occur in women categorised as low risk and cannot be predicted or prevented. Therefore, the single most important inter­ vention to reduce maternal mortality is to ensure access to a trained provider with midwifery skills at every birth.4 Ensuring that transport is available to referral services and that quality, affordable emergency obstetric care is available is also a priority.

VESICOVAGINAL FISTULAE Avoidable loss of life from obstetric causes is devastating, but it is estimated that 10 to 20 million per year will escape death only to suffer serious childbirth complica­ tions, including infertility, psychological distress and obstetric fistulas.3 A vesicovaginal fistula is an abnormal opening between the bladder and the vagina.9 This results in con­ tinuous insensible leakage of urine. Estimates of numbers of inflicted individuals vary and it is difficult to quantify due to the shame associated with the condition. The number could be as high as 3.5 million worldwide, with up to 130 000 new cases yearly.9 In low to middle income countries a vesicovaginal fistula is almost exclusively due to prolonged obstructed 342

labour. The tissue damage is usually over a broad area, and the fistula extensive and surgically difficult to repair. The rates of successful surgical repair range from 16 to 100%, depending on severity.9 Contributing factors include the relatively narrow anatomy of the African pelvis, childhood malnourish­ ment, childhood marriage and subsequent pregnancy prior to achieving full growth.8,9 These factors combine with poor or absent intrapartum care, and distant or prohibitively expensive emergency obstetric care in areas of high prevalence. As predicted by the risk factors, women affected by obstetric fistulae are often young, uneducated, live in an isolated area, and have experienced a prolonged labour > 2 days, with a fetal death as the outcome in > 90% of cases.8 Seventy to 90% are abandoned by their partners and isolated from their communities as they are seen as unclean and often incorrectly blamed for their affliction due to superstition and misinformation. The physical, emotional and social burdens inflicted by obstetric fistu­ lae on these young women cannot be overstated, and prevention and surgical correction remains a focus of international efforts to improve women’s health.

ABORTION Another important contributor to maternal mortality is unwanted pregnancy from either contraception failure or lack of contraception entirely. If there is subsequent inability to access safe and legal terminations, women will seek out unsafe abortions. These are defined as abortions performed by those without the requisite skills and/or in environments that are below minimum standards.10 Unsafe abortions claim the life of approximately 68 000 women each year, which represents 13% of mater­ nal mortality and should be seen as a persistent, prevent­ able pandemic.8,10 In 2003, there were an estimated 42 million induced abortions worldwide. Of these, the number of unsafe abortions was approximately 20 million per year and 97% were in developing countries.2 Develop­ ing countries are over-represented mostly due to restric­ tive laws, but even in developing countries with liberal abortion laws, poverty and inadequate health systems make safe abortion out of reach for the majority. Legal abortion in developed countries is a very safe procedure. With modern techniques, case fatality rates are < 1 per 100 000. The estimated case fatality from unsafe abortion is 367 per 100 000.10 Leading causes of death from unsafe abortion are haemorrhage, infection and poisoning from substances used to induce abortion. Morbidity from the procedure is also high, with many requiring hospitalisation post-procedure for complica­ tions.10 Ongoing long-term health consequences include infertility, chronic infection and subsequent pregnancy complications, such as ectopic pregnancies, miscarriage and preterm labour. Not only does the treatment of abor­ tion complications burden impoverished healthcare systems, but they exact ongoing indirect costs.

Chapter 42  Maternal and Perinatal Mortality and Morbidity and Global Reproductive Health

Access to modern contraception can reduce the need for abortion but will never eliminate it.10 Making abor­ tion legal, safe and accessible does not increase demand. In fact, in a number of countries, granting women safe and legal access to abortion along with access to modern contraceptives and sex education has been shown, in the long run, to reduce the number of abortions. Safe abor­ tion should be just one facet of comprehensive reproduc­ tive health services, which should be accessible to and affordable for all women. Abortion, legal or illegal, is highly stigmatised and is often censured by political and religious leaders; it remains the greatest taboo of global women’s health.11 Twenty-six per cent of the world’s population live in countries where abortion is illegal or allowed only to save a woman’s life.2 Where restrictive abortion laws make it difficult to obtain a safe abortion, they do not decrease the frequency of the procedure; they simply increase maternal mortality and morbidity. International organisa­ tions increasingly regard the denial of safe abortion ser­ vices as a violation of human rights. Unfortunately, efforts to reduce unsafe abortions worldwide seem to have stalled in recent times.

CONTRACEPTION The use of contraception allows women and men to have control over the timing and the number of desired chil­ dren by preventing an unintended pregnancy. For indi­ viduals it may help overcome traditional gender roles, allow girls to stay in school longer, allow women into the labour force and improve maternal health.8 Use of contraception in couples worldwide in 2007 approached 63% (and was as high as 70% in developed countries).2 In particular, the developing world has seen a revolution in contraceptive use. From 1960 to 1965, rates of contraception use in couples in developing countries was only 9%.10 This approached 62% in 2007.2 This increasing use has cut the number of maternal deaths by 40% over the past 20 years merely by reducing unwanted pregnancies.12 A further 30% of maternal deaths could be avoided by fulfilment of unmet need for contraception.12 The majority of this unmet need is in Africa, where only 28% of couples use contraception. An estimated 22% of African women of reproductive age are in need of family planning.2 Contraception has other benefits. Barrier methods of contraception help protect individuals from HIV and other sexually transmissible infections (STIs), and increas­ ing inter-pregnancy intervals decreases perinatal morbid­ ity with the reduction in preterm delivery and low birth weight babies.12

HIV HIV infection is the leading cause of death of women in their reproductive years in low to middle income

countries.1 In 2007, of the approximately 33 million people living with the disease, two-thirds were from subSaharan Africa and more than 50% were women. 2,8,13 The toll exacted by HIV/AIDS extends beyond the physical health of women to the families and communities that depend on them.2 Women have an increased susceptibility to acquisi­ tion of HIV due to biological factors and this is further exacerbated by social vulnerability.8 Women are less likely to be able to negotiate safe sex practices, especially if subjected to partner violence, and forced sex can con­ tribute to HIV transmission due to tears and lacerations from the force their partner uses. Women are less edu­ cated and only 38% of young women worldwide have accurate knowledge of HIV prevention—far less in subSaharan Africa (approximately 10%).2,13 Economic insta­ bility and disadvantage in high-risk areas often leads women to engage in sex work. Even married women are at risk due to cultural norms that encourage men to have more sexual partners and older men to have sexual rela­ tions with much younger women.13 Mother to child transmission in the developing world is a major issue, with transmission rates between 20 to 30%. Most pregnant women are unaware of their HIV status. This is due to a combination of lack of knowledge about the disease, no access to testing, the stigma sur­ rounding the diagnosis and a lack of available treatment in those who are found to be positive.

CERVICAL CANCER Cervical cancer is the second most common cancer in women worldwide. There are approximately 500 000 new cases of cervical cancer annually, half of which lead to death.8 The disease burden once again falls on developing countries, where 80% of these deaths occur.8 Cervical cancer is caused by persistent infection with the high-risk subtypes of the human papilloma virus (HPV). If the infection is detected early with screening programs and treated, cancer will never develop and the prognosis is excellent. Screening programs, which are well established in developed countries, are not feasible in resource-poor settings, where there are often compet­ ing health priorities, weak health systems, no local exper­ tise and limited infrastructure.14 Alternative approaches to screening and treatment, such as visual inspection with acetic acid (VIA) followed by immediate treatment with cryotherapy, are used in isolated, resource-poor settings.14 Although there is a ‘trade off’ in quality of both screening and treatment, it reduces barriers to accessing care and increases screening test coverage. HPV immunisation programs against high-risk sub­ types also offer promise in reducing cervical cancer mor­ bidity and mortality. HPV vaccination is targeted at girls from 9 to 13 years old who have not yet become sexually active and, thus, not yet exposed to HPV. Despite being 343

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the population with the most to gain, vaccination cover­ age is harder to achieve in low to middle income coun­ tries. The target population is often difficult to find with poor school enrolment rates for girls, and the costs of the vaccination and its delivery are prohibitive to these coun­ tries even with subsidies.

FEMALE GENITAL MUTILATION AND VIOLENCE AGAINST WOMEN One of the most extreme forms of discrimination against women is female genital mutilation (FGM). FGM is a harmful traditional practice that is also closely linked to the status of girls and women; it has social, cultural and religious underpinnings. Some cultures consider FGM a rite of passage into womanhood and believe it preserves chastity and ensures marriageability, improves fertility and enhances sexual pleasure for men.15 It is now recog­ nised as a violation of human rights and in December 2010, the UN general assembly accepted a resolution on the elimination of FGM.16 Despite international condemnation, there are about 140 million women currently living with the conse­ quences of FGM.16 These women are predominantly in western, eastern and northeast Africa, and some coun­ tries in Asia and the Middle East. FGM includes procedures that intentionally alter or cause injury to the female genital tract for non-medical reasons.16 These procedures usually occur between infancy and 15 years of age and are categorised into four major types. 1. Clitoridectomy: partial or total removal of the clitoris. 2. Excision: partial or total removal of the clitoris and the labia minora, with or without removal of the labia majora. 3. Infundibulation: narrowing of the vagina by creation of a covering seal. 4. Other. FGM has both immediate and long-term complica­ tions. Immediate complications include pain, shock, haemorrhage, sepsis, urinary retention and tetanus. Longterm issues include recurrent urinary tract infections, urinary retention, cysts, infertility and childbirth complications.15 REFERENCES 1) World Health Organisation. Women and health; today’s evidence tomorrow’s agenda. Executive summary. Geneva: WHO; 2009. Online. Available: ; [9 Dec 2014].

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2) Department of Economic and Social Affairs. The World’s Women 2010: Trends and Statistics. New York: United Nations Statistics Division. Online. Available: ; [9 Dec 2014]. 3) Filippi V, Ronsmans C, Campbell OM, et al. Maternal health in poor countries; the broader context and a call for action. Lancet 2006;368:1535–41. 4) Rosenfield A, Min CJ, Freedman LP. Making motherhood safe in developing countries. N Engl J Med 2007;356(14):1395–7. 5) United Nations Secretary General. Ban Ki-moon. Global strategy for women’s and children’s health. New York: United Nations; 2010. 6) World Health Organisation, UNICEF, UNFPA and the World Bank. Trends in maternal mortality: 1990–2010. Geneva: WHO. Online. Available: ; [9 Dec 2014]. 7) World Health Organisation. Maternal and reproductive health, maternal mortality. Online. Available: ; [9 Dec 2014]. 8) Lester F, Benfield N, Fathalla M. Global women’s health in 2010: facing the challenges. J Women’s Health (Larchmt) 2010;19(11):2081–9. 9) Wall L. Obstetric vesicovaginal fistula as an international public health problem. Lancet 2006;368:1201–9. 10) Grimes DA, Benson J, Singh S, et al. Unsafe abortion; the preventable pandemic. Lancet 2006;368:1908–19. 11) Horton R. Women’s and children’s health: no time for complacency. Lancet 2012;380: 1123–5. 12) Cleland J, Conde-Agudelo A, Peterson H, et al. Contraception and health. Lancet 2012;380: 149–56. 13) World Health Organisation. Gender, women and health. Gender inequalities and HIV. Geneva: WHO. Online. Available: ; [Apr 2013]. 14) World Health Organisation. Comprehensive cervical cancer prevention and control; a healthier future for girls and women. Geneva: World Health Organisation; 2013. 15) Nour MN. An introduction to global women’s health. Rev Obstet Gynecol 2008;1(1):33–7. 16) World Health Organisation. Media centre: female genital mutilation. Geneva: World Health Organisation. Online. Available: ; [Apr 2013].

Chapter 43  AUSTRALIAN INDIGENOUS WOMEN’S HEALTH IN PREGNANCY Jacqueline Boyle and Marilyn Clarke

In this chapter we respectfully use the term ‘Indigenous’ to refer to the two Indigenous populations of Australia: Aboriginal and Torres Strait Islander.

KEY POINTS Although many Indigenous women have a positive experience and outcome in their pregnancy, there is still a considerable disparity in the rate of adverse perinatal and maternal outcomes between Indigenous and non-Indigenous women. Indigenous women are twice as likely to have babies preterm and of low birth weight. They are also 1.5 times more likely to suffer perinatal mortality and have a maternal mortality rate five times higher than the non-Indigenous population. Barriers to improved health outcomes include: ■ decreased health literacy ■ decreased English literacy ■ poorer socioeconomic factors ■ racism or discrimination ■ health systems and services that are often not culturally appropriate or easily accessible. Risk factors in pregnancy that are increased in Indigenous women include: ■ poor nutrition, smoking, excessive alcohol intake and obesity ■ anxiety and depression ■ diabetes and cardiovascular disease ■ domestic violence. Ways to improve Indigenous women’s health include: ■ improving mechanisms to identify Indigenous patients ■ engaging interpreters and Aboriginal health liaison officers and Aboriginal healthcare practitioners where available to assist with providing culturally appropriate and accessible services ■ being aware of the increased health risks facing Indigenous women ■ being aware of diversity among Indigenous Australians, understanding the differing concepts of health and wellness, and undertaking regular cultural training.

AUSTRALIAN INDIGENOUS WOMEN’S HEALTH IN PREGNANCY Indigenous people comprise 2.5% of the Australian population, and while the majority of Indigenous women live in cities and non-remote regional areas (75%), they are

still more likely to live in outer-regional, remote or very remote areas than non-Indigenous people.1 Overall, they experience a greater burden of disease compared with non-Indigenous women across reproductive health, chronic disease, injury and social and emotional well­ being. Contributors to this increased burden include: experiences of racism or discrimination decreased health literacy and English literacy

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•

healthcare systems and services that are often not culturally acceptable or easily accessible, leading to a lack of engagement with all levels of healthcare from health promotion through to hospitals high rates of poor health behaviours such as smoking and socioeconomic factors such as unemployment and low incomes. In 2010, 3.9% of all Australian births were to mothers reported as Indigenous. This varies by state and territory, with the highest proportion in the Northern Territory at 36.3%.2 Indigenous women have their children younger; the average age at birth for Indigenous women in 2010 was 25.2 years compared with 30.2 years for nonIndigenous mothers.2 Teenage pregnancy (19.7%) is also more common than in non-Indigenous mothers (3.2%).2 Indigenous women experience double the rate of preterm birth and low birth weight, 1.5 times the perinatal mortality rate and five times the maternal mortality rate.2 The risks are increased for women who live in remote areas compared to those who live in urban areas, and this may be related to increased socioeconomic disadvantage in non-urban areas and limited access to a wide range of birthing services.

•

FACTORS INFLUENCING HEALTH CULTURAL CONCEPTS OF HEALTH Concepts of health vary and most medical practitioners have a biomedical framework of health that focuses on disease processes within the individual patient, and will manage ill health by addressing the disease-causing agents. Health for many Indigenous people, in contrast, is a holistic concept that encompasses all aspects of a person’s life including land, family, community, law, spirituality and ceremony in addition to the more traditional biomedical concepts of physical and emotional wellbeing. In the National Aboriginal Health Strategy Newfong states that ‘In Aboriginal society there was no word, term or expression for “health” as it is understood as in Western society’, making translation almost impossible.3 Indigenous Australian societies are also grounded in gendered realities, which translates into healthcare for Indigenous women and Indigenous men being separated pending the issue and context. Thus, the term ‘Women’s Business’ is used by Indigenous women within healthcare environments that pertain to women, and includes birthing.

EDUCATION, LANGUAGE AND HEALTH LITERACY Education impacts on health through improved literacy, which increases the ability to learn and increase health knowledge as well as improving employment prospects, 346

income and access to services. Nationally, school completion of Year 12 has improved for Indigenous people and in 2008, nearly one-third (30%) of young Indigenous adults aged 24 to 35 had completed Year 12. However, this is still lower than Year 12 completion rates for nonIndigenous young adults of the same age (73%).1 Indigenous people between 25 to 64 years of age were also less likely to have completed a non-school qualification than non-Indigenous people (40% compared with 61%), particularly in remote areas.1 For some Indigenous people, English is not their first language and this adds to their difficulty in achieving health literacy. In 2008, around 1 in 9 Indigenous Australians aged over 15 years spoke an Indigenous language as their main language at home; this was greatest in remote areas (42%). Many more (40%) spoke some words of an Indigenous language and again this was highest in remote areas (73%).1 Some Indigenous people in urban areas may speak a combination of an Indigenous language, Aboriginal English and standard English, which will not be recorded in data collection as speaking an Indigenous language. While poor literacy presents barriers to the development of health literacy, the latter can be achieved through the use of appropriate resources in media that are accessible and understandable. Community engagement is vital as the simple translation of words into local language and simplified pictorial images often assumes background knowledge people may not possess.

DISCRIMINATION A significant proportion (27%) of Indigenous people aged over 15 years report experiencing discrimination in the previous 12 months.1 Discrimination and racism may be associated with a number of health conditions in Indigenous people, including anxiety and depression, as well as increasing the chance of negative health behaviours such as smoking, increased alcohol use and substance abuse.1 This may also affect people’s confidence in attending for healthcare since they may have previously experienced or anticipate incidents of discrimination.

BARRIERS TO ACCESSING HEALTHCARE For those living in remote areas, healthcare may be difficult to access due to a lack of facilities and/or staff. Staff turnover is often high, hampering the establishment of trust in healthcare providers. Women may need to travel into regional centres/cities for screening such as mammograms, investigation, treatment and giving birth. This may be difficult for many women: travel and a small amount of accommodation is usually paid for but other expenses will be incurred; they may be afraid to travel, not feel safe if accommodation is not secure and worry about leaving family and children. Women either travel

Chapter 43  Australian Indigenous Women’s Health in Pregnancy

alone or are supported by one family member who may need to assist in their care. Experiences of racism and discrimination and a lack of culturally appropriate healthcare will deter women and their families from attending healthcare. Culturally appropriate healthcare will vary in different locations and it is important for healthcare providers and students to access training on cultural awareness and cultural competence. Some regional areas have small Indigenous birthing support programs which compliment mainstream services.

SOCIOECONOMIC DETERMINANTS OF HEALTH Many Indigenous women experience higher risk factors for poor health including social determinants such as inadequate housing, unemployment, low incomes and low levels of formal education. Health behaviours such as smoking, decreased exercise and poor nutrition can exacerbate poor health and are often influenced by social and environmental factors. Women experiencing social isolation, no transport, unsafe environments and low incomes are more likely to buy cheaper, nutrient-poor (but calorie-dense) foods that are high in sugar or fat, and may be less likely to exercise, more likely to experience mental distress and less likely to prioritise their own health.

PREGNANCY Prior to colonisation, Indigenous women had selfdetermination over every facet of their lives, including pregnancy and birthing practices. These processes were led and guided by elders, ensuring the survival of Indigenous people through hundreds of generations. In colonial times, Indigenous women also assisted non-Indigenous women to birth. Indigenous pregnancy and birthing practices have altered through Western medical intervention, although in some areas Indigenous women attempt to use a combination of knowledge. It is important that women be offered services where they feel comfortable and that healthcare providers understand the complexity of incorporating both Indigenous and contemporary Western health systems in different locations and for individual women in their pregnancy journey. Women are more likely to attend antenatal care at services that meet these and other complex needs with approaches that include community control, Indigenous healthcare providers, transport, flexibility and childcare.4,5 Pregnancy complications, including low birth weight, preterm delivery and higher mortality, are increased in Indigenous women. Contributing factors include poor access or attendance for care, socioeconomic disadvantage, maternal nutritional status, parity, higher prevalence of anaemia, urinary tract infections, sexually transmitted infections, smoking, alcohol use, significant social stressors and chronic disease.

SPECIFIC HEALTH ISSUES AFFECTING PREGNANCY RISKS Obesity and underweight In 2006, 56% of Indigenous women over 15 years were overweight or obese6 and the proportion was greater than that for non-Indigenous women in all age groups. Being overweight/obese prior to pregnancy as well as gaining excess weight during pregnancy increases the risks of pregnancy complications such as miscarriage, hypertension, caesarean section and gestational diabetes. Excess weight gain in pregnancy may also increase the risk of long-term obesity. Contributing factors include a lack of physical activity and poor nutrition with a low intake of fruit and vegetables. A history of being either sedentary (0 to 100 minutes of activity a week) or undertaking low-level exercise (100 to 1600 minutes a week) was selfreported by 75% of Indigenous people from non-remote areas in 2004 to 2005.6 Conversely, maternal undernutrition remains a significant problem in some areas and is associated with increased risks of preterm birth and fetal growth restriction.5 BMI should be measured at the first visit and advice given about appropriate weight gain during the pregnancy. Discussion of diet and nutrition within their cultural context, safe physical activity in pregnancy and barriers women may be experiencing that affect their ability to undertake these is important and may require discussion with a dietician or Aboriginal health care practitioner.

Nutrition Poor nutrition can contribute to being underweight but also to being overweight/obese. In non-remote Indigenous women, the vegetable intake is similar to that of non-Indigenous women; however, in remote areas the intake of fruit and vegetables is lower, possibly due to lack of access to food and/or the high costs of nutritious food.1,6 Inadequate diet contributes to a high proportion of Indigenous women who are anaemic in pregnancy. Women wishing to conceive are advised to have folate supplementation before and during the first trimester of pregnancy to prevent neural tube defects such as spina bifida. The rate of neural tube defects in Indigenous babies is almost double that of non-Indigenous babies.4,5 Knowledge of the benefits of folate and folate use is less than for non-Indigenous women. Nearly half of Indigenous women report using folate supplements before or during the pregnancy, although the percentage is lower in remote areas (35%).1

Social and emotional wellbeing Anxiety and depression constitute the highest burden of disease in Indigenous women (10%).7 Social and emotional wellbeing can influence general health. A person’s ability to engage with healthcare and good health behaviours, as well as high levels of stress and depression, can 347

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increase the risk of preterm birth and adversely affect the developing fetal brain.4,5 Indigenous women report significant stress in their lives; 50% of South Australian Indigenous women reported having three or more social issues to cope with during pregnancy such as death of a family member, family violence and housing problems.8 It is important to identify appropriate supports for women and to ask about psychosocial factors such as past history of mental health disorders, current levels of support, current life stressors and current and/or past exposure to violence or abuse.4 Screening for depression in Indigenous women can be difficult as the tools used may not be culturally appropriate or understandable, or there may be mistrust of mainstream services.4 Indigenous women are much more likely to experience domestic violence and to receive treatment in hospital for injuries due to assault, with one-fifth of women over 15 years of age reporting threatened or physical violence in the past year.4 Factors that contribute to this include racism, poverty, dispossession, and systems and practices such as institutionalisation and the removal of children that have led to the loss of land, the breakdown of culture and kinship systems, trauma and grief.4

Smoking is a key preventable factor of poor perinatal outcomes such as low birth weight, preterm birth and perinatal death; 49% of Indigenous women smoke in pregnancy, three times more than non-Indigenous mothers.2 Maternal factors found to be associated with smoking during pregnancy include a high number of previous children, no partner, low income, low levels of social support and limited education. Other factors that have been reported in Indigenous women who continue to smoke in pregnancy include the normalisation of tobacco use in communities, smoking providing ‘time out’, its importance for social interaction, the perception that it reduces stress, and high levels of smoking in family and friends making it harder to quit. It is important to document smoking status, offer culturally appropriate smoking cessation advice and engage anti-tobacco workers if appropriate and available.4

Diabetes

Alcohol consumption

Diabetes is around three times more common in the Indigenous population compared to the general Australian population, with around 6% of Indigenous Australians having some form of diabetes, mostly type 2 diabetes (T2DM).1,7 T2DM occurs at a much younger age than for non-Indigenous Australians, with the peak incidence occurring at 35 to 55 years, resulting in an age-standardised rate of 12% compared with 4% for non-Indigenous Australians.1 Around 8% of Indigenous women nationally have diabetes in pregnancy, predominantly gestational diabetes (GDM), although this varies by region. In Cape York in 2008, 14.2% of women had GDM and 2.3% had T2DM.9 Good pre-conception control of blood sugars is important, as is early screening for GDM in women with risk factors such as previous GDM and high BMI.

Excessive alcohol intake during pregnancy is associated with a spectrum of disorders including alcohol withdrawal symptoms in the baby, fetal alcohol syndrome, neurodevelopmental disorders, birth defects and perinatal mortality.4,5 While less Indigenous women drink alcohol in pregnancy, those that do are more likely to drink at dangerous levels, and a national survey found alcohol use in pregnancy to be 14 times higher in Indigenous women than in non-Indigenous women.5 The documentation of alcohol consumption and assessment of psychosocial factors in a trusted and secure environment is important as alcohol use is associated with mental health issues and physical and emotional abuse, and additional support may be required.4

Cardiovascular disease Cardiovascular disease contributes significantly to the burden of disease in Indigenous women and occurs earlier, with a marked increase seen from 35 years of age onwards: 10 years sooner than is seen in the nonIndigenous population.6 Rheumatic heart disease (RHD) in Australia is rarely seen outside the Indigenous population and occurs mostly in remote areas in northern and central Australia. The prevalence of RHD in the Northern Territory is 1.3 to 1.7% and a similar burden of disease is seen across other parts of northern Australia.10 RHD poses additional risks in pregnancy as the usual cardiovascular changes place additional demands on women with preexisting heart valve problems. Pre-conception counselling in those with known RHD is important to assess the severity of 348

symptoms and particular risk factors such as pulmonary hypertension. It is important to exclude RHD in pregnant women at risk with a heart murmur or with onset of shortness of breath.

Smoking

Infection Chlamydia is more common in Indigenous women than non-Indigenous women, with rates 3.5 times higher in urban areas and up to 7 times higher in remote and very remote areas.4,5 Screening should be undertaken in young women and those in areas of high risk due to the risks of Chlamydia in pregnancy, including preterm birth, intrauterine growth restriction and low birth weight.4 Syphilis is a sexually transmitted infection that, if present in pregnancy, can cause spontaneous miscarriage, stillbirth or congenital syphilis. It is more common in Indigenous women, particularly in remote areas. Treatment is beneficial for mother and baby and screening is recommended at the first antenatal visit. Asymptomatic bacteriuria appears to be more common in Indigenous women than in non-Indigenous women. Screening is recommended in the first trimester

Chapter 43  Australian Indigenous Women’s Health in Pregnancy

as the condition is more likely to progress to pyelonephritis in pregnancy (30%) and is possibly associated with low birth weight and preterm birth if untreated.4,5

IMPLICATIONS FOR HEALTHCARE PROVIDERS Optimising health outcomes for Indigenous women depends on delivery of healthcare in a way that is respectful, well understood and culturally appropriate, as summarised below. Be aware of where the women you are looking after come from, and have mechanisms in place in your practice to aid in the identification of Indigenous clients. Engage interpreters and/or Aboriginal health workers/ community health workers as part of the team. Undertake a cultural awareness/cultural competence course. Understand the diversity of Indigenous Australians and the varying health risks which may influence the healthcare you provide. Also be aware of specific local/national guidelines.10 Utilise appropriate resources when explaining healthcare to women.

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REFERENCES 1) Australian Institute of Health and Welfare. The health and welfare of Australia’s Aboriginal and Torres Strait Islander people: an overview 2011. Cat. no. IHW 42. Canberra: AIHW; 2011. 2) Li Z, Zeki R, Hilder L, et al. Australia’s mothers and babies 2010. Canberra: Australian Institute of Health and Welfare; 2012.

3) National Aboriginal Health Strategy Working Party. A national Aboriginal health strategy. Canberra: Australian Government Publishing Service; 1989. 4) Australian Health Ministers’ Advisory Council 2012. Clinical practice guidelines: antenatal care—Module 1. Canberra: Australian Government Department of Health and Ageing; 2012. Online. Available: ; [9 Dec 2014]. 5) Sayers S, Boyle J. Indigenous perinatal and neonatal outcomes: a time for preventive strategies. J Paediatr Child Health 2010;46(9): 475–8. 6) Australian Bureau of Statistics. National Aboriginal and Torres Strait Islander Health Survey 2004– 2005. ABS Cat no. 4715. Canberra: ABS; 2006. 7) Vos T, Barker B, Stanley L, et al. The burden of disease and injury in Aboriginal and Torres Strait Islander peoples: Summary report. Brisbane: School of Population Health, University of Queensland; 2007. 8) Healthy Mothers Healthy Families research group, Murdoch Children’s Research Institute, Aboriginal Health Council of South Australia. Aboriginal families study policy brief #1 May 2013. Online. Available: ; [31 May 2013]. 9) Davis B, McLean A, Sinha AK, et al. A threefold increase in gestational diabetes over two years: review of screening practices and pregnancy outcomes in Indigenous women of Cape York, Australia. Aust N Z J Obstet Gynaecol 2013;53(4): 363–8. 10) Raymond M, MacGuire G. RHD: women and pregnancy. O&G Magazine 2011;13(3):47–50.

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Section 3 GYNAECOLOGY Section 3.1

Gynaecological assessment

Section 3.2

Menstrual disorders

Section 3.3

Reproductive endocrinology and infertility

Section 3.4

The menopause

Section 3.5

Sexuality

Section 3.6

Contraception, sterilisation and abortion

Section 3.7

Urogynaecology

Section 3.8

Pelvic pain and endometriosis

Section 3.9

The breast

Section 3.10

Neoplasia and other lumps

Section 3.1 GYNAECOLOGICAL ASSESSMENT Chapter 44

Gynaecological history and examination

Chapter 45

Gynaecological investigations

Chapter 44  GYNAECOLOGICAL HISTORY AND EXAMINATION Emma Readman and Kate McIlwaine

KEY POINTS The gynaecological interview is a specialised medical interview. The doctor can often touch on some very sensitive issues in the course of routine questioning and this means that it needs to be conducted in a compassionate and open manner. It may be an entrée into relationship issues, sexual abuse issues or adverse pregnancy outcomes. The doctor must ensure that he/she is open to other agendas and be alert to cultural sensitivities and issues surrounding gender and sexuality. The gynaecological examination must also be approached sensitively. If a parent presents with a child, or young adult, it is very important to make a time when the child can be examined without the parent present, or assess whether the parent should be present for the examination. If a patient is not sexually active, she should not be examined vaginally. Examination includes assessment of the entire body, with particular assessment of the abdomen and the pelvis abdominally followed by the vulva, vagina, cervix, uterus and adnexa vaginally. A swab or Pap smear may be taken at that time.

THE GYNAECOLOGICAL HISTORY When you first meet the patient, you need to introduce yourself to her and establish what she can call you. You then need to ask what the patient would like to be called. If there are other people present with the patient, then it is important to introduce yourself to these people also and establish their relationship to the attending patient (e.g. mother and daughter, relatives, friends). Special needs should be catered for, such as the requirement for an interpreter. It is important not to rely on family members as interpreters because sensitive issues may not be entirely grasped or passed on. Some patients may have a generally good grasp of English, but not be able to follow a discussion when there are medical terms used or medical concepts to discuss.

If a young person attends with their relatives, it is important to establish from the outset that a time will be allocated at the end of the interview for the patient to be seen without the relative. A good sentence to use is: ‘I usually talk to both of you together and then I would have a small time apart at the end to speak to your daughter. This will happen every time you present.’ Initially, a general history is taken.

PAST HISTORY Relevant past history can be surgical, medical, gynaecological and psychological.

Surgical history In particular, this should include history of abdominal or pelvic procedures. If there have been procedures, note whether there were complications from the procedures

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

and the position of the incisions. This is important if further surgery is to be planned.

Medical history Medical conditions that are relevant are histories of clot-based phenomena (e.g. deep vein thrombosis [DVT], pulmonary embolism [PE], cerebrovascular accident), bleeding problems (particularly of easy bruising or bleeding), cancers, contraindications to use of contraception/ hormone replacement therapy (HRT) and general medical conditions.

Obstetric history A history of any pregnancies, including the outcomes and any complications, should be taken. Particular attention should be paid to delivery mode and any negative outcomes from it.

Gynaecological history Previous gynaecological operations and/or conditions should be sought, particularly whether there have been any abnormalities of Pap smears and any previous procedures. Past contraceptive use, in particular the use of intrauterine devices (IUDs), may also be relevant.

Psychological history General psychological conditions should be explored, especially if there were any pregnancy-based or hormonal exacerbations of the condition.

MEDICATIONS It is important to note what medications the patient is on and whether they have any allergies. If they do have any allergies, the nature of the reaction needs to be documented, particularly angioedema or anaphylaxis. Homeopathic and herbal drugs should be recorded because some homeopathic medications can interfere with bleeding and/or pain, or be contraindicated in pregnancy/attempting pregnancy.

FAMILY HISTORY Significant family history includes gynaecological or nongynaecological cancers and the relationship of the cancer patient to the patient. Importantly, it should be established whether the relative with the cancer is still living to assess the possibility of genetic cancer screening. Other issues are diabetes, particularly if the patient has poly­ cystic ovarian syndrome, endometriosis, clots and cardio­ vascular disease. A history of early menopause and/or osteoporosis is extremely relevant. For women born before 1971, there may be a history of in utero exposure to diethylstilboestrol (DES).

SOCIAL HISTORY Social history is very important. It should be ascertained whether the patient lives alone or with someone 354

and the relationship of those at home to her. It is important to find out whether she is employed, studying or unemployed and whether there is a partner. When asking about a partner, it is important to be non-gender specific (e.g. ‘Do you have a partner?’). The patient will often volunteer if there is a same-sex partner and if not, it will usually become clear through the course of the consultation. The patient should be allowed to feel comfortable before they disclose that information to the doctor. The doctor should ascertain whether there are any issues between her and her partner and give her space to come back to that if she feels more comfortable later on. As part of a social history, it is important to ascertain whether the patient smokes, drinks alcohol, uses any other non-prescription drugs or medications and particularly injectable drugs or drugs of dependence, which may lead on to a discussion of ‘at-risk’ behaviours.

PRESENTING COMPLAINT The point at which the presenting complaint is discussed may vary from patient to patient, and doctor to doctor. It may be asked before all the other parts of the interview, or at the end. Sometimes it is addressed at different times throughout the history depending on the personality and style of the patient.

Menstrual history It is important to ask the patient when her last normal menstrual period was very early on in the interview or it may be forgotten about in the course of the consult. If her last period was more than 4 weeks ago, then a pregnancy test may need to be arranged. The onset of menarche and development of secondary sexual characteristics should be noted, especially if the patient is young. Period regularity should be assessed. A normal period cycle is between 23 and 35 days and it should be emphasised that it is taken from the first day of the menstrual bleeding to the next first day of menstrual bleeding. Often patients think that a cycle is measured from the end of the period to the beginning of the next period. The heaviness of the period should be established, and this is best approximated by asking how many pads or tampons are changed during the heaviest day, how long it is heavy for and whether there is any evidence of clots or flooding. Menorrhagia is generally regarded as changing pads or tampons more often than every 3 hours with clots and or flooding, or lasting longer than 10 days. If periods have been heavy, then the doctor should assess whether the patient is anaemic by asking for any recent haemoglobin results, iron studies and/or dizziness and extreme fatigue. Enquiry should be made into the presence of intermenstrual bleeding and/or postcoital bleeding and, if it occurs, whether there is a particular time of the cycle that

Chapter 44  Gynaecological History and Examination

it tends to occur. If the patient is postmenopausal, has there been any bleeding more than a year after her last period, which qualifies it as postmenopausal bleeding?

Pelvic pain Dysmenorrhoea should be elicited, and the relationship between it and the period. If the patient does have dysmenorrhoea, has it been present since menarche or is this a new occurrence? Is it getting worse? Does she need to take any medications for the pain and does she need to alter her activities because of the pain, especially taking time off work or school? In addition to dysmenorrhoea, the patient should be asked if she has any dyschezia (pain with bowel movements, especially during the period) or dysuria. Pain with intercourse (dyspareunia) should be discussed, and if present, it should be established whether the patient has pain all the time or only in certain positions, and whether the pain is on deep or superficial penetration.

Bowel and bladder function An assessment should be made regarding bowel and bladder function, especially enquiring as to the presence of constipation, diarrhoea, blood or mucous and/or symptoms of bladder problems including dysuria, frequency, nocturia, urgency, haematuria and incontinence. If there is incontinence, it should be elicited whether it is stress or urge incontinence, or insensible incontinence. Is there any difficulty initiating urination and/or problems with the flow?

Vaginal discharge and pruritus Discharge throughout the cycle should be assessed. Most people will produce physiological discharge which will change throughout the cycle. Typically, it will be thin discharge in the first part of the cycle, become stringy and long around mid-cycle and then become short and clumpy post-ovulation. This is normal. Hormonal contraception may change the discharge. Discharge that is green, offensive smelling or white and flocculent can indicate pathology. Information about itchiness of the vulva should be elicited, including whether or not it is accompanied by vulval and/or vaginal pain.

Contraception and fertility Contraception is an important part of the gynaecological discussion. If there is no contraception, ask also about plans for future pregnancy. It is important to note when the last Pap smear was and whether there have been any abnormalities with past smears.

Other system review If any issues are elicited in the general questioning, then some accessory questions may need to be asked. If a patient has amenorrhoea/oligomenorrhoea, assessment should be made as to the cause. This would include:

• • • • •

symptoms of hyperprolactinaemia (e.g. galactorrhoea and headaches) alteration in bowel habits and alteration in tolerance to heat, indicating thyroid disease symptoms of menopause (e.g. hot flushes and breast tenderness) symptoms of polycystic ovarian syndrome (e.g. hirsutism, acne) a BMI assessment and a history of sport/exercise. If menopausal symptoms are present, then risk factors for menopause need to be assessed such as cardiovascular disease risk factors, bone density risk factors and clotbased risk factors to assess for the suitability of HRT. From this history and examination, a problem list can be generated to ensure that each issue is addressed separately.

THE GYNAECOLOGICAL EXAMINATION It is important to obtain consent for the gynaecological exam. The whole body should not be exposed at any one time. The body can be exposed sequentially while the patient is covered by a sheet. The other important factor is the requirement for good lighting so usually there would need to be a ceiling light and/or a light that can be directed at the pelvis (Fig 44.1). Not every gynaecological patient will be examined vaginally and in general, no patient who has not been sexually active should be examined vaginally. It is important to take note of the patient’s general appearance, particularly their weight, height, blood pressure and pulse. Then a breast examination will be undertaken with consent, followed by examination for the thyroid; if there is any suggestion of a prolactinoma, then a neurological exam for visual fields should be undertaken. A general inspection of the abdomen should be undertaken, assessing for scars and hair distribution, and palpating for masses and tenderness. Guarding and rigidity would need to be assessed further. A pelvic examination is then undertaken. The patient is asked to lie on her back with her knees bent and her feet together. The legs are then gently abducted. The external genitalia are inspected, particularly for hair growth pattern, evidence of oestrogen deficiency, any masses or change in skin colour or ulceration. A bimanual exam should then be performed with one hand on the lower abdomen and the other hand palpating the organs through the vagina. The doctor is particularly palpating for the size and position of the uterus, the mobility of the uterus, the size and mobility of the adnexa and the presence of any fibroids or cysts (Fig 44.2). Tenderness should be noted, particularly on palpating the adnexa and the cervix. The presence of any nodules should be assessed in the pouch of Douglas to indicate the presence of severe endometriosis. 355

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

Sacral promontary

Ureter Sacrouterine ligament

Fallopian tube Ovarian ligament

Pouch of Douglas

Fundus of uterus Body of uterus Bladder

Cervix

Vagina

Fornix of vagina

Symphisis pubis Urethra

Levator ani muscle

Clitoris

External anal sphincter

A

Labium minus

Anus

Labium majus

Mons pubis

Clitoris Frenulum of clitoris Labium majus Labium minus Vestibule Fourchette

Pubic hair Prepuce External urethral orifice (meatus) Vaginal orifice Hymen Posterior commisure Anus

Perineum

B FIGURE 44.1 

Gynaecological anatomy and examination.

Source: Douglas G, Nicol F, Robertson C. Macleod’s Clinical Examination. 13th edn. Edinburgh: Churchill Livingstone, 2013. Elsevier 2013, with permission.

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Chapter 44  Gynaecological History and Examination

A speculum can be introduced and a Pap smear taken and/or any swabs that may be required. (Fig 44.3) This would include high vaginal swabs and all cervical swabs. If required at the gynaecological examination, a pipelle sample can be taken and this will be discussed further in Ch 45. An ultrasound may also be done.

SCREENING DURING THE GYNAECOLOGICAL ASSESSMENT

FIGURE 44.2 

An important thing to consider in the gynaecological interview is the opportunity for screening. Screening and education opportunities can be divided into two distinct age group categories: premenopausal and postmenopausal (Table 44.1).

Bimanual examination.

Source: Lentz GM, Lobo RA, Gershenson DM, Katz, VL. Comprehensive Gynecology. 6th edn. St Louis: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 7.12.

TABLE 44.1  SCREENING AND EDUCATION OPPORTUNITIES DURING A GYNAECOLOGICAL ASSESSMENT. Premenopausal

Postmenopausal

Cervical (Pap) smear

Cervical (Pap) smear

Sexually transmitted infection (STI) advice and screen if risk indicated by history

Mammogram

Contraceptive advice

Bone density, calcium, vitamin D, exercise advice

Prepregnancy screen and advice

CONCLUSION

FIGURE 44.3 

Speculum examination.

Source: Swartz MH. Textbook of Physical Diagnosis. 7th edn. Philadelphia: Saunders, 2014. Copyright © 2014 Saunders, An Imprint of Elsevier. Figure 16.20.

In conclusion, it is important that every patient who is seen for a gynaecological consult feels safe, comfortable and heard. It is incumbent on us to provide such an environment. The patient is much more likely to disclose all the important information and leave feeling well treated. FURTHER READING Goh J, Flynn M. Examination obstetrics and gynaecology history and examination. Sydney: MacLennan and Petty; 1996. p. 3–4.

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Chapter 45  GYNAECOLOGICAL INVESTIGATIONS Kate McIlwaine and Emma Readman

KEY POINTS As in any medical specialty, the investigations requested in the gynaecological setting should always be guided by the history and examination findings and the impact on the proposed management of the patient. Non-invasive gynaecological investigations are divided into blood tests, microbiological, cytological, histological and imaging modalities. Invasive gynaecological investigations comprise hysteroscopy and laparoscopy with attendant biopsy.

BLOOD TESTS The most logical way to consider blood tests in gynaecological investigation is to apply the test to the presenting problem. Accordingly, Table 45.1 lists the appropriate serological investigations for common presentations in gynaecology. The investigations requested are not exhaustive and will of course need to be tailored to the relevant history and examination findings.

OVARIAN CANCER SCREENING A screening test should have a high sensitivity and specificity as well as high positive and negative predictive values. There is no screening test currently available for ovarian cancer which meets these criteria. Ca125 may be elevated in cases of endometriosis, uterine leiomyoma, pelvic inflammatory disease (PID) and cirrhosis as well as in ovarian malignancy. Human epididymis protein 4 (HE4) when combined with Ca125 may help discriminate between malignancy and benign gynaecologic disease. Mortality data from the PLCO trial in the US1 showed no change in the stage of cancer detected by screening and no decrease in cancer-specific or overall mortality for women who underwent annual screening with Ca125 and transvaginal ultrasound. The trial also reported that

15% of women who underwent surgery for false-positive findings experienced a serious complication.

MICROBIOLOGY Not infrequently, an asymptomatic woman may present requesting an STI screen or check-up. As a baseline, an endocervical swab or first-catch urine sample should be taken for Chlamydia polymerase chain reaction (PCR) testing and, with appropriate counselling, serology for hepatitis B, syphilis and HIV. It is important to note that up to 80% of chlamydial infection in women is asymptomatic2 and can lead to ectopic pregnancy, infertility and chronic pelvic pain3. Genital Chlamydia is the most common notifiable STI in Australia, with 435 new cases per 100 000 population reported in 2011. This rate has more than tripled over the past decade, increasing from 130 notifications per 100 000 in 2001.4 Although there is currently no national screening program, annual Chlamydia screening is recommended for sexually active women under 25 years of age.5 Women at higher risk for STIs, including returned travellers, intravenous (IV) drug users and sex workers, should have the investigations performed as above with the addition of a vaginal swab cultured for trichomonas, an endocervical swab for gonococcal PCR and serology

Chapter 45  Gynaecological Investigations

TABLE 45.1  INVESTIGATIONS REQUIRED FOR COMMON GYNAECOLOGICAL PRESENTATIONS. Presentation

Investigations

Menorrhagia

Full blood examination Iron studies Thyroid-stimulating hormone (TSH) ± Coagulation studies (if occurring soon after menarche)

Amenorrhoea/oligomenorrhoea/ polymenorrhoea

Follicle-stimulating hormone (FSH) Luteinising hormone (LH) Prolactin Thyroid-stimulating hormone (TSH) Androgens (DHEA, androstenedione, calculated free testosterone, sex hormonebinding globulin (SHBG), testosterone) β-hCG +/− karyotype (amenorrhoea)

Hirsuitism/alopecia

Androgens 17OH progesterone +/− ACTH stimulation test (for CAH), TSH, Zinc, Fe studies

Polycystic ovarian syndrome

OGTT and fasting lipids in addition to amenorrhoea bloods +/− hirsuitism bloods

Subfertility

Semen analysis FSH & LH day 2 Mid-luteal progesterone Rubella and varicella serology

Recurrent miscarriages

Thrombophilia screen (antiphospholipid antibodies and hereditary thrombophilias) Thyroid-stimulating hormone (TSH) Karyotype woman and partner Rubella serology

Ovarian tumour markers

Ca 125 Alpha fetoprotein β-hCG Lactate dehydrogenase (LDH) Inhibin Carcinoembryonic antigen (CEA): bowel Ca 19-9 (pancreatic carcinoma) HE4 (human epididymis protein 4): marker of invasion for sex cord stromal tumours

Sexually transmitted infection screen

Hepatitis B serology Hepatitis C serology HIV serology Syphilis serology

for hepatitis C if there is a history of IV drug use. If there has been a recent exposure, the serology should be repeated at 3 months. Infectious vaginitis is one of the most common presentations in women seeking gynaecological care and includes three types of vaginal infections—bacterial vaginosis, candidiasis and trichomonas—with prevalence rates of 22 to 50%, 17 to 39%, and 4 to 35% respectively.6 Candidiasis and trichomoniasis are almost always associated with vulvar itching whereas bacterial vaginosis usually presents with malodour and no itch. A careful history (including

sexual history) and examination should be performed and swabs and skin scrapings taken as follows: vulval swabs for microscopy, culture and sensitivities and herpes simplex virus PCR of vesicular fluid if indicated a swab from the vaginal wall smeared onto a labelled glass slide for microscopy a vaginal swab of the discharge for culture a cervical swab for culture and Chlamydia PCR if cervicitis is suspected

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a vulval skin scraping for microscopy and culture if tinea is suspected. Identification of gram-negative diplococci in a cervical smear supports a provisional diagnosis of gonorrhoea which is confirmed by culture of Neisseria gonorrhoea (Fig 45.1). Gonococcal PCR is prone to false-positive results and must be confirmed by culture which also establishes an isolate for antimicrobial testing. Gonorrhoea is a marker of unsafe sex and patients testing positive for gonorrhoea may be co-infected with other STIs. Clue cells on microscopy indicate bacterial vaginosis (Fig 45.2). Pseudohyphae on microscopy (Fig 45.3) equate with actively dividing and therefore pathogenic yeasts and are highly indicative of candidiasis. Positive cultures for yeasts and Gardnerella vaginalis, without the accompanying microscopic features as above, usually indicate the presence of these organisms as normal flora.

the central bristles of the cervix sampler should be gently inserted into the endocervical canal and rotated completely three to five times in a clockwise direction. Additionally, an endocervical brush should be used in peri- and postmenopausal women where the transformation zone of the cervix is in the endocervical canal. If using both brush and cervical sampler, the ectocervical sample is first taken by rotating the tip of the spatula once or twice clockwise in the ectocervix and then taking the endocervical sample with the brush by rotating this

SCREENING FOR CERVICAL INTRA-EPITHELIAL NEOPLASIA One of the most successful public health measures in this country has been the implementation of the National Cervical Screening Program (NCSP). The current recommendations are discussed in Chapter 61.

OBTAINING THE CERVICAL SAMPLE The key to cervical sampling is to have the necessary equipment prepared before commencing the procedure (Fig 45.4). To obtain an adequate cervical smear,

FIGURE 45.2

Clue cells in bacterial vaginosis.

Source: Goering R, Dockrell H, Zuckerman M., et al. Mims’ Medical Microbiology. 5th edn. Philadelphia: Saunders, 2013. Copyright © 2013 Saunders, An Imprint of Elsevier. Figure 21.14.

FIGURE 45.1

Gonorrhoea. Gram-stained smear of urethral exudate showing intracellular gram-negative diplococci that are characteristic of gonorrhoea.

Source: Bennet JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th edn. Philadelphia: Saunders, 2015:2458. Copyright © 2015 Saunders, An Imprint of Elsevier. Figure 214.14.

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FIGURE 45.3

Candida. Pseudohyphae and yeast forms, some of them budding from pseudohyphae, are seen.

Source: Cibas ES, Ducatman BS. Cytology: Diagnostic Principles and Clinical Correlates. 4th edn. Philadelphia: Saunders, 2014. Copyright © 2014 Saunders, An Imprint of Elsevier. Figure 1.22.

Chapter 45  Gynaecological Investigations

National Immunisation Program the HPV vaccine is administered to 12- to 13-year-old schoolchildren. The current vaccine protects against infection due to HPV types 6, 11, 16 and 18, which cause around 70% of cervical cancers. At the time of publication, there is robust data for good immunity at 8.5 years post-vaccination and trials are continuing to assess long-term duration of immunity. Patients immunised against HPV are still required to participate in the National Cervical Screening Program as there are carcinogenic HPV subtypes not covered by the vaccine.

HPV TESTING FIGURE 45.4

Papanicolaou sampling devices. Left to right: Cervex-Brush, Cytobrush, wooden spatula, plastic spatula. Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 151.5.

gently one-quarter of a turn within the canal. The speculum is generally lubricated with warm water. If lubricant must be used, it should be applied sparingly on the outer portion of the speculum so as not to contaminate the sample.

PAPANICOLAOU (PAP) SMEAR To prepare the slide for a conventional Pap smear, each side of the cervix sampler should be smeared on the glass. If using an endocervical brush, each side of the cervical sampler should be smeared on the glass on one half of the slide and then the endocervical brush should be rolled out onto the other half of the slide to complete the specimen (Fig 45.5). The slide should be fixed immediately by spraying from a distance of 20 cm to avoid air drying of the specimen, which may compromise the sample.

LIQUID-BASED CYTOLOGY Liquid-based cytology (LBC) increases the detection of high-grade lesions by 27% and reduces the amount of unsatisfactory samples by 42% compared to taking a traditional Pap smear.7 The sample is sent to the laboratory where it is processed and a thin layer of representative cells are examined under the microscope. Liquid-based cytology avoids the issues of blood, mucus and inflammation obscuring the microscopic view as can occur with a conventional Pap smear (Fig 45.6 and 45.7).

HPV VACCINATION The National HPV Vaccination Program commenced in April 2007 and will have a substantial impact on the cervical screening program over the coming years. Under the

High-risk HPV serotypes include: types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82, with types 16 and 18 being implicated in over 70% of cervical cancers.8 Up to 80% of sexually active females will be infected with HPV at some stage in their lives and most will clear the virus within 1 to 2 years. HPV testing has become key in the algorithm for the National Cervical Screening Program.

IMAGING PELVIC ULTRASOUND A pelvic ultrasound is the most frequently ordered imaging modality of the gynaecological pelvis. It is a minimally invasive way of assessing the uterus, tubes, ovaries, cul-desac and kidneys, and can be performed abdominally or vaginally. A complete pelvic ultrasound evaluation may entail both a transabdominal and transvaginal examination. Three-dimensional ultrasonography is finding some use in the evaluation of gynaecologic disease. Endovaginal transducers use high-frequency probes and allow the transducer to be placed closer to the structures being studied. This means that the images produced have a better resolution, but the transducer does not provide a full view of the pelvis. It is also more invasive, and thus not suitable for all patients, especially those who have not been sexually active. The transabdominal approach uses a lower-frequency probe and is more suitable for the abdominal organs, such as the kidneys, and the pregnant uterus. This approach results in a broader view of the pelvis, albeit with images that suffer from attenuation and lower spatial resolution. The images may be obtained through either a full or empty bladder. A full bladder provides an acoustic window and optimal view (because sound travels better through water), displaces loops of bowel and aligns the uterus with its long axis parallel to the abdominal wall. The transabdominal approach places the probe further from the pelvic organs.9 The ultrasound can be performed by an ultrasonographer, a radiologist or an obstetrician gynaecologist with a special interest in imaging (ultrasonologist). Ultrasound is also increasingly used at the bedside by medical practitioners and other health professionals as an extension 361

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A

B

C

D

E

F

FIGURE 45.5

Technique for obtaining a smear for the Papanicolaou test. A Endocervical sample with Cytobrush; rotate 90° to 180°. B Ectocervical sample obtained with a wooden or plastic spatula. C A single-slide technique is preferred. First, the spatula sample is spread, which is then followed by ‘unrolling’ of the brush sample directly over the first sample. D Immediate fixation of the slide with cytologic fixative. E Alternatively, a single sampling device may be used (Papette, Cervex-Brush or ‘broom’) to obtain both ectocervical and endocervical samples at the same time. Rotate 360° five times. F Spreading the sample from broom device onto slide. Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care, 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 151.3.

of the physical examination. The accuracy of the assessment will depend on both the experience and training of the operator, and the resolution of the machine. The ultrasound is part of the first-line investigation of abnormal vaginal bleeding (including heavy menstrual bleeding and intermenstrual bleeding), pelvic pain or pelvic mass. It is also the investigation of choice to investigate early-pregnancy bleeding or pregnancy of unknown origin. It is useful in the assessment of complicated PID (Fig 45.8). A comprehensive pelvic ultrasound report should comment on the orientation of the uterus, the thickness of the endometrial lining, the myometrium, the presence of adenomyosis or fibroids and the position of these, the mobility and size of the ovaries, and the presence of ovarian cysts and whether they are simple cysts or contain septae or solid components. If there are tubal abnormalities (e.g. hydrosalpinges) the tubes should be commented 362

on. Recently, gynaecological ultrasound specialists have begun commenting on the posterior cul-de-sac and the presence or absence of endometriosis on the bowel, uterosacral ligaments and in the rectovaginal septum, as well as reduced mobility of these structures (Fig 45.9). A pelvic ultrasound is best performed in the first half of the menstrual cycle in order to minimise the endometrial thickness, so structures abutting the lining of the uterus are more clearly seen (e.g. polyps and submucous fibroids). If the endometrial lining is poorly delineated, then a saline infusion sonohysterogram could be requested. The ultrasound specialist introduces a small amount of saline into the endometrial cavity through the cervix, which is particularly useful in assessing for the presence or absence of polyps. An ultrasound may be used therapeutically to localise and guide the drainage of pelvic collections or ovarian cysts, in egg pick-up for in vitro fertilisation (IVF) or to

Chapter 45  Gynaecological Investigations

1.

2.

A

1.

2.

B

1.

2.

C

1.

2.

3.

D FIGURE 45.6

Liquid-based (ThinPrep) methods using plastic spatula (A), endocervical brush (B) or broom-like device (C). D shows the final three steps for each method. A 1. Obtain an adequate sampling from the ectocervix using a plastic spatula. 2. Rinse the spatula as quickly as possible into the PreservCyt Solution vial by swirling the spatula vigorously in the vial 10 times. Discard the spatula. B 1. Obtain an adequate sampling from the endocervix using an endocervical brush device. Insert the brush into the cervix until only the bottom-most fibres are exposed. Slowly rotate a quarter or a half turn in one direction. Do not over-rotate. 2. Rinse the brush as quickly as possible into the PreservCyt Solution by rotating the device in the solution 10 times while pushing against the PreservCyt vial wall. Swirl the brush vigorously to further release material. Discard the brush. C 1. Obtain an adequate sampling from the cervix using a broom-like device. Insert the central bristles of the broom into the endocervical canal deep enough to allow the shorter bristles to fully contact the ectocervix. Push gently, and rotate the broom in a clockwise direction five times. 2. Rinse the broom as quickly as possible into the PreservCyt Solution vial by pushing the broom into the bottom of the vial 10 times, forcing the bristles apart. As a final step, swirl the broom vigorously to further release material. Discard the collection device. Be sure entire transformation zone has been sampled. D 1. Tighten the cap so that the torque line on the cap passes the torque line on the vial. 2. Record the patient’s name and ID number on the vial, and record the patient information and medical history on the cytology requisition form. 3. Place the vial and requisition in a specimen bag for transport to the laboratory. Source: Courtesy of HOLOGIC, Inc. and affiliates.

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A

B

FIGURE 45.7

Comparison between the conventional Pap smear (A) and the ThinPrep Pap test (B).

Source: Bieber EJ, Sanfilippo JS, Horowitz IR, eds. Clinical Gynaecology. Philadelphia: Churchill Livingstone, 2006 Copyright © 2006 Churchill Livingstone, An Imprint of Elsevier. Figure 44.6, p. 654.

FIGURE 45.8

Trilaminar appearance of endometrial echo.

Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 30.12.

guide the injection of methotrexate in a pregnancy outside the uterine cavity or in a caesarean scar pregnancy. It may also be used transabdominally to guide a hysteroscopy if there is a difficult procedure.

PELVIC MRI Magnetic resonance imaging (MRI) of the pelvis is a useful imaging modality in selected cases in gynaecology. The images produced by MRI have excellent soft tissue resolution and specificity. They are not degraded by bony artefact, and they can be generated in multiple planes. The applications of MRI in gynaecology include diagnosing adenomyosis, leiomyomas (Fig 45.10), Müllerian duct anomalies (Fig 45.11), gestational trophoblastic disease, diagnosis and staging of endometrial and cervical carcinoma (Fig 45.12), evaluation of adnexal masses and 364

FIGURE 45.9

Polycystic ovary. Typically, there are more than 10 peripherally located small follicles (2 to 8 mm in diameter) and increased central dense stroma. Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 30.15.

assessing rectal, ureteric and bladder involvement in deep infiltrative endometriosis.10 Pelvic MRI is highly accurate in the diagnosis of recto­sigmoid, colon, vaginal, and bladder endometriosis and has excellent inter-observer agreement.11 Pelvic MRI is particularly useful in the diagnosis of ovarian endometriomas, having a sensitivity and specificity of greater than 90%.12 MRI also has the ability to detect nodular endometriosis and involvement of the rectovaginal septum.13,14 Several studies have shown that sensitivities and specificities of MRI for intestinal endometriosis were 76.5 to 88.3% and 76 to 80%, respectively. MRI is somewhat limited in its ability to detect small endometrial implants of < 3 mm and adhesions; however, fat

Chapter 45  Gynaecological Investigations

A

FIGURE 45.10

Leiomyoma, MRI. T2-weighted sagittal MRI.

Source: Adam A, Dixon AK, Grainger RG, Allison DJ. Grainger and Allison’s Diagnostic Radiology. 5th edn. Philadelphia: Churchill Livingstone, 2007. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 54.12.

B

∗

FIGURE 45.11

Bicornuate uterus, MRI. T2-weighted MRI demonstrating two endometrial canals. Source: Adam A, Dixon AK, Gillard J, et al. Grainger and Allison’s Diagnostic Radiology. 6th edn. Philadelphia: Churchill Livingstone, 2014. Copyright © 2014 Churchill Livingstone, An Imprint of Elsevier. Figure 42.10.

saturation sequences have been shown to increase the detection of such lesions.15 Pelvic MRI offers an optimal preoperative mapping of deep endometriosis as part of a multidisciplinary approach to the management of this disease.16 Pelvic MRI is also used to aid therapeutic treatments in gynaecology such as MRI-guided focused ultrasound, where ultrasound waves are used to treat uterine fibroids in select patients. The usefulness of pelvic MRI is still somewhat limited both by expense and access to MRI scanners.

C FIGURE 45.12

Endometrial carcinoma, MRI.

Source: Adam A, Dixon AK, Gillard J, et al. Grainger and Allison’s Diagnostic Radiology. 6th edn. Philadelphia: Churchill Livingstone, 2014. Copyright © 2014 Churchill Livingstone, An Imprint of Elsevier. Figure 41.3A to C.

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ENDOMETRIAL SAMPLING The main indications for endometrial sampling are to exclude endometrial neoplasia in women presenting with abnormal uterine bleeding and surveillance for women at high risk of endometrial hyperplasia or malignancy. Endometrial sampling is contraindicated in known or suspected pregnancy. Acute cervical or uterine infections are relative contraindications. The sampling procedure is straightforward and may be easily undertaken in the outpatient setting. Endometrial sampling is usually performed in conjunction with hysteroscopy to visually evaluate the endometrium; however, this may not be necessary in the context of a normal pelvic ultrasound result where the clinical suspicion of endometrial neoplasia is low. Numerous studies have demonstrated that the endometrium is adequately evaluated with office sampling techniques. A sample can be obtained in 90% or more of patients.17 The procedure for obtaining an endometrial sample involves visualising the cervix with a speculum and passing an endometrial sampling device such as a Pipelle or Rocket endometrial sampler through the internal os into the uterine cavity. In many cases, the endometrial sampling device can be inserted without grasping the cervix with a tenaculum. If a tenaculum is used, local anaesthetic spray should be applied to the anterior cervical lip to reduce patient discomfort. The device is activated by withdrawing the plunger to create a suction effect and slowly retracted against the uterine wall to obtain a strip of endometrium, which is placed in formalin and sent for histopathology. In the inpatient setting, a global endometrial sample is usually obtained by dilating the cervix and passing a sharp curette into the uterine cavity to obtain the specimen.

HYSTEROSCOPY Abnormal uterine bleeding accounts for as many as onethird of all presentations to gynaecologists and requires further evaluation to establish a diagnosis in the most efficient and least invasive manner possible.18,19 Hysteroscopy has long been considered the gold standard for diagnosing the cause of abnormal uterine bleeding and misses less than 0.5% of serious pathology such as endometrial cancer.20 Indications for hysteroscopy are as follows: abnormal uterine bleeding endometrial thickening or polyps submucosal fibroids intrauterine adhesions Müllerian anomalies (e.g. uterine septum) retained intrauterine contraceptives or other foreign bodies retained products of conception

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desire for sterilisation endocervical lesions. Contraindications to hysteroscopy are: viable intrauterine pregnancy active pelvic infection known cervical or uterine cancer (relative). Hysteroscopy under general anaesthesia is advantageous where an operative procedure (e.g. removal of endometrial polyps, resection of uterine adhesions or septae, resection of submucosal fibroids, endometrial ablation) is required or there is a clinical suspicion of significant endometrial pathology (e.g. malignancy). In patients with significant medical comorbidities requiring the procedure be performed in the operating theatre, the procedure may be more safely performed under regional anaesthesia.

INSTRUMENTATION There are many different types and sizes of hysteroscopes. The outer diameter of a hysteroscope refers to the diameter of the sheath, a metal tube which houses the telescope and instruments. Sheath outer diameters range from 3.1 to 10 mm. Smaller diameter hysteroscopes are more suited to diagnostic procedures, especially in the ambulatory setting, whereas larger-diameter scopes lend themselves to operative procedures performed under general anaesthesia. The rigid hysteroscope includes an outer sheath surrounding channels for the telescope, distending fluid inflow and outflow, and in some cases operative instruments. Operative sheaths usually have dual ports that provide continuous laminar flow of distending media, which enables improved visualisation of the cavity where there is blood or debris obstructing the view. In addition, some operative sheaths facilitate the aspiration of pieces of tissue from the uterine cavity. The telescope consists of three parts: the eyepiece, barrel and lens. The image depends on characteristics of these components. Hysteroscopes are monocular, and thus provide little depth perception. Viewing angles range from zero to 70° with the 30° angle being most commonly used. The image is usually viewed via a videomonitoring system which also allows still photographs and video recordings for documentation. Most hysteroscopes are rigid, but narrow-diameter scopes may also be semi-rigid or flexible. Rigid hysteroscopes offer better optics and are less expensive than flexible scopes but may cause more intraoperative pain. Flexible hysteroscopy lends itself to procedures in women with irregularly shaped uterine cavities, as the distal tip can be deflected upwards or downwards (e.g. for tubal cannulation or lysis of adhesions near the tubal ostia). Illumination for hysteroscopy is provided by a light source connected to the hysteroscope by a fibreoptic cable or ‘light lead’. Most light sources are either halogen or xenon. Fiberoptics allow transmission of bright light without significant heat transfer.

Chapter 45  Gynaecological Investigations

There are generally three types of operative hysteroscopes: operative sheaths with instruments inserted through channels; electrocautery resectoscopes; and the hysteroscopic morcellator. The electrocautery resectoscope may use monopolar or bipolar current. When a monopolar resectoscope is used, the patient must be grounded and a non-conducting distending medium (e.g. glycine) used. Bipolar resectoscopes can be used with electrolyte distending media (e.g. normal saline).

TECHNIQUE The patient must be appropriately evaluated and have consented for the procedure prior to attending for hystero­ scopy. The potential risks of bleeding, infection, uterine perforation and laparoscopy if there is any concern regarding visceral damage in the event of a perforation should be discussed with the patient and clearly documented. For premenopausal women with regular cycles, the proliferative phase is ideal for visualisation of the uterine cavity. Consideration should be given to pre-treating patients attending for a first-generation endometrial ablation or operative hysteroscopy with a 2-month course of danazol or a GnRH agonist to thin the endometrium. Patients attending for a first-generation endometrial ablation should be pre-treated with a 2-month course of danazol or a GnRH-agonist to thin the endometrium. In operative hysteroscopy or in patients with cervical stenosis, it is also advantageous to prepare the cervix with 400 mcg of misoprostol per vaginum several hours ahead of the procedure. The initial steps for hysteroscopic procedures are the same as for all other transcervical procedures (patient in dorsal lithotomy position, preparation of the vagina and cervix with povidone iodine, placement of speculum, use of tenaculum or mechanical dilation as required). The vaginoscopic approach to hysteroscopy may be used as an alternative to the traditional technique (see ambulatory hysteroscopy). The cervix should not be dilated beyond the size of the hysteroscope, since this may cause leakage of distending medium. The hysteroscope is gently inserted under endoscopic vision through the cervical os and into the uterine cavity. The speculum is then removed and a systematic inspection is made of the cavity noting the tubal ostia, the appearance of the endometrium and any intrauterine pathology including endometrial thickening, abnormal vascularity, polyps, submucosal fibroids, uterine septa or adhesions (Fig 45.13). Still photographs and/or video can be taken for documentation purposes. At the conclusion of the procedure, the cavity should be sounded and a note made of the uterine size and an endometrial sample should be obtained and sent for histopathology.

AMBULATORY HYSTEROSCOPY Outpatient hysteroscopy with endometrial biopsy is the preferred modality of investigation for abnormal uterine

FIGURE 45.13

Uterine polyp resection.

Source: Goldberg JM, Falcone T, Goldberg JM, Falcone T. Atlas of Endoscopic Techniques in Gynecology. London: Saunders, 2000:187. Copyright © 2000 Saunders, An Imprint of Elsevier.

bleeding and other conditions of the uterine cavity.21 Hysteroscopy under general anaesthesia should be reserved for cases where there is a clinical suspicion of endometrial polyps, fibroids or malignancy, or where the patient is unsuitable for the ambulatory procedure (e.g. advanced age, cardiovascular issues, morbid obesity or cervical stenosis).

Rigid hysteroscope The traditional approach involves the insertion of a bivalve speculum into the vagina and application of 0.1% lignocaine spray to the anterior cervical lip prior to grasping the anterior cervix with a tenaculum. A 3-mm rigid hysteroscope with a 4-mm sheath is then passed through the internal cervical os into the uterine cavity. Saline is the common distension medium for ambulatory hysteroscopy procedures. At the conclusion of the hysteroscopy procedure, an endometrial sample is obtained and sent for histopathology. Variations to the standard procedure include an intracervical, paracervical or intrauterine block as required and the use of cervical dilation, up to Hegar 4, if necessary. Pain is the main limiting factor in patient acceptance and large-scale uptake of outpatient hysteroscopy22,23 with acceptability rates reported in the literature (83 to 99%).18

Vaginoscopic approach Bettocchi et al.24 demonstrated that the vaginoscopic approach to outpatient hysteroscopy reduces patient discomfort associated with the traditional procedure and strongly increases patient compliance. In a series of over 11 000 hysteroscopic procedures. Bettocchi and his colleagues eliminated the need for any type of premedication analgesia or anaesthesia. In this technique, the 367

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vaginal cavity is distended with saline (30 to 40 mmHg) and gentle hand movements are used to correctly direct the hysteroscope into the cervix and through the internal cervical os. The weight of the saline provides sufficient vaginal distension to visualise the portio. The entire cavity is viewed by rotating the hysteroscope on its axis without any lateral movement. The vaginoscopic approach facilitates the procedure in anatomic situations where the speculum may limit the vertical and horizontal movements of the scope (e.g. marked anteflexion or retroflexion of the uterus). At the conclusion of the procedure, an endometrial sample is taken either under direct vision or with an endometrial sampling device. There is significantly less use of anaesthetic with the vaginoscopic approach without a significant difference in pain experienced during the procedure.

LAPAROSCOPY A laparoscopy is an invasive procedure usually performed under general anaesthetic. It can be done under local or regional anaesthetic. It is the gold standard investigation of pelvic pain, endometriosis and infertility, and is a therapeutic procedure where investigation and treatment can take place simultaneously.

INSTRUMENTATION The equipment required for a laparoscopy are a telescope, usually either 5 mm or 10 mm in diameter (viewing angles are usually 0° or 30°), a light lead, a camera and gas tubing for CO2 insufflation. Like hysteroscopy, illumination for laparoscopy is provided by a light source connected to the laparoscope by a fibreoptic cable. Most light sources are either halogen or xenon. These are connected to a stack, which has a light box, a monitor, gas insufflation machine and image capture devise to take photos and videos.

TECHNIQUE Initially, the patient is placed in lithotomy position in the operating theatre with her feet in stirrups, her knees flexed at 45° and her hips abducted and externally rotated. The operating table is flat. Entry is achieved usually via the umbilicus using one of three methods: 1. a modified Hassan open entry; 2. a Veress needle followed by a closed trocar insertion; or 3. a direct entry closed technique. Alternative entry sites are at Palmer’s point (midclavicular line at the level of the first floating rib in the left upper quadrant), as that has been shown to have the least risk of adhesions, or at the pubic symphysis, as the risk of major vascular injury at entry is reduced at this site. There is no clear consensus as to the optimal method of entry into the peritoneal cavity. There are closed-entry techniques and open-entry techniques. The closed-entry 368

methods are those where there is no direct vision of the abdomen when inserting the initial trocar. Closed entry is achieved either using a Veress needle to create a pneumoperitoneum followed by the blind insertion of a trocar, or via direct entry of a trocar. The open-entry technique is a modified Hassan approach which uses a scalpel under vision to enter the abdomen then insert a trocar. There is a hybrid closed/open technique of using an optical trocar for direct entry. This involves the insertion of a trocar with the laparoscope inserted into the tip, and a clear window in the tip which allows the surgeon to view the layers of the anterior abdominal wall as the trocar is travelling through. This is reasonably new. To design a study to try and differentiate between the complications of different entry techniques would be almost impossible as large numbers of participants would be needed because the risk of serious complications is so small. The recent Cochrane Database assessment of the different entry techniques has concluded that an openentry technique is associated with a significant reduction in failed entry when compared to a closed-entry technique, with no difference in the incidence of visceral or vascular injury. It also noted that significant benefits were shown with the use of a direct-entry technique when compared to the Veress needle. The use of the Veress needle was associated with an increased incidence of failed entry, extraperitoneal insufflation and omental injury; direct-trocar entry is therefore a safer closed-entry technique. It was very clear that the results should be interpreted with caution, as the numbers were not enough to detect a significant difference.25 Once the initial entry has been achieved, CO2 gas is insufflated into the abdomen and pelvis to reach a pressure of 12 to15 mmHg, enabling vision of the pelvis. The anaesthetist places the patient in steep Trendelenburg (head down) of 12 to 15° to facilitate the displacement of the bowel from the pelvis and the gynaecologist inserts the accessory ports. Steeper Trendelenburg can be used in some procedures. Up to three ports are traditionally placed, two fingers’ breadth above the left and or right anterior superior iliac spine on a line to the umbilicus and superior to the pubic symphysis, above the bladder. Possible port placements sites are marked in Figure 45.14. Once the ports have been placed, the gynaecologist completes a survey of the pelvis. The uterus is usually mobilised by the use of an intrauterine manipulator, and the bladder is visualised by retroverting the uterus. The pouch of Douglas is visualised by anteverting the uterus and an instrument is introduced via an accessory port to manipulate the ovaries and tubes to view the entire span of the ovary and the pelvic side walls. The uterosacral ligaments are assessed, and the pararectal spaces, the posterior vagina and rectum and sigmoid are visually inspected. The appendix is localised and assessed, and the liver and gall bladder inspected. The patency of the tubes can be tested by introducing a cannulation device through the cervix into the uterus and injecting indigo carmine or methylene blue dye into the uterine cavity and back

Chapter 45  Gynaecological Investigations

through the fallopian tubes, until it passes out the tubal ostia bilaterally, confirming tubal patency (Fig 45.15).

CONSENT TO LAPAROSCOPY Consent to laparoscopy is important. There are general surgical risks, specific risks related to the surgery, and risks related to the patient. These risks are short, medium and long term. General risks of surgery are related to the anaesthetic, infection, heavy bleeding and uncommon cardiovascular risk in surgery, including deep vein thrombosis (DVT). Specific risks are damage to the blood vessels, bowel, bladder or ureter. The risk of injury to the blood vessels is 0.9 per 1000 procedures, with mortality from vessel

Superficial vessels

Deep vessels Inferior epigastric

Superficial epigastric Superficial circumflex iliac

injury estimated at around 1 in 17 000 procedures with closed-entry techniques. Bowel injury occurs in around 1.8 per 1000 procedures. This may become obvious at the time of surgery or the patient may not develop symptoms until she is discharged. The patient may require a laparotomy to repair the damage, and can become systemically unwell. In severe cases there have been deaths, largely from initially unrecognised hollow viscus injuries, or catastrophic vessel damage; 50% of these injuries will occur on entry. Gas embolism is a common event at laparoscopy, as CO2 gas is insufflated to maintain vision. A bubble of CO2 can enter a vessel and travel to the heart, the lungs or the brain, and there is approximately a 1 in 60 000 risk of serious adverse outcome, including death. There can be risks of persistent pain in the operated area, an incisional hernia, a nerve injury or scar-healing complications. Specific patients at increased risk are those with obesity as they are more at risk of entry complications and/or difficulty for the surgeon completing the operation, or the very thin, as they are at risk of major vessel injury on entry. Older patients are more likely to have concomitant medical problems which can trigger cardiac complications intraoperatively, and prior abdominal surgery increases the risk of adhesions and injury to organs on entry or during the case.

RECOVERY FIGURE 45.14

Ideal port site placement.

Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 44.2.

Most laparoscopic procedures are performed as day cases, with the patient being discharged the same day. Different institutions will have different rates of overnight stay, depending on their population groups and the structure of the hospital. Most uncomplicated patients will return to work by 5 to 7 days, with more complex procedures (e.g. laparoscopic hysterectomy) requiring 2 to 4 weeks off work.

APPLICATIONS OF LAPAROSCOPY Uterus

Round ligament Pouch of Douglas

Ovary

Fallopian tube

FIGURE 45.15

Laparoscopic view of female pelvis. Source: Courtesy of Lenore Ellett.

If endometriosis is found, it can be either resected or diathermied, and adhesions divided. Fibroids can be removed and the uterus can be removed either as a laparoscopic hysterectomy or as a laparoscopically assisted vaginal hysterectomy. Ovarian cysts or tubal pathology can be removed, and if it is necessary to remove these structures from the pelvis without spill, then a bag can be introduced into the pelvis and the specimen placed in that prior to being removed. PID involving a tubo-ovarian or pelvic abscess can be drained. Tubal patency can be disrupted by a tubal ligation, and can also be microsurgically re-opposed. Müllerian abnormalities can be corrected. Some urinary incontinence and or prolapse can be addressed laparoscopically, and foreign bodies can be removed (e.g. an intrauterine contraceptive device [IUCD] that has become located within the peritoneal cavity after a uterine perforation at IUCD insertion). 369

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REFERENCES 1) Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomised Controlled Trial. JAMA 2011;305(22):2295–303. 2) Peipert JF. Genital chlamydial infections. N Engl J Med 2003;349:2424–30. 3) Stamm WE. Chlamydia trachomatis infections of the adult. In: Holmes KK, Sparling PF, Mardh P-A, et al., editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hill; 1999. p. 407–22. 4) Australian Bureau of Statistics. Australian social trends, June 2012. Cat no. 4102.0. Online. Available: ; [16 September 2012]. 5) Royal Australian College of General Practice. The red book: guidelines for preventive activities in general practice. 6th ed. South Melbourne, Victoria: RACGP; 2005. 6) Ilkit M, Guzel AB. The epidemiology, pathogenesis, and diagnosis of vulvovaginal candidosis: a mycological perspective. Crit Rev Microbiol 2011;37(3):250–61. 7) Davey E, d’Assuncao J, Irwing L, et al. Accuracy of reading liquid based cytology slides using the ThinPrep® Imager compared with conventional cytology: prospective study. BMJ 2007;335(7609): 28. 8) de Sanjose S, Quint WG, Alemany L, et al. Human papilloma virus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010;11:1048. 9) Harrison B, Crystal C. Imaging modalities in obstetrics and gynecology. Emerg Med Clin North Am 2003;21:3. 10) Hricak H. Widespread use of MRI in gynecology: a myth or reality? Abdom Imaging 1997;22:579–88. 11) Bazot M, Gasner A, Lafont C, et al. Deep pelvic endometriosis: limited additional diagnostic value of post contrast in comparison with conventional MR images. Eur J Radiol 2011;80:e331–9. 12) Gao X, Yeh YC, Outley J, et al. Health-related quality of life burden of women with endometriosis: a literature review. Curr Med Res Opin 2006;9:1787–97. 13) Del Frate C, Girometti R, Pittino M, et al. Deep retroperitoneal pelvic endometriosis:

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14)

15) 16)

17)

18) 19) 20)

21)

22)

23)

24) 25)

MR Imaging appearance with laparoscopic correlation. Radiographics 2006;26(6): 1705–18. Roseau G, Dumontier I, Palazzo I, et al. Rectosigmoid endometriosis: endoscopic ultrasound features and clinical implications. Endoscopy 2000;32:525–30. Barlow DH, Glynn CJ. Endometriosis and pelvic pain. Baillieres Clin Obstet Gynaecol 1993;7:775–90. Bazot M, Darai E, Hourani R, et al. Deep pelvic endometriosis: MR imaging for diagnosis and prediction of extension of disease. Radiology 2004;232(2):379–89. Dijkuizen FP, Mol BJ, Brölmann HA, et al. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000;89(8):1765. Readman E, Maher P. Pain relief and outpatient hysteroscopy: a literature review. J Am Assoc Gynecol Laparosc 2004;11:315–19. Hatasaka H. The evaluation of abnormal uterine bleeding. Clin Obstet Gynaecol 2005;48:258–73. Brooks P. In the management of abnormal uterine bleeding, is office hysteroscopy preferable to sonography? The case for hysteroscopy. J Minim Invasive Gynecol 2007;14:12–14. Sagiv R, Sadan O, Boaz M, et al. A new approach to office hysteroscopy compared with traditional hysteroscopy: a randomized controlled trial. Obstet Gynecol 2006;108(2):387–92. Campo R, Molinas CR, Rombauts L, et al. Prospective multicentre randomized controlled trial to evaluate factors influencing the success rate of office diagnostic hysteroscopy. Hum Reprod 2005;20(1):258–63. McIlwaine K, Readman E, Cameron M, et al. Outpatient hysteroscopy: Factors influencing post-procedure acceptability in patients attending a tertiary referral centre. Aust N Z J Obstet Gynaecol 2009;49:650–2. Bettocchi S, Nappi L, Ceci O, et al. Office hysteroscopy. Obstet Gynecol Clin North Am 2004;31:641–54. Ahmad G, O’Flynn H, Duffy JMN, et al. Laparoscopic entry techniques. Cochrane Database Syst Rev 2012;(2).

Section 3.2 MENSTRUAL DISORDERS Chapter 46

Paediatric and adolescent gynaecology

Chapter 47

The menstrual cycle and menstrual disorders

Chapter 46  PAEDIATRIC AND ADOLESCENT GYNAECOLOGY Sonia Grover

KEY POINTS Sensitive communication regarding gynaecological issues is always important. When dealing with paediatric and adolescent gynaecological issues, this may be even more complex. Gender issues of the newborn require high-level communication skills with often very anxious parents; there will often be unspoken concerns regarding long-term outcomes. In young prepubescent girls with reasonable comprehension, communication should be directly with the patient in ‘age-appropriate’ language. Clinical examination should carefully avoid anything that may be traumatic to them. Direct and sensitive communication becomes even more important with the adolescent. Part of the consultation needs to occur without parents and include a clear discussion regarding confidentiality and the opportunity to explore issues relating to sexuality, safe sex, contraception and other adolescent health risk behaviours. Any examination needs to be very carefully considered, and often genital examinations need to be very limited.

FETAL GYNAECOLOGICAL PROBLEMS

for discussion regarding the long-term outcomes of these conditions may be appropriate, as outlined in this chapter.

ANTENATAL OVARIAN CYSTS

GYNAECOLOGICAL PROBLEMS OF THE NEONATE

The majority of antenatal ovarian cysts will resolve spontaneously. Simple follow-up with postnatal ultrasound is usually all that is required to ensure resolution occurs. These physiological ovarian cysts can occasionally precipitate ovarian torsion when the cyst becomes more complex in appearance. Surgical intervention is thus sometimes required. Antenatal diagnosis of congenital anomalies increasingly occurs and this may include conditions that impact on the reproductive tract of the fetus. Antenatal referral

CONGENITAL ANOMALIES Imperforate hymen This can present with a bulging lump at the perineum with the vagina distended by physiological secretions secondary to in utero oestrogens. This volume usually reduces over time, and the imperforate hymen is generally best managed in the peri-menarcheal age.

Chapter 46  Paediatric and Adolescent Gynaecology

Occasionally it can be associated with significant vaginal distension with acute urinary retention; these require drainage.

Genital ambiguity

vaginoscopy under general anaesthetic is required to exclude both of these. Lichen sclerosis can cause vulval itch and skin changes. Management is steroid cream and specialist referral.

This requires input from a specialist team to ensure that appropriate investigations and discussions occur. Gender uncertainty in the neonate is very challenging for all concerned and care with communication to the parents by all staff involved is essential. It is important to give parents psychological support while investigations are undertaken. Important diagnoses such as congenital adrenal hyperplasia, which can be associated with collapse and neonatal death, need to be identified.

ABDOMINAL PAIN

Discordance of gender phenotype and genotype

PUBERTY

With increasing antenatal diagnosis of fetal karyotype, the possibility of a healthy-appearing baby of the opposite gender to that expected can occur. Careful repeat karyotype and investigation involving specialist team is required.

NEONATAL VAGINAL BLEEDING Postnatal vaginal bleeding associated with oestrogen withdrawal can occur on days 3 to 7.

PREPUBERTAL GIRLS

Abdominal pain in girls can represent ovarian torsion, usually in the context of an enlarged ovary. There is often associated nausea. An ultrasound demonstrating an enlarged ovary should provoke serious consideration of this diagnosis with a laparoscopy to diagnose, untwist the ovary and potentially perform the ovarian cystectomy.

The normal progression through puberty consists of pubic hair development, breast bud development and a growth spurt (Fig 46.1). The process is initiated by the hypothalamus becoming less sensitive to negative feedback from endogenous oestrogen and progestogen. Gonadotrophinreleasing hormone (GnRH) signalling from the hypothalamus to the pituitary causes a rise in follicle-stimulating hormone (FSH) and luteinising hormone (LH), which in turn stimulates ovarian oestrogen production. Oestrogen then drives breast and uterine development. Ovulatory cycles with progesterone production often take another 1 to 3 years post-menarche.

LABIAL ADHESIONS

PRECOCIOUS PUBERTY

Labial adhesions or labial agglutination is a common finding and is often detected by maternal and child health nurses. It is usually asymptomatic. Spontaneous resolution occurs; for many during childhood, but for a small number the adhesions may persist until peri-menarcheal. Given their natural history of spontaneous resolution, no intervention is required.

Precocious puberty is defined as the onset of menarche prior to 8 years of age. Investigation of early pubertal changes is influenced by the rate of changes and the clinical findings. If there is evidence of hirsutism and clitorimegaly, consideration should be given to diagnoses related to excess androgen production including nonclassical congenital adrenal hyperplasia (CAH), androgenproducing tumours and disorders of sex development.

VULVOVAGINITIS This condition presents with dysuria, vulval burning, redness and/or vaginal discharge. The possibility of sexual abuse needs to be excluded. In the prepubertal girl, the vulval and vaginal skin is relatively atrophic and thus easily irritated. The normal flora of the vagina is bowel bacteria. Overgrowth of this flora can cause a low-grade discharge, which can irritate the thin skin; this is most apparent on the contact surfaces between the labia majora. Simple measures including bathing, with the possible addition of a small amount of vinegar to alter the vaginal pH, combined with barrier cream applied to the vulva is all that is required. Vulval swab is only required in the setting of a persistent profuse vaginal discharge. Overgrowth with Streptococcus, E. coli or haemophilus may occur and require specific treatment. Vaginal bleeding may be associated with a foreign body or, rarely, with a vaginal tumour. A

DELAYED PUBERTY The average age of menarche in developed countries is 12 years; it usually follows breast development which commenced 2 years earlier. Failure to have any secondary sexual characteristics by the age of 14 years and to achieve menarche by 16 years requires consideration. History and examination should establish any potential underlying problem. For example, the absence of breast development indicates a lack of oestrogen.

Hypothalamic–pituitary causes Delay in the hypothalamic initiation of pubertal changes can occur due to familial patterns (siblings or parents may be similarly affected), low body weight (eating disorder), excess exercise or a general health issue (e.g. inflammatory bowel disease). Hypothyroidism and hyperprolactinaemia also cause hypothalamic-pituitary 373

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1 Prepubertal, elevation of papilla only

2 Breast buds are noted or palpable, enlargement of the areola

3 Further enlargement of the breast and areola with no separation of the contours

4 Projection of the areold and papilla to form a secondary mound above the level of the breast

5 Adult contour breast with projection of papilla only, areola recesses to breast contour

FIGURE 46.1

Pubertal rating according to Tanner stage. Breast development in girls is rated from 1 (prepubertal) to 5 (adult). Stage 2 breast development (appearance of the breast bud) marks the onset of gonadarche. For girls, pubic hair stages are rated from 1 (prepubertal) to 5 (adult). Stage 2 marks the onset of adrenarche. Source: Phelps K, Hassed C. General Practice: The Integrative Approach. Copyright © 2011 Elsevier Australia, pp. 805–13. Figure 56.2.

dysfunction. Idiopathic hypogonadotrophic hypogonadism is a rare explanation. These conditions all exhibit a low FSH and low LH.

Ovarian causes In contrast to hypothalamic-pituitary dysfunction, primary ovarian failure will reveal an elevated FSH and LH. The most common cause for this is Turner’s syndrome. There are often other features for this including a history of recurrent otitis media, coarctation or other cardiac problem. There are also clinical findings of short stature and wide carrying angle. Mosaic Turner’s syndrome may not have these features. Other possibilities include previous chemotherapy for childhood malignancy, premature ovarian insufficiency and other gonadal dysgenesis (e.g. 46 XY gonadal dysgenesis).

DELAYED MENARCHE Progression through puberty may be slow or delayed by many of the same diagnoses as for delayed puberty (see earlier), and thus history and examination may be informative. Obesity may also cause a delay in menarche.

Delayed menarche with normal pubertal development Delayed menarche with a history of cyclic pain suggests an obstructive problem, which may include an imperforate hymen or obstruction due to a transverse vaginal septum or cervical agenesis. Abdominal palpation may reveal a suprapubic mass (a haematocolpos and/or 374

haematometra) in these girls with well-developed secondary sexual characteristics. Menses usually starts within 2 years of breast development, but where there has been a 4-year delay then Müllerian agenesis (uterovaginal agenesis) should be considered. A pelvic ultrasound will demonstrate normal ovaries and follicles but an absent uterus. (Renal ultrasound is also valuable as approximately 25% will have an associated renal anomaly.) Most young women with vaginal agenesis will successfully make a vagina with dilators and/or sexual activity. Surrogacy gives these women the possibility of their own child as their ovarian function is normal. Uterine transplant is a novel option being explored, and may be a possibility in the distant future.

Delayed menarche with atypical pubertal development Absence of secondary sexual hair The absence of pubic or axillary hair suggests a diagnosis of androgen insensitivity syndrome. The diagnosis can be confirmed with a serum testosterone and karyotype. In these young women, testes produced testosterone and Müllerian inhibitory substance in utero, causing regression of the Müllerian structures (i.e. the uterus and tubes) but the lack of testosterone receptors results in the absence of any other virilisation. Testosterone converts to oestrogen in peripheral fat tissue; hence, breast development occurs at puberty. The malignancy risk of these testes is low. There is usually no gender uncertainty in these women. Vaginal length is usually adequate. Sensitivity with communication is essential.

Chapter 46  Paediatric and Adolescent Gynaecology

Androgen excess Where there are minor degrees of hyperandrogenism (some excess hirsutism, acne), polycystic ovary syndrome (PCOS) is the likely cause—particularly where there is obesity or a family history of the metabolic syndrome. If the patient is obese, weight management is the cornerstone of management for this condition. Where there is evidence of significant virilisation (e.g. extensive hirsutism, clitoromegaly, voice change), then the cause is more often an androgen-producing tumour or a disorder of sex development (e.g. partial androgen insensitivity syndrome, mixed gonadal dysgenesis).

POST-MENARCHE MENSTRUAL PROBLEMS Menorrhagia Irregular menses are common and this may persist for 1 to 3 years after puberty. This simply reflects anovulatory cycles and is normal. Intervention is only required if this is causing problems due to either heaviness of loss or prolonged bleeding. Cyclic progestogen therapy is usually effective with either oral medroxyprogesterone acetate 10 mg daily or norethisterone acetate 5 mg daily for 14 to 21 days per month for a few months while waiting for maturation of the hypothalamic–pituitary–ovarian axis. The combined oral contraceptive pill (OCP) can be used if this approach fails. Heavy bleeding requires careful history because the definition of heavy loss varies, with teenagers having little experience with respect to normal menstrual loss. Where there is very heavy loss and a low haemoglobin, admission for resuscitation and transfusion is sometimes required. Tranexamic acid reduces menstrual loss by 50% and can be used for all heavy menses. Higher dose progestogens given 2 hourly can be used acutely. Cyclic progestogens or the combined OCP will reduce heavy menses and can be used in extended cycles. There is no evidence that withdrawal bleeds are required, so prolonged ‘skipping off periods’ is acceptable. For teenagers with heavy menses, an underlying bleeding disorder is present in approximately 10%. There will often be a family history of heavy periods as well as other features of a bleeding diathesis such as gum bleeds, epistaxis and easy bruising. Investigation in the presence of other features should include von Willebrand’s screen and platelet function studies.

Dysmenorrhoea Period pain or dysmenorrhoea is reported to occur in up to 80% teenage girls, with an impact on schooling and participation in physical and social activities. The majority of dysmenorrhoea is related to the physiology of the menstrual cycle, with inflammatory cytokines and prostaglandins causing the frequently associated symptoms of nausea, vomiting, diarrhoea and feeling dizzy or faint. Non-steroidal anti-inflammatory drugs commencing

prior to the onset of the pain are quite effective. Adolescents with heavy menses may also report a different pattern of period pain, likely to reflect retrograde bleeding and irritation of the peritoneum. Reduction in menstrual loss will assist in the reduction of this pain. The combined OCP, including extended-cycle or continuous combined OCP, is required in a substantial number of adolescents to avoid disruption to quality of life. Depot medroxy progesterone acetate and levonorgestrel intrauterine systems (inserted under general anaesthetic in the non-sexually active teenager) are options that are occasionally required. Secondary causes or dysmenorrhoea are uncommon (< 8%) but include obstructive congenital anomalies, ovarian cysts and endometriosis. Endometriosis has been shown to be more common in women who bleed more often and more heavily. Moderately severe endometriosis is found in adolescents with obstructive anomalies; however, after correction the endometriosis will almost always resolve spontaneously. There is also an increased rate of endometriosis in women with mild bleeding disorders. Thus, aiming to minimise bleeding to avoid this is valuable.

Secondary amenorrhoea Pregnancy needs to be excluded. Most causes for primary amenorrhoea can also present as secondary amenorrhoea.

Menstrual management in the presence of an intellectual disability The age of onset of puberty and menarche are normally unchanged in adolescents with intellectual disabilities. In general, the same measures for controlling heavy or painful periods apply for these young women. In some of these young women, seizure control may fluctuate with the menstrual cycle and achieving a stable hormonal environment may assist. The aim of optimising quality of life in these young women applies just as for any patient. If menses are having a negative impact, bleeding can be minimised with the combined OCP (administered continuously) or the levonorgestrel intrauterine system (IUS). Sterilising procedures, including hysterectomy, endometrial ablation and tubal ligation, require approval from appropriate authorities (this varies in different parts of Australia), but these procedures are rarely required.

SEXUAL ACTIVITY Adolescence is a development stage where there is a transition to physical, emotional and cognitive maturity. Part of this involves exploring relationships and sexuality. Discussion regarding sexuality needs to be in the context of a confidential consultation. A helpful approach with the young person is to explore less-threatening issues and move to more personal topics while rapport is established. A discussion of home life, work, study and social activities can be followed by an exploration 375

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of health-risk behaviours including smoking, alcohol intake, depression and unsafe sexual activity. Intervention to reduce and limit these health-risk behaviours can clearly have long-term beneficial effects. There is evidence that young people who are undertaking one health-risk behaviour are likely to be doing others.

PELVIC PAIN Ovarian cysts The vast majority of ovarian cysts in adolescents are physiological cysts. Over 25% of 20-year-old women have 20 follicles on an ovary. This is normal and should not be used as an indication for further investigation, remembering that in teenagers irregular menses and some acne are also normal findings. Pain at the time of ovulation can lead to the identification of a 4 to 5 cm cyst. This is physiological and explanation is all that is required. Complex ovarian cysts may represent a haemorrhagic corpus luteum if < 6 cm and should resolve on subsequent ultrasound. Larger complex ovarian masses in young women are more likely to be germ cell tumours than the tumours that are seen in adult women.

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Ovarian torsion The majority of ovarian torsions occur in the setting of an enlarged ovary, although this may be as a result of a physiological ovarian cyst. Pain is usually a sudden onset with associated nausea and dizziness. Examination findings are mild to moderate tenderness, so suspicion on the basis of history is important. Ultrasound allows identification of the enlarged ovary, but the presence of blood flow to the ovary does not exclude the diagnosis. Management is usually laparoscopic de-torsion. Oophorectomy is not usually required, even in the setting of prolonged symptoms or an ischaemic-looking ovary, as follicles have been identified in > 90% of these ovaries on follow-up.

CONTRACEPTION Contraception is addressed in Chapter 53. FURTHER READING Goldenring JM, Rosen DS. Getting into adolescent heads: an essential update. Contemp Pediatr 2004;21:64–90.

Chapter 47  THE MENSTRUAL CYCLE AND MENSTRUAL DISORDERS Carol Vance

KEY POINTS Menstrual cycle ■ Normal menstrual cycles occur every 21 to 35 days and the duration of bleeding is 2 to 8 days. Average blood loss is 30 to 40 mL. ■ Menstruation occurs in response to progesterone withdrawal in the presence of an oestrogen-primed endometrium. ■ Features associated with the menstrual cycle may include mood changes, breast symptoms, migraines and changes in libido. ■ Cultural beliefs regarding menstruation vary widely and it is important to recognise the impact of these beliefs on the experience of each individual patient. Dysmenorrhoea ■ Primary dysmenorrhoea is thought to be due to prostaglandin production causing increased uterine tone and uterine contractions, which result in uterine ischaemia. ■ The first-line treatment for primary dysmenorrhoea is non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis. ■ The combined oral contraceptive pill (OCP) and progesterone-only forms of contraception are also effective in treating primary dysmenorrhoea. Their use may be combined with NSAIDs. ■ In patients who do not respond to first-line treatments, further investigation may be warranted to exclude pelvic pathology. ■ Secondary dysmenorrhoea is pain during menstruation that is secondary to pelvic pathology such as endometriosis. Secondary dysmenorrhoea is more common in older women. Premenstrual syndrome ■ Premenstrual syndrome (PMS) is defined as physical, psychological or behavioural symptoms occurring in the luteal phase of the menstrual cycle where symptoms resolve completely by the cessation of menstruation. ■ PMS has a spectrum of severity, the most severe form may be classified as premenstrual dysphoric disorder (PMDD). ■ PMS is thought to be caused by oestradiol and progesterone interacting with central neurotransmitters. ■ General lifestyle measures such as dietary modification, exercise and relaxation should be suggested for symptom control and may be of benefit to some women but many will require a pharmacotherapeutic approach with SSRI/SNRIs or the combined OCP.

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

KEY POINTS—cont’d Heavy menstrual bleeding ■ Excessive menstrual bleeding may occur in the form of menorrhagia (heavy menstrual bleeding), polymenorrhoea (frequent menstrual periods) or metrorrhagia (bleeding between menstrual periods). These three conditions commonly occur together. ■ Excessive menstrual bleeding may be due to anatomical causes, medical conditions or hormonal dysfunction. ■ Dysfunctional uterine bleeding (DUB) should be diagnosed only after other causes have been excluded. ■ DUB is common in the perimenopausal years. ■ Women with excessive menstrual bleeding and a thick endometrium should have an endometrial biopsy to exclude endometrial hyperplasia or malignancy. ■ Women with excessive menstrual bleeding and iron deficiency or iron deficiency anaemia should have iron replacement or blood transfusion. Prompt, effective treatment to reduce bleeding should also be provided. ■ Rarely, heavy menstrual bleeding may be so extreme as to be life-threatening. If medical therapy is unsuccessful in these cases, the patient may require emergency surgical treatment. Postmenopausal bleeding ■ The most common cause of postmenopausal bleeding (PMB) is genital tract atrophy. ■ Approximately 5% of women with PMB will have endometrial malignancy. ■ History, examination and transvaginal ultrasound (TVS) should be part of the initial assessment. ■ Where endometrial biopsy is required, this should be performed with hysteroscopy to reduce the chance of a false-negative result.

INTRODUCTION Most women experience problems associated with the menstrual cycle at some stage in their lives. Although these problems are often successfully self-managed, many women require some form of medical intervention. Dysmenorrhoea (menstrual pain) occurs in 50 to 90% of women, premenstrual syndrome (PMS) occurs in 30% of women and its severe form (premenstrual dysphoric disorder [PMDD]) affects around 5% of women. Excessive menstrual bleeding (menorrhagia, polymenorrhoea or metrorrhagia) occurs in 10% of women and is more common in the perimenopausal years. Primary dysmenorrhoea is common in young women. It is thought to be caused by prostaglandin release causing uterine contractions and uterine ischaemia. Secondary dysmenorrhoea is pain during menstruation that has an underlying pathological cause. PMS is characterised by the presence of physical, psychological and behavioural symptoms that occur in the second half of the menstrual cycle and which impair the woman’s daily activities in some way. PMDD is a severe form of PMS which has specific diagnostic criteria. The causes of excessive menstrual bleeding fall into three groups: local pathology (e.g. fibroids); hormone dysfunction (e.g. anovulation); or medical disorder (e.g. 378

bleeding diathesis). Dysfunctional uterine bleeding (DUB) is a diagnosis of exclusion given to excessive menstrual bleeding where local pathology and medical disorders have been ruled out. Postmenopausal bleeding (PMB) is a symptom of endometrial malignancy and therefore patients should be informed of the importance of reporting this symptom. Where PMB occurs, it should be investigated appropriately by a specialist gynaecologist.

MENSTRUATION: GENERAL DESCRIPTION AND TERMS The onset of menstrual activity occurs during puberty at the time of the menarche (average age 13 years). Menstrual cycles continue until the time of menopause but may be irregular in the first few years after menarche and also in the perimenopausal years (Fig 47.1). Menstruation is a cyclic phenomenon occurring every 21 to 35 days (an average of 28 days as shown in Fig 47.2). Menstrual bleeding usually occupies 4 to 5 days of each cycle, although the normal range is 2 to 8 days. Disorders of cycle length include polymenorrhoea (frequent menstruation), metrorrhagia (bleeding between normal cycles, which is also termed inter-menstrual bleed­ ing [IMB]), oligomenorrhoea (infrequent menstruation),

Intermenstrual interval (days)

Chapter 47  The Menstrual Cycle and Menstrual Disorders

60

1

8

15

Day 22

1

8

40

20

20 Menstrual year

0

40

A

Normal

B

Amenorrhea

C

Menorrhagia

D

Metrorrhagia

FIGURE 47.1

Median menstrual cycle lengths (purple line) from menarche until menopause. The green lines indicate the 95% confidence limits. Source: Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967;1291 Pt 2):77–126.

16

FIGURE 47.3

Types of uterine bleeding. A Normal 28-day cycle. B Amenorrhea. After a menstrual flow of 5 days, the period does not recur. C Menorrhagia. Note that the flow occurs at 28-day intervals, but the amount of flow is heavier, and its duration is longer than normal. D Metrorrhagia. In this condition there is bleeding between the normal menstrual flow cycles.

Incidence (%)

12

8

Source: Swartz MH. Textbook of Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 19.37.

4

2 20

22

24

26

28

30

32

34

36

38

40

Length of menstrual cycle in days

FIGURE 47.2

Variation of the duration of the menstrual cycle in women with regular cycles.

Source: Cunningham FG, ed. Williams Obstetrics, 19th ed. Stamford, CN: Appleton & Lange, 1993:81–109. © McGraw-Hill Education.

irregular menstruation (cycle length varying by more than 8 days) or amenorrhoea (absent menstruation) (Fig 47.3). The average blood loss during menstruation is 30 to 40 mL; losses in excess of 80 mL are classed as menorrhagia. Hypomenorrhoea is the term used for very light menstruation. Volumetric measurement is difficult and usually not required as specific clinical questions and

appropriate investigations are sufficient to diagnose these conditions. Bleeding occurring only after intercourse is termed postcoital bleeding (PCB) and bleeding occurring more than a year after the last menstrual period is termed postmenopausal bleeding (PMB). Because of the risk of cervical or endometrial cancer, it is necessary to warn all women that any bleeding except that occurring in a normal menstrual pattern must be reported to a doctor. Continuing or excessive bleeding is always abnormal and may lead to iron deficiency anaemia. It is important to exclude pregnancy in women presenting with menstrual disorders.

THE MENSTRUAL PROCESS Menstruation occurs due to hormonal influences that cause the endometrium to shed in a menstrual cycle where conception has not occurred (Fig 47.4). Reduced levels of oestradiol and progesterone lead to spasm, ischaemia and rupture of the spiral arterioles and vascular lakes in the endometrium, with separation of the bulk of this layer. The endometrium disintegrates and is shed as 379

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1200

FIGURE 47.4

Luteal phase

Follicular phase

A, B, C and D show plasma concentrations of ovarian hormones and gonadotrophins in women during normal menstrual cycles. Values are the mean ± standard deviation of 40 women. The shaded areas indicate the entire range of observations. Day 1 is the onset of menstruation. E and F show diagrammatically the changes in the ovarian follicle and the endometrium during the cycle. Ovulation on day 14 of the menstrual cycle occurs with the mid-cycle peak of luteinising hormone (LH), represented by the vertical dashed line. Abbreviations: A = arterioles; FSH = follicle-stimulating hormone; V = venules.

FSH

(ng/mL)

800 400 0

A

600

Oestrogens

(ng/mL)

400

Source: Based on van de Wiele RL, Dyrenfurth I. Gonadotropin–steroid interrelationships. Pharmacol Rev 1973;25:189–207.

200 0

B

small fragments mixed with blood from the open vessels (Figs 47.5 and 47.6). Occasionally, larger pieces of endometrium are shed and the shed blood may clot within the uterus, particularly if the flow is heavy. The menstrual loss is comprised of about 50% endometrial tissue and 50% blood. Menstrual fluid is reddish-brown, a slightly darker colour than blood. The process of menstruation involves dynamic changes in both endometrium and myometrium, as well as in the blood vessels and platelets. There is considerable experimental evidence to suggest that prostaglandins (PGE2 and PGF2α) are implicated in the endometrial shedding and the uterine contractions that accompany menstruation. Calcium stabilisation is related in part to the ratio of prostaglandin to progesterone; this ratio is upset as prostaglandins increase and progesterone falls late in the cycle, and membrane stability is lost with the resultant menstruation. Apart from the ovarian steroid hormones, other key substances are prostacyclin and thromboxane A2 as well as the fibrinolytic system components.

1800 LH

1500

(ng/mL)

1200 900 600 300

C

0 28 Progesterone

(ng/mL)

20 10

D

0 Ovulation Follicle

Endometrial thickness

E Endometrium A

F

0

7

14 Day of menstrual cycle

V Blood vessels 21

28

Proliferative phase (11 days)

Secretory phase (12 days)

Menstrual phase (5 days)

FIGURE 47.5

Phases of endometrial growth and menstruation during each monthly female sexual cycle.

Source: Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th edn. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 81.8.

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B

F B L

A

B

C

FIGURE 47.6

Endometrium: onset of menstruation. A Haematoxylin–eosin stain (H&E) ×8. B H&E ×100. C H&E ×300. In the absence of implantation of a fertilised ovum, degeneration of the corpus luteum results in cessation of oestrogen and progesterone secretion. Spasmodic constriction in the spiral arterioles of the endometrial stratum functionalis (F) occurs due to cessation of oestrogen and progesterone secretion. The resulting ischaemia is initially manifested by degeneration of the superficial layers of the endometrium and leakage of blood (L) into the stroma; this is seen in micrographs A and B. Stromal cells disaggregate and the endometrial glands collapse. These features are indicative of early necrosis of glands and stroma. At high magnification in micrograph C, nuclear debris of endometrial cells (apoptotic bodies) B can be seen at the onset of menstruation. These cells have died by apoptosis. Further ischaemia leads to degeneration of the whole stratum functionalis, which is progressively shed as menses. By day 3 to 4 of menstruation, most of the stratum functionalis has been shed and proliferation of the basal layer of the endometrium has begun again. Source: Young B, Lowe JS, Stevens A, Heath JW. Wheater’s Functional Histology. 5th edn. Oxford: Elsevier, 2006. Figure 19.16.

Uterine contractions are induced by prostaglandins and vary in frequency and in type throughout the menstrual cycle.1 Strong contractions during menstruation cause high uterine pressures (Fig 47.7). When the uterine pressure becomes higher than arterial pressure, ischaemia occurs that may result in dysmenorrhoea. The bleeding diminishes over 2 to 5 days and then becomes a brownish discharge as the endometrium reforms and develops in the next proliferative phase. Endometrial repair is largely independent of oestrogen and is relatively rapid: it begins between the second and third cycle days and is complete by the fifth day. Regeneration occurs from the bottom functional layer (i.e. the basal secretory cells).

are very common; for example, irritability is found in 30 to 60% of women during the late luteal phase. Depressed mood occurs most frequently premenstrually (50% of women) but sometimes during menstruation or at mid-cycle. Changes in libido are common during the menstrual cycle and there is a wide variation. In approximately 40% of women, there appears to be little change. In the remainder, interest may be higher perimenstrually and at midcycle. This may be an issue for women where cultural taboos forbid intimacy during menstruation. Migraine occurring mainly during the first day or two of menstruation is well described. Oestrogen withdrawal is thought to be a key aetiological factor in this condition.

FEATURES ASSOCIATED WITH MENSTRUATION

MENSTRUAL HYGIENE

Emotional changes of all kinds are reported, both premenstrually and perimenstrually. Some affective changes

Women have several options for managing their menstrual loss. Sanitary (or menstrual) pads are usually 381

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attached to the underwear and may be either disposable or re-useable (Figs 47.8 and 44.9). Tampons (Fig 47.10) are disposable and are placed by the woman into the lateral fornix of the vagina. The woman should not be able to feel the tampon when it is placed correctly. Some women use a re-useable menstrual cup (Fig 47.11), which sits in the vagina and catches the menstrual fluid.

Type A: cervicofundal contraction Type B: fundocervical contraction Type C: isthmical contractions

3

Contractions/min.

2.5 2

At the menarche, some adolescents may start with pads for menstrual protection and then progress to tampon use, while others may feel comfortable using tampons from the menarche. Although some women may find the thought of inserting a tampon daunting initially, it may enable a woman to swim and perform other activities during menstruation. Many women also find tampon use more comfortable than sanitary pads, particularly where sanitary pads are causing vulval irritation. Tampons and pads need to be changed more frequently when flow is heavier. The need to change a large pad more frequently than every hour is usually considered a sign that bleeding is very heavy and the women requires urgent medical attention. While sanitary pads only need to be changed for comfort, tampons should be

1.5 1 0.5 0

Late Early Midfollicular Late Midluteal menstrual follicular follicular period Phase of cycle

Late luteal

FIGURE 47.7

Histogram demonstrating the frequency of the uterine peristaltic waves during menstruation, the early-, mid- and late follicular and mid- and late-luteal phases of the cycle, respectively, as obtained from video sonography of uterine peristalsis in healthy women. The relative distribution of cervico-fundal (type A) versus fundocervical (type B) and isthmical (type C) contractions is also shown. Source: Leyendecker G, Kunz G, Kissler S, Wildt, L. Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 2006 Aug;20(4):523–546.

FIGURE 47.9

FIGURE 47.8

FIGURE 47.10

Disposable menstrual pad. 382

Re-useable menstrual pad.

Tampon.

Chapter 47  The Menstrual Cycle and Menstrual Disorders

have intercourse or physical intimacy, or even pass things to another person. Several cultures require a ritual bath after menstruation before normal activities can resume. These factors mean that variations in her menstrual pattern (which may be considered trivial to health professionals) may have a huge impact on the everyday life of a woman.

DYSMENORRHOEA OVERVIEW

FIGURE 47.11

Menstrual cup.

changed at least every 5 hours due to the increased risk of toxic shock syndrome. Toxic shock syndrome occurs due to Staphylococci and is a rare but life-threatening complication of tampon use. The risks of toxic shock syndrome can be minimised by using pads rather than tampons at night, by changing tampons at least every 5 hours, and by taking care to avoid tampon contamination from hands and perineum. Women with intellectual impairment (and their carers) often encounter significant problems with menstrual hygiene management. Medical therapies may be employed to make this task easier.

CULTURAL ATTITUDES TO MENSTRUATION Menstruation is an important event and its significance to the individual depends on physiological, social and cultural factors. Historically, menstruating woman were often considered sacred and powerful, with healing and psychic abilities. In modern Western culture, attitudes towards menstruation vary from those who feel that menstruation is a natural function which should not interfere with activity in any way, to those who find it a source of embarrassment which they are reluctant to discuss. Many women hold the belief that menstruation is an important cleaning out process and therefore feel concern about treatments which result in amenorrhoea. When assessing a woman with a menstrual disorder, it is important to consider treatments appropriate to her cultural framework and beliefs. In many cultures, there are certain practices which surround menstruation. Women may not be allowed to enter their place of worship, perform domestic activities or their usual work, sleep in the same room as others, wear their usual clothes,

Primary dysmenorrhoea is the development of recurrent crampy lower abdominal pain which occurs at the time of menstruation, in the absence of any organic pelvic disease. It should be distinguished from secondary dysmenorrhoea, which usually occurs later in life and is related to organic pelvic disorders such as endometriosis (Fig 47.12), adenomyosis, chronic pelvic inflammation, acquired cervical stenosis, uterine fibroids, endometrial polyps or an intrauterine contraceptive device. Occasionally, non-gynaecological pathology can also mimic menstrual pain. One form of dysmenorrhoea that is important to recognise in the young woman is due to uterine malformation, particularly unilateral horn of a bicornuate uterus (Fig 47.13). Obstruction to menstrual outflow may cause pain. Dysmenorrhoea affects around 50% of the female population between the ages of 15 to 24 years (which is the time of its peak incidence); it is severe in nature in 15% of women.2 It usually does not commence until ovulatory menstrual cycles begin. Severe dysmenorrhoea may lead to an inability to attend work or school and perform other daily activities.

AETIOLOGY Excess endometrial prostaglandins (PGF2-α and PGE2) are thought to be responsible for primary dysmenorrhoea. These compounds are released just prior to and during menstruation. They cause uterine contractions and increased uterine muscle tone in order to ensure evacuation of blood and debris from the uterine cavity. Excessive levels have been found in women with dysmenorrhoea, and their escape into the circulation is thought to cause some of the associated symptoms of severe dysmenorrhoea (nausea, diarrhoea). Strong, high-frequency contractions in the uterus result in very high uterine pressures. When the uterine pressure exceeds arterial pressure, ischaemia results and an accumulation of anaerobic metabolites subsequently stimulates type C pain fibres, which causes pain (Figs 47.14 and 47.15).

CLINICAL FEATURES The pain of dysmenorrhoea is cramping in nature and is usually worse on the first days of the menstrual flow. It 383

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A

B

C

D

FIGURE 47.12

Appearance of old endometriosis with ‘tattooing’ (blue-grey lesions), and red, brown and black raised lesions of active endometriosis at the time of laparoscopy. Source: Hacker NF, Gambone JC, Hobel CJ. Hacker and Moore’s Essentials of Obstetrics and Gynecology. 5th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 25.2A to D.

is commonly bilateral, localised to the lower abdomen or the lower back and may radiate down the inner and front aspects of the thighs. In severe dysmenorrhoea, there is often associated diarrhoea, nausea, vomiting, fainting and headaches. It usually occurs in most or all menstrual cycles. The effect of the dysmenorrhoea on the woman’s life should be elicited (e.g. limiting activity, missing school or work). Clinical examination is usually unremarkable in primary dysmenorrhoea. 384

TREATMENT Organic disease is responsible for dysmenorrhoea in a minority of young women and can usually be excluded by history and physical examination. Only where a secondary cause is thought likely from history or exami­ nation (or where initial treatment has failed) are other investigations such as ultrasound or laparoscopy required.

Chapter 47  The Menstrual Cycle and Menstrual Disorders

Medical: non-hormonal Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and are more effective than paracetamol for treatment of primary dysmenorrhoea.3 They inhibit prostaglandin synthesis (via inhibition of cyclo-oxygenase, which is the enzyme that catalyses the formation of prostaglandins from arachidonic acid) and thereby reduce uterine contractions and pressure (Fig 47.16). Significant improvement in symptoms may be achieved by commencing therapy before the period occurs. Fenamate NSAIDs (e.g. mefenamic acid) and phenylproprionic acid derivative NSAIDs (ibuprofen, naproxen) are both effective, although the fenamate class may be more effective as it blocks prostaglandin action as well as synthesis. FIGURE 47.13

Medical: hormonal

Source: Emans, Laufer, Goldstein’s Pediatric and Adolescent Gynecology, 6th edition, Emans SJ, Laufer MR. © 2011 Lippincott Williams & Wilkins..

The combined oral contraceptive pill (OCP) is an effective treatment for primary dysmenorrhoea. It may be used in those women also requiring contraception, or in those who do not achieve relief with NSAIDs alone. The combined OCP is believed to work by thinning the endometrium, thereby reducing the amount of arachidonic acid (and consequently prostaglandins). Continuous use of the

Unicornuate system with a right obstructed hemi-uterus. Note the blue dye coming from the left fallopian tube after injection of dye into the single cervix.

5 PAIN (a) ↑Uterine activity (b) Uterine ischemia (c) Sensitization of nerve terminals to prostaglandins and endoperoxides

4

Reduced blood flow (ischaemia)

Corpus luteum (regression) 1 Progesterone (Menstrual flow) 2

3 Increased myometrial contractions

↑ Prostaglandins + Endoperoxides + Metabolite

FIGURE 47.14

Postulated mechanism of pain generation in primary dysmenorrhoea.

Source: Modified from Dawood MY: Hormones, prostaglandins and dysmenorrhea. In Dawood MY [ed]: Dysmenorrhea. Baltimore, Williams & Wilkins, 1981.

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Phospholipase A2

Arachidonic acid Cyclooxygenase

5-lipooxygenase

Cyclic endoperoxides

Leukotriene A4

Mean % change from baseline

40

Endometrium cell wall

Placebo

20 0 –20

Meclofenamate

–40 –60 –80

p ≤ 0.05 0

1

2 3 Study hour (200-mg dose)

LTC4

FIGURE 47.16

LTD4

Source: Adapted from Smith RP. The dynamics of nonsteroidal antiinflammatory therapy for primary dysmenorrhea. Obstet Gynecol 1987, 70(5):785.

PGF2α, PGE2

4

Average uterine pressure, meclofenamate versus placebo.

LTE4 Myometrial contraction Vascular vasoconstriction

Ischemia

FIGURE 47.15

Prostaglandin metabolism in the endometrium. Decrease in serum progesterone in the luteal phase results in the release of arachidonic acid from phospholipids in the cell membrane. Abbreviations: PG = prostaglandin; LT = leukotriene. Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 14.1.

combined OCP (skipping the pill-free interval) may be helpful in those women who do not experience symptom control with the combined OCP in a standard regime. Progesterone-only contraceptive methods (e.g. progesterone-only pill, etonogestrel subdermal implant, depot medroxyprogesterone acetate [DMPA] and the levonorgestrel-releasing intrauterine system [IUS]) also result in thinning of the endometrium and have been shown to be effective in treating dysmenorrhoea.

Surgery If medical treatments fail after several months of treatment, laparoscopy may be considered to exclude endometriosis.

Other treatments Rest, relaxation, a heat pack and general exercise may be helpful for pain management. Vitamins E, B1, B6 and D 386

and fish oil have all been shown to be of some benefit in clinical trials, but conclusive evidence is lacking.

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER OVERVIEW The term ‘premenstrual syndrome’ (PMS) refers to the combination of distressing physical, behavioural and psychological symptoms that regularly occur in the second half of the menstrual cycle and significantly improve by the end of menstruation. Premenstrual symptoms occur in 75% of women, but clinically significant PMS (where the symptoms interfere with daily activities) occurs in 20 to 30% of women. Severe PMS has been included in the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association and is termed premenstrual dysphoric disorder (PMDD).4 This severe form of the disorder is present in about 5% of women. Where symptoms are exaggerated by menstruation but fail to resolve completely when menstruation ends, this may be better termed pre-menstrual exaggeration of a background condition.5 Figure 47.17 shows the range of premenstrual syndromes.

CLINICAL FEATURES In both PMS and PMDD, symptoms occur in the luteal phase of the menstrual cycle. Symptoms should be absent (at minimum) from day 4 to day 12 of a 28-day cycle. Some women have exactly the same symptoms each month, whereas others find that symptoms vary

Chapter 47  The Menstrual Cycle and Menstrual Disorders

Spectrum of premenstrual syndromes Severe (PMDD) Premenstrual syndrome severity

Moderate (PMS) Mid (PMS) None

FIGURE 47.17

Spectrum of premenstrual syndromes: premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).

Source: Hacker NF, Gambone JC, Hobel CJ. Hacker and Moore’s Essentials of Obstetrics and Gynecology. 5th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 36.1.

considerably. Diagnosis should be based on a prospective diary of symptoms over at least 2 months. To record symptoms, patients may use a tool such as the daily record of severity of problems (DRSP) (Fig 47.18).6 Physical symptoms include abdominal bloating, extreme fatigue, breast tenderness, headaches, gastro­ intestinal upset, acne, hot flushes, increased appetite, heart palpitations and dizziness. Psychological symptoms include labile mood, irritability, tension, depressed mood, anger and easy crying. Behavioural symptoms include forgetfulness, difficulty concentrating and reduced visuospatial and cognitive abilities.

DSM-5 diagnostic criteria for PMDD The following are the diagnostic criteria for diagnosing PMDD. Such definitions are important for therapeutic research, but in practice the diagnosis may be made with a less stringent definition.4 A. Presence of at least 5 out of 11 of the following symptoms during the week prior to menses (including at least 1 of the first 4 listed): markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts marked anxiety, tension, feelings of being ‘keyed up’ or ‘on edge’ marked affective lability (e.g. feeling suddenly sad or tearful or experiencing increased sensitivity to rejection) persistent and marked anger or irritability or increased interpersonal conflicts decreased interest in usual activities (e.g. work, school, friends and hobbies) subjective sense of difficulty in concentrating lethargy, easy fatigability or marked lack of energy marked change in appetite, overeating or specific food cravings hypersomnia or insomnia

• • • • • • • • •

• •

a subjective sense of being overwhelmed or out of control other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of bloating, or weight gain.

The symptoms must have been present for most of the time during the last week of the luteal phase, must have begun to remit within a few days of the onset of menstrual flow, and must be absent in the week after menses. B. Symptoms interfere with social, occupational, sexual or school functioning. C. Symptoms are discretely related to menstrual cycle and not merely a worsening of other disorders. D. Criteria A, B and C must be confirmed prospectively by daily ratings for at least two consecutive menstrual cycles.

AETIOLOGY The proposed causes of PMS and PMDD are shown in Figure 47.19. Theories of aetiology suggest that ovarian hormones (oestradiol and progesterone) interact with central neurotransmitters (serotonin, GABA) and the autonomic nervous system.6 Studies suggest a genetic/ heritable component contributing to the development of PMS and PMDD. The oestrogen receptor alpha gene (ESR1) has been implicated. Women with PMS/PMDD do not have abnormal levels of ovarian hormones, but seem to have increased responsiveness to their fluctuating concentrations. Women with PMS and PMDD are more likely to experience psychiatric disorders during their lifetime, and excluding an underlying major psychiatric disorder is important when making a diagnosis of PMS or PMDD.5

TREATMENT Many cases of PMS will be managed in a primary care setting. For those with PMDD or severe PMS, a multidisciplinary approach (counsellor, gynaecologist, psychiatrist, and so on) is appropriate.5

Medical: non-hormonal First-line treatment of moderate or severe PMS and PMDD requiring treatment is a selective serotonin selective reuptake inhibitor (SSRI) or a serotonin and noradrenaline reuptake inhibitor (SNRI).5 They have been shown to improve both the behavioural and physical symptoms of PMS and PMDD and demonstrate a response rate of 60 to 90%. Fluoxetine 20 mg/day has been well studied; other studies have also shown sertraline, paroxetine, citalopram and venlafaxine (SNRI) to be effective. SSRIs may be used either continuously or only in the 387

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Please print and use as many sheets as you need for at least two FULL months of ratings.

Name or Initials Month/Year Each evening note the degree to which you experienced each of the problems listed below. Put an “x” in the box which corresponds to the severity: 1 — not at all, 2 — minimal, 3 — mild, 4 — moderate, 5 — severe, 6 — extreme. Each day (Monday=”M”, Thursday=”R”, etc) > Note spoing by entering “S” > Note menses by entering “M” >

Begin rating on correct calendar day > 6 5 4 or felt hopeless; or felt worthless or 3 guilty 2 1 6 2 Felt anxious, tense, “keyed up” or 5 4 “on edge” 3 2 1 6 3 Had mood swings (i.e., suddenly feeling 5 4 sad or tearful) or was sensitive to 3 rejecton or feelings were easily hurt 2 1 6 4 5 Felt angry, or irritable 4 3 2 1 6 5 Had less interest in usual activities 5 4 (work, school, friends, hobbies) 3 2 1 6 6 Had difficulty concentrating 5 4 3 2 1 6 7 Felt lethargic, tired, or fatigued; or 5 4 had lack of energy 3 2 1 6 8 Had increased appetite or overate; 5 4 or had cravings for specific foods 3 2 1 6 9 Slept more, took naps, found it hard to 5 4 get up when intended; or had trouble 3 geing to sleep or staying asleep 2 1 6 10 Felt overwhelmed or unable to cope; 5 4 or felt out of control 3 2 1 Had breast tenderness, breast swelling, 6 11 5 bloated sensation, weight gain, 4 headache, joint or muscle pain, or 3 2 other physical symptoms 1 6 At work, school, home, or in daily routine, 5 at least one of the problems noted above 4 3 caused reduction of productivity or 2 inefficiency 1 6 At least one of the problems noted above 5 4 caused avoidance of or less participation 3 2 in hobbies or social activities 1 6 At least one of the problems noted above 5 4 interfered with relationships with others 3 2 1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

1 Felt depressed, sad, “down” or “blue”

@ Jean Endico, Ph.D. and Wilma Harrison, M.D.

FIGURE 47.18

Daily record of severity of problems (DRSP).

Source: Springer and Arch Women’s Mental Health, Vol 9, Issue 1, 2006, pp. 41–9, Daily Record of Severity of Problems (DRSP): Reliability and Validity, Jean Endicott, PhD and Wilma Harrison, M.D., Copyright © 2005, Springer-Verlag/Wien.

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Chapter 47  The Menstrual Cycle and Menstrual Disorders

PMS or PMDD

Ovarian steroid fluctuation Normal cyclic changes in ovarian steroids cause dramatic changes in various body systems.

CNS neurotransmi ers

Genetic predisposition

Neurotransmi er levels are affected by ovarian steroid changes. The serotonergic, adrenergic, opioid and GABAergic systems are implicated.

Development or severity of premenstrual symptoms may be hereditary.

Social expectations Sociocultural beliefs about menstruation may influence what a woman expects to experience.

FIGURE 47.19

Proposed causes of PMS and PMDD.

Source: Ling F, Mortola J, Pariser S et al. Premenstrual Syndrome and Premenstrual Dysphoric Disorder: Scope, Diagnosis, and Treatment. Association of Professors of Gynecology and Obstetrics, Crofton, MD, 1998.

luteal phase (days 15 to 28) of the cycle. It should be noted that several cycles may be required before an effect is noted and that significant side effects (nausea, insomnia, reduced libido) are experienced by approximately 15% of women, which may cause discontinuation of treatment. Several vitamins have been shown to be beneficial in some studies, although quality evidence (including safety data) is generally lacking in this area. Pyridoxine is required for the production of serotonin; however, metaanalysis has shown no benefit. Small trials have shown the benefit of daily doses of vitamin E, calcium/ vitamin D and magnesium. Vitex agnus-castus fruit extract is thought to antagonise prolactin and, although benefit has been shown in a small trial, safety information is not known.

Medical: hormonal treatments Although the combined OCP inhibits ovulation, it does not improve PMS or PMDD in many patients. This is theorised to be due to the progesterone component (levonorgestrel or norethisterone) producing similar symptoms to those of PMS. The combined OCP with newer generation progesterone (drospirenone) and a shortened pill-free interval (4 days) has been shown in small trials to be effective.5 Continuous use of the combined OCP may result in better symptom control than standard cyclical use.

GnRH agonists suppress ovarian hormone production and are an effective form of treatment for those with severe PMS who have failed to respond to first-line treatments such as SSRIs or the combined OCP. Addback hormone therapy (continuous combined HRT) would be appropriate for the majority of patients as prolonged use of GnRH agonists has a serious negative impact on bone density and may cause severe menopausal symptoms. Danazol (200 mg twice daily) is an effective treatment for PMS but the androgenic side effects (some irreversible) make it undesirable for most patients. Contraception must be used in women using danazol.

Surgical treatment Bilateral oophorectomy is a radical treatment for PMS or PMDD and should only be considered in women with severe symptoms where medical therapy has failed. Medical oophorectomy with GnRH agonist and add-back therapy should have been tried and found to be effective before surgery is considered.

Other Exercise, stress reduction, relaxation and improved diet may be helpful for symptom control and should be discussed with all women.5. Cognitive behavioural therapy (CBT) may also be of benefit.6 389

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EXCESSIVE UTERINE BLEEDING (MENORRHAGIA, METRORRHAGIA AND POLYMENORRHOEA) OVERVIEW Excessive uterine bleeding occurs in approximately 10% of women; bleeding may be prolonged and/or heavy. Risk of excessive bleeding is highest in women aged 40 to 44 years of age. Quantifying the exact amount of menstrual loss is difficult and not usually warranted. Women who present seeking treatment for excessive bleeding usually warrant treatment of some kind; the severity of the symptoms may guide the doctor towards appropriate treatment options. As a guide, particularly heavy bleeding may be indicated by the presence of clots, the need to change a pad or tampon more often than every 3 hours or the need to change a pad overnight. The presence of iron deficiency or iron deficiency anaemia in the setting of menorrhagia necessitates timely treatment. Significant polymenorrhoea or metrorrhagia may also cause iron deficiency and will often require treatment. These three conditions frequently co-exist. The three main steps in management of these conditions are to: 1. identify pathology that may be contributing or causing the bleeding 2. identify and treat anaemia 3. provide appropriate treatment to improve the bleeding pattern.

AETIOLOGY The causes of heavy menstrual bleeding can be divided into three groups: dysfunctional uterine bleeding (DUB) (due to hormone dysfunction), pelvic pathology or medical disorder. DUB is a diagnosis of exclusion, given only after anatomical pathology has been ruled out. DUB may be ovulatory or anovulatory. DUB in ovulatory women is thought to be related to loss of local endometrial haemostasis and increased vasodilatory prostaglandins. In anovulatory DUB (which is common in the perimenopausal years as well as in women with polycystic ovarian syndrome [PCOS]), there is high oestrogen unopposed by progesterone which leads to a thickened endometrium. The thick endometrium may ‘outgrow’ its blood supply, becoming necrotic with partial shedding, which causes bleeding at irregular times in the cycle. Anatomical causes of excessive uterine bleeding include both uterine and cervical abnormalities. Uterine causes include endometrial polyps (Fig 47.20), uterine fibroids (Fig 47.21), adenomyosis (Fig 47.22), copper 390

FIGURE 47.20

Management of endometrial polyps diagnosed before or during intracytoplasmic sperm injection (ICSI) cycles.

Source: Tiras B, Korucuoglu U, Polat M, et al. Reprod Biomed Online. Jan 2012;24(1):123–8. Figure 1.

intrauterine device, or rarely, pelvic infection. Cervical causes include polyps, dysplasia or malignancy. Fibroids are extremely common and found in 30 to 70% of women. Submucous and intramural fibroids can cause heavy menstrual bleeding by expanding the endometrial surface area. The area is enlarged either by a fibroid growing adjacent to the endometrium (submucous fibroid) or by intramural fibroids significantly enlarging the total uterine volume and thereby the endometrial surface area. It should be noted that uterine fibroids will often by co-existent with a separate cause of heavy menstrual bleeding and may be totally asymptomatic. Endometrial hyperplasia (Figs 47.23 and 47.24) or endometrial carcinoma may cause abnormal menstrual bleeding. Suspicion should be higher in those with risk factors for these conditions, including a history of chronic anovulation (e.g. PCOS), exposure to unopposed oestrogen, exposure to tamoxifen, Lynch syndrome (may be suggested by a strong family history of endometrial or colon cancer), nulliparity, obesity, hypertension or diabetes. Medical conditions may also cause excessive uterine bleeding. These include hypothyroidism and bleeding disorders (haemophilia, platelet disorders; von Willebrand’s disease).

CLINICAL FEATURES AND DIAGNOSIS History and examination It is helpful to determine how severe the problem is; for example, the duration of maximal bleeding, whether clots are passed, how often pads/tampons are changed and the

Chapter 47  The Menstrual Cycle and Menstrual Disorders

effect that the bleeding has on the woman’s daily life. Unfortunately, the pattern and severity of bleeding are often not helpful in establishing the cause. Associated symptoms (e.g. pain or dyspareunia) should be ascertained and symptoms of anaemia should be specifically asked about. Specific questioning is also required to exclude pregnancy, endocrine and haematological causes as indicated earlier in this chapter. Both general and pelvic examination (including inspection or the vulva, vagina and cervix) will clarify aspects of the history and pinpoint pelvic pathology. Pap smear and swabs should be performed.

and examination. If there is suspicion of a bleeding disorder, then coagulation profile, coagulation factors and von Willebrand’s factor should be measured.7 Other tests will depend on the clues obtained from the history and examination and may include a full hormone profile in women with a history suggesting anovulation or PCOS (see Chs 49 and 50).

Imaging

Investigations

Pelvic ultrasound is routinely used for detection of uterine anatomical abnormalities (fibroids and polyps) and to measure endometrial thickness. Saline infusion sonography may be used to clarify where routine ultrasound does not provide a diagnosis as demonstrated in Figure 47.21.

Blood tests

Biopsy

Full blood examination is required to establish the presence of anaemia and measure the platelet count. Iron studies (iron, ferritin, saturation and transferrin) reflect the adequacy of iron stores. Thyroid function tests should be performed as hypothyroidism may be missed from history

Outpatient endometrial biopsy has high accuracy in diagnosing endometrial cancer and hyperplasia and should be employed when serious endometrial disease is suspected in both premenopausal and postmenopausal women. Women with heavy menstrual bleeding and an

A

B

C

D

FIGURE 47.21

A Transvaginal ultrasound demonstrates an inhomogeneous endometrial echo. Mild thickening of the endometrium is noted. B Saline infusion sonography of the same patient reveals a 3-cm intracavity leiomyoma arising from the fundus. C Hysteroscopic view of the same fibroid. D Hysteroscopy with a lower uterine segment fibroid in the foreground and an endometrial polyp distally. Continued

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E

F

FIGURE 47.21, cont’d

E Hysteroscopic view of dense synechiae and a small leiomyoma. F Transvaginal ultrasound with homogeneous echo (central brightness) shows a fibroid displacing the endometrium.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 10.8A to H.

endometrial lining between 4 and 12 mm should have an endometrial biopsy as an outpatient. If endometrial biopsy is unable to be performed as an outpatient then formal dilatation and curettage should be performed. Women with an endometrial thickness < 4 mm would usually not require an endometrial sample as the risk of hyperplasia or malignancy is extremely low.

Dysfunctional uterine bleeding Medical: non-hormonal

In women in whom excessive bleeding is a secondary symptom of some haematological, endocrine or anatomical disorder, treatment should be directed to the primary cause. Endometrial polyps may be removed via operative hysteroscopy. Treatment of endometrial hyperplasia and endometrial carcinoma is discussed in Chapter 62.

Tranexamic acid (TEA) is an antifibrinolytic agent that can be used as first-line therapy for most women with heavy menstrual bleeding.9 Studies have shown that TEA reduces the amount of bleeding by 40 to 60%. TEA will not help to regulate bleeding and is taken only on the heaviest 3 to 4 days of the cycle. TEA can be safely prescribed even in those women who are at high risk of thrombosis. NSAIDs act to reduce local prostaglandins. It is theorised that this reduction in prostaglandin may cause vasoconstriction and thus reduce bleeding. There is conflicting evidence regarding their efficacy for treatment of heavy menstrual bleeding, although a meta-analysis has shown some evidence of benefit. Iron supplements should be prescribed for women who are iron deficient. Those with iron deficiency anaemia may require doses of 200 mg oral elemental iron per day. Iron supplements at this dose often have significant side effects; therefore, these should be enquired about and managed to ensure the patient remains compliant with the therapy. Blood transfusion may be required where women have symptomatic anaemia.

Fibroids

Medical: hormonal

Surgical treatment for fibroids may include hysteroscopic resection (if submucous; Fig 47.25), myomectomy (if large and intramural) or hysterectomy (multiple fibroids, no desire for ongoing fertility). Interventional radiology techniques may also be used to treat fibroids. Embolisation (Fig 47.26) and MRI-guided focused ultrasound (MRGFUS) treatment both work by causing fibroid necrosis.

Oral progesterone (e.g. norethisterone) is an effective treatment to reduce uterine bleeding by creating a thin endometrium. It may be used immediately in an emergency situation to reduce bleeding or it may be used in the long term. Progesterone may be used in a short cyclic (10 days per month during luteal phase) or long cyclic (days 5 to 26) pattern. When progesterone is used continuously, irregular bleeding is almost universal. Most women

Hysteroscopy Hysteroscopy (accompanied by endometrial sampling) is useful in excluding endometrial cancer in those with a thickened endometrium.8 Hysteroscopy may be therapeutic as well as diagnostic in those with uterine polyps or submucous fibroids.

TREATMENT Organic disorders

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A

B

C

D

E

F

FIGURE 47.22

Adenomyosis. Sagittal (A, B) and coronal (C) transvaginal ultrasound demonstrates a heterogeneous focal region felt at the time to represent a fibroid. Axial T1-weighted (D), axial T2–weighted (E), and coronal (F) images from an MRI performed on the same patient show the changes of adenomyosis, a region of decreased signal in T2 containing punctate foci of high signal on T1-weighted and T2-weighted sequences, corresponding to blood degradation products. Note in the affected area the loss of a well-defined junctional zone. Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 31.14A to F.

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do not wish to remain on long-term oral progesterone as they experience significant side effects (predominantly mood changes, bloating and irregular bleeding). Other forms of progesterone-only contraception (e.g. Depot medroxyprogesterone acetate [DMPA] or etonogestrel implant) may also improve heavy bleeding but often result in significant irregular bleeding.

The levonorgestrel intrauterine system/device (levonorgestrel IUS; Fig 47.27) releases 20 mcg of levonorgestrel daily for 5 years and is highly effective in treatment of DUB.10 At three months, 94% of patients reported decreased blood volume and 76% of patients continued the treatment at this stage. In one trial, 64% of women with ovulatory DUB who were booked for hysterectomy for treatment elected to cancel their operation after six months of treatment (compared to 14% with other medical management). The levonorgestrel IUS may be less effective in those with anovulatory DUB compared to those with ovulatory DUB. Frequent spotting and

FIGURE 47.23

Endometrial hyperplasia. Transvaginal sagittal ultrasound image of uterus of a 67-year-old woman shows marked endometrial thickening (arrow), raising concern for endometrial carcinoma. Dilatation and curettage was performed and revealed endometrial hyperplasia with no evidence of malignancy.

Source: Middleton WD, Kurtz AB, Hertzberg BS. Ultrasound: The Requisites. 2nd edn. St Louis: Mosby, 2004. Copyright © 2004 Mosby, An Imprint of Elsevier. Figure 22.17.

A

B

FIGURE 47.25

Hysteroscopic resection of submucous fibroid.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 8.24.

C

FIGURE 47.24

Endometrial biopsies of normal proliferative endometrium (A), simple endometrial hyperplasia without atypia (B) and complex endometrial hyperplasia with cellular atypia (C).

Source: Hacker NF, Gambone JC, Hobel CJ. Hacker and Moore’s Essentials of Obstetrics and Gynecology. 5th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 19.8A to C. From Espindola D, Kennedy KA, Fischer EG. Management of abnormal uterine bleeding and the pathology of endometrial hyperplasia. Obstet Gynecol Clin North Am 2007;34:717–37.

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Levonorgestrel intrauterine system (LNG IUS)

Fibroid Catheter 32 mm

Steroid reservoir

Femoral artery Uterine artery

A

Fibroid

Levonorgestrel 20 µg/day

PVA particles

FIGURE 47.27

Levonorgestrel intrauterine system.

Source: Lentz GM, Lobo RA, Gershenson DM, Katz VL. Comprehensive Gynecology. 6th edn. St Louis: Mosby, 2012. Figure 13.25. Copyright © 2012 Mosby, An Imprint of Elsevier. Uterus

Uterine artery

Catheter

B FIGURE 47.26

Schematic representation of uterine fibroid embolisation (UFE) procedure. The goal of UFE is to infarct and shrink the uterine fibroid. A Unilateral or bilateral femoral artery punctures are performed by the interventional radiologist. B Placement of particles. Choice of particle size is determined by the interventional radiologist. The differential in vascularity between fibroid and normal tissue makes it possible for the occluding agents to selectively infarct the leiomyoma from a proximal uterine artery catheter. Myometrium is spared. Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 12.10A to B.

intermenstrual bleeding is a common side effect, particularly in the first few months after insertion. The combined OCP can be used for treatment of heavy and irregular bleeding. Its mechanism of action in to reduce bleeding by causing a thin endometrium.

Due to the oestrogen component in the combined OCP, this treatment may not be suitable for women in their 40s, especially if they have other risk factors for thrombosis or cardiovascular disease. Danazol is an infrequently used treatment for heavy menstrual bleeding. Although 50% of women get improvement in menstrual flow on danazol, as mentioned previously the potential androgenic side effects (which may be irreversible) limit its use. GnRH agonists (e.g. goserelin) are effective in reducing menstrual loss but need to be used with add-back HRT to prevent severe menopausal side effects.

Surgical Endometrial ablation may be performed under vision with a ‘roller ball’ technique or with new generation methods. Diathermy (radiofrequency electrothermal; Fig 47.28) or thermal balloon techniques are available. New-generation techniques report 90% success rates (with equal hypomenorrhoea and amenorrhoea). Endometrial ablation is not compatible with a desire for future pregnancy and effective contraception must be used, as a pregnancy occurring in this setting can be life-threatening. Hysterectomy may be required for women where none of the above treatments are successful and when there is no wish to preserve reproductive function. Hysterectomy may be performed abdominally, laparoscopically or vaginally depending on patient suitability. Often 395

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A

B

C

D

FIGURE 47.28

NovaSure procedure (radiofrequency electrothermal ablation technique). A Step 1: The NovaSure bipolar electrode expands from the sheath to conform to the contours of the uterine cavity. B Step 2: The system insufflates the uterine cavity with CO2 to perform the cavity integrity assessment. C Step 3: NovaSure delivers bipolar radiofrequency energy for a complete and contoured ablation in approximately 90 seconds. D Step 4: The electrode array is retracted into the sheath for easy removal, leaving the uterine lining desiccated down to the superficial myometrium. Source: Courtesy of HOLOGIC, Inc. and affiliates.

these women have other reasons to benefit from hysterectomy (pelvic pain, dyspareunia, dislike of or relative contraindication to hormone therapy).

Treatment of acute blood loss When haemorrhage is severe, prompt control is necessary. An oral progestogen such as norethisterone (5 to 10 mg) is given 2-hourly for four doses, followed by 5 mg two to three times daily for at least 14 days. Intravenous oestrogen was previously also used in this setting but is not currently available in Australia. Blood transfusion may be required. Hysteroscopy and curettage or, rarely, hysterectomy may need to be performed as an emergency procedure in order to control life-threatening bleeding.

POSTMENOPAUSAL BLEEDING OVERVIEW Postmenopausal bleeding (PMB) is defined as any vaginal bleeding which occurs after menopause (i.e. bleeding 396

which occurs more than 1 year after the last period). It is important to differentiate vaginal bleeding from urinary or gastrointestinal tract bleeding through careful history taking and examination. Although most postmenopausal bleeding is due to a benign cause, it is important to rule out malignancy as a cause.

AETIOLOGY Causes of PMB include endometrial carcinoma (approximately 5% of presentations; Figs 47.29 to 47.31), endometrial hyperplasia, cervical cancer or other genital tract malignancy. Genital tract atrophy (vagina, vulva or endometrium) is the more common cause. Endometrial polyps or fibroids may also cause PMB. Postmenopausal women on HRT may experience vaginal bleeding as an expected side effect of the medication and therefore bleeding in the first 6 months of HRT use would not usually need to be further investigated. Bleeding after 6 months of therapy should be considered abnormal and investigated.7

Chapter 47  The Menstrual Cycle and Menstrual Disorders

A

B

C

D

FIGURE 47.29

Endometrial carcinoma: varying appearance in two patients. A Transabdominal scan, and B transvaginal scan, show a large, heterogeneous endometrial mass (arrowheads) compressing the surrounding myometrium. C and D Transvaginal scans show localised irregular endometrial thickening with echogenic polypoid projections (arrows) into the fluid-filled endometrial canal. Source: Rumack, CM, Wilson SR, Charboneau JW, Levine D, eds. Diagnostic Ultrasound. 4th edn. Philadelphia: Mosby, 2011. Mosby, An Imprint of Elsevier. Figure 15.20 A to D.

CLINICAL FEATURES AND ASSESSMENT History The amount of bleeding, precipitating factors and timing in relation to cessation of menstruation should be determined. Careful history taking should enable differentiation of vaginal bleeding from urinary or gastro­intestinal tract bleeding. Risk factors from endometrial carcinoma

and endometrial hyperplasia such as nulliparity, diabetes, obesity and age should be ascertained. Medications history, particularly HRT use, is important to ascertain.

Examination Women should have a thorough pelvic examination including inspection of the external genitalia and vagina. Any abnormal lesions seen would usually require biopsy. A Pap smear should be taken. 397

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FIGURE 47.31

Endometrioid endometrial carcinoma. A large polypoid mass fills the endometrial cavity and superficially infiltrates the myometrial wall. Source: Nucci MR, Oliva E. Gynecologic Pathology. Philadelphia: Churchill Livingstone. Copyright © 2009 Churchill Livingstone, An Imprint of Elsevier. Figure 7.7.

FIGURE 47.30

Endometrial carcinoma, MRI. Sagittal gadolinium-enhanced T1-weighted fat-suppressed MR image shows an endometrial cancer (T) with deep myometrial invasion. Note the thin rim of normal myometrium (black arrows). The disease extends to the upper third of the vagina (white arrow).

Source: Adam, A., Dixon AK, Grainger RG, Allison DJ. Grainger and Allison’s Diagnostic Radiology. 5th edn. Philadelphia: Churchill Livingstone, 2007. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 54.17.

Investigations All women with PMB should have a transvaginal pelvic ultrasound performed to assess the endometrial thickness and be referred for specialist assessment. The exception to this is women with PMB who are on tamoxifen. Due to the effects of tamoxifen on the endometrium, ultrasound is neither specific nor sensitive in the diagnosis of endometrial carcinoma. Women on tamoxifen with PMB should proceed directly to hysteroscopy and endometrial biopsy.7 A thin endometrium (< 4 mm) on ultrasound is associated with a very low risk of malignancy (0.4 to 0.8%), and in the absence of other genital tract pathology need not be investigated further.7 If the bleeding is persistent then further evaluation may be warranted. An endometrium ≥ 4 mm (or where the endometrium is not well seen) should be investigated with a hysteroscopy and endometrial sample.8 398

Treatment PMB usually ceases without treatment and therefore the main aim is to exclude malignancy. Genital atrophy (vulval, vaginal or endometrial) is a common cause of PMB. Therefore, in those women where no other cause for the PMB is identified, vaginal oestrogen may be used. PMB due to endometrial polyps should resolve once a polypectomy has been performed. Submucosal fibroids causing PMB may be suitable for hysteroscopic resection. Endometrial hyperplasia or carcinoma should be managed as discussed in Chapter 62. Recurrent PMB which does not improve with oestrogen treatment suggests an abnormality and may need to be treated with a hysterectomy. REFERENCES 1) Leyendecker G, Kunz G, Kissler S, et al. Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 2006;20(4):523–46. 2) Dawood M, Yusoff MD. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol 2006;108(2):428–41. 3) Marjoribanks J, Proctor M, Farquhar C, et al. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 2010;(1). 4) Adapted from American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013. 5) Royal College of Obstetricians and Gynaecologists. Management of pre-menstrual syndrome. Greentop Guideline No. 48. London: RCOG; Dec 2007.

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6) Yokers KA, Shaughn O’Brien PM, Eriksson E. Premenstrual syndrome. Lancet 2008;371: 1200–10. 7) Cancer Australia. Abnormal vaginal bleeding in pre-, peri- and post-menopausal women: a diagnostic guide for general practitioners and gynaecologists. March 2011. 8) Lee DO, Jung MH, Kim HY. Prospective comparison of biopsy results from curettage and

hysteroscopy in postmenopausal uterine bleeding. J Obstet Gynaecol Res 2011;37:1423–6. 9) Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev 2000;4. 10) Lethaby A, Cooke I, Rees MC. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005;(4).

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Section 3.3 REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY Chapter 48

Infertility

Chapter 49

Amenorrhoea, hyperprolactinaemia and ovulation induction

Chapter 50

Androgen excess, including PCOS, hirsutism and acne

Chapter 48  INFERTILITY Sameer Jatkar

KEY POINTS Approximately 85% of couples will conceive within the first year of attempting. Common causes of infertility are male factor, anovulation, tubal disease and endometriosis. Less common causes include coital factors, uterine abnormalities, cervical mucus inadequacy and defects of oocyte quality. About one-quarter of infertility is ‘unexplained’. Advances in assisted reproductive technology have transformed the management of almost all cases of sustained subfertility. In the case of in vitro fertilisation (IVF), a single stimulation cycle can be expected to produce a live birth in approximately 30% of those with unexplained infertility, 40% with tubal infertility and greater than 20% with oligospermia undergoing intracytoplasmic sperm injection as a component of the IVF.

DEFINITION

AETIOLOGY

Infertility is defined as the failure to conceive after 1 year of regular, appropriately timed intercourse in the absence of contraception. Approximately 85% of couples will manage to conceive within this time frame; therefore, it is appropriate to defer investigation for most until at least a year’s attempted conception. However, some groups warrant earlier investigation. Those with a known past history of tubal disease, including those with past ectopic pregnancy or pelvic inflammatory disease (PID), may present requesting earlier investigation. Similarly, earlier basic investigation for causes of anovulation ought to occur for women who do not have a regular menstrual cycle. In these cases and older women, investigation should be initiated when the couple presents for review. History, examination and investigations undertaken in the setting of infertility should involve both the female and male partner, as male factor infertility can account for up to 30% of those seeking specialist review.

A number of factors are required for a successful pregnancy (Fig 48.1). An oocyte must be released from the ovary on a regular basis. It needs to negotiate the peritoneal cavity for pick up by the fimbriae of the fallopian tubes and travel along patent tubes with proper ciliary function to a uterus capable of sustaining a pregnancy. Along the way, the oocyte has to encounter an adequate number of sperm that have been deposited in the female genital tract at an appropriate time in the cycle to allow fertilisation of the oocyte to occur in the fallopian tube. Finally, the endometrium needs to be receptive to a developing euploid embryo for a normal ongoing pregnancy to occur. Defects can occur at any stage of this process, and can be broadly divided into a number of categories depending on the step at which such dysfunction occurs (Fig 48.1). Identifiable dysfunction can be approximately equally attributed to: 1. the female partner; 2. the male; or 3. both partners. Despite a thorough investigative

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work-up, approximately 25% of couples will have no identifiable dysfunction and therefore suffer so-called ‘unexplained’ infertility. Tubal factors

Uterine factors

Oocyte quality

Anovulation

Endometriosis Cervical mucus Semen quality Coital factors

FIGURE 48.1

Causes of infertility.

EVALUATION Involvement of both partners in the infertile couple is crucial, ideally in a joint consultation. Basic history, examination and certain investigations should be undertaken for all couples, with further guidance towards other and more invasive testing depending on the potential

dysfunction identified in the basic work-up. Table 48.1 lists the comprehensive evaluation with regards to history, examination and investigation of the infertile couple, although not all elements will apply to all couples, and again this will be guided by the preliminary basic work-up. Initial history includes the medical, surgical, social and reproductive histories of both partners. Additional important information involves the sexual history, including duration of attempted conception, awareness of the fertile period, symptoms of ovulation and frequency and timing of intercourse. In the female, the menstrual history is crucial because the absence of regular cycles suggests dysfunction of cyclical ovulation. It is important to enquire about common associations with infertility such as symptoms suggestive of endometriosis (e.g. dysmenorrhoea, dyspareunia) or polycystic ovarian syndrome (PCOS) (e.g. acne, hirsutism, weight gain). Past contraceptive use, exposure to gonadotoxins such as chemotherapy and family history of early menopause or hereditary illnesses are all important to note. For the male partner, past history of note includes previous paternities, as well as a history of undescended testes, mumps or genital trauma. As for the female, history of exposure to gonadotoxic substances such as chemotherapy should be elicited, as well as specific exposures that can interfere with sperm production such as smoking, heavy alcohol intake and anabolic steroid abuse. It is also important to note a change in libido and to enquire regarding problems with erection and ejaculation. This may be indicative of organic pathology such as diabetes or vascular disease or psychological disorders that may benefit from counselling.

TABLE 48.1  INFERTILITY EVALUATION CHECKLIST. Female

Male

1. History • Age • Past reproductive history and previous pregnancy outcomes • Past gynaecological history • Menstrual history, including frequency and regularity, symptoms of ovulation • Sexual history: frequency, problems, lubricant use, timing in fertile window • Weight gain, acne, hirsutism • Dyspareunia, dysmenorrhoea • Galactorrhoea, visual disturbance • Duration of infertility, previous investigations • Contraceptive history: type and duration • Past STI history, previous PID • Medical, surgical, psychiatric, general health • Previous chemotherapy or gonadotoxic therapy • Family history, genetic illness • Medications, smoking, drug and alcohol intake

1. History • Previous paternities • Past history of mumps, undescended testes, genital trauma or surgery including vasectomy • Libido, shaving, frequency of erections • Ability to sustain erection and ejaculation during intercourse • Past STI history • Occupation: heat and toxic agents • Medical, surgical, psychiatric history, general health • Previous chemotherapy or gonadotoxic therapy • Family history, genetic illness • Medications, smoking, drug and alcohol intake, anabolic steroid use

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TABLE 48.1  INFERTILITY EVALUATION CHECKLIST—cont’d. Female

Male

2. Examination • Body habitus, height, weight and BMI • Hirsutism, body hair distribution (Ferriman– Gallwey score to rate hirsutism) • Acne • Presence of galactorrhoea • Thyroid • Routine gynaecological examinations, including Pap smear and STI screens

2. Examination • Body habitus, height, weight, BMI, muscle mass and strength, fat distribution • Secondary sexual characteristics: hair thickness and distribution • Breasts (gynaecomastia), signs of endocrinopathy • Blood pressure lying and standing • Inguinal canals • As indicated, testicular examination: determine size (with aid of orchidometer), consistency, masses, hydrocoele, varicocele; palpate for presence of vas deferens and epididymis

3. Investigations Basic Prepregnancy investigations • Rubella ab, varicella ab (if no past history) • Pap smear Ovulation confirmation • Mid-luteal progesterone Tubal patency and uterine integrity investigations • Hysteroscopy, laparoscopy and dye studies or hysterosalpingogram or saline sonohysterography Endometriosis diagnosis • Laparoscopy (and treat any endometriosis) Ovarian reserve assessment • FSH & LH day 3 • Anti-Müllerian hormone (AMH) STI screen if indicated Additional investigations if anovulation or menstrual disturbance • FSH, LH, prolactin • Thyroid function testing • Androgens: testosterone, DHEA-S, androstenedione • β-hCG • MRI pituitary, visual field testing Additional investigations if ovarian failure • Karyotype • Galactosaemia screen • Fragile X screen

3. Investigations Basic • Semen analysis (WHO criteria 2010) • Volume > 1.5 mL • Count > 15 × 106/mL • Total count > 39 × 106/ejaculate • Normal forms > 4% (strict criteria) • Motility (total) > 40% • Progressive motility > 32% • Live > 58% • STI screen As indicated • Prolactin • FSH/LH, testosterone • Other endocrine: thyroid, adrenal • Karyotype • Y chromosome microdeletions • Cystic fibrosis gene mutations (associated with congenital bilateral absence of the vas deferens) • Sperm autoantibodies • Testicular ultrasound, transrectal ultrasound • Testicular biopsy • Post-ejaculatory urinalysis • MRI pituitary

Examination and initial basic investigations should be undertaken as outlined in Table 48.1. Further investigations will be guided by what is revealed at the initial evaluation, and will be discussed later in this chapter with reference to the major causes of infertility. However, it is important to note that the most fundamental work-up may be done at the primary care level and involves testing both partners. For the female, basic tests include a test of ovulation (the mid-luteal progesterone) in those who menstruate, and a test of ovarian function or reserve

(namely the day 3 FSH and LH). Thyroid function and prolactin is often performed routinely to exclude secondary causes of anovulation. An anti-Müllerian hormone (AMH) investigation may be performed in those with suspected diminished ovarian reserve, with a low AMH seen in this setting. A pelvic ultrasound can rule out a major anatomic abnormality; look for ultrasound evidence of ovulation and measure the endometrial thickness to exclude endometrial hyperplasia in the setting of chronic anovulation. 403

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For the male, the semen analysis is the most important single laboratory investigation in determining the contribution of a male factor. General prepregnancy advice for all couples is also important, including an evaluation of rubella immunity and folate supplementation in the female to identify those requiring vaccination and to reduce the risk of neural tube defects respectively. Pap smears should be up to date and general lifestyle counselling should occur to cease smoking and maintain a moderate alcohol intake. Finally, couples should be made aware of fertile timing as well as symptoms of ovulation to ensure that further attempts to conceive are timed appropriately while undergoing the infertility evaluation.

MAJOR CAUSES OF INFERTILITY MALE FACTOR INFERTILITY The quality and quantity of sperm available for fertilisation has an obvious impact on the chance of conception. Therefore, the semen analysis is fundamental to the evaluation of the male factor. However, a number of disorders can impact on the semen parameters and it is important to recognise that any severe intercurrent illness will cause a transient reduction in sperm quality and quantity even in the normal, healthy male. Therefore, an initial abnormal semen analysis should be repeated to confirm if any abnormality is transient or persistent. See Table 48.1 for the parameters measured in the semen analysis and normal results.1 Male factor infertility can be classified as follows: 1. hypothalamo-pituitary dysfunction 2. testicular failure with absent, reduced or abnormal sperm production 3. obstructive azoospermia (no spermatozoa or spermatogenic cells in semen).

Hypothalamo-pituitary dysfunction Dysfunction at the hypothalamus and pituitary can result in disordered spermatogenesis, although this is a relatively rare cause for infertility in the male. Congenital absence of GnRH-producing neurons will result in hypogonadotrophic hypogonadism and when associated with anosmia is known as Kallman’s syndrome. Pituitary dysfunction resulting in disordered FSH and LH production can also occur in the male. This includes hyperprolactinaemia, infiltrative disorders of the pituitary and pituitary tumours. Anabolic steroid abuse will also result in hypogonadotrophic hypogonadism due to the negative feedback of high androgen levels.

Management Diagnosis involves findings of a low serum testosterone (except when exogenous androgens are present), FSH and LH. An evaluation of serum prolactin as well as other aspects 404

of pituitary function is also necessary. MRI of the pituitary is required for unexplained hypogonadotrophic hypogonadism. Treatment of any pathology identified, withdrawal of exogenous anabolic steroids and/or administration of gonadotrophins via injection may restore spermatogenesis, although this may take many months or longer to occur.

Testicular failure Impaired spermatogenesis may occur despite normal or high levels of endogenous gonadotrophins, suggesting testicular dysfunction. This may be due to congenital disorders of the sex chromosomes such as Kleinfelter’s syndrome (47 XXY and mosaicism) or Y chromosome microdeletions. Other congenital disorders include undescended testes, testicular dysgenesis or anorchia. There are also a number of acquired causes of testicular failure. Testicular torsion, trauma, and orchitis (for instance, due to mumps) can all cause hypergonadotrophic hypogonadism. Similarly, exposure to gonadotoxins such as chemotherapy or radiotherapy can result in a similar picture.

Management Diagnosis usually involves the finding of a raised FSH/ LH, often in the setting of a normal testosterone level, depending on the exact underlying cause. Karyotype should be performed, as well as specific tests to identify Y chromosome microdeletions. The prognosis for these patients is variable and will depend on whether sperm can be identified on biopsy of the testicle to allow the use of IVF with intra-cytoplasmic sperm injection (ICSI) whereby only very small numbers of sperm are necessary for successful fertilisation.

Obstructive disorders Physical obstruction to the passage of sperm from the site of production can be due to congenital or acquired bilateral lesions of the seminal ducts. Obstructive disorders are less common than non-obstructive causes of azoospermia, accounting for 10 to 20% of all azoospermia. Obstruction can occur at the level of the epididymis, vas deferens or ejaculatory ducts. The site of obstruction for the majority of these normogonadotrophic men will be the epididymis, and the obstruction is most commonly acquired due to previous trauma or inflammation such as epididymitis. Congenital bilateral absence of the vas deferens can occur and is associated with the cystic fibrosis carrier state. Thus, cystic fibrosis testing for these patients and their partners is extremely important to gauge any potential risk to the fetus. Previous surgery may also result in obstruction, such as removal of epididymal cysts or, rarely, after hernia repair, while a small but significant number of men seek treatment having previously undergone vasectomy for permanent contraception.

Management These men present with azoospermia with the findings of normal testosterone, FSH and LH levels. They also

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have normal testicular volume on examination. Management depends on the cause and site of lesion, but the two basic options are either surgery to restore the anatomical disturbance or simply obtaining enough sperm for IVF with ICSI via fine-needle aspiration of the epididymis or testes. Microsurgical reversal of a previous vasectomy results in good patency rates and can avoid the need for undergoing IVF.

Pathophysiological classification of anovulation

ANOVULATION

Hypothalamic dysfunction

The female partner may fail to release an oocyte from the ovary in the normal cyclical manner. This is usually accompanied by absent or irregular menstruation, which normally depends on oestrogen production from the developing follicle followed by progesterone secretion and withdrawal from the corpus luteum. There are both clinical and biochemical markers of ovulation. Mid-cycle or ‘mittelschmerz’ abdominal pain may indicate follicular rupture and ovulation. Monitoring of the basal body temperature can also detect the progesterone mediated rise in temperature of 0.5 to 1.0°C after ovulation and corpus luteum formation (Fig 48.2). Urinary dipsticks can also identify the LH surge and impending ovulation when done serially in the mid cycle. However, the more convenient and reliable means of detecting ovulation is a serum progesterone measurement in the mid-luteal phase of those with regular cycles. This would be on day 21 of the normal 28-day cycle or 7 days prior to anticipated menstruation in cycles of different lengths (e.g. day 28 of a regular 35-day cycle). For those with regular periods but of occasionally varying length, serum progesterone may be repeated serially in the luteal phase to identify ovulation that may occur later than predicted. A progesterone level over 20 nmol/L in the mid-luteal phase is a reliable indicator that ovulation has occurred.

Anovulation can be further divided into three areas: 1. hypothalamic dysfunction 2. pituitary dysfunction 3. ovarian failure (raised FSH/LH). Hypothalamic dysfunction occurs in situations of stress, overexercise and weight loss that is either sudden or severe, or in the situation of very low body weight. Athletes who undergo a demanding exercise regime or maintain a very low body fat percentage fall into this category, as do those with anorexia nervosa and low BMI. Intercurrent severe illness will also cause this sort of hypothalamic dysfunction whereby there is a reduction in the GnRH production that is essential for the pulsatile release of FSH and LH from the pituitary gland. Hyper- and hypothyroidism can also cause disruption to the central regulation of ovulation. Chronically high TSH seen in hypothyroidism may alter the dopaminemediated control of prolactin secretion, resulting in hyperprolactinaemia that will resolve with thyroxine replacement therapy. Thus, TSH should be performed in patients presenting for infertility evaluation. The most common cause for hypothalamic dysfunction is the condition of PCOS (described in detail in Chapter 50). In this condition, there are normal serum levels of FSH and LH; however, the ratio of FSH to LH on day 3 of the menstrual cycle is often reversed, meaning that LH exceeds FSH, usually by a factor of at least 2:1. Androgen levels are raised, and there is a fall in sex hormone-binding globulin (SHBG) that results in a raised free androgen index (FAI). However, in contrast to central causes of amenorrhoea, there is a normal serum

Degrees Celsius

37.5 .4 .3 .2 .1 37.0 .9 .8 .7 .6 .5 .4 .3 .2 .1 36.0 Symptoms B B B B D B B M M M M M M E E E M M M M M M M M M M M M M M M D Day of cycle 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 2930 31 32 33 34 35 36

FIGURE 48.2

Basal body temperature chart showing biphasic pattern consistent with ovulation.

Source: Mackay EV, Beischer NA, Pepperell RJ, Wood C. Illustrated Textbook of Gynaelcology. Sydney: Saunders, 1992. Copyright © 1992 Saunders, An Imprint of Elsevier. Figure 14.2.

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oestrogen level, meaning that these women will experience a withdrawal bleed in response to orally administered progesterone (the progesterone challenge test). Importantly, PCOS should not be thought of as primarily an ovarian disease but rather a complex hormonal imbalance that causes hypothalamic dysfunction just as other hormonal disorders (hypothyroidism, hyperprolactinaemia) also produce hypothalamic dysfunction.

Pituitary dysfunction Dysfunction may also occur at the level of the pituitary gland. Excess production of prolactin from a prolactinoma may cause anovulation through negative feedback mechanisms. More rarely, the pituitary gland may be damaged from trauma, radiation, infiltration or necrosis (Sheehan’s syndrome). Again, this results in the failure of the pulsatile release of FSH and LH needed to stimulate folliculogenesis.

Ovarian failure In ovarian failure, the ovaries can fail to respond to gonadotrophin stimulation in the setting of a raised FSH and LH. This is termed ovarian failure, meaning there is a complete cessation of ovarian follicular activity even in the setting of supranormal levels of gonadotrophins. This condition is also associated with low oestrogen levels. There are a number of possible causes for premature ovarian failure including genetic abnormalities such as Turner’s syndrome (45XO), Turner’s mosaicism (45XO/46XX) and fragile X carrier states. Other causes of ovarian failure include autoimmune disease, especially co-existent with autoimmune adrenal disease, radiation therapy, chemotherapy and galactosaemia.

Luteinised unruptured follicle syndrome and luteal phase defect Finally, dysfunction of ovulation has been described in the luteinised unruptured follicle syndrome, whereby follicles fail to release the developing oocyte despite the LH surge and luteinisation. Also, deficient production of progesterone during the luteal phase may occur and this short or luteal phase defect may result in a situation whereby progesterone levels fail to support an implantation and ongoing pregnancy. Both these diagnoses are areas of controversy in terms of their definition and frequency, although the logical treatment for a potential luteal phase defect is progesterone supplementation during the luteal phase. Note that these diagnoses are associated with normal day 3 FSH and LH and normal dominant follicular development on ultrasound but with absent or low mid-luteal progesterone levels.

osteoporosis in both central hypogonadism and ovarian failure (which are associated with a low oestrogen state). A detailed explanation of differing means of ovulation induction and management of anovulation in the setting of hyperprolactinaemia is contained in Chapter 49, while the detailed management of PCOS is discussed in Chapter 50. PCOS is the most common cause of anovulation. The options to restore ovulation include lifestyle modification and weight loss, medical treatment or surgical management (laparoscopic ovarian drilling or cautery). However, the majority of these patients can be made to successfully ovulate using oral anti-oestrogen medications such as clomiphene citrate. Anti-oestrogens are given as a short course during the follicular phase of the menstrual cycle for courses typically of 5 days duration. For instance, clomiphene can be given in doses from 25 to 150 mg for cycle days 2 through 6 with ovulation expected at about day 14 of a 28-day cycle. The interruption to negative feedback on the hypothalamic–pituitary axis causes an increased release of endogenous gonadotrophins to stimulate ovulation. However, the main concern with this mechanism is multiple pregnancy, and dosing should begin in the lower range with a gradual escalation over a number of cycles to utilise the minimum dose successful in restoring ovulation (as determined by a mid-luteal progesterone level). For those with PCOS who fail to ovulate on clomiphene, options include other oral anti-oestrogens such as letrozole, gonadotrophin injections or laparoscopic ovarian drilling as described in Chapters 49 and 50. Importantly, the chronic anovulation in PCOS leads to chronic exposure of the endometrium to oestrogen without the protective effect of progesterone that results from ovulation. Therefore, in the longer term, these patients must be managed with cyclic progestogens, the contraceptive pill or progesterone-releasing intrauterine device (IUD) to prevent endometrial hyperplasia. Central anovulation can be successfully treated with gonadotrophin injections to replace the FSH and LH activity lacking in this condition. Clomiphene and other anti-oestrogen medications do not restore ovulation in central hypogonadism as they rely on a properly functioning hypothalamic–pituitary–ovarian axis to release endogenous FSH and LH. In the longer term, these patients also require close monitoring to prevent osteoporosis and should be maintained on the contraceptive pill when not desiring pregnancy. Monitoring bone density should be considered in these patients.

Management of anovulation

TUBAL FACTORS

Management of anovulation is directed towards addressing the cause identified, restoring ovulation and managing the potential long-term consequences of chronic anovulation. These long-term consequences include the risk of endometrial hyperplasia in PCOS that occurs due to chronic unopposed oestrogen exposure (due to absence of cyclic endometrial protection from progesterone) or

The fallopian tubes are essential for the collection of the released oocyte from the ovary, as well as for transport and fertilisation of the oocyte as it moves towards the uterine cavity. In order for the oocyte to be successfully captured by the fimbriae, they must migrate to lie over the developing follicle while the cilia lining and muscular action of the tube have important roles in the subsequent

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transfer of oocyte and then zygote. Fertilisation occurs in the ampulla of the fallopian tube, and the epithelium lining the tube has an important role in maintaining the appropriate microenvironment for fertilisation and nutrition of the developing embryo. Tubal dysfunction has numerous causes, although the most important is that caused by pelvic infections. Acute PID is most often sexually transmitted in the younger population and is mainly due to Chlamydia trachomatis and to a lesser frequency by Neisseria gonorrhoea, although other organisms can be involved. Pelvic infection may also arise due to instrumentation of the uterus such as after an abortion or in the setting of placement of an IUD. In this situation, polymicrobial infection has been implicated, with organisms such as Escherichia coli, streptococci and anaerobes often isolated from specimens. Other causes of pelvic infection include ruptured acute appendicitis and peritonitis, although the resultant scarring is more likely external to the tube and therefore affecting tubal mobility. Tubal infection and acute salpingitis may result in scarring and tubal occlusion, causing a physical obstruction to ovum transport and fertilisation. In the acute phase of infection, the tube may fill with pus to form a pyosalpinx or, alternatively, the chronically obstructed tube may dilate and fill with fluid to form a hydrosalpinx (Figs 48.3 and 48.4). Tubal hydrosalpinges may not only cause pain and prevent ovum transport through the ipsilateral tube, but also reduce the chance of spontaneous conception through a contralateral patent tube or IVF conceptions by as much as 50%. This is thought to be due to the effluent

FIGURE 48.3

A grossly dilated tubal hydrosalpinx is seen on hysterosalpingography.

Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 8.23.

of fluid from the hydrosalpinx into the uterine cavity being toxic to the embryo and preventing implantation in the uterine cavity. Identifying and treating tubal hydrosalpinx is thus important in the setting of tubal disease. Other intraperitoneal factors can affect tubal function and fertility. Peri-tubal adhesions can impair tubal function, particularly the proper migration of the fimbriae involved in oocyte collection from the follicle.

Management of tubal disease Prevention of pelvic infection is extremely important as most tubal damage is not amenable to repair. All patients attempting conception should be screened for Chlamydia and gonorrhoea by PCR on either endocervical or first-pass urine samples. Screening and/or prophylactic antibiotics may also be considered with any uterine instrumentation such as hysterosalpingogram. Diagnosis of tubal factor disease can be achieved by either hysterosalpingography (HSG), saline or hysterosalpingo contrast sonography (HyCoSy) or laparoscopy and tubal dye studies (Fig 48.5). The two former techniques involve infusion of a contrast medium and X-ray or ultrasound assessment of tubal patency respectively. The advantage of these is that they are quick and relatively less invasive. However, both will fail to adequately evaluate the peritoneal factor or diagnose other impediments to tubal function such as peritubal adhesions. Laparoscopy can diagnose and treat these, but as this is a more invasive technique requiring general anaesthesia it is often deferred until all other potential contributory factors are excluded. However, laparoscopy is also the only way to definitively diagnose endometriosis. Hydrosalpinges should be removed by laparoscopy if found during the diagnostic evaluation. Also, release of peritubal adhesions and treatment of endometriosis at laparoscopy can improve fertility and natural conception rates. If both tubes are occluded on evaluation, neosalpingostomy may potentially be performed for distal occlusion.

FIGURE 48.4

Gross tubal hydrosalpinx at excision. Note the dilated thin-walled tube with agglutinated fimbriae.

Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 29.7.

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Laparoscope Sleeve with valve Pneumoperitoneum

Fibre optic cord

Tubing for gas insufflation

Uterine cannula

FIGURE 48.5

Laparoscopy and hysteroscopy performed together with tubal dye studies allow a thorough evaluation of tubal and peritoneal factors.

Source: Mackay EV, Beischer NA, Pepperell RJ, Wood C. Illustrated Textbook of Gynaelcology. Sydney: Saunders, 1992. Copyright © 1992 Saunders, An Imprint of Elsevier. Figure 14.2.

However, given the high rate of failure of this procedure and a potentially unacceptably high tubal ectopic pregnancy rate in this situation, IVF is the recommended management for most occlusive tubal disease.

ENDOMETRIOSIS Endometriosis is discussed in detail in Chapter 58. An epidemiological association with infertility is unquestioned and therapy of endometriosis has been shown to improve infertility in randomised studies.

Explanations of the epidemiological association of endometriosis with infertility How does endometriosis predispose to infertility? Pelvic peritoneal endometriosis may contribute to infertility through three principle mechanisms. The endometriosis can adversely affect the peritoneal fluid with toxic effects on the released oocyte. Dyspareunia will reduce intercourse frequency while pelvic adhesions may distort or obstruct the tube or impair fimbrial capture of the oocyte.

Could infertility predispose to endometriosis? The development of endometriosis may be enhanced by repeated menstrual cycles without conception and 408

without any progestogen. For 2 weeks every month, the follicular phase will provide a time of enhanced endometriotic growth. This will occur for long durations in women abstaining from sexual intercourse and those having sexual intercourse but not conceiving and not on progestogen therapy (e.g. infertility of any cause including male infertility).

COITAL FACTORS Sexual intercourse is obviously necessary for natural conception but surprisingly little attention is paid to the frequency and timing of sexual intercourse for optimal chances of conception. Even though the sperm density will reduce with very frequent sexual intercourse, high sexual frequency is associated with higher conception rates. That is, if the sperm density is low because of male pathology, fertility is markedly impaired. If the density is reduced by high rates of sexual intercourse, fertility is normal or increased. Sperm survive in the fertile pre-ovulatory cervical mucous for up to 5 days but an oocyte will only survive for approximately 24 hours in the absence of fertilisation. The optimum timing of sexual intercourse can therefore be deduced to be in the days leading up to ovulation but not more than a day after.

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UTERINE FACTORS For successful pregnancy, the uterine cavity must be adequate to receive and support the pregnancy. Congenital uterine anomalies such as a uterine septum may exist or adhesions may be acquired through previous instrumentation of the uterine cavity. Endometrial polyps may form and prevent implantation of the embryo; alternatively, uterine fibroids may impinge on the uterine cavity, again making successful implantation less likely. Uterine factors may be diagnosed by ultrasound, HSG or saline/contrast ultrasound; however, the gold standard for evaluation when suspected from noninvasive imaging is hysteroscopy. Hysteroscopy also allows for intervention such as fibroid resection, polypectomy and breakdown of intrauterine adhesions.

Intrauterine adhesions (Asherman’s syndrome) Three factors are commonly necessary to create intrauterine adhesions: 1.curettage; 2. infection; and 3. recent pregnancy. The common sequence of events is the development of Asherman’s syndrome following a curette for

Müllerian anomalies Uterine anomalies may be associated more with recurrent miscarriage than with inability to conceive, depending on the exact nature of the anomaly. The prognosis of more complicated uterine anomalies is harder to predict, although pregnancies are often able to be carried to near term in one horn of adequate capacity of a bicornuate uterus (Figs 48.6 and 48.7). A uterine septum may be resected hysteroscopically (Figs 48.8 and 48.9).

FIGURE 48.7

Profound bicornuate uterus with a pregnancy established in the right uterine horn. Indentation of the serosal surface is clearly visualised. Source: Callen PW. Ultrasonography in Obstetrics and Gynecology. 5th edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 31.19.

FIGURE 48.6

Ultrasonographic scan of bicornuate uterus with gestational sac in the right horn.

Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 127.1.

FIGURE 48.8

A wide-based uterine septum noted at hysteroscopy.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 14.18.

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FIGURE 48.9

Uterine cavity after resection of the septum.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 14.19.

FIGURE 48.10

Hysteroscopic view of intrauterine adhesions (Asherman’s syndrome).

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 14.8.

infected retained products of conception after a miscarriage or retained placental cotyledon. Presentation may be with amenorrhoea, dysmenorrhoea or recurrent miscarriage. If pregnancy succeeds, a morbidly adherent placenta (placenta accreta) is more likely. The intrauterine adhesions (synechiae) run between anterior and posterior walls and are readily diagnosed with a contrast hysterogram, sonogram or hysteroscopically (Fig 48.10). The adhesions can usually be easily divided hysteroscopically (Fig 48.11) and recurrence of adhesions avoided with the placement of an IUD to keep the anterior and posterior walls apart and oestrogen therapy to rapidly resurface the denuded endometrium.

CERVICAL MUCUS QUALITY As stated previously, fertile cervical mucus is an important reservoir of sperm that are progressively released into the upper genital tract to maximise the chances of a successful fertilisation of the oocyte within 24 hours of its release. Factors that may rarely reduce fertility at a cervical level include extensive resection of the endocervix (e.g. successive cone biopsies for cervical intraepithelial neoplasia [CIN], trachelorrhaphy, Manchester repair) that may substantively reduce cervical mucus production.

OOCYTE QUALITY Oocyte quality progressively decreases with advancing maternal age as evidenced by reduced oocyte retrieval, fertilisation and pregnancy rates with IVF. While no specific test exists to determine if oocyte quality is 410

FIGURE 48.11

Hysteroscopic view after breakdown of adhesions. Note the volume of the uterine cavity has been restored.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 14.9.

contributing to infertility, it is reasonable to assume that this is a factor in women of advancing age.

UNEXPLAINED INFERTILITY Unexplained fertility is a diagnosis of exclusion, whereby all investigations for the factors discussed have been

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performed and no abnormality has been found in the male or female partner. This may represent a subset of reproductive function for which current testing is inadequate to detect contributory factors, or indeed those with largely normal reproductive function who by chance still fail to fall pregnant after numerous cycles of attempted conception.

Multifactorial minor cause infertility The third and possibly most common explanation is that there is no single cause but rather a combination of factors that, on their own, would be insufficient to cause infertility but in combination can lead to lengthy periods of failing to conceive. An example would be a woman of 39 years of age (oocytes suboptimal) who is overweight (mild PCOS with occasional anovulation), who had one episode in her teens of Chlamydia (tubes patent but cilial function suboptimal), whose husband is away interstate occasionally (intercourse frequency reduced), has a few spots of endometriosis (partly as a consequence of years of no conception and no pill) and whose husband has a sperm count still in the normal range but worse than average on most parameters (density, morphology, motility). It is therefore possibly to be within the ‘normal range’ for each possible cause of subfertility, but the collective impact of having multiple factors below average might be quite profound. Laparoscopy is required to definitively exclude any contributory factors in infertility before labelling a patient as suffering from unexplained infertility, but it may be avoided in those who decide to pursue IVF as long as noninvasive means have excluded a tubal hydrosalpinx.

IVF AND RELATED PROCEDURES Laboratory techniques involving the handling and manipulation of gametes have revolutionised the management of female and male factor infertility. Since the birth of the first IVF baby in 1978, a number of significant advances have been made in both the techniques utilised to obtain suitable numbers of oocytes from the female partner and the laboratory techniques involved in the fertilisation and culture of embryos. These techniques mainly include uterine insemination (IUI) with or without controlled ovarian hyperstimulation (COH) and IVF including the use of intracytoplasmic sperm injection (ICSI). The major difference between these two techniques is that during IVF, fertilisation occurs in vitro (literally, ‘in glass’) in the laboratory, as opposed to in the body with IUI. Hence for IVF, gametes have to be collected from both the male and female partners in order for fertilisation to take place. Much of the variation in IVF regimes involves different means of stimulating the ovaries to obtain oocytes and well as techniques used to achieve fertilisation after collection. Other techniques occasionally used include gamete intra-fallopian transfer (GIFT) and zygote intra-fallopian transfer (ZIFT), although these are less commonly performed given the success of IVF. The major limitations

of these techniques are the need for laparoscopy to transfer either gametes or zygotes directly to the fallopian tubes, potentially higher multiple pregnancy rates and often poorer success rates when compared with conventional IVF. They are also not suitable for those with tubal infertility. However, these techniques are sometimes utilised when there is a personal objection to the creation of embryos outside the body. Finally, more recent advances in technology have expanded the scope of what can be achieved using the assisted reproductive techniques. Genetic disease can now be screened for in embryos prior to transfer back to the patient through the technique of pre-implantation genetic diagnosis (PGD). PGD can detect aneuploidy, sex chromosome disorders, translocations and single gene disorders where these are known to exist in the family of patients undergoing IVF. Also, newer freezing techniques have expanded the range of possibility for fertility preservation and potentially even postponement of the menopause though the techniques of oocyte freezing and ovarian tissue freezing respectively.

INTRAUTERINE INSEMINATION (IUI) AND CONTROLLED OVARIAN HYPERSTIMULATION (COH) Partner semen may be washed and deposited in the uterus at the appropriate time in the menstrual cycle to overcome mild male factor and unexplained infertility. It is also used in anovulatory infertility in combination with agents to stimulate the ovary, whether using oral medication or injections (controlled ovarian hyperstimulation [COH]). COH/IUI is more effective than IUI alone but any technique using IUI relies on normal patent fallopian tubes and a sufficient number of sperm being available for fertilisation. It is therefore not suitable for tubal disease or moderate to severe male factor infertility.

IVF AND INTRACYTOPLASMIC SPERM INJECTION (ICSI) IVF overcomes the need for patent fallopian tubes due to the fact that oocytes are collected directly from the stimulated ovary and fertilised in the laboratory before embryos are returned to the uterus via an embryo transfer catheter. The earliest forms of IVF involved the aspiration of a single oocyte from a natural menstrual cycle to yield one embryo for transfer, but relied on collection of the oocyte at a precise moment prior to ovulation and resulted in low embryo numbers. Advancement in medications has allowed hyperstimulation of the ovary to obtain multiple oocytes from a single cycle of IVF as well as GnRH agonist or antagonist medication to allow an appropriate timing for oocyte collection at convenient timing during the day. These advances have remarkably improved the yield of embryos from a single IVF cycle, thus improving the per cycle success rate for pregnancy. 411

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Another breakthrough has involved the development of micromanipulation techniques so that a single sperm may be injected into a single collected oocyte. This is known as intracytoplasmic sperm injection or ICSI. This has revolutionised the management of male factor infertility. Prior to this, for successful IVF a male semen count of millions per millilitre of ejaculate would still be required for conventional IVF. However, ICSI allows for fertilisation to occur with sperm counts far lower than this, including small amounts of surgically retrieved sperm from patients with degrees of testicular failure or obstructive azoospermia.

OOCYTE AND OVARIAN TISSUE FREEZING IVF allows for the preservation of fertility in those undergoing treatment that may be gonadotoxic or destructive to the ovary. IVF may be performed prior to chemotherapy or radiotherapy in order to preserve the option for later child bearing. As in any other IVF cycle, embryos can be stored through the process of cryopreservation for transfer back to the recipient at a later date. In certain situations, such as when the patient does not have a current male partner, it might be more suitable to preserve oocytes without fertilisation to obviate the need for donor-unrelated sperm leading to embryos that are genetically unrelated to any future male partner. However, the conventional ‘slow freeze’ technique is damaging to the fragile oocyte, meaning that there is often irreparable damage to oocytes during the freeze/thaw process that renders them unsuitable for fertilisation. The newer freezing technique of vitrification is associated with less cell damage and therefore much greater success with regards to fertilisation and embryo development. Indeed, there have been successful pregnancies following use of this technique. More recently, there has been success with the freezing through vitrification of whole ovarian cortical tissue collected via wedge resection of the ovary at laparoscopy for patients due to undergo gonadotoxic treatment like chemotherapy. This can be achieved much more quickly than a stimulation cycle to store oocytes or embryos, and so will not delay treatment for cancer. Pregnancy can result through natural ovulation or through the use of IVF after frozen tissue is later reimplanted in the patient’s own ovary. This same technique could potentially be used to delay or prevent the menopause, although there is no clinical use of this technique for such an indication at this time. Both oocyte freezing and ovarian cortical tissue freezing can potentially be used in the attempt to preserve fertility for social reasons when a patient needs to delay conception for whatever reason. However, tissue and oocytes harvested at the latter part of the naturally fertile age are likely to yield poorer results than those preserved at an earlier age and therefore shouldn’t be relied on to 412

necessarily postpone conception in women of late reproductive age.

COMPLICATIONS OF IVF AND RELATED TECHNIQUES The main complications of all the assisted reproductive techniques include multiple pregnancy and ovarian hyperstimulation syndrome. Multiple pregnancy is associated with poorer pregnancy outcomes, including greater maternal risks of medical complications such as gestational diabetes, and greater fetal risks, including prematurity and cerebral palsy. Multiple pregnancy is associated with higher order follicular development during COH, and if too many follicles develop, IUI cycles should be abandoned or converted to IVF cycles. Similarly, given that the risk of multiple pregnancy is related to the number of embryos transferred back to the patient, single embryo transfer should be the norm for most patients. Ovarian hyperstimulation syndrome can occur after any medical ovarian stimulation but is most frequently associated with the higher gonadotrophin doses used for IVF. It is characterised by generalised capillary leakage leading in severe cases to renal impairment, haemoconcentration, the accumulation of ascites and the accumulation of pleural effusions. In its most severe form, it is a potentially life-threatening condition with major morbidity due to thromboembolism and also the consequences of renal failure and respiratory compromise. Modification of the stimulation regime for those at high risk (including patients with PCOS) is extremely important, and management for those severe cases may involve abdominal paracentesis and treatment with intravenous albumin infusion. REFERENCE 1) World Health Organisation. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010. FURTHER READING American Urological Association Education and Research, Inc. The optimal evaluation of the infertile male: AUA best practice statement. Linthicum (MD): American Urological Association, Inc; 2010. Andersen CY, Silber SJ, Berghold SH, et al. Long-term duration of function of ovarian tissue transplants: case reports. Reprod Biomed Online 2012;25(2):128–32. Burmeister L, Kovacs G, Osianlis T. First Australian pregnancy after ovarian tissue cryopreservation and subsequent autotransplantation. Med J Aust 2013;198(3):158–9. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organisation reference values for human semen characteristics. Hum Reprod Update 2010;16(3):231–45.

Chapter 48  Infertility

Dohle G, Diemer T, Giwercman A, et al. Guidelines on male infertility. Arnhem, The Netherlands: European Association of Urology; 2010. ESHRE Capri Workshop Group. Intrauterine insemination. Hum Reprod Update 2009;5:265–77. Harper J, Wilton L, Traeger-Synodinos J, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update 2012;18(3):234–47. Hori Y, SAGES Guidelines Committee. Diagnostic laparoscopy guidelines. Surg Endosc 2008;22(5):1353–83. Johnson N, van Voorst S, Sowter M, et al. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev 2010;(1):CD002125. Levine J, Canada A, Stern C. Fertility preservation in adolescents and young adults with cancer. J Clin Oncol 2010;28(32):4831–41. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 1997;337(4):217–22.

National Collaborating Centre for Women’s and Children’s Health. Fertility: assessment and treatment for people with fertility problems. Commissioned by the National Institute for Clinical Excellence. London: RCOG Press; 2004. Online. Available: ; [18 Dec 2014]. Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 2012;98(2):294–307. Propst A, Bates G. Evaluation and treatment of anovulatory and unexplained infertility. Obstet Gynecol Clin North Am 2012;39(4): 507–19. Silber SJ. Ovary cryopreservation and transplantation for fertility preservation. Mol Hum Reprod 2012;18(2):59–67. Verhulst SM, Cohlen BJ, Hughes E, et al. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev 2012;(9):CD001838.

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Chapter 49  AMENORRHOEA, HYPERPROLACTINAEMIA AND OVULATION INDUCTION Sameer Jatkar

KEY POINTS Amenorrhoea ■ Amenorrhoea is the absence of menstruation and a common reason for clinical presentation to a general practitioner or gynaecologist. ■ Aetiology is best described in terms of the hypothalamic–pituitary–ovarian axis with uterine and obstructive causes further down the pathway. ■ Clinical problems that often occur in parallel with amenorrhoea include infertility and oestrogen deficiency. ■ The first step of management is to determine and treat the aetiological factor, where possible. ■ The treatment of amenorrhoea will often be dictated by the desire or otherwise to be pregnant. The patient desirous of fertility will want to ovulate but the patient who does not wish to be pregnant can have any hormonal deficiency treated by replacement. Hyperprolactinaemia ■ Hyperprolactinaemia is the most common adenoma of the pituitary and blocks ovulation by negative feedback of prolactin on the hypothalamic–pituitary axis. ■ A pituitary macroadenoma can have a space-occupying effect with pressure on the optic chiasm and impairment of pituitary function. ■ Prolactinomas reduce in size and functionality in response to bromocriptine or cabergoline. Ovulation induction ■ Ovulation induction is indicated in the patient who wishes to ovulate, has a functioning ovary but has not responded completely to correction of any underlying aetiology. ■ Oral treatments include clomiphene, which increases endogenous gonadotrophin secretion by blocking negative feedback of oestrogen on the hypothalamic–pituitary axis. ■ Injectable gonadotrophins (FSH and LH) can be used for those without a functioning hypothalamic– pituitary axis or refractory to oral therapy, but they carry a higher risk of multiple pregnancy.

AMENORRHOEA DEFINITIONS Amenorrhoea is the absence of menstruation. A woman who has not had a period for 7 weeks will often be termed to have 7 weeks of amenorrhoea. Primary

amenorrhoea is defined as the failure of spontaneous menstruation to commence by 16 years of age, or by 15 years of age if there is an absence of secondary sex characteristics. Secondary amenorrhoea is the absence of menstruation for greater than 6 months’ duration in a woman who has previously menstruated. Oligomenorrhoea describes a reduced frequency of periods where

Chapter 49  Amenorrhoea, Hyperprolactinaemia and Ovulation Induction

cycles are between 6 weeks and 6 months of duration and often irregular in timing. Secondary amenorrhoea is approximately 85% hypothalamic–pituitary in origin. Primary amenorrhoea is only about 50% hypothalamic–pituitary, with the other 50% being due to ovarian, uterine and lower genital tract causes, which are responsible more often than in a case of secondary amenorrhoea. Oligomenorrhoea and secondary amenorrhoea share many clinical features and aetiologies. Hypogonadotrophic hypogonadism is a term that is sometimes used to refer to reduced ovarian function (hypogonadism) in combination with low levels of stimulatory hormones to the ovary. Thus, the pattern seen is low oestrogen and progesterone in the setting of low FSH and LH. Hypogonadotrophic hypogonadism is seen in hypothalamic–pituitary causes of ovarian insufficiency. In contrast, if it is a failure of ovarian response to adequate hypothalamic–pituitary stimulation, the lack of negative feedback to the hypothalamus and pituitary from ovarian oestrogen and progesterone would result in high FSH and LH and is therefore sometimes termed hypergonadotrophic hypogonadism.

PATHOGENESIS It is important to note that normal menstrual function requires the functioning of the hypothalamic–pituitary– ovarian axis, as well as a functional uterine endometrium and patent lower genital tract (Fig 49.1). Hence, disturbance at any of these levels may manifest in disorders of menstruation.

AETIOLOGY Primary amenorrhoea The failure to commence menstruation has a diverse range of aetiologies, although the most common cause is simply a constitutional delay and is often associated with a positive family history. However, this is a diagnosis of exclusion and other causes should be ruled out prior to this diagnosis. Primary amenorrhoea may be encountered in the setting of normal or absent secondary sexual development. In the absence of secondary sexual development, investigation ought to begin earlier than in the normally developing female, at the age of 14 years. While the full evaluation of primary amenorrhoea is detailed in earlier chapters, broadly speaking the absence of secondary sexual characteristics is suggestive of genetic disorders, primary gonadal failure and central failure of gonadotrophin release, while the presence of normal pubertal development is more suggestive of anatomic disturbance to menstruation. These include the Müllerian duct anomalies such as uterine or vaginal agenesis, transverse vaginal septum or imperforate hymen. The latter three conditions involve an obstruction to menstrual outflow and these women actually suffer from cryptomenorrhoea. This refers to the situation where

Hypothalamus

GnRH

Pituitary FSH LH Ovary Oestrogen Progesterone Endometrium Menstrual shedding Lower genital tract

FIGURE 49.1

The endocrine control of menstruation and associated disorders.

menstrual bleeding occurs in the presence of a functioning endometrium, and these patients can present with cyclical abdominal pain and pelvic masses due to the accumulation of menstrual blood. The treatment for these conditions involves surgery to relieve the obstruction; for instance, excision of a transverse septum or a hymenectomy for an imperforate hymen. Finally, it is important to remember that any severe systemic illness can result in amenorrhoea, so adolescents with chronic illness may experience primary amenorrhoea even in the absence of any known endocrine or gynaecological dysfunction. Basic investigations in primary amenorrhoea include measurement of serum hormones and gonadotrophins (oestrogen, progesterone and FSH/LH respectively), exclusion of other endocrine disorders through the appropriate tests (e.g. thyroid function, prolactin levels) and an evaluation of the pelvis using ultrasound and, less frequently, by CT, MRI or laparoscopy for complicated anomalies of the lower genital tract.

Secondary amenorrhoea Secondary amenorrhoea and oligomenorrhoea is much more frequently encountered in clinical practice and, as already indicated, involves the cessation of menstruation for 6 or more months in those with previously regular periods. 415

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The functioning of an intact hypothalamic–pituitary– ovarian axis is paramount to the presence of regular menstruation, as well as the presence of a responsive endometrium and intact outflow tract. However, anatomical disturbance is less common in those who have previously menstruated. The important exception to this rule is when an anatomical dysfunction has been acquired, for instance in the form of uterine adhesions after uterine instrumentation or infection. It is useful to consider causes of secondary amenorrhoea according to the level at which disturbance may occur (Fig 49.1). Amenorrhoea may be divided into central causes (hypothalamus and pituitary dysfunction— associated with low FSH and LH) or peripheral causes (end organ dysfunction of ovaries or endometrium— associated with high or normal FSH and LH respectively). The most common cause of secondary amenorrhoea is pregnancy, and this is easily diagnosed by serum or urinary pregnancy testing. Apart from pregnancy, the most frequently encountered conditions include (in order): 1. the polycystic ovarian syndrome (PCOS); 2. hypothalamic amenorrhoea (hypogonadotrophic hypogonadism); 3. hyperprolactinaemia (discussed later in this chapter); and 4. premature ovarian failure. Oligomenorrhoea and amenorrhoea can have important implications for fertility as well as leading to adverse consequences such as osteoporosis in settings of low oestrogen states or endometrial hyperplasia in cases of chronic anovulation (leading to a lack of progesterone, which is protective against endometrial hyperplasia). Thus, while a reduced frequency of menstruation might not need specific treatment unless the patient currently desires fertility, it is important to exclude causes that require treatment (such as hypothyroidism) or administer treatment to prevent the adverse consequence of prolonged amenorrhoea.

CAUSES OF AMENORRHOEA The most frequently encountered causes of amenorrhoea will now be discussed. See Table 49.1 for a summary of aetiology and management, including the more rare causes of this clinical presentation.

1.  Hypothalamic causes Regular cyclical menstruation is reliant on the pulsatile release of GnRH from the hypothalamus. a. Constitutional hypothalamic dysfunction refers to a situation where the woman has a relatively low threshold for ceasing GnRH pulsatility, often under stress (see point b). Such a tendency may be familial. Kallman’s syndrome involves the association between a lack of GnRH-producing neurons and anosmia, most commonly genetic in origin. b. Stress from psychological causes, systemic illness, overexercise and weight loss, or low body mass index 416

(BMI) will cause a decrease in GnRH secretion and hence result in reduced stimulation to the pituitary for pulsatile FSH and LH release. Eating disorders, in particular anorexia nervosa, can be responsible for this presentation and peak prevalence of this disease occurs in young women. Competitive athletes often suffer from amenorrhoea due to the impact of frequent exercise by a similar central mechanism. c. Medications can also act centrally to cause amenorrhoea. For instance, the contraceptive pill taken continuously or depot medroxyprogesterone acetate will cause negative feedback on the hypothalamus, leading to suppression of its function. d. Endocrine disorders may impact on hypothalamic function. These include hyperprolactinaemia, hypothyroidism, hyperandrogenism (e.g. PCOS) and conditions associated with elevation of oestrogen and progestogen such as the oral contraceptive pill, pregnancy and oestrogen-producing tumours of the ovary. It is important at this point to remember that PCOS does not cause ovarian failure but rather hypothalamic– pituitary dysfunction through hyperandrogenism.

2.  Pituitary causes Diminished production of FSH and LH may be the result of lesions of the pituitary gland. The anterior pituitary is responsible for the pulsatile secretion of FSH and LH in response to GnRH from the hypothalamus. a. Neoplasia of the pituitary may impact endocrinologically (e.g. prolactin secreting) or via a mass effect on the pituitary gonadotrophin secretion function. Tumours are classified as either microadenomas (microprolactinomas) of < 1 cm or macroadenomas (macroprolactinomas) ≥ 1 cm in diameter. Given that mass lesions may reach a size of 2 to 3 cm before becoming symptomatic, so when masses do cause symptoms, visual disturbance in the form of a bitemporal hemianopia may occur due to pressure on the optic chiasm. Surgical or radiation treatment of a previous neoplasm is one of the more common causes of pituitary dysfunction. b. Postpartum pituitary necrosis or Sheehan’s syndrome is now a rarely encountered cause of hypopituitarism, due to the fact that obstetric haemorrhage can be aggressively managed with fluid resuscitation and blood transfusion.

3.  Ovarian failure Most often when the ovary fails to respond to gonadotrophin stimulation, it is due to the absence of oocytes within the ovary. Essentially, the ovary has ‘run out of eggs’ or never had any. The FSH and LH levels rise in the absence of negative feedback of oestrogens and progesterone. This is a normal occurrence at the time of the menopause but when it occurs prior to 40 years of age, it may be termed premature ovarian failure (POF).

Chapter 49  Amenorrhoea, Hyperprolactinaemia and Ovulation Induction

TABLE 49.1  AMENORRHOEA: CLASSIFICATION OF AETIOLOGY ACCORDING TO PATHOGENESIS. Location

Aetiology

Specific causes

Hypothalamic

Stress

• • • •

Psychological Exercise Weight loss Systemic disease

Congenital

• •

‘Constitutional’ (familial) Kallman’s syndrome: GnRH failure with anosmia

Endocrine

• • • •

Hyperprolactinaemia Hypothyroidism Hyperandrogenism, including PCOS Pregnancy, hormonal contraception

Medications

•

Antipsychotic drugs (e.g. phenothiazines)

Neoplasm

• • •

Prolactinoma Other hormone-secreting tumours (Cushing’s, acromegaly) Non-hormone-secreting tumours

Trauma

•

Surgery or radiation (usually for a previous pituitary neoplasm)

Infarction

•

Sheehan’s syndrome (postpartum severe sustained hypotension causing pituitary necrosis)

Infiltration

•

Sarcoidosis, haemochromatosis, histiocytosis, Wegener’s granulomatosis

Congenital

• • •

Gonadal agenesis (ovarian or testicular both present with female phenotype) Turner’s syndrome (XO) and mosaics Familial premature ovarian failure

Trauma

•

Surgery or radiation

Metabolic

•

Galactosaemia

Inflammatory

• •

Mumps oophoritis Autoimmune ovarian failure

Medications

•

Chemotherapy

Congenital

•

Uterine agenesis, including androgen insensitivity syndrome

Inflammatory (adhesions)

•

Asherman’s syndrome

Congenital

•

Atresia

Surgery

•

Cervical stenosis (e.g. after cone biopsy)

Neoplasia

•

Endometrial or cervical cancer occluding cervix but usually some bleeding occurs

Congenital

• •

Vaginal atresia or septum Imperforate hymen

Pituitary

Ovaries

Uterus

Cervix

Vagina

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Premature ovarian failure has a number of diverse causes including ovarian agenesis, chromosomal disorders, autoimmune disease, chemotherapy and radiation exposure as well as metabolic causes such as galactosaemia and haemochromatosis.

4.  Uterine disorders Congenital absence of the uterus (Mayer-RokitanskyKüster-Hauser syndrome) may occur in isolation or in association with androgen insensitivity syndrome. In the latter, a testis produces anti-Müllerian factor, preventing uterine development; however, an absence of androgen effect during embryonic development and beyond results in a normal female phenotype. Uterine dysfunction can be acquired due to intrauterine adhesions or synechiae caused by previous uterine instrumentation or infection. This condition, known as Asherman’s syndrome, arises due to denudation of the endometrium resulting in adherence of the uterine walls such that the uterine cavity may be partially or totally obliterated. Diagnosis is by hysterosalpingography (HSG) or hysteroscopy, the latter sometimes being therapeutic as well when adhesiolysis can be performed under vision.

5.  Lower genital tract obstruction Cryptomenorrhoea is a term that may be used to describe the situation where menstruation is occurring normally but is not revealed due to obstruction to menstrual flow. Dysmenorrhoea will usually be present. Accumulation of menstrual fluid may occur in the vagina (haematocolpos), the uterus (haematometra) and tubes (haematosalpinges). Increased retrograde menstruation into the peritoneal cavity may cause severe endometriosis in a young woman. Sometimes the obstruction is only on one side of a completely or partially duplicated system, resulting in features of obstructed menstrual flow (pain, mass) but with menstruation still occurring—through the patent side. Cervical obstruction to menstrual flow may be due to congenital cervical atresia or cervical stenosis as a consequence of surgery or cancer. At a vaginal level, a complete vaginal septum or area of atresia will prevent menstrual flow, as will an imperforate hymen at the introitus.

MANAGEMENT OF AMENORRHOEA Initial assessment Evaluation involves a detailed history of diet, exercise and intercurrent psychological stressors, as well as enquiring about medication use. Symptoms of endocrine disorders should be sought such as galactorrhoea, cold intolerance, acne and hirsutism. Examination should begin with general appearance, height, weight and vital signs. Due to the myriad causes, examination is necessarily comprehensive. Neurological examination should focus on eliciting bitemporal hemianopia as a sign of a pituitary neoplasm. In the woman with primary amenorrhoea who is not as yet 418

sexually active, the external genitalia should be inspected for the presence of an intact hymen but further gynaecological examination should be avoided and information gleaned from a transabdominal ultrasound. Investigation involves measurement of FSH, LH, prolactin, thyroid function, androgens and β-hCG. If these are normal and there is no other explanation, imaging of the pituitary may be required. MRI gives the most sensitive evaluation of the soft tissue of the pituitary. If there is any doubt regarding uterine or obstructive causes, a progesterone challenge test may be performed to determine if a normally oestrogenised endometrium is responsive to progesterone withdrawal, and will confirm the existence of a patent outflow tract.

Further management Further assessment may then occur dependent on the findings. Essentially, following a detailed history, examination and investigation as discussed, the diagnosis can commonly be categorised to one of: hypothalamic (constitutional/stress) (diagnosis of exclusion) hypothalamic (endocrine) (hormonal levels diagnosis) ■ hyperprolactinaemia ■ hypothyroidism ■ hyperandrogenism (most often PCOS) ovarian failure (high FSH) uterine cause or obstruction (clinical diagnosis ± ultrasound).

• • • •

Hypothalamic: constitutional/or stress Diagnosis This is usually a diagnosis of exclusion in the presence of no clinical findings that would point to other causes and normal hormone levels (FSH, LH, prolactin, TSH, androgens).

Treatment Treatment may involve restoration of a normal body weight, a reduction in psychological stressors or normalisation of exercise patterns. For those not desiring fertility, treatment with the combined oral contraceptive pill (OCP) or combined hormone replacement is usually recommended to maintain bone health as well as to avoid the other adverse effects of oestrogen deficiency such as urogenital atrophy and adverse lipid profile. In the woman wishing to conceive, ovulation induction is indicated if correction of ‘stress’ does not bring this about. However, ovulation induction may be ill-advised if, for example, a low body weight meant that pregnancy was potentially dangerous for both mother and child.

Hypothalamic: hyperandrogenism including PCOS This condition is discussed in Chapter 50.

Chapter 49  Amenorrhoea, Hyperprolactinaemia and Ovulation Induction

Hypothalamic: hyperprolactinaemia This condition is discussed later in this chapter.

Ovarian failure Diagnosis Ovarian failure is simply diagnosed by a high FSH. The only differential diagnosis is the LH surge, but in that event the LH is very much higher.

Assessment Investigation should include a karyotype, presence of autoantibodies and evaluation of the anatomy using ultrasound. More rarely, an abdominal CT or MRI may be necessary.

Treatment As for hypothalamic amenorrhoea, treatment with the combined OCP or combined hormone replacement is usually recommended to maintain bone health as well as to avoid the other adverse effects of oestrogen deficiency. Fertility options for those with ovarian failure involve the use of donor eggs with IVF treatment. Although conceptions have occurred at some time in the future from the few remaining follicles ovulating, such conceptions are very uncommon. Legitimate alternatives to discuss include accepting childlessness and adoption.

HYPERPROLACTINAEMIA Elevations of serum prolactin may present with a variety of symptoms depending on the aetiology, although more common presentations include menstrual disturbance, infertility or galactorrhoea. There are numerous causes of hyperprolactinaemia, although one of the most important is the presence of a pituitary tumour or prolactinoma, which has been detected in up to 10% of females on postmortem examination; however, the great majority of these are asymptomatic microadenomas.

PHYSIOLOGY Prolactin is a polypeptide hormone synthesised by the lactotroph cells of the anterior pituitary and released under the control of central nervous system neurotransmitters. Dopamine released from the hypothalamus reaches the pituitary via the hypophyseal-portal system of vessels and tonically inhibits the secretion of prolactin (dopamine is also known as prolactin inhibiting factor). Prolactin release is increased by high levels of serum oestrogen as well as by thyroid releasing hormone (TRH), the latter accounting for the moderately raised prolactin levels often associated with untreated hypothyroidism. Moderately raised prolactin is also seen occasionally in association with the polycystic ovarian syndrome, possibly due to the effect of increased unopposed oestrogen in the setting of chronic anovulation.

Functions of prolactin include aiding breast development in preparation for lactation, as well as directly facilitating milk production with high serum levels present during pregnancy and lactation. High prolactin levels have a suppressive effect on FSH and LH production by a negative feedback mechanism on the hypothalamic– pituitary axis at both hypothalamic and pituitary levels.

AETIOLOGY The causes of hyperprolactinaemia can be classified into three groups (see Table 49.2 for an expanded list of causes of hyperprolactinaemia). 1. Physiological: including pregnancy and lactation. 2. Drug induced: especially drugs which antagonise dopamine action and hence interfere with the dopamine mediated inhibition of prolactin release. 3. Pathological: for example, tumours (both functioning and non-functioning). Microprolactinomas (micro­ adenomas) are associated with lower serum prolactin levels (up to 3000 mU/L) while macroprolactinomas (macroadenomas) with a diameter greater than 10 mm can be associated with much higher levels. Nonprolactin-secreting tumours may also cause a raised prolactin by causing compression of the pituitary stalk that interrupts the passage of dopamine from the hypothalamus. This results in release from the tonic control over prolactin secretion by the pituitary even when the tumour itself may be non-functioning.

CLINICAL FEATURES Elevation of serum prolactin is commonly encountered in the infertile population and may be detected during the routine work-up. Alternatively, patients may present with symptoms such as galactorrhoea, menstrual disturbance or symptoms associated with large pituitary tumours such as visual disturbance or headache. However, this latter presentation is in fact relatively rare as most pituitary tumours are microadenomas which do not cause mass effects. Hyperprolactinaemia is an important cause of disruption to the menstrual cycle due to negative feedback of high prolactin levels on the hypothalamic–pituitary axis. Effects of raised prolactin include a shortening of the luteal phase due to inadequate pre-ovulatory follicular development or, as levels rise causing negative feedback, hypogonadotrophic hypogonadism with resultant anovulation and/or amenorrhoea.

MANAGEMENT Assessment Evaluation of the patient with symptomatic or asymptomatic hyperprolactinaemia should begin with a detailed history, particularly with regards to medications and the possibility of pregnancy and especially in the setting of amenorrhoea. It is important to elicit the pattern of any 419

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TABLE 49.2  CAUSES OF HYPERPROLACTINAEMIA. Aetiology

Specific causes

Physiological

• • • • • • •

High oestrogen levels (e.g. pregnancy) Lactation Nipple stimulation (e.g. breastfeeding, sexual activity) Stress Exercise Sleep Hypoglycaemia

Drug induced

• • • • • •

Dopamine antagonists (e.g. phenothiazines, antipsychotics) Metoclopramide Diazepam Methyldopa (depletes dopamine levels) Oestrogens Opiates

Pathological

•

Prolactin-secreting pituitary tumours ○ Microprolactinoma (< 10mm diameter) ○ Macroprolactinoma (≥ 10mm diameter) Non-prolactin-secreting pituitary tumours (stalk compression) Hypothyroidism (TRH directly stimulates lactotrophs) PCOS (chronic elevated oestrogen stimulates lactotrophs) Chronic renal failure Chest wall stimuli (e.g. surgery, chest trauma, herpes zoster) Hypothalamic dysfunction/infiltration (e.g. craniopharyngioma, sarcoidosis, histiocytosis)

• • • • • •

menstrual disturbance, visual field changes, headache and specific questioning regarding galactorrhoea. Examination ought to note whether galactorrhoea is directly observed and include examination of visual fields. Given that small elevations of prolactin may occur physiologically, those noted with small to moderate degrees of hyperprolactinaemia ought to undergo repeat testing to confirm a persistent elevation in levels. Additionally, serum thyroid function testing should be performed to exclude hypothyroidism as well as hormone evaluation to detect biochemical evidence of PCOS, being a major differential diagnosis of oligo-amenorrhoea and infertility in association with mild to moderate hyper­ prolactinaemia. β-hCG testing will exclude pregnancy. In those without an obvious clinical cause, imaging should be undertaken to exclude a pituitary tumour. MRI is the optimum imaging modality due to excellent visualisation of the soft tissues (Fig 49.2), although CT scanning may be undertaken. Formal assessment of visual fields is necessary for those with demonstrated pituitary tumours and may be performed serially in monitoring response after treatment (e.g. with dopamine-antagonising medications).

Expectant management

Treatment

Patients experiencing anovulation due to raised prolactin who desire fertility, as well as all those with macroadenomas, should undergo first-line treatment with dopamine receptor agonists. Bromocriptine and cabergoline are the most frequently used of this class of medication and

Optimum management of hyperprolactinaemia depends on the cause, symptoms present and the woman’s desire for fertility. 420

Those with raised prolactin in the setting of a micro­ adenoma or functional hyperprolactinaemia in the absence of any structural cause, and not desiring immediate fertility, may elect to undergo observation with yearly measurement of serum prolactin levels, especially if menstruation remains regular. Those whose symptoms are drug induced will usually experience resolution with withdrawal or reduction of medication if this is feasible. For those who are oestrogen deficient, replacement therapy ought to be considered in order to prevent loss of bone mineral density. This can be in the form of combined oestrogen-progestogen hormone therapy or the contraceptive pill. Although concern has been raised that high oestrogen levels could in fact increase the secretion of prolactin by direct action on pituitary lactotrophs, studies have shown this not to be the case in practice. Additionally, those with adequate oestrogen levels who are not menstruating regularly should have some cyclical progestogen therapy to prevent endometrial hyperplasia from prolonged exposure to unopposed oestrogen.

Medical treatment

Chapter 49  Amenorrhoea, Hyperprolactinaemia and Ovulation Induction

A

B

FIGURE 49.2

MRI demonstrating A a pituitary microadenoma and B a pituitary macroadenoma.

Source: Aminoff MJ, ed. Neurology and General Medicine. 4th edn. Philadelphia: Churchill Livingstone. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 23.1.

result in both lowered serum levels of prolactin and a reduction in size of both macro- and microadenomas. Bromocriptine is a shorter acting agent that is usually administered twice daily, but troublesome side effects of orthostatic hypotension leading to dizziness and fainting as well as nasal congestion, constipation, nausea and vomiting can occur, especially early on in treatment. Therefore, bromocriptine is usually started at a low nighttime dose and gradually increased over a period of weeks. Cabergoline is a longer acting agent that allows administration twice per week with at least similar efficacy and fewer reported side effects to bromocriptine. Whichever agent is chosen, withdrawal of therapy for a number of weeks after 12 months of therapy should be considered to assess whether spontaneous remission has occurred, with reinstatement of therapy if raised prolactin is detected off medication.

Surgery and radiation therapy Surgical resection of pituitary tumours is usually reserved for situations where symptomatic tumours fail to respond to medical treatment or patients suffer intolerable side effects from such treatment. This is usually performed via a transsphenoidal approach and, where possible, medical treatment should continue until the time of surgery to prevent tumour re-expansion and reduce the volume for resection. Radiation, either external or brachytherapy, has been used in the treatment of macroadenomas but has been associated with higher rates of damage to surrounding normal structures.

PREGNANCY AND PROLACTINPRODUCING TUMOURS Given that elevated prolactin may be detected as part of the work-up of infertility, and also that a substantial

number of young women will desire fertility, the effects on pregnancy and breastfeeding of pituitary adenomas and of various treatments are important. While the dosing regimen for cabergoline is more favourable, there is more clinical experience with bromocriptine in those desiring fertility, although no deleterious side effects have been noted to date with those who do in fact conceive on cabergoline. Dopamine agonists are successful in achieving ovulation and pregnancy in up to 90% of women where this is the sole cause of infertility. Despite a lack of evidence of teratogenicity, bromocriptine does cross the placenta and it is recommended that dopamine agonist therapy be ceased at diagnosis of pregnancy for most patients. In some cases of macro­ adenoma, patients may be continued on medication under close specialist supervision. Alternatively, the bromocriptine may be ceased during pregnancy and only reintroduced if there is clinical suspicion of pituitary expansion on regular visual field measurement during pregnancy after MRI has confirmed the diagnosis. Pregnancy may cause enlargement of the pituitary gland with clinical consequences, and this occurs in approximately 2% of microprolactinomas and 20% of macroprolactinomas. There is no contraindication to breastfeeding in the setting of prolactinomas; however, if treatment with dopamine agonists is needed in the postnatal period, they will cause suppression of lactation.

OVULATION INDUCTION As discussed in this and other chapters, anovulation is an important cause of female infertility and is the causative factor for at least a quarter of couples diagnosed with infertility. Hence, specific treatment of this anovulation 421

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is an important part of gynaecological management as it can avoid the need for more invasive assisted reproductive techniques when anovulation is the sole cause. A number of techniques are available to assist ovulation for these women, including medical treatment (in the form of oral medications or injectable gonadotrophins) and surgical techniques (such as laparoscopic ovarian diathermy in the setting of polycystic ovarian syndrome). The aim of all methods of ovulation induction is to restore unifollicular development, leading to the release of a single ovum in order to achieve a singleton pregnancy. However, due to the very nature of medications used to achieve ovarian stimulation, multiple pregnancy can result if the monitoring of response to treatment is inadequate. This is especially so given the fact that different women can have a remarkably different ovarian response to the very same dose of ovulation-inducing medication.

ORAL OVULATION-INDUCTION AGENTS Anti-oestrogens All anti-oestrogen medications act by blocking the negative feedback action of oestrogen at the hypothalamus and pituitary, signalling to the central regulatory mechanisms a state of relative oestrogen deficiency. The response to such altered negative feedback is an increased release of FSH and LH from the anterior pituitary and hence greater resultant stimulation to the ovary. Given that these medications work by increasing secretion from the anterior pituitary, they are only appropriate in situations of intact hypothalamo-pituitary function and therefore do not work in the setting of hypogonadotrophic hypogonadism.

Clomiphene citrate Clomiphene citrate is administered for 5 days in the early part of the menstrual cycle, usually from day 2 to day 6 or from day 5 to day 9. Women with PCOS can be quite sensitive to clomiphene and a reduced dose should be utilised initially for these patients. The manufacturers recommend a maximum of 100 mg daily, but many clinicians will increase to 150 mg or even 200 mg before resorting to gonadotophin therapy. Ultrasound can be used to track response to the medication and detect multifollicular development that will increase the risk of multiple pregnancy and lead to advice to avoid unprotected intercourse for that cycle. Testing of the mid-luteal progesterone level will give an indication if the dose of clomiphene utilised in that cycle was sufficient to induce ovulation or needs to be escalated for future cycles.

Letrozole Letrozole is an aromatase inhibitor which blocks the conversion of androgens to oestrogen. This results in a state of relative oestrogen deficiency, as for clomiphene treatment, resulting in increased FSH and LH stimulation to 422

the ovaries due to the interruption to negative feedback. It is given for 5 days in the follicular phase of the cycle, similar to clomiphene; however, it is less likely to cause negative effects of oestrogen deficiency on endometrial thickness due to its shorter half-life when compared to clomiphene. Despite this, it still remains a second-line agent due to the comparatively less experience with its use and safety profile compared with clomiphene, although the available data fails to demonstrate any known increased rate of congenital malformations with its use.

Tamoxifen Tamoxifen is a selective oestrogen receptor modifier that has differing effects on the oestrogen receptors at different sites in the body. It is an antagonist at the hypothalamus while exerting an agonist effect on the bone and endometrium. Hence, it can induce ovulation when given in the follicular phase in a manner similar to clomiphene. However, it again is not used as widely for this indication due to there being less experience with it than with clomiphene and a lack of regulatory approval for this indication.

Other oral ovulation-induction agents Metformin Metformin is a biguanide medication used in type 2 diabetes that decreases hepatic gluconeogenesis and acts peripherally as an insulin sensitising agent. In women with PCOS, a condition frequently associated with insulin resistance, metformin treatment may help restore regular menstruation and ovulation. However, given the efficacy of drugs that directly act to restore ovulation, such as clomiphene, there is debate about the role of metformin for this indication. Metformin is probably better reserved for those with proven insulin resistance on formal glucose tolerance testing and for those with a body mass index above the normal range. It may also be of use for patients with PCOS who fail to ovulate on a maximum dose of clomiphene alone, and can be used in addition to clomiphene in such situations.

Bromocriptine As discussed earlier in this chapter, dopamine agonists will restore ovulation in the majority of patients with hyperprolactinaemia.

INJECTABLE GONADOTROPHIN THERAPY The original gonadotrophins used clinically for ovarian stimulation were derived from the urine of postmenopausal women, and hence named human menopausal gonadotrophins (hMG), containing both LH and FSH activity in combination. The earlier preparations suffered from problems with residual content of urinary proteins; however, preparations of highly purified hMG (hp-hMG) are now more commonly used. Alternatively,

Chapter 49  Amenorrhoea, Hyperprolactinaemia and Ovulation Induction

recombinant FSH produced from Chinese hamster ovary cell lines is available that avoids the need for collection of the large amounts of postmenopausal urine, as well as addressing concerns about contamination with urinary proteins. These preparations therefore contain FSH activity only, as opposed to the hMG products which also have LH activity. Gonadotrophins are given by daily self-administered injection, and a combination of serum oestradiol levels and ultrasound is used to gauge response to treatment after a number of days of injections (Fig 49.3). Close monitoring is vitally important in these cycles to detect those who over-respond to medication, with a higher risk of multiple pregnancy compared with other medical treatments for anovulation.

SURGICAL APPROACH TO OVULATION INDUCTION IN PCOS Laparoscopic ovarian diathermy or ‘drilling’ may benefit those with PCOS who are otherwise refractory to ovulation induction. A number of diathermy punctures are made to the ovary that result in cautery to the ovarian tissue at a number of points. The exact mechanism of action is unknown but it is assumed that some destruction of ovarian stroma occurs that results in a reduction of androgen production. This procedure in itself can induce ovulation for a large proportion of anovulatory PCOS sufferers, including those resistant to conventional medications such as clomiphene. Ovarian drilling has

FIGURE 49.3

Ultrasound demonstrating the development of a dominant follicle in the stimulated ovary.

Source: Allan PL, Baxter GM, Weston MJ. Clinical Ultrasound. 3rd edn. London: Churchill Livingstone. Copyright © 2011 Churchill Livingstone, An Imprint of Elsevier. Figure 34.18 B.

the advantage of restoring a monofollicular response, meaning that complications of gonadotrophin therapy such as multiple pregnancy and ovarian hyperstimulation are avoided. FURTHER READING American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists No. 34, February 2002. Management of infertility caused by ovulatory dysfunction. Obstet Gynecol 2002;99(2):347–58. Farquhar C, Lilford RJ, Marjoribanks J, et al. Laparoscopic ‘drilling’ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 2007;CD001122. Fenichel P. Delayed puberty. Endocr Dev 2012;22:138–59. Gell JS. Müllerian anomalies. Semin Reprod Med 2003;21:375–88. Gillam MP, Motlich ME, Lombardi G, et al. Advances in the treatment of prolactinomas. Endocr Rev 2006;27:485–534. Hoffman B, Bradshaw KD. Delayed puberty and amenorrhea. Semin Reprod Med 2003;21(4): 353–62. Kaiser U. Hyperprolactinemia and infertility: new insights. J Clin Invest 2012;122(10): 3467–8. Klibanski A. Prolactinomas. N Engl J Med 2010;362(13):1219–26. Li RH, Ng EH. Management of anovulatory infertility. Best Pract Res Clin Obstet Gynaecol 2012;26(6):757–68. March CM. Intrauterine adhesions. Obstet Gynecol Clin North Am 1995;22:491–505. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96(2):273–88. Molitch ME. Prolactinoma in pregnancy. Best Pract Res Clin Endocrinol Metab 2011;25(6):885–96. Practice Committee of American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril 2008;90(5 Suppl.): S219–25. Rebar RW. Premature ovarian failure. Obstet Gynecol 2009;113:1355–63. Requena A, Herrero J, Landeras J, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008;14(6):571–82. Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19(1):41–7. 423

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Roy KK, Baruah J, Sharma JB, et al. Reproductive outcome following hysteroscopic adhesiolysis in patients with infertility due to Asherman’s syndrome. Arch Gynecol Obstet 2010;281(2):355–61. Royal College of Obstetricians and Gynaecologists. Long-term consequences of polycystic ovary syndrome. Guideline No. 33. London: RCOG; Dec 2007. Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med 2003;349(21):2035–41. Steiner AZ, Terplan M, Paulson RJ. Comparison of tamoxifen and clomiphene citrate for ovulation

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induction: a meta-analysis. Hum Reprod 2005;20(6):1511–15. Tang T, Lord JM, Norman RJ, et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2012;(5):CD003053. Vujovic S. Aetiology of premature ovarian failure. Menopause Int 2009;15:72–5. Yu D, Wong YM, Cheong Y, et al. Asherman syndrome—one century later. Fertil Steril 2008;89:759–79.

Chapter 50  ANDROGEN EXCESS, INCLUDING PCOS, HIRSUTISM AND ACNE Chris Russell

KEY POINTS Hyperandrogenism ■ Excessive levels of serum androgens can lead to distressing symptoms such as acne and hirsutism. Occasionally, very high levels of androgens can lead to voice change or virilisation. ■ Hirsutism is most commonly due to ‘idiopathic hirsutism’ in which a genetic predisposition causes either a subtle increase in serum androgens or an increased sensitivity to normal androgen levels. ■ After idiopathic hirsutism, the next most common alternative diagnosis is PCOS. Less commonly, non-classical congenital adrenal hyperplasia and occasionally androgen-secreting tumours are responsible for hyperandrogenism. ■ All women with signs or virilisation should be investigated for possible androgen secreting tumours. ■ If cosmetic measures fail, the first-line treatment for hirsutism is the combined oral contraceptive pill (OCP). Anti-androgen medications such as spironolactone can be added as needed. Polycystic ovarian syndrome (PCOS) ■ PCOS is the most common cause of oligomenorrhoea and hirsutism ■ Diagnosis requires at least two of the following: ○ oligomenorrhea or anovulation ○ hyperandrogenism, either clinical or on biochemical testing ○ polycystic-appearing ovaries on ultrasound. ■ Patients with only polycystic ovaries on ultrasound should be reassured that it is a normal finding. ■ PCOS may be associated with hyperandrogenism, anovulatory infertility, menstrual symptoms, endometrial hyperplasia and metabolic syndrome. ■ Women who are overweight with PCOS should be encouraged to lose weight. ■ Women who want to conceive but are anovulatory can use clomiphene citrate to induce ovulation. Women who are not trying to conceive should be offered the combined OCP, which will treat the hyperandrogenism and menstrual symptoms and prevent endometrial hyperplasia.

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ANDROGEN EXCESS AND HIRSUTISM BACKGROUND Hirsutism is a common, clinically diagnosed condition whereby women have excessive amounts of terminal hair growth in androgen-sensitive areas. While it is predominantly genetic, it is sometimes the result of endocrinopathies such as polycystic ovarian syndrome (PCOS) or androgen-secreting tumours, and so requires careful evaluation. Hirsutism is a relatively common finding in women: 20% will have noticeable hair on the upper lip and in 5% it is also present on the chin and/or side of the face. Other androgen-sensitive areas that may be involved include the chest, upper back and lower abdomen. There is often considerable psychological disturbance and sometimes social withdrawal. Androgen excess can also cause acne vulgaris, a similarly distressing disorder. Signs of more excessive androgen increase are androgenic alopecia (male-pattern balding), clitorimegaly and voice deepening. These signs and symptoms should prompt a more detailed evaluation, in particular for an androgen-secreting tumour of the ovary or adrenal gland. PCOS is a common cause of hirsutism, and is discussed in detail later in this chapter.

PATHOGENESIS Androgen excess The source of androgens in women is mainly the ovary and adrenal gland, with the liver and peripheral tissues making important transformations. In women, 98 to 99% of androgen is bound, mainly to sex hormone-binding globulin (SHBG), and is therefore inactive. In the ovary, androstenedione and testosterone are key intermediaries in the production of oestradiol from progesterone and dehydroepiandrosterone (DHEA), which in turn arise from such precursors as cholesterol and pregnenolone. In the adrenal gland, DHEA, testosterone, androstenedione and a number of weaker androgens are produced. Dehydroepiandrosterone sulphate (DHEA-S) is primarily an adrenal androgen. Under the influence of the enzyme 5-alpha-reductase, both androstenedione and testosterone are converted to dihydrotestosterone, especially in the skin; dihydrotestosterone is particularly active in stimulating the pilosebaceous follicle. Androgen excess may result from increased secretion from the ovary (PCOS, Leydig cell tumour) and/or adrenal (congenital adrenal hyperplasia, adrenal tumours), a decrease in SHBG (PCOS) or an altered metabolism of peripheral androgen. It is also possible to be the result of exogenous androgens or medication (e.g. phenytoin, danazol). 426

Normal hair growth and idiopathic hirsutism There are two main types of hair. Vellus is soft, fine and non-pigmented, while terminal hair is coarse and pigmented. In androgen-sensitive areas (upper lip, face, chest, abdomen, back and buttocks), terminal hair can predominate if androgen levels are sufficient or if pilosebaceous glands are sensitive enough to the circulating androgens. It is common for women to have some hair growth in androgen-sensitive areas; 25% of Caucasian women have terminal hair on the upper lip, 10% have terminal hair on the chin, 5% have sideburns and many have periareolar hair. Idiopathic hirsutism is the excessive growth of this androgen-sensitive hair (Fig 50.1). Its distribution and density is largely genetically determined, with the major factors being the number of androgen receptors in the skin and the amount of circulating free androgen. Generally, women with idiopathic hirsutism have androgen levels that are mildly elevated or at the upper end of normal and by definition there is no identifiable cause.

PCOS PCOS is the most common cause of hirsutism. Its pathogenesis is discussed in detail later in the chapter.

Non-classical congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is caused by a deficiency of an enzyme involved in the production of

FIGURE 50.1

Example of a girl with hirsutism; terminal hair on the upper lip.

Source: Goldbloom RB. Pediatric Clinical Skills. 4th edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 16.22.

Chapter 50  Androgen Excess, Including PCOS, Hirsutism and Acne

cortisol in the adrenal gland. The most commonly deficient enzyme is 21-hydroxylase. The result is diversion of substrates away from the production pathway of cortisol and aldosterone, and towards the pathway for androgen production via increased levels of 17-OH progesterone. Unlike classical CAH that presents at birth, nonclassical CAH can present with premature adrenarche or hirsutism, oligomenorrhoea and acne in later life because cortisol production is maintained, probably due to increased ACTH levels.

Ovarian hyperthecosis Ovarian hyperthecosis is seen typically in postmenopausal women, and is caused by the luteinisation of nests of theca cells within the ovarian stroma. It leads to severe hyperandrogenism and insulin resistance. Women present with slow onset of hirsutism and acne, often with signs of virilisation. Testosterone levels are almost always > 5.2 nmol/L. The treatment is bilateral oophorectomy after consideration of other potential causes.

Acne vulgaris Acne is a characteristic skin disorder consisting of inflammatory lesions and comedones predominantly on the face, but also on the back, neck and chest (Fig 50.2). The pathogenesis is multifactorial, but elevated androgens have a role by stimulating the growth of sebaceous glands and augmenting sebum productions. The use of antiandrogen medications can see a reduction in the amount of acne lesions present.

CLINICAL ASSESSMENT History History is in many ways the best way to assess the severity of hirsutism. Some women with mild hirsutism may be especially distressed, while others with mild symptoms may be partially treating themselves with cosmetic measures. It is important therefore to assess the level of patient distress on history, and to treat the patient on the basis of this. History can give important clues to possible causes, such as the following. Duration and timing of onset. Onset at menarche suggests PCOS or CAH. Rapid onset of severe symptoms, or late onset, suggests a tumour. Menstrual history. Infrequent periods is diagnostic of PCOS. Weight gain. Onset with weight gain can be seen with PCOS and Cushing’s syndrome. Ethnicity. Idiopathic hirsutism is uncommon is SouthEast Asian women, but more common in Mediterranean, subcontinental and Middle Eastern women. Medication and drug history. It may be related to androgenic medications such as anabolic steroids, danazol and phenytoin.

• • • • •

Examination The most important aspect of clinical examination is to look for signs of virilisation, which could indicate an androgen-secreting tumour, and signs suggestive of endocrine disorders that can lead to hirsutism. Signs of virilisation are: androgenic alopecia (male pattern balding) deepened voice Adam’s apple muscular physique clitorimegaly. Signs of Cushing’s syndrome should also be checked; these include truncal obesity, buffalo hump, supraclavicular fat, thin skin, bruising and striae. The Ferriman–Gallwey score is a system that can be used to classify the physical extent of androgen-sensitive hair. Its clinical use is limited. Being an objective score system, it is poor at assessing a condition that is subjectively experienced by patients.

• • • • •

FIGURE 50.2

Acne vulgaris and hirsutism. A young woman with inflammatory papules of acne vulgaris and significant hirsutism.

Source: Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology. 4th edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 8.5.

DIAGNOSIS AND INVESTIGATIONS The diagnosis of hirsutism is made clinically based on the symptoms and level of distress experienced by the patient together with the clinical examination findings mentioned above. Clinically significant hirsutism should be investigated to elucidate a possible cause (Table 50.1). Idiopathic hirsutism is a diagnosis of exclusion. A common alternative diagnosis is PCOS, with non-classical 427

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TABLE 50.1  GUIDE TO INTERPRETING STANDARD INVESTIGATIONS FOR WOMEN WITH HIRSUTISM. Investigation

Investigation finding

Serum total testosterone

Normal value = idiopathic hirsutism Mild elevation suggests an ovarian source (i.e. PCOS) > 5.2 nmol/L suggests possible tumour, usually ovarian

Serum DHEA-S

Normal value = idiopathic hirsutism Mild elevation suggests adrenal source > 19 µmol/L suggests possible adrenal tumour

Pelvic ultrasound

Common: Polycystic ovary syndrome Uncommon: Androgen-secreting ovarian tumours (Sertoli-Leydig, Granulosa-theca and Hilus-cell tumours)

Serum 17-OH Progesterone

Increase = congenital adrenal hyperplasia due to 21-hydoxylase deficiency

CAH another possibility. PCOS is excluded on the basis of regular menses and a pelvic ultrasound showing nonpolycystic ovaries. Normal ovaries on ultrasound probably excludes an androgen-secreting ovarian tumour as well, although these are very uncommon and sometimes tumours invisible to ultrasound can secrete significant amounts of androgen. Non-classical CAH due to 21hydroxylase deficiency is excluded on the basis of a normal serum 17-OH progesterone level, although other uncommon enzyme deficiencies that can cause nonclassical CAH will be missed by this test. Early morning testing of 17-OH progesterone should be conducted in the follicular phase of the menstrual cycle. Serum androgen levels are useful to guide the need for further investigation, especially given that clinical signs (such as the Ferriman–Gallwey score) correlate poorly with serum androgen levels. The most useful hormones to test are testosterone and DHEA-S; the former is usually from an ovarian source, the latter from the adrenal gland. Generally, in the absence of signs of virilisation and with normal or subtly raised androgen levels, no more investigations are required to diagnose idiopathic hirsutism or exclude more serious diagnoses. If features of virilisation are present or DHEA-S levels are markedly raised, it is prudent to investigate further with imaging of the adrenal glands using CT scanning to check for tumours. If testosterone is markedly elevated and the 428

ovaries are normal on ultrasound (raising the possibility of a tumour that is not detectable on ultrasound), paired blood samples can be taken radiologically from the adrenal and ovarian veins; the sample with the higher testosterone level is thus identified, allowing removal of that ovary. This is a complicated procedure, and in postmenopausal women, or women whose families are complete, bilateral oophorectomy may be more sensible. A 24-hour urinary cortisol level for Cushing’s syndrome should be performed if the patient has characteristics suggestive of this condition (e.g. centripetal obesity, hypertension, purple striae).

MANAGEMENT Mild or idiopathic hirsutism Many women with hirsutism will often present already using cosmetic measures to minimise the appearance of hair. These include waxing, shaving, plucking and depilation, and all are temporary. Laser hair removal is easily available commercially, and will reduce hair, but with regrowth expected after 12 months. Similarly, electrolysis is readily available at beauty salons, and is theoretically permanent; however, if performed incorrectly (as is common) regrowth will occur, and ongoing hyperandrogenism will also lead to more growth of hair. These methods should be discussed with patients, together with medical treatments, allowing them to decide the level of treatment required. It is not recommended to base treatment on examination findings, and similarly, the success of treatment should be assessed wholly on the patient’s perceived improvement in symptoms. Despite this, it is important to manage the patient’s expectations; curing excess hair is uncommon, and improvement in symptoms is a more reasonable aim for treatment. The first-line treatment for idiopathic hirsutism is the combined oral contraceptive pill (OCP). The mechanism of action for the combined OCP is through negative feedback on luteinising hormone (LH) secretion, increased SHBG from hepatic synthesis, and inhibition of adrenal androgen secretion. These actions are all irrespective of the type of progesterone in the pill, so inexpensive preparations should be trialled first. More expensive preparations containing cyproterone acetate or drospirenone, which have additional anti-androgenic properties, can be tried if the patient is unhappy with the side effects or response. It is worth trialling treatment for 6 months, given that hair turnover is slow, meaning it will take months to see any benefit. The combined OCP can be used cyclically or continuously for hirsutism. For women who fail to achieve an adequate response, an anti-androgen medication should be added. Two are commonly used in Australia—spironolactone and cyproterone acetate—and both are equally effective. Spironolactone could be taken as an alternative to the combined OCP, but should be ceased prepregnancy or by not later

Chapter 50  Androgen Excess, Including PCOS, Hirsutism and Acne

than 6 weeks amenorrhea. The blocking of androgen receptors by spironolactone (or cyproterone acetate) in a male fetus can lead to ambiguous genitalia. Spironolactone competitively blocks androgen receptors and inhibits androgen biosynthesis. An initial dose of 50 mg twice daily can be increased to 100 mg twice daily to the desired effect. Cyproterone acetate is usually commenced at a dose of 50 mg for 10 days each month. The dose can usually be subsequently decreased to around 10 mg daily for 10 days each month.

Hirsutism due to specific causes If a specific cause for hirsutism is diagnosed, it should be treated, as well as institution of cosmetic procedures mentioned earlier. The management of PCOS is discussed later in the chapter, and hirsutism specifically due to PCOS is managed in the same way as idiopathic hirsutism. Treatment of non-classical CAH with glucocorticoids tends to improve serum androgen profiles; however, it is probably not as effective as anti-androgens such as cyproterone acetate at treating symptoms of hirsutism.1 As such, first-line treatment in those not desiring pregnancy should still be the combined OCP with an antiandrogenic progesterone. Dexamethasone, however, is the treatment of choice for women who desire pregnancy but are anovulatory due to non-classical CAH, as it will promote ovulation and can also reduce hirsutism. Masses of the ovary and adrenal gland thought to be androgen secreting are generally removed surgically. Surgery results in rapid resolution of symptoms and a tissue diagnosis is able to exclude malignancy. Management of ovarian tumours is discussed in the Chapter 63.

POLYCYSTIC OVARY SYNDROME BACKGROUND Polycystic ovary syndrome is a heterogeneous disorder with a multifactorial pathogenesis that describes a broad spectrum of patient presentations. The cardinal features of PCOS are ovulatory dysfunction and androgen excess, together with the ultrasound finding of polycystic ovaries. It is also frequently associated with obesity and insulin resistance and sometimes endometrial hyperplasia. PCOS is a common condition, with a prevalence estimated at 12% among Australian women of childbearing age when using the Rotterdam 2003 criteria for diagnosis.2 It is the most common cause of anovulation in young women, and therefore a common cause of subfertility.

PATHOGENESIS PCOS was first described in 1935 by Stein and Leventhal, who noted that women with amenorrhea were often seen to have polycystic ovaries (Fig 50.3).3 The precise pathogenesis of PCOS proved elusive for good reason, and it is now thought that the complex

FIGURE 50.3

Surgical specimen of polycystic ovaries.

Source: Lentz GM, Lobo RA, Gershenson DM, Katz, VL. Comprehensive Gynecology. 6th edn. St Louis: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 40.6.

interplay between various genetic and environmental factors is what leads to the clinical syndrome seen (Fig 50.4). Despite strong familial clustering seen in twin and family studies, no single causative gene has been definitively implicated in the development of PCOS.4 Similarly, multiple endocrine abnormalities are frequently seen in women with PCOS; however, the causes remain unclear. These include altered LH function, hyperinsulinaemia and elevated free serum androgens that are predominantly ovarian in origin. Excessive serum levels of LH are frequently seen in women with PCOS, and their ovaries often also overexpress LH receptors. The effect of this is increased ovarian androgen secretion by theca cells in the ovary. Insulin resistance from any cause perpetuates this problem by further stimulating androgen synthesis in the ovarian theca, as well as causing a reduction in circulating SHBG. SHBG is the plasma carrier protein for testosterone, thus a reduction in its levels leads to an increase in circulating unbound free testosterone. Environmental factors associated with PCOS (such as obesity and a poor diet) further accentuate the insulin resistance. While obesity in this way worsens the clinical features of PCOS it is unclear if obesity itself is causative of PCOS or if obesity is part of the phenotype expressed by women who have a shared predisposition to both conditions. Rates of PCOS in slim and obese women are remarkably similar.5 The higher concentration of serum androgens is reflective of androgen concentration in developing ovarian follicles. As follicular androgen concentrations rise above normal, dominant follicle selection is interrupted and ovulation fails to occur. This leads to anovulatory subfertility, while the lack of an ensuing progesterone surge because of the absent luteal phase allows oestrogen to be chronically unopposed on the endometrium, risking endometrial hyperplasia and cancer. 429

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Inherent insulin resistance

CAH Insulin resistance

Inherent ovarian sensitivity to LH

sSHBG

Androgen

Obesity

Ovarian androgen form theca lutein cells Inherent ovarian LH receptor number

LH

Aromatisation of androgen in adipose tissue

Positive feedback of oestrogen on pituitary

Oestrogen

Inherent pituitary sensitivity to oestrogen positive feedback

FIGURE 50.4

Pathogenesis of PCOS. Increased LH levels, LH receptor numbers, relative hyperinsulinaemia and PCO morphology can all be due to a genetic predisposition. Multiple positive feedback loops occur.

CLINICAL PRESENTATION Women with PCOS most commonly present with infrequent menstrual periods, but also may present with hirsutism. Frequently, women present with the incidental finding of polycystic ovaries (PCO) on a pelvic ultrasound; in the absence of any other features of PCOS, these women should be reassured that PCO is a normal finding and that they don’t have the clinical syndrome. Menstrual irregularity in PCOS is often variable, and sometimes becomes more severe with increasing weight. There are many causes for menstrual infrequency, and women should be quizzed on history for symptoms of the following conditions: pregnancy premature ovarian insufficiency (hot flushes, vaginal dryness) hypo- and hyperthyroidism (weight gain, although this is common also with PCOS, and weight loss) hyperprolactinaemia (nipple discharge, lateral visual field defects). Women presenting with hirsutism should be assessed as described earlier in the chapter. Hirsutism with PCOS often begins at menarche and appears coincidentally as menstrual cycles become less regular or as weight increases.

diagnosed, the Rotterdam criteria require the presence of at least two of the following: polycystic ovary morphology on ultrasound oligomenorrhoea or anovulation hyperandrogenism, either clinical or biochemical. The ultrasound diagnosis of PCOS requires either: the presence of 12 or more follicles, on either ovary, measuring between 2 and 9 mm; or ovarian volume greater than 10 mL on transvaginal scanning (Fig 50.5).

• • •

• • • •

DIAGNOSIS

FIGURE 50.5

The diagnostic criteria for PCOS have been revised and refined over time, and it is now the Rotterdam 2003 criteria that are used in Australia.6 For PCOS to be

Source: Falcone T. Clinical Reproductive Medicine and Surgery. St Louis: Mosby, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figure 15.1.

430

Transvaginal ultrasound scan of a polycystic ovary.

Chapter 50  Androgen Excess, Including PCOS, Hirsutism and Acne

TABLE 50.2  INVESTIGATIONS TO HELP DIAGNOSE PCOS. Investigation

Finding

Pelvic USS

Polycystic ovary morphology or ovarian volume > 10 mL Sometimes normal

Total testosterone

Mildly elevated

LH

Elevated

SHBG

Reduced

DHEA-S

Sometimes slightly elevated

Oligomenorrhoea is defined as menstrual periods greater than 35 days in length or fewer than nine menstrual periods per year, while anovulation is the proven absence of ovulation by a variety of methods that can include mid-luteal phase serum progesterone levels (measured 7 days prior to the next expected menstrual period), urinary LH surge test kits or basal body temperature charting. Ovulation is demonstrated if progesterone levels are elevated in the luteal phase, or if there is an LH surge or rise in basal body temperature mid-cycle; a lack of one of these findings implies anovulation. It is important to assess ovulatory status over more than one menstrual cycle in women with regular periods; it is not abnormal to have occasional anovulatory cycles. Biochemical hyperandrogenism is diagnosed on the basis of elevated serum testosterone and free androgen index (FAI). Reduced SHBG is a common finding, but this is not diagnostic. It is important to consider other endocrine disorders that can mimic the presentation of PCOS. Non-classical congenital adrenal hyperplasia has a similar presentation

to PCOS with oligomenorrhoea and hirsutism. Confounding conditions such as premature ovarian insufficiency, thyroid dysfunction or hyperprolactinaemia can also cause oligomenorrhoea, and should be excluded. Hirsutism has many potential causes, and conditions to exclude were discussed earlier in this chapter. Tables 50.2 and 50.3 provide an overview of investigations performed in assessing for PCOS and its differential diagnoses.

MANAGEMENT The management of a woman with PCOS is dependent on her desire for fertility. The key points of management are assessment and prevention of associated complications, treatment of symptoms and optimisation of fertility if it is desired (Table 50.4).

Weight loss Women with PCOS are frequently, but not always, overweight or obese. It is well described that weight loss of as little as 5% body mass is associated with: reduced serum testosterone levels reduced hirsutism greater menstrual regularity increased frequency of ovulatory cycles reduced insulin resistance. As such, weight loss should be the first-line treatment for women with PCOS who are overweight or obese. It can be considered in normal weight women who have noticed symptoms develop with weight gain despite their weight remaining in the healthy range. It must be remembered that morbidly obese women require greater weight loss to prevent future comorbidities even if their PCOS symptoms improve with subtle weight loss. The best method of weight loss is difficult to recommend; however, education on low carbohydrate diets and

• • • • •

TABLE 50.3  INVESTIGATIONS TO EXCLUDE DIFFERENTIAL DIAGNOSES OF PCOS. Test

Condition to exclude

Finding in PCOS

Testosterone total

Androgen-secreting tumour, moderate elevation

Mild elevation or normal

17-OH progesterone

Congenital adrenal hyperplasia, elevated

Normal

Thyroid function testing

Hyperthyroidism Hypothyroidism

Normal

FSH LH

Premature ovarian insufficiency (menopause), raised Hypothalamic hypopituitarism, reduced

LH often raised FSH normal

Serum prolactin

Hyperprolactinaemia, raised

Normal

24-hour urinary cortisol

Cushing’s syndrome, elevated

Normal

DHEA-S

Adrenal tumour, moderately elevated

Sometimes mildly elevated 431

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TABLE 50.4  POSSIBLE OUTCOMES OF THE DIFFERENT MANAGEMENT OPTIONS FOR WOMEN WITH PCOS. Hirsutism

Ovulation

Endometrial protection

Obesity and insulin resistance

Contraception

Weight loss

✓

✓

✓

✓

✗

Combined OCP

✓

✗

✓

✗

✓

Spironolactone

✓

✗

✗

✗

✗

Mirena IUD

✗

✗

✓

✗

✓

Clomiphene

✗

✓

✓

✗

✗

increasing exercise initially or referral to a dietician for instruction on meal replacements and very low energy diets might be useful.7 Gastric banding surgery is of proven benefit in women with a BMI > 40, reducing weight, diabetes, dyslipidaemia, hypertension and sleep apnoea. It should be offered to all women with BMI > 40 who have failed with conventional weight loss efforts.

Combined oral contraceptive pill The combined OCP has many useful actions for women with PCOS. It is the first-line treatment for hirsutism and provides protection from endometrial hyperplasia.8 It is not a useful treatment for women who desire pregnancy immediately. Any combined OCP preparation can be effective against hirsutism regardless of the progesterone used. Pills containing ethinyl oestradiol 30 mcg with levonorgestrel 150 mcg (e.g. Microgynon 30, Levlen ED) are a good first choice. If hirsutism persists, combined OCPs containing anti-androgenic progesterones such as cyproterone acetate (e.g. Brenda-35 ED, Diane-35 ED) or drospirenone (Yasmin, Yaz) can be tried. It does not matter if the combined OCP is used continuously or cyclically.

Hirsutism treatment The treatment of hirsutism with PCOS is the same as for idiopathic hirsutism, and is discussed earlier in the chapter.

Endometrial protection Women who have menstrual cycles lasting more than 3 months are at risk of endometrial hyperplasia, as are women with shorter anovulatory cycles with thickened endometrium on ultrasound scan. Their endometrium should be sampled prior to commencing treatment. Treatment options to prevent endometrial hyperplasia are cyclical oral progesterones, a combined OCP or Mirena IUD.

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Metabolic syndrome assessment Given the association with type 2 diabetes, women with PCOS should have a glucose tolerance test (GTT) at the time of diagnosis, then every 2 years. REFERENCES 1) Spritzer P, Billaud L, Thalabard JC, et al. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1990;70(3):642. 2) March WA, Moore VM, Willson KJ, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010;25(22):544. 3) Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181. 4) Vink JM, Sadrzadeh S, Lambalk CB, et al. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 2006;91(6):2100–4. 5) Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93(1):162. 6) Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19(1):41. 7) Tsai AG, Wadden TA. The evolution of very-lowcalorie diets: an update and meta-analysis. Obesity (Silver Spring) 2006;14(8):1283–93. 8) Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93(4):1105.

Section 3.4 THE MENOPAUSE Chapter 51

The menopause, climacteric and hormone replacement therapy

Chapter 51  THE MENOPAUSE, CLIMACTERIC AND HORMONE REPLACEMENT THERAPY Michael Rasmussen, Samantha Mooney and Michael Permezel

KEY POINTS Menopause occurs at an average age of 51.7 years and coincides with the disappearance of ovarian primordial follicles. The principal consequences of the oestrogen deficiency postmenopause include vasomotor symptoms, urogenital atrophy, osteoporosis and adverse lipid profile. Hormone replacement therapy (HRT) can minimise or reverse the effects of oestrogen deprivation but is associated with increased risks of breast cancer, thromboembolism and thrombosis of established atheroma. There is a school of thought that it should be ‘hormone therapy (HT)’ rather than ‘hormone replacement therapy (HRT)’ as the latter implies that hormone absence is an abnormal state. For consistency, HRT will be used in this chapter. Increase in the risk of breast cancer is minimal within the first 5 years postmenopause and probably lessened if only oestrogen rather than oestrogen plus progestogen is used. Myocardial infarction and stroke are genuine problems of HRT if administered to women at high cardiovascular risk (e.g. older women, obesity, hypertension) but may be lessened if administered to women at low cardiovascular risk through a beneficial effect on lipid profile.

DEFINITIONS The menopause is the physiological and permanent cessation of natural menstruation, and is due to a loss of ovarian follicular activity. The number of primordial follicles is fixed at birth and there is progressive loss of ovarian follicles (mostly though atresia) throughout childhood and reproductive life until essentially none are left by the time of menopause. Menopause is commonly defined as 12 months free of menstruation and occurs at an average age of 51.7 years. However, given the numerous other reasons for amenorrhoea, such as endometrial ablation, hysterectomy or intrauterine device, a more pragmatic definition for menopause is the permanent cessation of ovarian follicular function. The perimenopause, or climacteric, is the varying time of declining ovarian function before and after the actual last menstrual period, characterised by declining

ovarian function. It may or may not lead to symptoms and clinical presentation. Premature menopause, or premature ovarian failure, refers to a menopause occurring before 40 years of age. A surgical menopause is one induced by surgical removal of the ovaries.

PHYSIOLOGY The approach of the menopause is characterised by a continued loss of ovarian follicle number and size, and an increasing ovarian resistance to FSH and LH. Serum FSH levels rise approaching the menopause, though measured levels may vary from month to month, until after the actual menopause when persistently high FSH and low oestrogen levels are seen. The levels of oestradiol, primarily produced in the ovary, fall significantly.

Chapter 51 

Postmenopausally, oestrone becomes the predominant oestrogen. The oestrone comes from peripheral aromatisation of androgens (e.g. adrenal androstenedione), particularly in adipose tissue.

CLINICAL FEATURES OF THE CLIMACTERIC MENSTRUATION The menstrual pattern leading up to the menopause is variable. Cycle interval tends to lengthen, and menstrual loss may either lessen or increase in amount and duration. Heavy periods may be attributed to luteal phase insufficiency and lower than normal levels of progesterone. After periods cease, there may be sporadic bursts of ovarian activity as the sparse remaining follicles occasionally return to activity rather than become atretic.

VASOMOTOR SYMPTOMS The most recognised symptom of the climacteric and menopause is the ‘hot flush’. Hot flushes are felt as a sensation of heat, redness and sweating in the upper chest and face, often coming in waves lasting 30 to 60 seconds or more. These occur with varying frequency, ranging from bursts of every hour to once or twice a day or less. Hot flushes may be associated with diaphoresis and palpitations and may provoke feelings of agitation and anxiety. They may be provoked by stressful situations or a change in temperature. Hot flushes are often distressing and embarrassing, with a very real impact on the sufferer’s ability to work and function. Hot flushes often occur at night and may be associated with night sweats that can cause interrupted sleep and daytime fatigue. Hot flushes are common, affecting up to 50% of women leading up to the last period, and up to 85% after. They are most common in the years around the actual menopause typically commonly lasting for 1 to 2 years postmenopause; however, it is becoming increasingly recognised that up to 30% of women still suffer hot flushes after 10 years. In fact, almost 10% of women are still reporting hot flushes in their 70s. Hot flushes are more common in smokers and less common in the obese and those taking regular exercise.

UROGENITAL ATROPHY Genital tissues and adjacent muscle and connective tissue respond to the withdrawal of oestrogen with atrophy. Uterine size decreases, any fibroids present reduce in size and endometriosis atrophies. Vaginal dryness is symptomatic in more than 40% of women, and the vaginal skin and labia may show progressive atrophy and loss of features. Thinning of the vaginal mucosa can lead to dyspareunia and bleeding, and a loss of vaginal glycogen can predispose to erosions and infections. Uterovaginal prolapse becomes more common, as does urinary urgency and urinary incontinence.

The Menopause, Climacteric and Hormone Replacement Therapy

BONE LOSS Oestrogen withdrawal at menopause accelerates the rate of bone loss that occurs as a normal component of ageing. Cortical bone loss, and to a lesser extent trabecular bone loss, is related to oestrogen withdrawal. The incidence of osteoporotic fracture of the hip or wrist and compression fractures of the vertebrae progressively increases after the menopause.

CARDIOVASCULAR RISK INCREASE The risk of cardiovascular disease increases after menopause. Premenopausal women have a risk of cardiovascular disease approximately one-fifth that of a male at the same age. The metabolic alterations associated with menopause compound traditional cardiovascular risk factors, such as increased abdominal fat deposition, impaired glucose tolerance and increased blood pressure. Oestrogen withdrawal leads to alterations in lipid profile, with postmenopausal women having increased total cholesterol and low-density lipoprotein cholesterol values. That is, a more ‘male’ profile arises. Other cardiovascular effects of declining oestrogen levels include impaired endothelial integrity and vascular inflammation.

MANAGEMENT OF THE MENOPAUSAL WOMAN ASSESSMENT The perimenopausal or postmenopausal woman requires a detailed history and examination and may require selected investigations. The objectives of this assessment should be to establish the following. 1. The presence of symptoms or risk factors favouring therapy (not necessarily HRT) and their impact on quality of life: a. vasomotor symptoms (e.g. hot flushes) b. urogenital atrophy or vaginal dryness c. osteoporosis. Predisposing factors for osteoporosis include family history, smoking, sedentary lifestyle, low calcium intake, and certain medical disorders and medications. When these risk factors are present, assessment of bone density should be performed, most commonly with dual absorption densitometry (DEXA). In this setting, the presence of osteopenia or early osteoporosis would have therapeutic consequences. 2. The presence of relative contraindications to HRT such as heightened risk for, or presence of: a. breast cancer b. atheroma or cardiovascular disease (all medical practitioners should be familiar with risk factors 435

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for atherosclerosis, including age, hypertension, diabetes mellitus, obesity and hyperlipidaemia) c. thromboembolism. 3. Compliance with recommended screening pro­ grams, including cervical cytology screening and mammography.

TREATMENT: HORMONE REPLACEMENT THERAPY (HRT) Considerable negativism has surrounded HRT following the publication of the Women’s Health Initiative (WHI) trial in 2002. Much of this was emotive and a more rational appraisal in the critique that followed has highlighted the considerable limitations of the WHI trial and returned HRT to its proper place as a legitimate alternative for women in the early postmenopausal years. Chief among the many WHI deficiencies was a mean age at entry of 63 years. Older postmenopausal women are at increased risk of established atheroma and accumulated cardiovascular risk factors. Thus, it should not be a surprise to note that overall, cardiovascular and cerebrovascular events were greater in the HRT group, taking a therapeutic agent known to enhance thrombosis. However, when women aged 50 to 59 years were analysed, there was a protective cardiovascular benefit from HRT. In fact, these women had a 30% reduction in mortality. The decision as to whether to recommend HRT is a simple decision equation balancing the pros and cons, as illustrated in Figure 51.1. In order to make an individualised recommendation, the clinician needs a clear

Vasomotor symptoms Although alternatives are available, HRT is the most effective treatment available for the management of hot flushes and night sweats. The consequent improved sleep and improved quality of life may have psychological benefits.

Bone loss prevention HRT reduces bone loss after the menopause and reduces the risk of fracture—even in women at low risk of osteoporosis. The following is the recommendation of the International Menopause Society (IMS): Based on evidence of effectiveness, cost and safety, HRT can be considered as one of the first-line therapies for the prevention and treatment of osteoporosis in postmenopausal women, younger than 60 years, with an increased risk of fracture. The initiation of HRT for the sole purpose of the prevention of fractures after the age of 60 years is not recommended.1

Concerns with HRT in older women are discussed on the next page.

Lipid profile and cardiovascular disease Dramatic concern about increased cardiovascular morbidity followed the publication of WHI in 2002. However,

Breast cancer Cardiovascular risk (older patient) Stroke Thromboembolism

Favours HRT

Favours NO HRT

The hormone replacement therapy decision equation. 436

Benefits of HRT

Vasomotor symptoms Psychological changes Urogenital atrophy Osteoporosis Cardiovascular risk (young patient) Colorectal cancer Endometrial cancer

Alzheimer’s?

FIGURE 51.1

understanding of how the evidence underlying each element of the decision equation would apply to the particular circumstances of the patient.

Chapter 51 

The Menopause, Climacteric and Hormone Replacement Therapy

the influence of HRT on cardiovascular health appears to be related to the timing of commencing therapy. Initiation near the menopause appears to be associated with benefit but initiation after the age of 60 years (as in WHI) appears to be associated with harm. A fundamental principle of HRT centres around the knowledge that the thrombotic tendency of HRT will increase the risk of thrombosis of previously established atheroma. However, the favourable vascular protective effects and improved lipid profile will retard the development of future atheroma. This is exactly what the research has found. Early initiation of HRT in a patient at low risk of atheroma is actually beneficial to cardiovascular risk and probably (possibly by the same mechanism) will reduce the risk of later Alzheimer’s disease. Initiation of HRT in a woman with a likelihood of established atherosclerosis (e.g. older than 60 years or other risk factors such as smoking or chronic hypertension) will accelerate cardiovascular and cerebrovascular events.

hyperplasia and endometrial cancer. In women without a uterus, oestrogen-only therapy is more appropriate and probably has lower rates of breast cancer than the combined regimen. The levonorgestrel intrauterine contraceptive device (IUCD) can be used to administer a protective dose of progestogen for women who have not had a hysterectomy, thereby avoiding any adverse consequences of systemic progestogen.

Cancers other than breast

Cyclical versus continuous therapy

HRT is associated with a reduction in cancers other than breast (especially colon) such that the overall cancer risk of HRT is not increased, despite the definite rise in breast cancer risk. Endometrial cancer is reduced if HRT contains combined oestrogen and progestogen and is used continuously.2

Adverse effects of HRT Increased cardiovascular and cerebrovascular events in women with established atheroma is discussed above.

Venous thromboembolism (VTE) HRT increases the risk of thromboembolism twofold, although the absolute incidence remains low. The risk is further increased by positive factor V Leiden status, increasing age and obesity, and previous VTE. Transdermal HRT is associated with a lesser VTE risk than oral therapy as the ‘first pass effect’ on the liver is avoided.

Breast cancer Combined (oestrogen and progestogen) HRT increases the incidence and mortality of breast cancer. WHI and other studies have suggested that the incidence may be less for oestrogen alone. The background risk for the development of breast cancer is approximately 30 per 10 000 per year in the age group 55 to 60 years. This increases by approximately 8 per 10 000 women per year after 5 years of use. This might also be expressed as a relative risk of 1.25 times increase relative to background.

HRT regimen Oestrogen alone versus oestrogen and progestogen in combination For women with an intact uterus, oestrogen must be given with a progestogen to prevent endometrial

Oral versus transdermal patches, gels or implants Initial therapy is usually oral but alternatives include transdermal patches or gels. The latter avoids first pass metabolism in the liver, resulting in a null effect on hepatic coagulation proteins, reduced overall dose and usually improved convenience. Adverse effects, such as venous thromboembolism, are reduced compared to oral therapies. Thus, transdermal preparations may be an option for women with severe symptoms, who also possess thrombotic risk factors. In women around the menopause, cyclical treatment is recommended. Most often, an oestrogen is administered alone for the first 14 days and then in combination with a progestogen for the remaining 14 days of a 28-day cycle. A withdrawal vaginal bleed is usual but at recommended doses is not required to ensure endometrial protection. Beyond the menopause, continuous therapy can be considered.

Topical vaginal oestrogen Vaginal oestrogen cream or pessaries are useful for symptoms of vaginal dryness and, in conventional doses, accompanying progesterone therapy is not required. Small amounts of systemic absorption result in lower levels than are associated with adverse endometrial effects.

Tibolone Tibolone avoids the need for oestrogen and progestogen in combination. There is evidence showing no impact on endometrial hyperplasia risk. Evidence surrounding breast cancer risk is conflicting; however, it is likely that there is a small increased risk of primary breast cancer. Importantly, for women with a past history of breast cancer, recurrence risk is increased relative to placebo. Moreover, in clinical trials tibolone increases the overall risk of cerebrovascular events, particularly in older postmenopausal women and those with vascular risk factors.

Raloxifene Raloxifene is a selective oestrogen receptor modulator (SERM). It does not help at all with hot flushes but does protect bone without increasing the risk of breast cancer.

Testosterone Testosterone (cream, patch or implant) may have a special role in the improvement of libido in postmenopausal 437

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women, but further research is needed to quantify any benefit and better clarify potential adverse effects.

NON-HORMONAL ALTERNATIVES TO HRT Vasomotor symptoms No treatment is as effective for the control of vasomotor symptoms as conventional HRT. Clonidine is of marginal efficacy. SSRIs may be effective, with the best evidence of efficacy for venlafaxine. There is increasing evidence for gabapentin, but its use may be limited by side effects in many women. Evidence of efficacy is largely lacking for many complementary products in common use such as progestogen creams, phyto-oestrogens and black cohosh. Cognitive behavioural therapy is effective in reducing the impact of vasomotor symptoms and improving mood.

Osteoporosis A detailed account of the management of osteoporosis is beyond the remit of this chapter. However, advice should be given to all women regarding the importance of calcium in the diet, adequate vitamin D and exercise. In those at increased risk who elect not to take HRT, effective therapies include bisphosphonates, strontium, parathyroid hormone and raloxifene.

POSTMENOPAUSAL BLEEDING (PMB) All vaginal bleeding after the menopause is abnormal and requires investigation to exclude underlying endometrial hyperplasia or malignancy. Once excluded, alternative explanations such as vaginal atrophy can be considered. The minimum required assessment of any episode of PMB is a full history, examination, cervical smear and endometrial assessment by ultrasound or pipelle endometrial biopsy. Any unsatisfactory ultrasound assessment, endometrial thickness greater than 4 mm or persistent PMB requires a formal assessment by hysteroscopy and curettage. Ongoing bleeding despite a normal hysteroscopy and curettage needs to be considered carefully as there may be a ‘missed’ endometrial pathology or other gynaecological lesion.

PREMATURE MENOPAUSE Premature ovarian failure, or premature menopause, is defined as ovarian failure before the age of 40 years, with an incidence of 1%. An ‘early’ menopause has been referred to as one occurring before age 45 years.

AETIOLOGY Apart from surgical removal or radiation of both ovaries, premature menopause is idiopathic in up to 90% of cases. 438

A family history of early menopause may be elicited. Other predisposing conditions include X chromosome abnormalities (e.g. XX/XO mosaic), autoimmune disease, previous chemotherapy, haemochromatosis and fragile X carrier status.

CLINICAL FEATURES Amenorrhoea is usual, although infrequent periods can delay the diagnosis. Symptoms are common; the diagnosis may be ‘hidden’ by use of the combined pill or the medicated intrauterine device. Premature menopause may occasionally be revealed upon investigation for infertility.

MANAGEMENT Confirm the diagnosis A diagnosis of premature menopause is confronting, with significant implications for both fertility and the hormonal milieu. High gonadotrophin levels (FSH and LH) will confirm the diagnosis. Rising anti-Müllerian factor levels (AMF) are predictive of an approaching menopause.

Determine aetiology The cause may be obvious (e.g. surgical oophorectomy) but those in whom there is no obvious cause may be investigated for rare causes with other health implications (e.g. haemochromatosis or autoimmune endocrine disorders such as Addison’s disease and hypothyroidism).

Treatment The woman is at high risk of subsequent osteoporosis and adverse lipid profile in addition to vasomotor symptoms and urogenital atrophy. HRT should be instituted and continued until at least the age of a usual menopause. In the patient wanting children, the prospects of a spontaneous pregnancy are extremely low and there are no strategies known to increase the pregnancy rate from any remaining ‘dormant’ follicles. Egg donation, adoption and acceptance of childlessness should all be discussed as reasonable strategies. It is important to note, however, that HRT in these women is not a reliable contraceptive. REFERENCES 1) Sturdee DW, Pines A, International Menopause Society Writing Group. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. Climacteric 2011;14:302–20. 2) Beral V, Reeves G, Million Women Study Collaborators. Endometrial cancer and

Chapter 51 

hormone-replacement therapy in the Million Women Study. Lancet 2005;365(9470):1543–51. FURTHER READING Basson R. Testosterone therapy for reduced libido in women. Ther Adv Endocrinol Metab 2010;1(4):155–64.

The Menopause, Climacteric and Hormone Replacement Therapy

Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 2003;362:419–27. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progesterone in healthy postmenopausal women. JAMA 2002;288:321–33.

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Section 3.5 SEXUALITY Chapter 52

Normal sexuality, sexual and relationship dysfunction, and sexual assault

Chapter 52  NORMAL SEXUALITY, SEXUAL AND RELATIONSHIP DYSFUNCTION, AND SEXUAL ASSAULT Patricia Moore

KEY POINTS Human sexuality has many and diverse expressions. Culture, education, religion and past experience all impact on a person’s sexual development and expression. Sexual problems are common and the doctor needs to be comfortable with assessment and have a basic knowledge of the types of problems encountered and what treatment resources are available. Sexual assault has a high prevalence and will affect many of our patients. The effects may be profound and long lasting. The components of care following sexual assualt include a medical and forensic assessment (acutely) but, more commonly, dealing with a non-acute disclosure of past assault.

INTRODUCTION Sexuality refers to the way in which an individual views and expresses themselves as a sexual being in relationship to others. Cultural, religious and social factors are understood to play an integral part in how this sense of self develops. For many people sex is an enjoyable activity associated with pleasure, affection and positive interpersonal relationships. For the majority, at some time in their lives this will be connected to reproduction. However, for some people the sexual act is only permissible for procreation while for others there are very few, if any, positive associations. This may be because they have no choice in the terms of sexual behaviour they engage in, be they proscribed by the mores of the society in which they live or the result of abusive or exploitative relationships. The following definitions of sex, sexuality and sexual health have been proposed by the World Health Organisation.1 Sex refers to the biological characteristics that define humans as female or male. While these sets of biological characteristics are not mutually exclusive, as

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there are individuals who possess both, they tend to differentiate humans as males and females. In general use in many languages, the term sex is often used to mean ‘sexual activity’, but for technical purposes in the context of sexuality and sexual health discussions, the above definition is preferred. Sexuality is a central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy and reproduction. Sexuality is experienced and expressed in thoughts, fantasies, desires, beliefs, attitudes, values, behaviours, practices, roles and relationships. While sexuality can include all of these dimensions, not all of them are always experienced or expressed. Sexuality is influenced by the interaction of biological, psychological, social, economic, political, cultural, ethical, legal, historical, religious and spiritual factors. Sexual health is a state of physical, emotional, mental and social wellbeing in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful

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approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence. For sexual health to be attained and maintained, the sexual rights of all persons must be respected, protected and fulfilled. Patients often consult their doctors about sexual problems and expect them to have the knowledge and skills to understand their concerns and to help them. Our understanding of sexuality has evolved greatly in the latter half of the 20th and first decades of the 21st century. In that time, the body of knowledge has developed by application of a wide variety of approaches, including the biomedical model and psychological and sociological methodologies, and has been contributed to significantly by feminist theorists. At various times, one model or Orgasm

another has predominated within society in general and within the approach of the medical profession in particular. Initially, the focus was on defining normality with a view to treating or eradicating deviance from that norm. It is now more generally accepted that human sexual experience is widely diverse and that in the majority of instances a disorder is only defined as such if it causes distress to the individual. The obvious exceptions to this are when harm occurs to others. A very significant contribution was made in the 1960s by Masters and Johnson, who observed and recorded the physiological responses of men and women during sexual acts in a laboratory setting and devised a model of the phases of sexual response. These phases were seen as distinct entities and named excitement, plateau, orgasm and resolution (Fig 52.1).

Female

Plateau

Male

Excitement

Resolution

A Multiple reasons for sex

Original goals fulfilled —increased emotional intimacy, wellbeing

Initial/spontaneous sexual desire (variable)

Sexual satisfaction

Biological factors The mind’s information processing

More arousal triggered desire

B

Sexual stimuli in appropriate context

Subjective arousal +ANS response

Psychological factors

FIGURE 52.1 

A The four phases of the human sexual response cycle as postulated by Masters and Johnson. Because the resolution phase is prolonged considerably in men, men can experience refractoriness to further stimulation for varying lengths of time before they can achieve another orgasm. As discussed in the text, understanding of the human sex response cycle has evolved substantially since the publication of this work. B The circular human response cycle of overlapping phases. It is increasingly recognised that the human sexual response involves much more complexity, circularity and flexibility than is reflected in Masters and Johnson’s original model. ‘Desire’ may or may not be present initially; it can be triggered during the experience. Arousal and desire overlap. Multiple psychological and biological factors influence the information processing of sexual stimuli. Underlying this processing may be the individual’s unique tendency for excitation versus inhibition. Abbreviation: ANS = autonomic nervous system. Source: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. Williams Textbook of Endocrinology. 12th edn. Philadelphia: Saunders. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 20.1 A and B.

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Chapter 52  Normal Sexuality, Sexual and Relationship Dysfunction, and Sexual Assault

While this work represented a huge move forward in the understanding of sexual response, some of the applications (also hugely influential at the time) have now been successfully challenged. For example, Masters and Johnson developed treatment regimes, often involving sex surrogates, whose aims were to cure homosexuality and other deviations from the defined ‘norm’. Further, their assertion that nearly all cases of erectile dysfunction, then labelled ‘impotence’, were psychological in nature has been largely disproved in the last two decades with better understanding of erectile physiology. Indeed, psychiatry too focused on a model of normality with the Diagnostic and Statistical Manual of Mental Disorders (DSM) definitions of abnormal sexual behaviour developed from 19th-century descriptions of sexual psychopathology.2 Revisions have occurred over the course of time. The bestknown revision was the removal of homosexuality as a category of disorder in 1973. This represented the degree of change in societal views and acceptance of diversity. Further, in the last decade definitions of female sexual dysfunction in DSM-IV have been revised significantly. Since the late 20th century, sexology has emerged as a distinct, if multidisciplinary, field of study with international and national journals and conferences dedicated to a rational, evidence-based approach to a human sexuality. The discovery of sex hormones in the mid-20th century led to hormonal contraception, IVF, chemotherapy of breast and prostate cancer, and the controversial treatments of sexual offenders. Latterly, medicines for erectile dysfunction, menopausal symptoms associated with sexual problems, anxiety and compulsion disorders have contributed to improved personal resources in managing sexual problems. However, these developments have witnessed increased expectations regarding what normal sexual function might be and how it may be enhanced. This tension is witnessed by the recent trend in increasing numbers of cosmetic gynaecological procedures claiming to rejuvenate or enhance sexual functioning, despite RANZCOG and ACOG official guidelines cautioning against any evidence base for the safety or efficacy of such procedures.3,4 Sexual relationships may be understood as highly diverse and may be supported or stigmatised depending on social, cultural and religious contexts. Most sexual relationships involve some degree of mismatch in terms of beliefs, desires and behaviours. It is the necessity to articulate our own viewpoint and to negotiate with others that presents the greatest challenge in interpersonal relations of all kinds. Therefore, we can understand that these differences when encountered in a sexual context may result in sexual problems. These can present in numerous ways to healthcare professionals, and may not always be articulated as a sexual health issue. Finally, engaging in sexual relationships requires ethical decision making. While this may be influenced by knowledge and reason, ultimately such decisions are based on a much personalised sense of what is right and wrong. These are the issues we need to be aware of and sensitive to in order

to help those who seek our advice. The role of the generalist is not to behave as a sex therapist but rather to have the necessary knowledge regarding sexual experience, diversity and problems in order to educate and reassure patients when appropriate and to know when to refer to other health professionals as necessary.

SEXUAL DEVELOPMENT Sexuality is rarely expressed before puberty but gender identity is experienced as young as the preschool years. Identification with gender roles, significant relationships with parents and caregivers and their attitudes towards sexuality obviously impact on early development. For many, puberty is when they begin exploring their own bodies and sexual responses, become aware of attraction to others and later commence sexual activity with others.

SEXUAL ORIENTATION This refers to the sexual attraction that an individual experiences towards others, be they of the same, the opposite sex or either sex. Sexual orientation may be based on biological factors, social factors or both. There is awareness that sexual orientation is a highly complex entity, again with great diversity. Three dimensions are important: sexual identity; that is, self-identity as lesbian, gay, bisexual, heterosexual or transgender sexual desire or sexual attraction towards others, whether acted on or not sexual behaviour: past present and future. It is important to note that sexual identity does not define sexual behaviour; for example, a man who has sex with men may not identify as gay, while some lesbian women may have sex with men too. Sexual identity may be fluid and change over time. Much same-sex attraction is not exclusive and can be unstable in early adulthood, especially in women.5 It seems that in young men samesex behaviour is more often associated with same-sex orientation, whereas in young women same-sex relations seem to be more exploratory. A process of ‘coming out’ is recognised as involving self-recognition of attraction, experience with same-sex partners, self-identification and finally disclosure to a significant other rather then to wider society. Negative personal attitudes, perhaps the result of cultural or religious factors in a young person’s upbringing, can lead to significant psychological distress and greater risk-taking behaviours. It is important to recognise how significantly different this process is from those for young people whose developing sexuality is assumed to be the norm.6 The incidence of various sexual orientations appears to be similar across cultures.7 In the Sex in Australia study, 8% of women reported same-sex experiences with 0.1 % identifying as lesbian and 1.4%

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as bisexual. With men, 5.9% reported same-sex experience with 1.6% identifying as gay and 0.9% as bisexual. Gay and lesbian individuals are represented in all socioeconomic and cultural groupings and there are many lesbian, gay, bisexual and transgender (LGBT) subcultures.8 Bisexuality has been difficult to define and quantify as the boundaries between same-sex attraction and bisexual behaviour are indistinct. Bisexual individuals speak of the difficulty of not being accepted in gay and lesbian communities or in heterosexual groupings. There are other sexual orientations which do not conform to these categories. Men who cross-dress but are exclusively heterosexual in their behaviour have a distinctly different orientation from men who seek sex with transvestites. Those who derive sexual pleasure from wearing rubber describe it as difficult to find a heterosexual partner. It may be that trying to define sexual orientation only limits our understanding and acceptance of diversity.9

GENDER IDENTITY Usually this is sexual (i.e. one identifies with the gender associated with one’s biological sex). However, for transsexual people there is a persistent cross-gender identification associated with significant distress with the assigned sex. Often these feelings originate in early childhood, with the onset of puberty a time of crises. The incidence is low, being 1:12 000 males and 1:30 000 females. There is mounting evidence for a very early development biological cause, and transsexuals who seek and receive gender reassignment have good psychological outcomes compared to those individuals who had no access to such a service.10 The term ‘transgendered people’ refers to those who are undergoing or have completed gender reassignment.

SEXUAL DYSFUNCTION AND SEXUAL PROBLEMS CLASSIFICATION OF SEXUAL DISORDERS Sexual disorders have been defined by the American Psychological Association in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V, 2013) as a disturbance in the processes of the sexual response cycle. Drawing heavily on Master’s and Johnson’s work, the system divides female sexual dysfunction into disorders of interest/arousal, orgasm and genitopelvic pain/penetration. Male disorders are classified as erectile disorder, hypoactive sexual desire disorder and disorders of ejaculation (premature and delayed). The International Consensus Development conference has suggested the female disorders may be too rigid a model of sexual arousal for women and now includes psychogenic and organic causes of desire, arousal, orgasm and 444

sexual pain disorders in women. It has been established recently that the prevalence and nature of women’s sexual problems varies significantly depending on the survey instruments used.11 It is also important to note that people do not present neatly with a complaint in just one aspect of their sexual response. Rather, a man may develop decreased desire and sexual avoidance in response to erectile difficulties or performance anxiety while a woman who has severe pain on intercourse after a traumatic birth often will experience vaginismus in response to this, and avoidance of sexual interaction with a partner. Bearing these features in mind, there do exist some broad categories of dysfunction described by men and women (Table 52.1).

Sexual problems It is now recognised that sexual problems are common.12 Reporting on a large national survey, the Australian Study of Health and Relationships revealed that 25% of men lacked interest in sex, 24% had premature ejaculation and 16% experienced performance anxiety. In contrast, the majority of women (55%) lacked interest, 29% did not experience orgasm, 27% did not enjoy sex and 20% experienced pain during intercourse. These findings have been reproduced in other work.13

Assessment of sexual problems It is important to take a very full medical and sexual history when someone presents with a sexual problem (Box 52.1). If they have a partner, it is important to include them by offering to speak to each person individually and then as a couple. A history of family, cultural and religious contexts in their upbringing and current lifestyle is essential, as is the presence of negative or abusive experiences as either a child or an adult. Seeking to understand as fully as possible what the issue is for the patient and to what extent it is affecting, mood, relationships and other aspects of life may require several

TABLE 52.1  CATEGORIES OF SEXUAL DYSFUNCTION. Male sexual dysfunction

Female sexual dysfunction

Hypoactive desire disorder

Hypoactive desire

Erectile disorder

Sexual aversion disorder

Delayed or inhibited ejaculation

Orgasmic disorder

Premature ejaculation

Sexual pain/dyspareunia/ vaginismus

Sexual pain

Chapter 52  Normal Sexuality, Sexual and Relationship Dysfunction, and Sexual Assault

consultations. It is important to remember that anxiety and mood disturbances are very common in those seeking help for sexual problems, and to screen for them. Whether the problem has been persistent or whether it is situational only is of note. For example, if a woman describes inability to orgasm with a partner present but has no problem when masturbating in private, this may require the need to educate both partners on the nature of female orgasm or to explore more fully her desires and orientation. Answers to these questions can provide key features that may be addressed by treatment options. Intercurrent medical problems such as diabetes, hypercholesterolemia, hypertension and symptoms of menopause are relevant not only in terms of risk factors for erectile function in men and decreased desire in women but also with regard to the possible side effects of medical treatments. Similarly, serious illness such as cancer or events such as childbirth or hysterectomy are associated with physiological, hormonal and emotional changes relevant to the history of dysfunction.

Disparate sexual desire This is the most frequent sexual complaint occurring within relationships and may not be associated with any sexual dysfunction. It may be a persistent theme throughout the relationship or occur after some time. Often the person with lower desire may feel anxious that they are abnormal or failing to please their partner. This may be reinforced by the partner’s behaviour. Given the nature of relationships over time, with reproductive and illness events intervening, it is not uncommon for intermittent mismatches of desire. Decreased desire is extremely common in women, cited as approximately 50% in some studies.14 However, a smaller proportion, approximately 30%, are distressed by this. There is a strong influence of

BOX 52.1  Approach to history taking in patients with sexual problems. Patient’s own description of the problem and how it affects/distresses them ✚ Affect on relationship/s and partner/s ✚ Patient’s thoughts on cause Onset age ✚ Persistent or situational ✚ Precipitating factors Change over time ✚ Specific events Past treatments and effects Physical factors Medications Psychological factors Attitude to change

sex hormones on desire. Assessing for gonadial failure is therefore an important part of such a presentation in both sexes. Men often report an increase in interest after androgen treatment and women may respond to oestrogen and or androgens. Androgen therapy can, however, produce unwanted or harmful effects in both sexes and requires careful monitoring. Reassuring both partners that disparate desire is common and often entirely normal can be very therapeutic and allows for the exploration of other aspects of the relationship. Sexual desire is most often limited by the lack of psychological intimacy arising from an inability to recognise or express feelings, or indeed fear about expressing feelings. Sometimes external demands such as work commitments, young children and childcare, caring for elderly parents and so on become overwhelming. Familiarity reduces desire over time and desire may need to be stimulated by varying routines and working on quality time alone in long-term relationships. If a person has always had a low desire, psychological issues may require more exploration. If a person has lost desire within a relationship, physical, medical and relationship issues become more prominent in the assessment. Treatments include couples counselling and addressing any medical issues (including any medications that may be adversely affecting sexual function, as outlined in Box 52.2). Another treatment option is graduated, non-threatening exercise in exploring sensual experiences, often termed sensate focus (Box 52.3); this was originally described by Masters and Johnson. Excessive sexual desire is much less common than decreased desire and may be caused by neurological damage, mental illness (particularly mania) or certain drugs. In some disturbed or abused adolescents, this behaviour may be understood as acting out. Excessive sexual behaviours in adults such as pornography viewing and involuntary masturbation may be assessed as compulsive disorders and have shown some response to SSRIs.

BOX 52.2  Some medications that can decrease sexual functioning in women. Antihypertensive: beta blockers, diuretics Antidepressants: tricyclics, SSRIs Sedatives: alcohol, marijuana, benzodiazepines, barbiturates Narcotics: heroin/methadone Antipsychotics: chlorpromazine, fluphenazine Stimulants: cocaine or amphetamines Hallucinogens: LSD 445

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BOX 52.3  Sensate focus. A series of gradated exercises aimed at increasing awareness of and pleasure in sensual stimuli, including touch. Partners contract that no sexual touch or performance demand are made during sessions. May start with very non-threatening activity such as listening to music together fully clothed. Progresses slowly towards sensual massage, self-exploration and guided masturbation. Used in the treatment of performance anxiety, decreased desire and arousal and male ejaculatory disorders. Used as a prelude to, and in conjunction with, graduated vaginal dilators for vaginismus and some cases of dyspareunia.

MALE PROBLEMS ERECTILE DYSFUNCTION Many conditions can lead to problems with penile erection, including smoking, alcohol, prescription and recreational drugs, diabetes and cardiovascular disease. Spinal cord injury and prostate surgery are also implicated. Among the psychological problems that can cause erectile problems, performance anxiety is probably the most important. Treatment may include management of the underlying medical condition, or the use of phosphodiesterase inhibitors such as sildenafil (Viagra) that improve the response of the erectile tissue to neural input. Cognitive behavioural therapy and psychotherapy may be helpful for addressing performance anxiety. Among the non-drug treatments are vacuum devices and penile implants.15

PREMATURE EJACULATION The cause of the most commonly described sexual problem for men is not well understood. Biological factors (e.g. prostatitis) and psychological factors (e.g. performance anxiety) may both contribute. Techniques such as sensate focus have been described as helpful. Other measures to decrease stimulation include condom usage, female dominant positions with slow thrusts and the squeeze manoeuvre. This involves communicating when ejaculation is about to occur. A partner then holds the shaft of the penis firmly in both hands for up to 1 minute. This usually decreases the ejaculation reflex. The aim is to slowly show an increase in time to ejaculate. SSRIs have also been demonstrated to help some men.16 446

INHIBITED OR DELAYED EJACULATION While uncommon in men, it is associated with certain drugs, particularly SSRIs. It may be treated by changing the medication regimen or sensate focus exercises aimed at increasing genital stimulation. Decreasing anxiety may also be useful.

FEMALE PROBLEMS SEXUAL AVERSION DISORDER This refers to the situation where a woman is so profoundly fearful and anxious about any sexual touch that she avoids all situations where she sees this as a possible risk. Often this is associated with severe trauma or a history of sexual abuse. This disorder usually requires intensive psychological therapy and warrants early referral. Physical therapies are introduced later in the treatment process.17

FEMALE SEXUAL AROUSAL DISORDER This refers to difficulties with vaginal lubrication, engorgement or clitoral erection. Usually lubrication is insufficient, so this problem is common in breastfeeding or postpartum women and associated with menopause. Awareness of the uses of lubricant, hormone therapy (either topical or systemic) and exercises such as sensate focus may be helpful. Sildenafil has not been demonstrated as useful in female sexual arousal disorder.

DIFFICULTY OR INABILITY TO EXPERIENCE ORGASM Many women have problems with orgasm. A biological cause for anorgasmia is extremely rare. Indeed, even the nature of female orgasm, whether it depends entirely on clitoral stimulation or has a vaginal enervation component, is still debated. Often education regarding clitoral position and how to stimulate this during penetrative sex is extremely helpful to patients and their partners. Sensate focus with progression to masturbatory techniques, either manually or with vibrators, is also worthwhile for many. Recently, a vacuum-creating handheld device has been developed to aid clitoral hood retraction and clitoral erection.18

PAINFUL COITUS (DYSPAREUNIA) This type of complaint is relatively common and can result for a wide variety of causes. The distinction is made between superficial and deep dyspareunia, which may have separate aetiologies. Insufficient lubrication is the most common cause and may be linked to decreased desire. Education, lubrication and sensate focus have all been described as treatments. Excluding an underlying

Chapter 52  Normal Sexuality, Sexual and Relationship Dysfunction, and Sexual Assault

biological cause, such as endometriosis in deep dyspareunia or lichen sclerosis with superficial dyspareunia, is important. Pelvic physiotherapy may also be helpful.

VAGINISMUS Understood as profound vaginal spasm prohibiting penetration, vaginismus is often a secondary association with sexual pain. It may be primary, or it may be secondary such as after a difficult birth or gynaecological surgery. There is a strong association with previous sexual abuse. An explanation that the spasm is involuntary and that it is treatable is often very reassuring to both partners. Treatment includes supportive exploration of possible triggers, pelvic relaxation techniques, sensate focus and the use of graduated vaginal dilators. Psychotherapy may be necessary for chronic or persistent cases.

PARAPHILIAS DSM-V classifies paraphilias as atypical sexual interests that cause distress to those with the interest themselves or may injure, cause distress or death to the subject of their atypical sexual interest. These disorders include exhibitionistic disorder, fetishistic disorder, frotteuristic disorder, paedophilic disorder, sexual masochism disorder, sexual sadism disorder, transvestic disorder and voyeuristic disorder. Individuals with paraphilias often have a dual diagnosis of personality disorder. They tend not to seek help for themselves but rather come to the attention of the authorities due to criminal acts such as paedophilia. In Australia, the legal system prohibits sexual behaviours which harm others. For example, bondage and many sexual acts involving domination and submission for sexual pleasure are not illegal if consent is proven. However, there is a legal requirement in Australia for doctors and other health and education workers to report any knowledge of child abuse or sexual assault to the police.

SEXUAL ASSAULT The definitions of sexual assault and rape vary consi­ derably between countries. However, a broadly agreed concept is that a sexual act performed on a person without their consent is a sexual assault. Rape is frequently classified as penetration by a penis, finger or object of the anus, vagina or mouth. In the case of vaginal penetration, only the slightest penetration of the vulva is required. Sexual assault and rape are common, with the reported incidence varying depending on the survey instrument and the cultural definitions. Between 33% and 40% of women will have been affected by attempted or completed sexual assault in their lifetime and for a significant number there will be more than one incidence. The figures for men sit at between 10 to 15%.19 Many victims are frightened of retribution, not being

listened to, the judicial system and public disclosure. This is further complicated by the majority of assaults being perpetrated by someone known to the victim. The minority of reports result in conviction due to difficulties in providing evidence and the necessity of argument around the issue of consent. For all the reasons just given, under-reporting is extremely common. While medical personnel may be called on to examine an acute case of sexual assault, this represents the least common presentation. Teams of forensically trained physicians are available across Australia and can respond in a timely manner when a police report has been made. However, if the woman does not wish to make a report or is undecided, this facility is not provided. Rather, the presentation is often delayed by days, weeks and in some cases years. Most often the needs of the patient include information as to whether any damage or permanent signs of the abuse are present and concerns regarding infection, pregnancy risk and indeed future fertility. It is therefore extremely important that the generalist be aware of the requirements of the medical and forensic examination and sensitive to the needs of patients who may disclose previous sexual abuse within the context of gynaecological or obstetrical consultations or examinations. Providing a safe environment in which the victim can begin to make decisions regarding how they wish to proceed is essential at a time when a great deal of pressure may be placed on them. Childhood sexual assault requires mandatory reporting throughout Australia. Specialist teams trained in the assessment of child abuse and neglect are to be alerted and will manage such cases. These personnel are contacted via the closest paediatric hospital service.

COMPONENTS OF CARE Medical care This refers to attending to the immediate medical and psychological needs of the patient. Assessment of acute injuries includes not only a careful genital inspection but also examining the entire body for other injuries such as scratches, burns, bite marks or restraint injuries. Treatment of injuries, consideration of emergency contraception and hepatitis prophylaxis are the mainstays of management. Psychological symptoms such as anxiety, insomnia, mood swings and head and pelvic pains are common and may benefit from a brief course of sedation or analgesia. Collection of specimens to screen for sexually transmitted infection needs to take into account the incubation period of infections: 10 to 14 days for microbial and up to 12 weeks for viral infections. Consideration of HIV prophylaxis is given when the assailant is known to be HIV-positive, is from a population with a high incidence of the virus or in cases where multiple assailants were involved.20 Contact with counsellor advocates is essential. In Australia, statefunded support groups are available in all urban centres 447

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under the banner of CASA (Centre Against Sexual Assault). Twenty-four-hour cover and access to help, advocacy and ongoing support are provided. There are also several national 24-hour crisis phone lines.

Forensic examination Forensic examination refers to the gathering of evidence that may contribute to a criminal conviction: it is important to note that rape is not a medical diagnosis. Evidence that links the perpetrator to the victim (such as DNA from saliva, blood or semen) or which links the event to a location (such as the presence of sand, soil, plant or other material) is highly relevant. The role of the medical examiner is not to determine whether consent occurred but rather to detail the facts of the examination on behalf of the victim in order to provide the context in which those arguments are made under the adversarial court system. Specimens for DNA and other material may be obtained from clothing. This necessitates the victim removing all of their clothing, unless changed or showered, which is then held in a sealed bag till examined. DNA may be obtained from fingernail scraping, and from swabs of buccal mucosa, vagina, cervix, perineum or any affected area where secretions may be obtained. DNA is only rarely cultured from hair. The swabs must be dried before storage without any medium as overgrowth of bacteria or fungi destroys DNA evidence. It is very important to perform careful documentation, including anatomical diagrams with location and size of any lesion. This author does not recommend the taking of photos by anyone other than the forensic team due to issues with image quality and confidentiality. In the cases which do go to court, the time delay is very significant and the medical record becomes an essential document and often the only aid to memory. Timing of the incident, timing of the examination and whether the patient has washed or changed are also important as these alter the likelihood of the presence of forensic evidence. A chain of evidence must be maintained. This means that any specimens must be labelled with a witness present who then observes them being sealed in a tamper-proof container and handed to the investigating team. In cases where the victim is undecided, collection of samples can be offered, with all evidence held by the examining doctor in a secure place under their responsibility until an agreed date. This has proved valuable to some patients who were incapable of decision making at the time.21

Aftercare planning This involves the appropriate timing of a review appointment to assess and treat infection and to exclude pregnancy. Establishing an appropriate general practitioner, sexual health physician or gynaecologist for follow-up and liaising with them on the patient’s behalf is extremely important. Ongoing counselling and support are available via CASA, with links to other services. 448

DISCLOSURE OF PREVIOUS ASSAULT It is very important to listen to and validate the patient’s disclosure. An expression of sorrow that this has happened establishes empathy. A statement that they are believed is also very therapeutic. You may well be the first person they have told. As with acute assault, establish what the patient’s needs are and address those before providing information regarding the options available for ongoing supportive care. In Australia, a limited number of counselling sessions are available free of charge to anyone who has ever experienced sexual assault. REFERENCES 1) World Health Organisation. Defining sexual health: report of a technical consultation on sexual health, 28–31 January 2002, Geneva. Geneva: WHO; 2006. 2) Levay S, Valente S. Perspectives on sexuality in human sexuality. 2nd ed. Massachusetts: Sinauer Associates; 2006. p. 4–26. 3) RANZCOG. College statement. C-Gyn 24 Vaginal ‘rejuvenation’ and cosmetic vaginal procedures (C-Gyn 24); July 2011. 4) American Congress of Obstetricians and Gynecologists. Vaginal ‘rejuvenation’ and cosmetic vaginal procedures: ACOG committee opinion no. 378. Obstet Gynecol 2007;110:737–8. 5) Levay S, Valente S. Sexual relationships in human sexuality. 2nd ed. Massachusetts: Sinauer Associates; 2006. p. 287–309. 6) Howard J. Sexual orientation issues. In: Howard J, ed. Helping people with sexual problems. Melbourne: IP Communications; 2010. p. 212–32. 7) Levay S, Valente S. Sexual minorities in human sexuality. 2nd ed. Massachusetts: Sinauer Associates; 2006. p. 451–91. 8) Ricters J, Russel C. Doing it down under: the sexual lives of Australians. Sydney: Allen & Unwin; 2005. 9) Ward T, Laws DR, Hudson SM, editors. Sexual minorities: issues and controversies. London: Sage; 2006. 10) Ceglie D, ed. A stranger in my own body: atypical gender identity development and mental health. London: Karnac Books; 1998. 11) American Psychiatric Association. DSM-5: diagnostic and statistical manual for mental disorders. 5th ed. Arlington: American Psychiatric Press; 2013. 12) Lauman E, Pack A, Rosen R. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281(6):537–44. 13) Nojman J, Dunne M, Boyle F, et al. Sexual dysfunction in the Australian population. Aust Fam Physician 2003;32(11):951–4.

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14) Lauman E, Nicolson A, Glasser DB, et al. Sexual problems among women and men aged 40–80 years: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviour. Int J Impot Res 2005;17(10):39–57. 15) Alexander W, Carson C. Erectile dysfunction and related disorders. London: Mosby; 2003. 16) Leblum S, Rosen R. Principles and practice of sex therapy. New York: Guildford Press; 2007. 17) Carnes PJ, Moriarity J. Sexual anorexia: overcoming self-hatred. Centre City: Hazelden; 1997.

18) Howard J. Women’s sexual problems. In: Helping people with sexual problems. Melbourne: IP Communications; 2010. p. 186–92. 19) Australian Centre for the Study of Sexual Assault (ACSSA). . 20) Wells D, Welborn A. Medical responses to adults who have experienced sexual assault: an interactive module for doctors. Victorian Institute of Forensic Medicine. Melbourne: RANZCOG Publications; 2005. 21) Wyatt J, Squires T, Norfolk G, et al. Oxford handbook of forensic medicine. Oxford: Oxford University Press; 2011.

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Section 3.6 CONTRACEPTION, STERILISATION AND ABORTION Chapter 53

Contraception, sterilisation and abortion

Chapter 54

Genital tract infections

Chapter 53  CONTRACEPTION, STERILISATION AND ABORTION Patricia Moore

KEY POINTS The ability of a woman to decide when, and how often, to become pregnant with effective and reliable contraception directly affects her life trajectory, reduces morbidity and mortality associated with pregnancy and childbirth, and confers some non-contraceptive health benefits. The medical eligibility criteria provide an evidence-based framework for assigning a risk category to each contraceptive method. The effectiveness of a contraceptive can be measured by the number of unintended pregnancies over 1 year for every 100 women using the method. Long-acting reversible contraceptive methods include contraceptive implants/injections and intrauterine contraceptive devices (IUDs). Contraceptive implants (Implanon NXT) and intramuscular injections (e.g. Depo-Provera) are highly effective and suitable during breastfeeding. The main disadvantage is unscheduled bleeding and—in the case of Depo-Provera—delayed return to fertility. Intrauterine contraceptive devices are highly effective, and the levonorgestrel releasing-system (Mirena) has the added benefit of decreased menstrual bleeding and discomfort. Combined hormonal contraception is available orally (‘the pill’) or as a vaginal ring. Combined hormonal contraception enables cycle control, reduces menstrual bleeding, and is easy both to access and administer; it is immediately reversible on cessation in the event of side effects. The progesterone-only pill is useful for women with contraindications to combined hormonal contraception, or who require a low dose or breastfeeding-friendly option. Barrier methods of contraception available in Australia include diaphragms and male and female condoms. Emergency contraception includes hormonal methods (single-dose levonorgestrel, or combined high-dose oestrogen and progesterone) and non-hormonal methods (copper-containing IUCD). Fertility awareness may be useful for some women, but this has reduced efficacy compared to other methods of contraception. They include symptom-based methods, calendar methods and lactational amenorrhoea. Permanent contraception has reduced among women due to the increased availability of long-acting reversible contraceptives; in contrast, vasectomy rates have remained static. Legislation regarding abortion varies from state to state across Australia. Over 90% of terminations of pregnancy are performed in the first trimester, where either medical or surgical methods may be used. Second-trimester abortion is most often managed medically, although surgical termination may be suitable after the first trimester where there are appropriately trained surgeons, and cervical ripening is performed prior. Contraceptive needs must be met at the time for women who attend an abortion service, as the provision of long-acting reversible contraceptives reduces the risk of repeat abortions.

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CONTRACEPTION Contraception and family planning represent one of the most important public health issues of our time. The capability to limit the number of children a woman has directly affects her ability to fulfil her life goals. Further, reduction in the number of pregnancies decreases the morbidity and mortality associated with pregnancy and childbirth, which are always more considerable in the developing world. There are also multiple noncontraceptive benefits, both social and medical, of the contraceptive technologies that have been developed. Evidence-based approaches to prescription practices have become predominant, with the World Health Organisation (WHO) and the United Kingdom (UK) each developing medical eligibility criteria (MEC) for women that are available as online resources for desktop consultation. An awareness of the differences in perfect and typical-use failure rates is reflected in the focused development of long-acting reversible contraceptive methods requiring little, if any, regular patient input. It is important to appreciate that no perfect contraceptive method exists and it is necessary to tailor the choice of methods to the specific patient’s requirements: medically, emotionally and socially. A full medical, sexual and social history is therefore required, and the practitioner must be comfortable and conversant with such a wide-ranging consultation and be non-judgmental in their approach. This chapter outlines the currently available methods, including permanent contraception and abortion practices with specific reference to the Australian situation. The World Health Organisation recognises the reproductive health of societies as being central to the development of overall physical and mental health. Reproductive health includes the ability to have a responsible, satisfying and safe sex life with the capability to reproduce and the freedom to decide when and how often.1 Central to this assertion is the right of men and women to have access to safe, effective, affordable methods of contraception alongside the development of health services to ensure safety of pregnancy, childbirth and infancy. Population control in a world of ever-decreasing resources can be argued to be one of the greatest priorities in global healthcare planning.2

EVIDENCE-BASED PRESCRIPTION OF CONTRACEPTION The Cochrane Collaboration has performed meta-analyses of hormonal and non-hormonal methods of contraception, and produced suggested practice guidelines as a result. Perhaps of greatest practical and clinical relevance to the health practitioner are the medical eligibility criteria. Two distinct sets are available online; these provide well-referenced practice guidelines which are presented in table format with four categories of risk. Useful resources for the clinician are summarised in Box 53.1. 452

BOX 53.1  Useful resources for the clinician. Faculty of Sexual and Reproductive Healthcare, Royal College of Obstetricians and Gynaecologists: http://www.fsrh.org ✚ UK Medical Eligibility Criteria for Contraceptive use: http://www.fsrh.org/pdfs/ UKMEC2009.pdf ✚ Clinical effectiveness unit (CEU) guidance documents, key statements and new product reviews: http://www.fsrh.org/pages/clinical _guidance.asp World Health Organisation (WHO) ✚ Medical Eligibility Criteria, 4th edn, 2010: http://www.who.int/reproductivehealth/ publications/family_planning/9789241563888/ en/index.html ✚ Selected Practice Recommendations for Contraceptive Use, 2008 update: http:// whqlibdoc.who.int/hq/2008/WHO_RHR_08.17 _eng.pdf Therapeutic Goods Administration (TGA) ✚ This government authority approves information that is included in the packaging and product information (PI). (Note that it is legal to prescribe outside the TGA PI, provided there is a recognised base for the practice.) Sexual Health and Family Planning Australia ✚ Contraception: An Australian Clinical Practice Guideline, 3rd edn, 2012. Source: Contraception: An Australian Clinical Practice Handbook and used with permission © 2012. Family Planning NSW, Family Planning Victoria and Family Planning Queensland.

The medical eligibility criteria The WHO MEC3 and the UK MEC4 provide an evidencebased framework for assigning a risk category to the use of a particular contraceptive method in specific circumstances. Conditions are defined as either an individual’s personal characteristic (such as being nulliparous) or an individual’s preexisting medical condition (e.g. asthma or diabetes). Both systems have used the same four categories (Table 53.1).

Pregnancy risk The average rate of pregnancy without contraception is approximately 20% per cycle. The effectiveness of a contraceptive method is the effectiveness with which the method prevents unwanted pregnancy. For example, 95% effectiveness can be understood as 95 out of every 100 women using the method for a year will be protected against unwanted pregnancy. Alternatively, 5 out of every 100 women using the method would become pregnant

Chapter 53  Contraception, Sterilisation and Abortion

TABLE 53.1  MEDICAL ELIGIBILITY CRITERIA CATEGORIES. Category

Description

MEC 1

A condition for which there is no restriction for the use of the contraceptive method

MEC 2

A condition where the advantages of using the method generally outweigh the theoretical or proven risks

MEC 3

A condition where the theoretical or proven risks usually outweigh the advantages of using the method

MEC 4

A condition which represents an unacceptable health risk if the contraceptive method is used

Note: Some conditions have a further MEC category depending on initiation (I) or continued use (C). For example, IUCD initiation in someone with untreated Chlamydia is MEC 4 but if the same diagnosis is made in someone currently using an IUD it is MEC 2.

in a year. This is distinct from the Pearl index, which is calculated by the number of unintended pregnancies divided by the number of years of exposure to the risk of pregnancy. Most methods offer a failure risk that hovers between what is referred to as perfect use and the typical use that is closer to the clinical application (Table 53.2). Notable from these statistics are several points. First, there exists an obvious discrepancy in method failure between typical and perfect use for those agents that require repeated or continual attention to the method (e.g. oral hormonal contraception and barrier methods). Conversely, those that require very little personal input after the original fitting have the greatest efficacy clustering around that quoted for sterilisation procedures. These methods are collectively referred to as long-acting reversible contraception (LARC) and are defined as those methods requiring administration of less than once per month. Practice guidelines from the UK National Collaborating Centre5 and the WHO Selected Practice Recommendations6 suggest these methods are more effective and should be considered in first-line counselling with all patients. Recent work has confirmed decreased repeat abortion rates in those in whom an LARC was provided at the time of the first abortion.7

Initiation of contraception When initiating contraception, convention has often dictated a delay until the commencement of the next menses. This is often unnecessary and associated with increased risk of pregnancy. The practitioner can make an assessment of risk of pregnancy at the time of considered

TABLE 53.2  CONTRACEPTION FAILURE RATES COMPARING TYPICAL USE AND PERFECT USE, EXPRESSED AS PERCENTAGE FAILURE IN 1 YEAR. Contraceptive method

Perfect use (%)

Typical use (%)

None

85.00

85.00

Male sterilisation

0.10

0.15

Female sterilisation

0.50

0.50

Copper IUD

0.60

0.80

Levonorgestrel IUS

0.10

0.10

Depot medroxyprogesterone acetate (DMA)

0.30

6.70

Etonogestrel (ENG) implant

0.05

0.05

Combined oral contraceptive pill

0.30

8.70

Progesterone-only oral pill

0.50

8.70

Diaphragm alone

6.00

12.00

Diaphragm with spermicide

6.00

16.00

Male condom

2.00

17.40

26.00

32.00

9.00

16.00

Spermicides

15.00

29.00

Fertility awareness

19.00

25.30

—

18.40

Cervical cap: parous Cervical cap: nulliparous

Withdrawal

Note: While spermicides are not available in Australia, some women will have access to spermicide (having purchased it elsewhere), and so these methods are included for completeness. Source: Contraception: An Australian Practice Handbook. 3rd edn. Queensland: Family Planning, 2012.

initiation and in many cases commence the method at the time of consultation. WHO and the UK Faculty have concordant criteria for assessment of the risk of pregnancy. If a woman meets one of the following and has no signs or symptoms of pregnancy, a physician can reasonably exclude pregnancy: 1. has not had sexual intercourse since the start of the last menstrual period 2. has been consistent and correct in the use of a reliable method (e.g. Mirena, combined OCP) 453

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3. is within 5 days of the onset of menses 4. has given birth within the last 21 days 5. has experienced an abortion or miscarriage in the last 5 days.

LONG-ACTING REVERSIBLE CONTRACEPTION CONTRACEPTIVE IMPLANTS Implanon NXT Implanon NXT is the only progesterone subcutaneous implant available in Australia. In the form of a straw-like malleable implant that is 4 cm by 2 mm, it secretes etonogestrel at a steady rate mediated by the matrix polymer of the plastic rod (Fig 53.1).

Advantages Implanon NXT’s efficacy lasts for 3 years. Similar devices in the form of Jadelle (a two-rod 5-year device) and Norplant are available elsewhere so it is important to ascertain which one the patient is using if removal or exchange is required. The Implanon NXT rod comes with an insertion device, recently upgraded by the manufacturer to decrease insertion failures, and is placed in the medial aspect of the non-dominant arm under a local anaesthetic. A basic insertion training course is mandatory. The main mode of action is to suppress ovulation, with studies indicating an average of 30 months’ anovulation postinsertion. Further, cervical mucus is very much thickened, prohibiting sperm transport, and it is this that contributes to ongoing efficacy until 36 months. The failure rates are the same for perfect and typical use, at 0.05%. Progesterone inserts may be used without reservation in lactating women and have few contraindications.

Contraindications Breast cancer, current or within the last 5 years, is an absolute contraindication (WHO MEC 4), while efficacy is reduced in women taking liver enzyme inducers such as phenobarbitone or phenytoin and indeed nonprescription medications such as St John’s wort (WHO MEC 3). This category also includes liver disease, undiagnosed genital tract bleeding and intercurrent ischaemic heart disease. Category 2 includes liver conditions with normal liver function, gallbladder disease, a family history of breast cancer and venous thromboembolism (VTE). Time to fertility after removal is rapid, providing a good choice for family spacing.

Disadvantages The main side effect is unscheduled bleeding, with as many as 20% of women finding the pattern intolerable. Approximately the same percentage will have amenorrhoea by 1 year. The combined oral contraceptive pill (OCP) can be prescribed as an adjunct to settle bleeding but the effect tends to be short lived. Minor side effects reported include headache, abdominal pain, breast tenderness, decrease in libido, acne and hair loss (rare). Weight gain when compared to a control group of IUD users showed no significant weight gain or difference in the groups.8 Bone density was also compared to IUD users and results showed no changes in Z scores over 2 years. It is recognised that sample sizes have been small and more long-term research is required.

Depo-Provera Depo-Provera is depot medroxyprogesterone acetate (DMA), an intramuscular injection with a 90-day efficacy. Again, it works by suppressing ovulation. The dose is 150 mg and the effects will take time, sometimes months, to wear off, unlike Implanon NXT, which can be removed. Contraindications and side effects are similar to those for the progesterone-only pill and Implanon NXT, with increased appetite and weight gain in some women. Cycle disturbance is greater at around 50% and the main disadvantages are waiting for effects to wear off, a slower return to fertility (the average being 9 months) and the need for 12-weekly injections. Long-term studies suggest possible adverse effects on bone mineral density in current users, with correction after cessation.9

INTRAUTERINE CONTRACEPTIVE DEVICES FIGURE 53.1 

Implanon NXT device.

Source: Jensen JT, Mishell DR. Family planning: contraception, sterilization and pregnancy termination. In: Lentz GM, Lobo RA, Gershenson DM, Katz, VL. Comprehensive gynecology. 6th edn. St Louis: Mosby; 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Chapter 13, 215–72. Figure 13.23.

454

There are two types of intrauterine devices available in Australia (Fig 53.2): the copper-containing device (IUD) and Mirena, a levonorgestrel-releasing system (IUS). They both offer pregnancy protection equivalent to sterilisation and demonstrate a rapid return to fertility, making them highly cost-effective long-acting reversible contraceptives. In Australia, the copper device is not on the pharmaceutical benefits scheme (PBS) listing, with cost being a factor for some women (prices vary between $98 and $136).

Chapter 53  Contraception, Sterilisation and Abortion

A

or painful periods is a relative contraindication and women are advised to check for the string each month to exclude expulsion with heavy blood loss. MEC category 4 for initiation is active infection or cancer of the cervix as yet untreated. Continuation is category 2 in a woman diagnosed with genital tract infection providing effective treatment is commenced, with uterine abnormalities being categories 2 and 3 depending on the degree of distortion of the intrauterine cavity. The risk of ectopic pregnancy is greater if a woman conceives with an IUD in place (5%) compared to spontaneous conception, but as the risk of pregnancy is so much decreased in the first place, so too is the overall rate of ectopic pregnancy. Past history of ectopic pregnancy is, therefore, not a contraindication. Counselling regarding protection against sexually transmitted infections (STIs) is important.

The levonorgestrel-secreting IUS (Mirena)

B

FIGURE 53.2 

Intrauterine contraceptive devices: A Lippies loop and copper 7 IUDs, which are no longer available in Australia; B (left to right) copper T, and multiload IUDs and the Mirena IUS.

Source: Greer IA, Cameron IT, Kitchner HC, et al. Mosby’s Colour Atlas and Text of Obstetrics and Gynaecology. London: Mosby, 2011, 66, 68. Copyright © 2011 Mosby, An Imprint of Elsevier.

The copper IUD Advantages There are two brands of copper-containing IUD in Australia. The multiload is approved as effective for 5 years but probably has an efficacy beyond this, while the TT 380 is for 10 years and the TT380 is shorter (5 years). The copper-containing device is associated with none of the contraindications for hormonal contraception and can be used in those women who have serious medical conditions, such as hypertension, stroke and epilepsy, and in lactating women. The copper device can be used as emergency contraception for up to 120-hours post-unprotected intercourse. This IUD works by the toxic effect of the copper on sperm together with delayed ovum transport and impaired implantation, and may be inserted in nulliparous and parous women,10 with expulsion rates slightly greater in the nulliparous.

Contraindications The copper IUD is, however, associated with increased menstrual bleeding and discomfort, so a history of heavy

Mirena releases levonorgestrel for 5 years. Its mode of action includes those of the copper IUD plus profound atrophy of the endometrial lining and thickening of cervical mucus. In the minority of women, in the first 6 months there has also been evidence of inhibited ovulation.11 The effect on the endometrium results in markedly decreased levels of menstrual bleeding and discomfort and represents a major non-contraceptive benefit of this method, with 20 to 30% of women achieving amenorrhoea after 6 months. Unscheduled bleeding is commonly reported in the first several months, usually settling without interventions. As with other IUDs, Mirena may be inserted in nulliparous and young women with slightly greater incidences of expulsion and discomfort. As the progestogen is locally delivered with minimal systemic absorption, the side effect profile is different from progestogen implants and the indication for use includes those who are on enzyme-inducing medications or have contraindications to systemic hormonal therapy such as hypertension, smoking in 40-year-old plus women, or taking anticoagulants. The low levels of systemic absorption of the progestogen decrease the incidence and intensity of progestogenic side effects, resulting in Mirena being extremely well tolerated by users. Mirena has proved very effective in the management of menstrual issues for young women with physical and mental disabilities.12

COMBINED HORMONAL CONTRACEPTION In Australia, combined hormonal contraception (i.e. those containing both an oestrogen and a progesterone) is available as oral tablets (‘the pill’) or as a vaginal ring. In the United States and Europe, a transcutaneous patch is also available. The oral preparations and the vaginal ring, while having different absorption modes, do work in the same way and can be considered together in terms of 455

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contraindications, side effects and drug reactions. The vaginal ring, however, has not been as thoroughly tested as oral preparations and while it contains the lowest dose of ethinyloestradiol (EE) available in Australia, there is as yet no evidence of increased safety or a lower side-effect profile.

ORAL COMBINED HORMONAL CONTRACEPTION As Table 53.3 indicates, there are a number of oral combined hormonal contraception (CHC) preparations available in Australia, all of which contain either ethinyl oestradiol (EE) or oestradiol valerate (EV), and one of a range of progestogens. All are packaged as 28 tablets, with the number of placebo tablets varying from 4 to 7. Formulations are either monophasic or multiphasic where there are two or more formulations within the active tablets. Note that the PBS does not cover low-dose oestradiol components nor any containing desogestrel, gestodene or cyproterone acetate as the progestogen.

Contraindications to CHC Containing both progestogen and oestrogen, the CHC preparations have potentially the greatest number of contraindications and adverse effects. The most important contraindications include a current, recent or high risk of breast cancer, liver disease, ischaemic heart disease, stroke, migraine with aura and venous thromboembolism. Potential drug interactions must be considered, while CHCs are not recommended in those establishing breastfeeding due to a potential for oestrogen to reduce lactation.

Advantages The advantages of CHC include cycle control, decreased bleeding and discomfort plus other hormonally mediated symptoms perimenstrually. Overall, in developed countries the medication is readily available and easy to administer, and can be stopped if side effects occur.

Side effects It should be noted that while many side effects are reported and included in product information leaflets, there isn’t a strong evidence base regarding the frequency and severity of adverse effects. Reported effects include headaches, nausea, breast tenderness, breakthrough bleeding, bloating, mood changes and decreased libido. Acne, while usually improving, occasionally necessitates a change in progestogenic formulation. Weight gain is commonly attributed to the combined OCP but this was not upheld by a large Cochrane Systematic Review.13 In theory, the lower oestrogen preparations should have fewer side effects than the 30-mcg or 50-mcg regimes, but there is no evidence for the combined OCPs available in Australia. The rate of unscheduled bleeding is recorded as greater with the lower dose preparations and this does result in higher discontinuation rates. 456

Disadvantages The daily commitment to the method is the main disadvantage, with forgotten pills a very common problem. Discontinuation rates for the combined OCP are high. The advice about what to do about a missed pill or other accident that could decrease absorption can be confusing and varies considerably between product information leaflets. Traditionally, the initiation of the combined OCP was to be day 1 to 5 of the menstrual cycle, starting with active tablets. This has meant many women have had no or inadequate contraception while waiting to commence. The Quick Start methodology (as described in Initiation of Contraception earlier in this chapter) has addressed this partially (see Box 53.2). It can take considerable time and several pill changes to find the best agent for an individual patient. The preparations with the newer progestogens, which are designed to lessen androgenic side effects or to aid in the treatment of hyperandrogenism (e.g. hirsutism and acne), are not available on the PBS.

THE VAGINAL RING Made of a vinyl acetate copolymer ring, the vaginal ring is 54 mm in diameter and releases a combination of 15 mcg EE and 120 mcg etonogestrel daily (Fig 53.3). It is placed in the vagina for 3 weeks and removed for 1 week, after which time a new ring is inserted. It is not removed for sexual intercourse. The indications for and contraindications against are the same as for the combined OCP. However, prolapse of the uterus or vaginal walls and chronic constipation may be exclusion criteria due to the increased risk of device expulsion.

BOX 53.2  The Quick Start technique. This refers to starting a hormonal method immediately, even if the woman is further than day 5 of the cycle. This method aims to balance the risk of pregnancy while waiting to start a method versus the chance of an early pregnancy having already occurred but not yet being diagnosable. This method was first described and trialled with respect to commencing the combined OCP within the medical consult14 but has since been extended to include initiation of vaginal rings, progesterone implants and the IUS. Indeed, the technique can also be employed with DMPA. This is a client-centred idea to prevent repeat appointments and delays and potentially will decrease the number of unplanned pregnancies. The initial report claimed fewer method failures, forgotten instructions and side effects, but this has not been explored with other methods. A disadvantage is the risk of missing an early pregnancy; the importance of ensuring adequate follow-up pregnancy testing cannot be overemphasised.

Chapter 53  Contraception, Sterilisation and Abortion

TABLE 53.3  ORAL COMBINED HORMONAL CONTRACEPTIVES AVAILABLE IN AUSTRALIA. Name

Oestrogen EE (mcg)

Progestogen levonorgestrel (mcg)

PBS listed

Loette Microgynon 20ED Microlevlen ED

20

100

no

Logynon ED Trifeme Triphasil Triquilar ED

6 × 30 5 × 40 10 × 30

6 × 50 5 × 75 10 × 125

yes

Levlen ED Microgynon 30 ED Monofeme Nordette

30

150

yes

Microgynon 50 ED

50

125

yes

Norethisterone Brevinor 21, 28 Norimin 21, 28

35

500

yes

Brevinor-1 21, 28 Norimin-1 28

35

1000

yes

Improvil 28 day Synphasic 28

7 × 35 9 × 35 5 × 35

500 1000 500

yes

Norinyl-1 21, 28

50 (mestranol)

1000

Marvelon 28

30

Desogestrel 150 mcg

no

Minulet

30

Gestodene 75 mcg

no

Diane 35 ED Estelle-35 ED Juliet-35 ED Brenda-35 ED Laila-35 ED

35

Cyproterone acetate 2 mg

no

Yasmin

30

Drospirenone 3 mg

no

YAZ

20

Drospirenone 3 mg

no

Valette

30

Dienogest 2 mg

no

Oestradiol Valerate

Dienogest

Qlaira

2 tablets, each with 3 mg of oestradiol valerate 5 tablets, each with 2 mg of oestradiol valerate 17 tablets, each with 2 mg of oestradiol valerate 2 tablets, each with 1 mg of oestradiol valerate

2 tablets, each with 3 mg of oestradiol valerate 5 tablets, each with 2 mg of oestradiol valerate and 2 mg of dienogest 17 tablets, each with 2 mg of oestradiol valerate and 3 mg of dienogest 2 tablets, each with 1 mg of oestradiol valerate

no

Zoely

Oestradiol 1.5 mg

Nomegestrol acetate 2.5 mg

no

Source: Adapted from Contraception: An Australian Clinical Practice Handbook and used with permission © 2012. Family Planning NSW, Family Planning Victoria and Family Planning Queensland.

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Again, the packs contain 28 pills but all are active and they are taken continuously. The mechanism of action is cervical mucus thickening, preventing sperm penetration. This mucus thickening is very dose dependent, with a short lead-in to efficacy and a rapid fall-off if a dose is missed. Other higher dose formulations are available overseas and may also inhibit ovulation. Perfect use provides 99.7% efficacy, with typical use significantly lower at 91%. Failure rates are reported as less in women over 40 years of age.

Contraindications

FIGURE 53.3 

The contraceptive vaginal ring.

Source: Melmed S, Polonsky KS, Larson PR, Kronenberg HM. Williams Textbook of Endocrinology. 12th edn. Philadelphia: Elsevier/Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 18.2.

Advantages of the vaginal ring compared to the combined OCP These include the decreased need for contraceptive action on a daily or event basis, thereby having the potential to improve compliance. However, 3 weeks on 1 week off may be hard to remember despite an arranged text message from the manufacturer. It provides an alternative delivery system which bypasses oral absorption and so does not require the precautions associated with vomiting and diarrhoea experienced by pill users; this may be useful for those with inflammatory bowel disease. Non-contraceptive benefits are the same for the combined OCP, and rings can be inserted without a week off, thereby missing a bleed. There is some evidence for better cycle control.

Disadvantages It does require adherence and compliance, which can be issues. Some women may experience expulsion or discomfort during sex or with tampon usage. There may be increased discharge or local irritation. Women need to be comfortable and confident with self-insertion and removal of the device. It is expensive at approximately A$1/day, not being PBS listed, and only 3 months’ supply is available at a time.

PROGESTERONE-ONLY CONTRACEPTION

Being a low-dose progesterone method, there are few contraindications. WHO MEC 3 conditions include past history of cancer of breast, active liver disease, SLE and unexplained/investigated vaginal bleeding. Having breast cancer active within 5 years is an absolute contraindication.

Advantages The POP provides easily accessible oral contraception as an alternative for women with contraindications to CHC or in whom fertility is naturally decreased and who seek a low-dose option. It is safe in breastfeeding and a good option for the perimenopause. Women with migraines with an aura, cardiovascular disease, diabetes, hypertension or who have had a VTE event may use the POP (WHO MEC 2: benefits outweigh risks.)

Disadvantages This method is highly vulnerable to time lapses in dosage. With only a 3-hour dosage safety window, this can prove too difficult for a lot of women. Unscheduled bleeding is common. A missed pill requires using alternative methods such as condoms for 48 hours. It is not recommended for women on long-term enzyme inducers.

BARRIER CONTRACEPTION These methods work by creating a physical barrier that prevents fertilisation. Some of these techniques, namely condoms (Fig 53.4), create a barrier against STIs. While this dual function is highly advantageous, barrier methods require the users to pre-contemplate and apply the method at each episode of intercourse, thereby leading to a decline in efficacy for typical usage. None of the condoms available in Australia have spermicidal additives. There is evidence that repeated and high doses of the spermicide nonoxynol-9 is associated with increased risk of genital lesions and HIV acquisition.15

THE PROGESTERONE ONLY PILL

THE MALE CONDOM

Also known as ‘the mini pill’, the progesterone-only pill (POP) contains only a progestogen. In Australia there are two brands both available on the PBS, one using levonorgestrel 30 mcg and the other norethisterone 350 mcg.

Possibly the oldest manufactured form of contraception, condoms were originally made from animal intestine. The most common form now is latex. A variety of sizes are available.

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Chapter 53  Contraception, Sterilisation and Abortion

Inner ring

Open end

positioning. Males often report decreased sensation, while females report vaginal and perineal irritation. The former complaint has been addressed by a variety of manufacturing techniques such as ribbing and minimising width, while irritation is helped for some by the addition of water-based lubricants. Latex sensitivity (MEC) is the only contraindication. For those with latex sensitivity, polyurethane condoms are manufactured. These tend to be much less available, however, and are associated with higher breakage and slippage rates. Latex condoms are sensitive to denaturing with extremes of temperature.

THE FEMALE CONDOM A

This is a polyurethane sheath, also designed for single use. It has a silastic ring at either end which holds it in place. The larger ring is external. It should not be used with a male condom as the friction between the two may cause breakage or slippage.

Advantages The condom is not latex so is suitable for those who are latex sensitive. It is in the control of the woman, which is preferred by many. It also may decrease spread of STIs. This condom can be inserted some hours prior to intercourse, which might aid spontaneity.

Disadvantages

B

This condom is significantly more expensive than the male condom and much less available. Many pharmacies do not carry this product and it is not available in other retail settings. Online purchases are available. Again, it must be used correctly with each episode of intercourse, is somewhat cumbersome, and requires a degree of comfort and confidence from both partners, to first insert the device into the vagina and then the penis into the condom sheath.

FIGURE 53.4 

Practice point

Source: Danakas GT. Practical Guide to the Care of the Gynecological and Obstetric Patient. 2nd edn. Philadelphia: Mosby/Elsevier, 2007. Copyright © 2007 Mosby, An Imprint of Elsevier. Figures 5.4 and 5.5.

Correct teaching and familiarity with condom insertion or application is essential to increase efficacy. Evidence suggests that increased comfort and decreased method failure accompany improved knowledge.

Correct fit for A female and B male condoms.

Advantages Condoms are relatively inexpensive. They can be made easily available to the public as they are highly amenable to vending machine distribution, for example. Initiation does not require a medical assessment, and use of condoms decreases the transmission of STIs, including HIV.

Disadvantages An application at each episode of intercourse is required. Further, they need to be applied prior to intromission and the penis and condom removed immediately postejaculation to prevent semen spillage in the vagina. An erection must be maintained to ensure correct

THE DIAPHRAGM This is made of silicone and consists of a flexible outer spring and a dome of material above (Fig 53.5). Prior to 2010, latex diaphragms were available in Australia but this is no longer the case. The method relies on entrapping cervical mucus behind the barrier of silicone, thereby prohibiting the upward passage of sperm. The acid vaginal milieu then results in sperm demise. The diaphragm must stay in situ for a minimum of 6 hours. No spermicides are available in Australia. Elsewhere, the diaphragm can be used to hold spermicide in place to possibly increase efficacy. No evidence exists to support this due to small study numbers. If spermicide is to be used, it is recommended to reinsert the diaphragm with 459

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A

B b

C

a

FIGURE 53.5 

A Diaphragm is folded for insertion. B Insertion of the folded diaphragm. C Proper diaphragm position: the cervix is palpable behind the diaphragm (a); the rim fits snugly behind the symphysis pubis (b).

Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 130.6 A, B, C.

each new episode of intercourse. Patients do need to be informed that the diaphragm has the lowest efficacy figures for typical use.

Advantages This is another example of a woman-controlled, nonhormonal contraception with very few contraindications. Diaphragms can be used with other barrier methods or as a method back-up (e.g. missed combined OCP and used intermittently).

Disadvantages No decrease in STI rates can be claimed and this method has a high failure rate even with good compliance. Diaphragms come in different sizes and require a bimanual examination to determine the correct fit. Weight changes, delivery and prolapse may all cause the fit to be compromised. They require a higher degree of commitment than other methods, need vigilance to examine the diaphragm itself for wear or damage and will not be acceptable to women who are not comfortable with self-insertion.

CERVICAL CAPS While these are not available in Australia, they have a degree of popularity in European countries and so may 460

be encountered clinically. These are smaller versions of the silicone diaphragm, designed to fit snugly over the cervix and prevent sperm passage. They are somewhat harder to fit and may be more prone to slipping. Their effectiveness is approximate to the diaphragm.

VAGINAL SPONGES Vaginal sponges are not commercially available in Australia. Generally, they are made of polyurethane but natural sponges are used by some women. They are impregnated with or covered in spermicide and provide a means of holding the spermicide in place rather than a true barrier.

EMERGENCY CONTRACEPTION Emergency contraception (EC) refers to an extremely important back-up method of contraception for episodes of unprotected sexual intercourse (UPSI) or method failure, condom slippage or breakage, missed combined OCP and so on. Postcoital contraception is a simile for EC. It is important to point out that EC is not abortifacient. Hormonal and non-hormonal methods exist. The availability and price become the essential elements in choice for this method. Progesterone EC is available over the counter in pharmacies without prescription. However,

Chapter 53  Contraception, Sterilisation and Abortion

some pharmacies in Australia refuse to supply it. Consideration should be given to a prescription for an advanced supply for those using barrier contraception, travelling or residing somewhere without supply. When assessing a patient for and supplying EC, long-term, ongoing contraceptive needs should be addressed.

HORMONAL EC Levonorgestrel EC (LNG-EC) This refers to a one-off dose of levonorgestrel 1.5 mg. The mode of action is to prevent or delay ovulation by disrupting follicular development. It does not work once the luteinising hormone (LH) surge has already occurred, nor does it stop fertilisation or implantation. If the method should fail and a pregnancy ensues, there is no evidence of harm. It is approved for use for up to 72 hours, has some effect for up to 4 days post-unprotected sexual intercourse and may be worth giving in some circumstances. LNG-EC does not affect ectopic risk. The LNG EC is delivered either as a single 1.5-mg dose or as two 0.75-mg tablets. Alternatively, it can be given as two doses of 0.75 mg separated by 12 hours. An alternative recipe is 50 tablets of Microlut X in two doses.

The Yuzpe method This should be used only if the LNG-EC method is not available, and consists of combined oestrogen and progesterone in two doses 12 hours apart. An antiemetic is required. The doses can be made up from four active tablets of Nordette, Microgynon 30 ED, Monofeme or Levlen ED or five tablets of Microgynon 20 ED, Loette or Microlevlen ED. Each use of EC is valid for only one episode of UPSI per cycle and, with a further dose given if more than 12 hours have elapsed between EC and intercourse. It can be very difficult for women to determine the nature of unscheduled bleeding after EC as it may have been taken in conjunction with missed pills. The method can delay menses; however, most women would have a period within 7 days of when it is expected. Follow-up to exclude pregnancy and arrange ongoing contraception is essential.

NON-HORMONAL EMERGENCY CONTRACEPTION: THE COPPERCONTAINING IUD The copper-containing IUD (Cu-IUCD) is an extremely effective alternative to hormonal EC and provides ongoing contraception. The availability of a trained practitioner within the limited time frame is, however, problematic in many cases. The Cu-IUCD interferes with sperm passage, inhibits fertilisation by direct toxic action and may prevent implantation. Mirena is not suitable as an EC method due to its different mode of action. The same circumstances, concerns and eligibility criteria apply as for insertion of an IUCD at any stage. An assessment needs to be made regarding the possibility of existing pregnancy and recommendations tend to be fairly conservative, based around

ovulation averages. Thus, insertion up to day 12 or within 5 days of the first episode of UPSI (whichever is later) is the recommendation from Family Planning Australia.16

FERTILITY AWARENESSBASED METHODS This term includes all those methods based on identifying the most fertile phase of the menstrual cycle and then committing to abstinence during these times. Methods are symptom-based, calendar-based or a combination of the two. While no real contraindication exists and they may be the only culturally or religiously acceptable alternative for some women, the methods require conscious effort by both partners and a degree of sophisticated knowledge of the menstrual cycle. Irregular cycles preclude the use of such methods. Very little efficacy data is available, with quoted rates varying from 75 to 98%. Combining them with barrier methods increases efficacy.

SYMPTOM-BASED METHODS Temperature method This is based on detecting the rise in body temperature that occurs post-ovulation. This is recorded as 0.2 or 0.5°C and will remain up until the next menstruation. The temperature must be taken first thing in the morning before any activity, including ingesting food or drink. Intercourse is to be omitted from the start of menstruation until 3 days of consecutive temperature increase. Note that the beginning of the fertile time cannot be identified and ovulation is noted retrospectively.

Mucus method This relies on daily observation of vaginal mucus. The Billings method is essentially a variation of this method. Different mucus types may be identified: post-menstrual infertile (dry flaky, sticky), ovulatory fertile (clear, more watery, stretchy, plus a subjective feeling of wetness) and post-ovulatory pattern (again dry and now stickier than at ovulation). Intercourse is to be avoided when menstruation is heavy, during the fertile time and for 3 days into the post-ovulatory mucus phase. Alternate-day sexual intercourse is permitted during the post-menstrual infertile phase.

Sympto-thermal method This is a combination of two or more methods. The most common is to note mucus change to herald the fertile phase and a combination of temperature and mucus change to indicate its end.

CALENDAR METHODS: RHYTHM METHOD This requires assessment by the women over three of her cycles to calculate her typical fertile range. She records 461

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her shortest and longest cycle, subtracts 21 days from the shortest cycle and 10 from the longest, avoiding intercourse between these parameters. This concept is based on calculated sperm survival of 5 days and a luteal phase of 11 to 16 days. The standard days method refers to approximates of average cycles and cannot be used for those with cycle variation. Intercourse is avoided from day 8 to day 19. The most obvious problem with natural methods can be understood to be the complexity of the methods, the variability between cycles and the rigid adherence required for perfect use.

Lactational amenorrhoea (LAM) method This refers to the relative contraceptive efficacy of lactational amenorrhoea. The woman must be amenorrhoeic, less than 6 months postpartum, fully breastfeeding (i.e. a gap of no more than 4 hours between feeds or expressions during the daytime and 6 hours at night). It has an estimated 98% effectiveness in these circumstances. Variation in any one criterion, however, markedly reduces effectiveness.

PERMANENT CONTRACEPTION: STERILISATION The WHO and the UK Faculty of Sexual and Reproductive Healthcare use different classifications for sterilisation and permanent contraception from those for other methods. As no contraindication truly exists, the categories involve the relative risk of pregnancy vis-à-vis risk from the method.17 The categories include category C (caution), category D (delay) and category S (special). The use of LARCs in Australia is accompanied by a decrease in the rates of female permanent contraception, while vasectomy remains static.

FEMALE METHODS Female sterilisation is dependent on occluding the fallopian tube, thereby preventing the passage of sperm to the ovum. Occlusion can be achieved by entry to the abdominal cavity at laparoscopy, mini-laparotomy or the time of caesarean section, and cutting or destroying a section of tube, using the Pomeroy method or occluding by insertion of a destructive clip (in Australia, the Filshie clip). Hysteroscopic occlusion can also be achieved, omitting the need for an invasive procedure. Local anaesthetic or light sedation may thus be used. Two methods are available in Australia. Essure involves hysteroscopic insertion of titanium/nickel coils into the ostium end of the tube under camera guidance (Fig 53.6), while Adiana is a low-frequency radio energy that is applied to the tubal lumen and then silicone matrices are inserted into each tube. For both these methods, complete occlusion has to be confirmed with hysterosalpingogram 462

FIGURE 53.6 

Essure placement.

Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler’s Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 148.4 G.

and alternative contraception provided for the 12-week interim period. In the case of Essure, nickel allergy precludes the use of this method. The advantages of permanent sterilisation are that no further conscious effort is required and the methods are relatively cost effective. The disadvantages include an ectopic pregnancy risk in the very small number of failures of this method, regret and a lack of reversibility, together with the possibility of surgical complication. The need for general anaesthesia for laparoscopy represents a greater risk than a hysteroscopic technique under local anaesthesia. The method uptake depends on the availability of trained personnel, funding of the equipment, hospital waiting list priorities and so on.

VASECTOMY As with female sterilisation, the WHO and UK Faculty refer to the three specific categories of caution, delay and special in advice as to whether or not to proceed, as again no absolute contraindication exists. One of the very few methods for men, vasectomy has the highest calculated efficacy rate at 99 to 99.9%. Sperm are prevented from entering the ejaculate by the transection of the vas deferens (Fig 53.7). This is permanent and can be performed as an outpatient. It is not intended to be reversed but microsurgery has been successful in some men. The technique may be open, mobilising each vas and transecting via one or two scrotal incisions. Alternatively, a ‘no scalpel’ technique involves making puncture sites and extending to expose the vas, which is then transected. Advantages include permanency, ease of technique, non-systemic side effects and retention of sexual spontaneity. Disadvantages include that vasectomy offers no STI protection, requires a trained practitioner, takes 3 months to establish efficacy and appears to have low acceptability, especially in some communities.

Chapter 53  Contraception, Sterilisation and Abortion

A

B

FIGURE 53.7 

Vasectomy technique. A Three-finger fixation of the left vas beneath the skin in the midline. B Three-finger fixation of the right vas. Source: From Li SQ, Goldstein M, Zhu J, Huber D. The no-scalpel vasectomy. J Urol 1991;145:341–4.

ABORTION Also referred to as therapeutic abortion or termination of pregnancy, this refers to a deliberate act to bring about the demise and loss of an ongoing pregnancy. When services are readily available, legal and provided within accredited institutions, abortion is associated with very little morbidity, in parallel with other gynaecological procedures such as hysteroscopy and curettage of the uterus, for example. However, in countries where this is not the case, complications from abortion continue to have an enormous impact on women’s health, with death from sepsis and other complications still being one of the major sources of maternal mortality (see Chapter 42). The provision of services is legislated for by national and state governments, resulting in a wide variety of practices, availability and acceptability. In Australia, abortion remains within the jurisprudence of criminal law in all but Victoria and Tasmania, where abortion law reform resulted in its removal from the criminal code. Throughout Australia, more than 90% of abortions are performed at or less than 12 weeks’ gestation. Indications for secondtrimester abortion include: fetal abnormality, which is increasingly discovered by screening programs; a delay in diagnosis of pregnancy; and social, medical and psychiatric issues. Indications for a termination at a gestation greater than 20 weeks’ may include the necessity to

save the woman’s life. Individual practitioners have distinctly variant viewpoints on the acceptability of the procedure within their practice, and RANZCOG and RCOG allow for opt-out from involvement in this aspect of women’s healthcare. It is, however, widely accepted within the Australian community that women who seek abortion for whatever reason have a right to be able to access that care in a timely manner. The options available to effect abortion vary with gestation, as do the complication rates. Generally speaking, after 14 weeks’ gestation the complication rates increase and surgical methods require specifically targeted training. Therefore, the choice of method depends on medical factors such as the availability of services and practitioner experience, patient factors such as the preference and the gestational age of the pregnancy. Considerable care is necessary when assessing the patient to establish the gestational age of the pregnancy, with ready access to pelvic ultrasound a feature of accredited services.

FIRST-TRIMESTER ABORTION Medical termination of pregnancy Medical termination of pregnancy (MTOP) is slowly becoming more available in Australia as a result of legislative change, but is not yet available in all states or from 463

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all clinics. MTOP involves the use of two medications: mifepristone, also referred to as RU486, and misoprostol. Mifepristone is an anti-progestational agent which primes the uterus and cervix for the actions of the prostaglandin, and reverses the acceptance of the fetal allograft. The dosage varies slightly between protocols, from 200 to 800 mg, and with the gestational age. Internationally, the dosage of mifepristone has varied between 200 and 800 mg; however, in Australia only one product is available, marketed by Marie Stopes. The product is referred to as ‘MS two step’ and calls for 200 mg of mifepristone followed by misoprostol between 36 to 48 hours later. This method has recently received PBS coverage for use in pregnancy up to 63 completed days’ gestation. Misoprostol is a prostaglandin analogue, originally developed for peptic ulcer, and can be given sublingually, buccally or vaginally. Abortion is complete in the majority within 8 hours following the misoprostol. As of Feb 2015, mifepristone and misoprostol are available on the PBS for medical abortion up to 63 days in a new combination pack that simplifies administration. Many models of delivering this service have been developed including day stay, outpatient and home-based care. Follow-up involves ascertaining completion by witnessing products of conception, follow-up β-hCG, pelvic ultrasound or a combination of these. Between 9 and 14 weeks’ gestation, the technique may not be as effective as surgical evacuation and may be associated with greater incidences of bleeding and return to theatre.

with retained products and an unscheduled examination under anaesthetic for removal of retained products of conception.

Surgical termination of pregnancy

•

Surgical termination of pregnancy (STOP) is a day-stay procedure and can be performed under a light general anaesthetic or sedation and cervical local anaesthetic block. Recently, a hand-generated suction aspirator has been developed for areas where suction equipment or electricity is not available. Misoprostol (oral or vaginal) is used as a prelude to soften the uterine cervix, thereby decreasing perforation risk and blood loss. A delay of 1 to 3 hours is preferable prior to surgery where, after prep and drape, the cervix is grasped and gently dilated from 6 to 10 mm depending on gestation. Suction curettage is performed using a plastic catheter. This method is associated with fewer perforation injuries and cases of postSTOP Asherman syndrome than occurred with previous sharp curette methods. There is no definite lower gestational limit for the procedure, but care needs to be taken not to miss the gestational sac with gestations of less than 7 weeks.

SECOND-TRIMESTER ABORTION After 16 weeks’ gestation, MTOP is the more common procedure in the UK and Australasia. At these gestations both surgical and medical terminations are associated with higher rates of bleeding and blood transfusion. Surgical methods are more associated with cervical tears or uterine trauma, while medical methods are associated 464

Medical termination of pregnancy Oral mifepristone 200 mg is followed by misoprostol 24 to 48 hours later and then subsequent, repeat doses of Misoprostol 400 mcg as needed up to five doses. The average length to delivery is 12 hours, with considerable variation depending on the gestation.

Surgical termination of pregnancy After 14 weeks’ gestation, specific training in the surgical technique is required. The surgery is referred to as dilation and evacuation (D & E) and requires greater cervical dilation—up to 18 mm at times. Therefore, cervical ripening becomes crucial, with 24-plus hours required to achieve this. Misoprostol can be used, while trials have revealed mifepristone also to be a successful adjuvant. Laminaria, a type of highly absorbent seaweed, can be inserted into the cervix under local anaesthetic the day prior to surgery, with the expanded rods removed just prior to evacuation. The procedure may be performed under local or general anaesthesia.

Complications Serious complications are rare. A 2-week follow-up is recommended to assess physical and emotional recovery and ensure contraceptive needs are met. Complications include the following. Endometritis. Features suggestive of endometritis include fever, pain and temperature increase +/– offensive discharge. This occurs in 1 to 2% of cases and is managed with antibiotics. Retained products of conception. Features suggestive of retained products of conception include pain and bleeding, with possible ultrasound evidence of retained products of conception. This occurs in 1 to 2% of cases and may respond to antibiotics. If symptoms persist, a repeat curette is required. Damage to the uterus. STOP can result in perforation of the uterus (0.1%). This has lessened with cervical priming. In MTOP, uterine rupture has been reported, especially if a scar is present on the uterus and multiple doses of misoprostol are used. Infertility. This has a very low incidence and is primarily associated with ascending pelvic infection. It is mandatory to screen for and treat STIs within the abortion care provision. Asherman syndrome. This refers to intrauterine adhesions forming post-STOP and resulting in amenorrhoea and a later lack of conception. The incidence has decreased with the advent of suction curettage and is treated by dividing the adhesions hysteroscopically. Psychological aspects. Multiple studies have now demonstrated very low levels of psychological problems

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Chapter 53  Contraception, Sterilisation and Abortion

such as regret or depression post-termination, and that women generally report improvement on qualityof-life scales.18 Nevertheless, given the psychosocial stress associated with abortion, pre- and postcounselling services are necessary and should be offered and available. Contraceptive needs must be addressed within an abortion care service. Studies reveal that up to 50% of women were not using contraception and that provision of LARCs is the most effective way of reducing the rate of repeat abortion.

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REFERENCES 1) World Health Organisation. Reproductive health. 2012. Online. Available: ; [5 Nov 2012]. 2) Guillebaud J. Population and sustainability. In: Guillebaud J, MacGregor A, editors. Contraception: your questions answered. 6th ed. Edinburgh: Churchill Livingstone/Elsevier; 2013. p. 1–10. 3) Department of Reproductive Health. Medical eligibility criteria for contraceptive use. 4th ed. World Health Organisation; 2010. Online. Available: ; [14 Jan 2014]. 4) Faculty of Sexual and Reproductive Healthcare. UK medical eligibility criteria for contraceptive use 2009. England: Faculty of Sexual and Reproductive Healthcare, RCOG; 2009. Online. Available: ; [14 Jan 2014]. 5) Faculty of Sexual and Reproductive Healthcare. Clinical effectiveness unit practice guidelines. England: Faculty of Sexual and Reproductive Healthcare, RCOG; 2009. Online. Available: ; [19 Jan 2014]. 6) World Health Organisation. Selected practice recommendations for contraceptive use. 2008 update. WHO; 2008. Online. Available: ; [14 Jan 2014].

7) Roberts H, Silvia M, Xu S. Post-abortion contraception and its effects on repeat abortion rates in Auckland, New Zealand. Contraception 2010;82(3):260–5. 8) Hohmann H, Crenin MD. The contraceptive implant. Clin Obstetrics and Gynaecology 2007;50:907–17. 9) Westhoff C. Depot-medroxyprogesterone acetate injection (depo-Provera): a highly effective contraceptive option with proven long-term safety. Contraception 2003;68:75–87. 10) Clinical Effectiveness Unit. Contraceptive choices for young people. 2010. England: Faculty of Sexual and Reproductive Healthcare, RCOG; 2010. Online. Available: ; [14 Jan 2014]. 11) Xiao B, Zeng T, Wu S, et al. Effect of levonorgestrel releasing intrauterine device on hormonal profile and menstrual pattern after-long term use. Contraception 1995;51(6):359–65. 12) Grover SR. Gynaecological Issues in adolescents with disability. J Paediatric Child Health 2011;47(9):610–13. 13) Gallo M, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev 2006;1. 14) Westhoff C, Kerns J, Morroni C, et al. Quick Start: novel oral contraceptive initiation method. Contraception 2002;66(3):141–5. 15) Barrier methods. In: Contraception: an Australian clinical practice handbook. 3rd ed. Family Planning NSW, Qld, Vic.; 2012. p. 147–55. 16) Emergency contraception. In: Contraception: an Australian clinical practice handbook. 3rd ed. Family Planning NSW, Qld, Vic.; 2012. p. 15–29. 17) Faculty of Sexual and Reproductive Heathcare. UK medical eligibility criteria for contraceptive use 2009. England: Faculty of Sexual and Reproductive Healthcare, RCOG; 2009. Online. Available: ; [14 Jan 2014]. 18) Adler N, David HP, Major BN, et al. Psychological factors in abortion: a review. Am Psychol 1992;47(10):1194–204.

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Chapter 54  GENITAL TRACT INFECTIONS Kathryn Anne Cook

KEY POINTS Lower genital tract infection ■ Infections of the lower genital tract may involve the vulva, vagina and ectocervix. ■ Symptoms may include discharge, discomfort, itch, pain (including dyspareunia), burning sensation, odour or any combination of these. ■ Signs may be florid or subtle and include vaginal discharge, inflamed cervix, vulval redness, swelling, or the presence of ulcers, skin fissures and lymphadenopathy. ■ In order to ascertain the diagnosis and therefore manage the infection appropriately, history, examination and laboratory tests need to be performed. ■ Vaginal discharge is one of the most common symptoms in obstetric and gynaecological practice. It may be physiological or due to infections of the cervix or vagina. Upper genital tract infection ■ Infections of the upper genital tract involve the endocervix, uterus and fallopian tubes. ■ Clinical features may include discharge, pelvic pain and sometimes abnormal uterine bleeding. There may be systemic upset with fever and rigors. ■ Some infections (e.g. Chlamydia) are often asymptomatic. ■ Tubal damage may result, with the possibility of chronic pelvic pain and/or infertility.

PHYSIOLOGY AND NORMAL DEFENCES EPITHELIAL CELLS A complex interplay between epithelial cells, genital tract microflora and the immune system is largely responsible for the health of the lower genital tract.1,2 Epithelial cells produce antimicrobial mucous and are the first line of defence as a physical barrier preventing the entry of pathogens.3 Should this defence be breached, further cellular immune mechanisms are activated.

HORMONES The female genital tract is further modified by hormonal effects, both in the life cycle of the female and in the menstrual cycle in women of reproductive age.4

VAGINAL PH Under the influence of oestrogen on the vaginal epithelium, glycogen is produced and Lactobacillus is the predominant organism. These bacteria produce large amounts of lactic acid resulting in a low pH (< 4.5) acid environment.5 Some lactobacilli also produce hydrogen peroxide

Chapter 54  Genital Tract Infections

(H2O2). A low pH helps protect against pathogen colonisation including some sexually transmitted infections (STIs) such as Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) but is favourable for candidiasis.

AGE-RELATED PHYSIOLOGY The neonatal vagina is still influenced by maternal oestrogen. Under this influence, some baby girls may even have a ‘period’ and transient breast swelling may be present in both sexes. The neonatal vagina has an acid pH and is susceptible to Candida. This influence declines after the first month of life. With puberty, the oestrogen levels rise and physiological vaginal discharge is cyclically produced. Cervical mucus secretion is scant in the follicular phase of the menstrual cycle; clear, profuse and like egg white at ovulation; and then returns to minimal in the luteal phase. The Billings method of contraception relies on the recognition and charting of these changes. Under the influence of oestrogen, the squamocolumnar junction may migrate from the external os onto the ectocervix: an ‘ectropion’. This squamous epithelium on the ectocervix may be the source of increased physiological discharge. An ectropion is more commonly seen when the oestrogen levels are increased, such as during pregnancy or on the combined oral contraceptive pill. Around the time of the menopause, oestrogen levels reduce as do lactobacilli, resulting in an increasing pH. This alkaline environment favours mixed bacteria including bowel commensals but candidiasis becomes less likely. Candida in the absence of other stimulants such as oestrogen or steroids should raise the possibility of diabetes in this age group. Oestrogen deficiency also results in thinning of the epithelial layer and atrophic vaginitis ensures. This may also be associated with vaginal discharge. This symptom can be managed by topical or systemic oestrogen.

VAGINAL DISCHARGE

2.

3. 4.

5. 6.

7.

bacterial vaginosis (BV) and candidiasis infect the vagina. Herpes simplex virus (HSV) can infect both squamous and columnar epithelia and can, therefore, infect the vulva and the cervix. STIs often ‘hunt in packs’ and the presence of one STI should alert a clinician to the possibility and hence testing for others. There is no reason why STIs and non-STIs cannot occur concurrently, such as an asymptomatic Chlamydia infection incidentally diagnosed in a young woman presenting with candidiasis. These infections usually involve the cervix or vagina and will be discussed in detail. Benign or malignant neoplasms in the genital tract may produce a discharge. It can be profuse, watery (in the rare case of fallopian tube tumour) or scant and blood stained. Enquire about the Pap test history. Endometriosis of the cervix or vaginal vault may produce a cyclical brown or bloody discharge. Enquire about cyclical pain or pelvic symptoms. Foreign bodies may present with abnormal discharge, often malodorous. Consider in children with purulent discharge (often toilet paper or a small toy). A retained tampon is an important cause of foreign body infection and will not be identified unless the woman is properly examined with a speculum. A further complication may be toxic shock syndrome, due to the release of Staphylococcus aureus toxins, and may present with fever, rash, vomiting, diarrhoea and collapse. Early pregnancy-related complications may present with bleeding or discharge, as can retained products of conception. Desquamative vaginitis is a poorly understood condition characterised by a purulent vaginal discharge and large numbers of parabasal cells (exfoliated immature epithelial cells) are seen on vaginal Gram stain. Erosive autoimmune dermatosis such as lichen planus may present with a vaginal discharge as well as pain or scarring. Rarely, fistulae from the bladder or bowel may be evident with vaginal discharge.

This may be present at any age. It is a common finding in the reproductive age group and may be physiological as previously discussed or pathological.

8.

PATHOLOGICAL CAUSES OF VAGINAL DISCHARGE

MAKING A DIAGNOSIS

The following are the pathological causes of vaginal discharge. 1. Infections are the most common cause. They can be non-STI or STI-related. STIs exhibit predilection for certain epithelia and therefore infect different parts of the genital tract. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) infect columnar epithelia and, therefore, the cervix is the site for infection. Trichomonas,

HISTORY Many women will be embarrassed by symptoms and signs relating to infections of the lower genital tract. This may be amplified if they are concerned regarding judgment or lack of understanding of their sexual behaviour. Sexual history taking should be appropriately performed by healthcare providers in any branch of medicine, but is particularly pertinent in the field of obstetrics and gynaecology. 467

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As with all good medicine, take a comprehensive general medical and surgical history as well of that of the presenting complaint. Age should be noted as Chlamydia trachomatis is more common in those younger than 30 years of age. Direct questioning regarding genital symptoms include vaginal discharge, its amount, character (colour, consistency and odour), whether it is intermittent or continuous, association with the menstrual cycle or sexual activity. Is there associated urethral, vaginal or rectal bleeding? Are there rashes, lumps, sores, itching or discomfort? Enquire regarding dyspareunia, abdominal pain and difficulties with micturition or defecation. Is douching practised? Take a history of drug allergies and recent topical or oral medications. In particular, ask about recent treatments including self-medicated over-the-counter preparations, as they may modify symptoms, signs and laboratory findings. Is there a history of sexually transmissible infections? Include a history of blood transfusion, intravenous drug use and blood-borne viruses. With particular reference to a sexual history, ask the easy questions first such as: ‘When did you last have sex?’, ‘Was it with a regular partner?’, ‘When was the last time you were with a different partner?’, ‘Are there any things you are worried about?’, and so on. Establish the nature of the sexual activity and never presume a patient’s sexual orientation. Do not label patients as ‘gay’, ‘lesbian’ and so on as they may not identify with this term. Rather, ask ‘Do you have sex with other women?’ Be sensitive and nonjudgmental at all times in history and examination.6 Language should be appropriate for the patient and some patients may favour non-technical terms. The patient should be assured that confidentiality will be respected. Note that a patient may be at risk of an STI only through their partner’s activity and may have no knowledge of their risk. Therefore, obtaining a history alone is insufficient for accurate diagnosis, and hence examination and laboratory testing are necessary.

EXAMINATION Explain the procedure to the patient and obtain their verbal consent. Ensure that this is performed in a safe, private environment and in a respectful manner. Make sure the patient is comfortable and that good lighting is available. Have all equipment available such as speculums and swabs. After noting the patient’s general examination, carefully inspect the vulva. Note the anatomy and skin of the vulva. Be aware of what is abnormal or an anatomical variant. Dermatosis such as lichen sclerosis may only be noted incidentally by an observant clinician at the time of Pap smear or investigation of presumed candidiasis. Cardinal signs include loss of the labia majora, thickened white areas and occasionally fusion over the introitus. 468

Rarely, vulval intraepithelial neoplasia (VIN) or even vulval cancer may present as a lump or an itch. Genital warts and molluscum contagiosum are common skin infections in this area and in this case clinical diagnosis is the standard. Note if the skin is red, oedematous or tender, or if any splits, fissures, blisters or ulcers are present. Blisters (vesicles) may be due to herpes viruses, most commonly HSV1 and 2, but also varicella zoster or cytomegalovirus (CMV). Epstein–Barr can also produce blisters. Occasionally, blistering can occur in severe candidiasis infection. Other rare causes of blisters include dermatological conditions such as bullous pemphigoid. Ulcers may result from many causes. The list is extensive and includes the following. Infectious causes. STI-related causes include HSV types 1 and 2, syphilis and rarely chancroid, donovanosis and lymphogranuloma venereum. Non-STI-related causes include Candida, herpes zoster and Epstein–Barr. Dermatological causes include dermatosis (lichen sclerosis, lichen planus), erythema multiforme, aphthous ulcers (may occur in young virginal girls/ women), drug reactions, pemphigoid, Behçet’s disease, Crohn’s disease and systemic lupus erythematosus (SLE). Neoplasm causes include squamous cell carcinomas and, rarely, basal cell carcinoma. Trauma, including factitious, may also present in this way. Note the characteristics of any introital discharge. Bacterial vaginosis can be thin, adherent and white. A fishy smelling odour may be noted. Acute Candida may have a cottage cheese appearance with associated redness of the vulva. Spotty satellite lesions can sometimes be seen. The inguinal nodes should be examined and the pubic hair inspected for lice. A vaginal discharge may be originating from the cervix or the vagina. Therefore, a speculum examination should be performed. Note if there is any pain on passing the speculum. Observe the cervix for any lesions, inflammation or mucopurulent discharge. Cervical ectropion are normally noted under the influence of oestrogen (i.e. are common in young women and those on the OCP). Rarely, a foreign body such as a tampon may be seen. Remove this and place immediately under water to control the smell. (A midstream-urine pot with the lid placed straight away is another alternative.) When taking any swabs from the cervix observe contact bleeding; this is more common with CT. If pelvic pain has been a symptom or a mucopurulent cervical discharge is noted, a bimanual pelvic examination should be performed. This should elicit cervical motion discomfort (‘cervical excitation’), adnexal tenderness or masses. Discomfort over the liver may also be present in pelvic inflammatory disease (PID).

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Chapter 54  Genital Tract Infections

INVESTIGATIONS These will be determined by the history and examination findings. Remember that many STIs are asymptomatic and therefore screening is required. The sensitivity of a laboratory test will be adversely affected by inadequate sampling, either by collection of the sample or ordering an inappropriate test; for example, swabbing an intact vesicle for HSV or using a Pap test result to diagnose infections of the cervix.7 The exact techniques used will be determined by the availability of onsite laboratory testing or the microscopy expertise of the clinician. The following are commonly used. Microscopy and culture. Many laboratories will supply swabs to be placed in transport media and the lab will then perform microscopy and culture. While this is adequate, it is preferable to make the microscopy slide directly from the swab. Roll the swab onto a labelled slide and air dry. (Do not ‘fix’ as you would a Pap smear; the slide is then Gram stained.) The swab should be then taken from the lateral vaginal wall and also the cervix. DNA testing. For any skin lesions such as fissures or vesicles, take a dry viral swab for HSV PCR multiplex. Remember to de-roof a blister for improved sensitivity. A dry cotton-tipped swab from the cervix can be sent for PCR. Many labs provide STI kits for the detection of Chlamydia by PCR; refer to their product use information. If the patient is in too much pain for or declines a speculum examination, a swab from the high vagina or first-pass urine (FPU) can be sent for Chlamydia. Vaginal pH. This is a useful and quick test. Place a sample vaginal discharge on the pH paper. In bacterial vaginosis, pH is > 4.5. Avoid contact with gel or water. Wet preparation. If a laboratory is at close hand, a wet prep may be useful. The lateral vaginal swab is placed on a slide and a drop of normal saline is mixed. A cover slip is placed on top and it is read. Candida or Trichomonas may be identified. The latter is motile and can be seen moving with this method. The addition of 10% KOH to the sample may result in a fishy odour which aids in the diagnosis of bacterial vaginosis (‘whiff test’).

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INFECTIONS Sexually transmitted infections (STIs) are particularly important in genital tract infections and include Chlamydia, gonorrhoea, syphilis, Mycoplasma, herpes simplex virus and human papilloma virus, bacterial vaginosis, Trichomonas, lymphogranuloma venereum, chancroid and donovanosis. Other infections such as bowel flora, hepatitis A and schistosomiasis may be sexually transmitted. The blood-borne viruses HIV, hepatitis B and, rarely, hepatitis C are globally important STIs. Although not

strictly lower genital tract infections, HIV is frequently spread via heterosexual intercourse. Its global impact on health and resources is inestimable. Interventions to prevent infection and spread are paramount to world health. Scabies and lice may also be sexually acquired. Remember that STI may also be vertically transmitted, that is, from mother to child (mother to child transmission [MTCC]).

INFECTIONS PREDOMINATELY AFFECTING THE VULVA Vulval HSV types 1 and 2 This is the most common cause of genital ulceration worldwide. These are DNA viruses and share 70% of their genome with some very different epitopes. They are responsible for cold sores as well as genital herpes. Most cases of recurrent genital herpes are due to HSV2; although primary genital herpes is almost equally distributed between HSV1 and HSV2. It is common for individuals not to be diagnosed with HSV as they have had mild disease and asymptomatic shedding. Hence, much HSV is unknowingly spread through skin-to-skin contact or via oral sex. A history of HSV1 (i.e. cold sores) in infancy confers some immunity. A non-immune adult is at risk of more severe symptoms. Decreasing rates of HSV1 in children is thought to be responsible for a greater susceptibility to HSV genital infection in adult years. Following initial infection, the virus becomes latent in the dorsal root ganglia of the nervous system. Intermittent reactivation and viral shedding occurs, though recent studies suggest constant replication with intermittent expression of the virus as a model. First infections are usually bilateral lesions (papules that develop into blisters that then erode) of various stages with associated lymphadenopathy. Systemic symptoms such as fever and headache are frequent. The most common complication is pain and dysuria; urinary retention may occur. Co-infection with Candida is common. Rarely, autonomic neuropathies, transverse myelitis and meningitis can occur. Primary infections are associated with prolonged shedding of the virus. Recurrent genital herpes symptoms and signs usually only involve the genital area (Fig 54.1). Prodromal symptoms such as a tingling feeling may herald a recurrence. Recurrent genital herpes is frequently undiagnosed as it may present as only slightly irritated skin or mild fissuring. Lesions that are noted are unilateral, small in numbers and short lived. HSV can also affect the cervix and present with vaginal discharge. Remember that recurrent lesions follow dermatomes, and blisters on the buttocks and back of thighs may well be herpetic lesions. When examining a case of severe clinical herpes, remember that it is very painful. Do not attempt a speculum examination but defer this for later. Consider testing for other STIs with first-pass urine polymerase chain reaction (PCR). 469

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FIGURE 54.1 

Primary genital herpes simplex virus infection.

Source: Buttaravoli PM, Leffler SM. Minor Emergencies. 3rd edn. Philadelphia: Elsevier/Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 80.3, adapted from Bolognia J, Jorizzo J, Rapini R. Dermatology, St Louis: Mosby, 2003.

Diagnosis PCR assays for HSV are the most sensitive and are the test of choice. They often come as a multiplex test that checks for HSV types 1 and 2 as well as varicella zoster. The sensitivity for viral culture is low. Type-specific serology is very assay dependent and difficult to interpret. It may be useful with: 1. recurrent genital symptoms or atypical symptoms with negative HSV cultures; 2. a clinical diagnosis of genital herpes without laboratory confirmation; or 3. a partner with genital herpes. This is of particular interest in pregnancy if the partner is HSV positive and the mother is of unknown immunity.

Management Patients are frequently very distressed by this diagnosis (often seemingly out of proportion to the illness) and require education, information and counselling. This may be done over several sessions and often needs reiteration. The following is a compilation of the recommendations of the Melbourne Sexual Health Centre and the Centers for Disease Control, and Prevention in the United States.8,9 Primary HSV The following treatment should be initiated for primary HSV infection (i.e. the initial episode). Antiviral drugs are most effective when commenced early. If vulval HSV is diagnosed clinically, treatment

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should not be delayed by waiting for swab results. Options include oral aciclovir or valaciclovir for 7 to 10 days, but topical therapy is generally ineffective and famciclovir is not established as a treatment for primary HSV. Rarely, very severe infections such as disseminated disease or neurological complications will need intravenous aciclovir.8 Lignocaine 2% jelly topically if needed (exercise caution with topical anaesthesia as it may cause sensitisation with prolonged use). Systemic pain relief such as paracetamol/codeine. Antifungal medication (preferably oral) for thrush if present; antibiotics if secondary bacterial infection is suspected. Hospitalisation may also be needed for catheterisation in the case of acute urinary retention.

Acute episode of recurrent HSV With an episode of recurrent (‘secondary’) vulval HSV infection, antiviral therapy needs to be commenced within 24 hours of symptom onset if it is to be effective in ameliorating the episode. Oral aciclovir, valaciclovir or famciclovir may be used. Suppression of recurrent HSV Frequent recurrences can be suppressed with ‘prophylactic’ antiviral therapy. Possible regimens include aciclovir (two 200 mg, twice daily), famciclovir (250 mg, twice daily) or valaciclovir (500 mg, once daily). In women who have frequent recurrences, higher doses may be needed for suppressive therapy.

Pregnancy Genital HSV is very common but there are some specific risks associated with pregnancy. In the mother, blood-borne viral dissemination in primary infection with organ involvement may occur and has been the cause of fatal fetal herpetic hepatitis or encephalitis.10 However, the greatest risk to the neonate is at delivery. Management of HSV in pregnancy is discussed in Chapter 19.

Human papilloma virus HPV Human papilloma virus (HPV) is a common infection of the genital tract. It is predominantly asymptomatic and subclinical. Approximately 50% of sexually active people are infected in a lifetime. It manifests as genital warts or as precancerous change detected on Pap screening. There are over 100 types of HPV and approximately 40 infect the genital tract. Those of greatest significance are HPV 6 and 11, which cause warts (and respiratory papillomatosis), and HPV 16 and 18, which are oncogenic.

Prevention HPV vaccines are now available. Gardasil protects against HPV 6, 11, 16 and 18. These are responsible for 75% of cervical cancers (HPV 16 and 18) and 90% of genital warts (HPV 6 and 11). There is also reduction in other

Chapter 54  Genital Tract Infections

genital tract cancers such as vaginal and vulval cancer and in anal cancer and head and neck cancer. Gardasil is given as three injections over a 6-month period and is now part of the secondary school immunisation program. Cervarix is a bivalent vaccine targeting HPV 16 and 18. Women who receive the HPV vaccination should still be screened for cervical abnormalities.

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Genital warts

Treatment of genital warts should be guided by the preference of the patient, available resources and the experience of the healthcare provider. No definitive evidence suggests that any of the available treatments are superior to any other, and no single treatment is ideal for all patients or all warts. Recurrences are common and frequently repeat treatments with different modalities are required. While this can prove disappointing for the patient and the clinician, be reassuring that it will resolve. Patient-applied treatment options include podo­ phyllotoxin 0.5% solution or imiquimod 5% cream. Provider-administered pharmacological therapy includes podophyllin resin 10 to 25%, trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80 to 90%. Alternatives include cryotherapy, electrocautery or surgical removal.11 In pregnancy, warts may grow to a large size but frequently spontaneously regress postpartum. The treatment of warts in pregnancy is limited to physical ablations including cryotherapy. Podophyllin is contraindicated and the effects of imiquimod during pregnancy are unknown.

Genital warts can present many ways. Lesions may be single, multiple, flat, raised, pigmented, flesh colour, symptomatic or asymptomatic. They often present at sites of micro trauma and in women, this frequently is the introitus. The diagnosis of genital warts is clinical (Fig 54.2). Any wart that has an atypical appearance or is very resistant to therapy should be biopsied.

Diagnosis Differential diagnosis of a genital wart involves the following. Anatomical variant; in women, vulval papillomatosis is a normal variant, as is pearly penile papules in men. Infections such as molluscum contagiosum, which is a pox virus and is very common. It is often multiple with a smooth dome and central umbilication. This is common in children.

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Rarely, the lesion of secondary syphilis, condyloma latum, can be seen as a warty growth. Vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN) and cancers may present as warty lesions.

Treatment

Syphilis

FIGURE 54.2 

Genital warts due to human papilloma virus (HPV).

Source: Bieber EJ, Sanfilippo JS, Horowitz IR, eds. Clinical Gynaecology. Philadelphia: Churchill Livingstone, 2006 Copyright © 2006 Churchill Livingstone, An Imprint of Elsevier. Figure 22.2.

Syphilis is a systemic disease due to the spirochete Treponema pallidum. It is rare in Australia but has recently seen epidemics in men who have sex with men. It is also more common in Indigenous communities and in people from overseas. Syphilis typically consists of three stages: primary, secondary and the late/latent stage. In the primary and secondary stages, syphilis is highly contagious and can be asymptomatic, allowing the spread of the disease as well as its undetected progression to the latent stage. It is in the latent stage that serious complications can arise. Syphilis can affect all organs and systems, and therefore may manifest in many ways. William Osler, the famous physician, said: ‘The physician who knows syphilis knows medicine’! Although uncommon, syphilis remains an important differential diagnosis for conditions ranging from dementia to skin rashes. It continues to be an important and preventable cause of congenital disease and hence it is part of the routine screening serology in all antenatal women. The primary infection is known as a chancre (see Fig 54.3); typically, it is a painless ulcer with a rubbery base that occurs at the site of infection. Note that in a 471

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azithromycin and ceftriaxone. Management of syphilis depends on the timeframe of the disease. For early syphilis (< 2 years’ duration), use benzathine penicillin 1.8 gm by intramuscular injection. For late syphilis (> 2 years duration), use benzathine penicillin 1.8 gm by intramuscular injection weekly for three doses. In pregnancy, penicillin remains the best treatment, with alternative drugs being associated with treatment failures due to not crossing the placental blood barrier. If a pregnant woman is penicillin allergic, admit and desensitise her under the care of a physician and then proceed to treat with penicillin. A complication of syphilis therapy is the JarischHerxheimer reaction, which is a self-limiting flu-like illness that occurs 2 to 24 hours after commencing antimicrobial therapy. In pregnancy, it may provoke threatened premature labour.

• •

FIGURE 54.3 

Primary syphilis of the vulva.

Source: Habif T. Clinical Dermatology. 5th edn. Edinburg: Elsevier, 2009. Copyright © 2009 Mosby, An Imprint of Elsevier. Figure 10.10.

woman, this may be visible on the vulva but undetected in the vagina or on the cervix. Secondary syphilis occurs 4 to 10 weeks after the primary infection and may present with flu-like symptoms, fever, myalgia, malaise, lymphadenopathy, muco­ cutaneous lesions or skin rash. This typically involves the palms of the hands and soles of the feet but may mimic any other form of rash. Secondary syphilis may overlap with primary syphilis. Untreated, syphilis then enters a latent phase. Tertiary syphilis is a disease of chronic inflammation, endarteritis and periarteritis. Any organ may be affected. Classically ascending aortic aneurysm and paralysis of the insane are examples of untreated syphilis.

Diagnosis If a chancre is present, PCR of the ulcer is becoming increasingly available. Very few laboratories have the expertise to perform dark field microscopy these days. The mainstay of diagnosis is syphilis serology, taking the form of either a ‘treponemal antibody’ test (e.g. enzymelinked immunoassay [EIA]) or a ‘non-treponemal serological’ test such as reactive plasma reagin (RPR) or the VDRL test. The latter are markers of disease activity, but may be negative in early or late latent disease. False positive RPR or VDRL may occur in the antiphospholipid syndrome. Interpretation of these results can be confusing and must be made in conjunction with a thorough history. Consultation with a microbiologist, infectious diseases consultant or sexual health physician is useful.

Treatment Surprisingly, penicillin remains the mainstay of treatment. Alternatives include tetracycline, doxycycline, 472

Chancroid Chancroid is caused by the bacterium Haemophilus ducreyi. Along with lymphogranuloma venereum (LGV) and donovanosis, it forms the tropical genital ulcer disease. All ulcers increase HIV acquisition. Chancroid is very rare in Australia but may present in a traveller through endemic areas. It is a cause of acute, very painful genital ulcers and associated tender inguinal lymphadenopathy and bubo formation. Diagnosis is made by the culture of H. ducreyi on specialised media. This is not widely available. Treatment is 1 g of azithromycin single dose, ceftriaxone 250 mg intramuscular injection single dose or erythromycin 500 mg three times a day for 7 days. Singledose treatments have greater compliance. Patients should be monitored for clinical improvement and this is usually very apparent by 3 days of treatment. Lack of response questions the diagnosis or the presence of immunosuppression. Buboes may need surgical incision and can scar.

Lymphogranuloma venereum The causative agent for lymphogranuloma venereum (LGV) is Chlamydia trachomatis serovars L1, L2 and L3. The initial lesion is a painless ulcer that frequently goes unnoticed. LGV causes acute to chronic lymphadenopathy and bubo formation. Rectal exposure causes a proctocolitis. Cases of this in men who have sex with men have been documented in Australia. Untreated fistulas and strictures may occur. PCR for Chlamydia will be positive; further genotyping in a specialist centre is then required to confirm the diagnosis. Treatment is initially with azithromycin 1 g on suspicion. With serovar confirmations, proceed to doxycycline 100 mg twice daily for 21 days. Pregnant and lactating women should be treated with erythromycin 500 mg four times a day for 21 days. The efficacy for azithromycin in therapy is pending.

Chapter 54  Genital Tract Infections

Donovanosis (granuloma inguinale)

Bacterial vaginosis

Donovanosis is caused by Klebsiella granulomatosis. This is a rare condition. Previously, it was endemic in parts of northern Australia and Papua New Guinea. Thankfully, it has largely been eradicated. It is a chronic, stigmatising disease characterised by beefy red vascular lesions. Diagnosis is made by the presence of donovan bodies on tissue crush or biopsy specimens. Treatment is azithromycin 1 g weekly for 4 weeks as an observed dose. If lesions are not then fully healed, repeat the therapy to 6 weeks. Doxycycline, erythromycin and ciprofloxacin have also been used but the simpler azithromycin regime has potentially better compliance. Treatment in pregnancy can be managed with azithromycin or erythromycin. In resource poor countries, syndromic management of the genital ulcer diseases is often used.

Worldwide, bacterial vaginosis (BV) is the most common cause of an abnormal vaginal discharge, often with a ‘fishy’ odour. However, up to 40% of affected women may be asymptomatic. The aetiology is unknown but the condition is characterised by a depletion of H2O2-producing lactobacilli, an increase in the vaginal pH (> 4.5) and the overgrowth of commensal anaerobic bacterium.12 These include Gardnerella vaginalis, Prevotella species, Mobiluncus, Ureaplasma urealyticum and Mycoplasma hominis. Recent molecular techniques have resulted in many more microorganisms being identified including Atopium vaginae. It is associated with adverse outcomes including increased risk of PID, and possibly adverse pregnancy outcomes including spontaneous abortion, preterm delivery and low birth weight. BV increases the risk for STI/ HIV acquisition. Risk factors associated with BV include: sexual activity including oral sex multiple male or female partners new sex partner unprotected sexual intercourse douching.

Ectoparisites Pubic lice are also known as ‘crabs’ due to the appearance of the Phthirus pubis. This generally infects the pubic areas but may involve body hair in men. Treatment consists of applying permethrin 1% lotion (B2) to the affected area. The patient should rinse this off thoroughly after 30 minutes and repeat in 1 week. Treat sexual contacts. Pediculosis of the eye lashes can be treated by smearing white soft paraffin (e.g. Vaseline) onto the eyelid margins twice a day for 10 days. Bedding and normal clothing should be hot washed and dried or dry cleaned. Pregnant women can use permethrin lotion but ivermectin is contraindicated. Scabies is caused by the mite Sarcoptes scabiei. Most people present with a generalised itch that is often worse at night. The face and scalp are spared. Sensitisation to the mite occurs. Itching may take several weeks to develop with the first attack but can occur within 24 hours with subsequent infestations. Burrows may be seen in the finger webs. Treatment involves applying permethrin 5% cream (B2) to the whole body at nighttime. The patient should allow the cream to dry before retiring and rinse off thoroughly in the morning. Antipruritic soothing lotions or 1% hydrocortisone cream will help with the pruritus, which may last for a further 2 weeks post-treatment. Repeat in 1 week if required. Treat all sexual and close household contacts. Manage beds and clothing as mentioned in pubic lice management. Norwegian/crusted scabies is a particularly virulent infection occurring in individuals who are severely debilitated by immunosuppression or malnutrition. Treatment failures can occur and require multiple drugs for increased duration of treatment.

VAGINAL INFECTIONS The three most common causes of vaginal discharge are bacterial vaginosis (BV), candidiasis and trichomoniasis.8

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Diagnosis Diagnosis is usually made on Gram stain and three or more of Amsel’s criteria:13 homogenous white vaginal discharge presence of clue cells on microscopy (epithelial cells coated with gram-variable cocci bacilli obscuring the cells borders) vaginal pH > 4.5 positive amine test (the addition of 10% KOH to a wet prep results in the release of volatile amine from bacteria, resulting in a fishy odour). A Gram stain shows an overgrowth of BV bacteria, clue cells and a lack of lactobacilli and polymorphs. Nugent’s score is a more complex scoring system used by experienced laboratory staff. A score of 7 to 10 is diagnostic for BV. It is considered the gold standard tool in research studies.14 Vaginal culture is not diagnostic for BV.

• • • •

Treatment Treatment of BV is as follows:15 metronidazole (B2) 400 mg orally twice daily for 7 days or clindamycin vaginal cream intravaginally for 7 days Although there is an association with sexual activity and BV, routine treatment of sex partners has not been shown to reduce the recurrence of BV and is not recommended. This is currently under further research.

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Sadly, recurrence of BV is very common and a source of distress to patients. Currently there is no established prophylaxis regime. Treatment is recommended for symptomatic pregnant women. Routine screening for BV in asymptomatic pregnant women not at risk of preterm labour shows no benefit and is not recommended. There is conflicting evidence for the screening and treatment of BV in asymptomatic pregnant women at risk of preterm delivery. Asymptomatic women due to undergo gynaecological procedures, especially prior to instrumentation of the upper genital tract (such as curette), should be treated.

addition of a drop of 10% KOH to a wet prep improves the visualisation of the yeast and increases its sensitivity. Culture should be taken and placed in transport media or plated onto Sabouraud agar. Candida can also be asymptomatic, with 10 to 20% of women harbouring the organism, and detection may be only on culture. This does not usually require treatment. Candida grows in a glycogen-rich (i.e. oestrogenised) epithelial environment. Therefore, it is common in reproductive age, combined OCP usage and pregnancy. It should not occur in children or natural post-menopause. Other predisposing factors include antibiotics, HRT, immunosuppressants including AIDS and diabetes mellitus. Most healthy women have no identifiable cause.

Vulvovaginal candidiasis (thrush)

Treatment

Pregnancy

This is a common cause of vulvovaginal symptoms with more than 75% of women experiencing it.16 It is usually caused by Candida albicans (85% of strains).17

Diagnosis Classic clinical symptoms for vulvovaginal candidiasis include a thick white ‘curdy’ or ‘cheesy’ discharge and irritation. It may also present with external dysuria, pain, oedema, redness, fissures, excoriation and dyspareunia (Fig 54.4). Candidiasis has a normal vaginal pH ( 38.3°C cervical or vaginal mucopurulent discharge increased polymorphs on examination of vaginal fluid raised inflammatory markers, C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) presence of CT or NG on swabs.8

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Management of PID Antibiotic treatment for PID needs to cover the potential polymicrobial nature of lower genital tract flora as well as target both Chlamydia and gonorrhoea. Treatment should be instigated as soon as the presumptive diagnosis of PID is made. Management for PID is considered in two groups: those with mild/moderate disease and suitable for outpatient/ambulatory treatment and those with severe disease requiring inpatient/intravenous treatment. Severe disease comprises the following: systemically unwell with gastrointestinal symptoms and or fever surgical emergencies (e.g. potential appendicitis) the patient is pregnant the patient is unable to tolerate oral medications or has failed response to oral antibiotics the presence of a tubo-ovarian abscess.8 In mild to moderate PID, oral therapy is as effective as parenteral treatment.25 Close follow-up of adolescent patients is important as compliance with oral antibiotic courses may be reduced.26 However, the decision to manage adolescence with inpatient therapy should be based on the same criteria for the general population as previously discussed. The effectiveness of outpatient therapy is similar between all age groups.8 A young woman with no other predisposing factors will probably have an STI-associated PID. The following dosage regimes are adapted from the Sexual Health Society of Victoria’s National Management Guidelines for Sexually Transmissible Infections.27 They are similar to the CDC guidelines.8 Outpatient treatment of STI-related mild to moderate PID involves: azithromycin (B1) 1 gm immediately orally plus doxycycline (D) 100 mg orally twice daily for 14 days plus metronidazole (BD) 400 mg twice daily orally for 14 days

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• • •

•

plus ceftriaxone 500 mg intramuscular injection immediately if gonorrhoea is suspected. Offer Candida prophylaxis with 150 mg fluconazole orally. Initial treatment of inpatient severe STI-related PID involves: cefotaxime (B1) 2 g 8-hourly intravenously or ceftriaxone 2 gm intravenously daily plus metronidazole (B2) orally 500 mg intravenously 12-hourly plus azithromycin 500 mg intravenously daily. Once the patient is afebrile and has improved, treatment is then continued with: doxycycline (D) 100 mg BD orally for 2 to 4 weeks or roxithromycin (B1) 150 mg BD or 300 mg daily orally as a single dose for 2 to 4 weeks.

• • • •

Note: If IUD is already in situ, treat as above for 24 to 48 hours and review clinically prior to removal of the IUD. The addition of metronidazole treats BV. In patients who develop PID after a recent pregnancy, abortion or gynaecological procedure, and those with a prior history of PID, or IUD insertion or removal, Chlamydia trachomatis, Neisseria gonorrhoea and Mycoplasma hominis may be implicated. However, BV organisms, mixed anaerobic and aerobic bacteria such as Bacteroides spp, anaerobic cocci, Streptococcus spp and enteric bacteria may also be involved. Outpatient treatment of mild to moderate procedurerelated PID involves: doxycycline (D) 100 mg orally twice a day for14 days or amoxycillin (A) 500 mg three times a day orally plus metronidazole (B2) 400 mg three times a day orally for 14 days. Inpatient treatment of severe procedure-related PID involves: clindamycin (A) 600 mg 6 hourly IV plus gentamicin (D) 1.5 mg/kg intravenously 8-hourly until afebrile then clindamycin (A) 150 to 300 mg four times a day orally for 14 days or cefoxitin (B1) 2 g 6-hourly intravenously plus doxycycline (D) 100 mg twice daily orally until afebrile then doxycycline (D) 100 mg twice daily orally for 14 days.

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Inpatient treatment of severe septicaemic, procedurerelated PID involves: amoxycillin (A) 2 g intravenously 4-hourly plus gentamicin (D) 1.5 mg/kg intravenously 8-hourly plus metronidazole (B2) 500 mg intravenously 8-hourly until afebrile then doxycycline (D) 100 mg BD orally for 14 days. Patients managed with an outpatient regime should be reviewed within 72 hours and significant clinical

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improvement noted. If this is not the case then admission, review of the diagnosis and further investigations are warranted. Women with IUDs need close monitoring. The risk of PID associated with the IUD is greatest in the first few weeks following insertion. If the woman presents in this time, imaging to locate the IUD and exclude a uterine perforation is prudent. In other cases of women presenting with acute PID and an IUD in situ, there is insufficient evidence to state that the IUD should always be removed. However, close clinical follow-up is required. PID in pregnancy has significant risk of sepsis to the mother and the foetus, including preterm delivery. Women should be admitted and treated with appropriate intravenous regimes. HIV positive women with PID are more likely to develop tubo-ovarian abscesses, otherwise their treatment is the same as previously outlined.

Post-abortal PID Many pregnancies result in termination. Worldwide, unsafe abortions are a significant cause of maternal deaths, with sepsis as a major contributor. Post-abortal infections including PID occurs in approximately 10% of induced abortions.28 Post-abortal infection is polymicrobial and includes CT, NG, BV and other lower genital tract microflora. The rate of infection can be reduced by preoperative screening for infections or the use of prophylactic antibiotics. Universal prophylactic antibiotic cover may be the cost effective model.29 Rarely, infection with Clostridium perfringens may complicate an unsafe abortion.

Pyometra This is a collection of pus within the uterine cavity. It is usually secondary to cervical stenosis. The cervical stenosis may be due to atrophy alone, follow previous cervical surgery (e.g. LETZ or diathermy) or be due to a malignancy of the uterus or cervix obstructing the flow from the uterus. Pyometra may present with pelvic discomfort, vaginal discharge and/or bleeding, or may be an incidental finding at ultrasound. The treatment is dilatation of the cervix and curettage of the uterus under broad antibiotic cover. Predisposing conditions need appropriate management.

Tuberculosis PID Though very rare in developed countries, tuberculosis (TB) endometritis is a significant cause for infertility worldwide. Incidence of TB increases with HIV prevalence. Approximately 8 to 15% of women with pulmonary TB will also have silent genital TB.30 It is usually diagnosed in premenopausal women, as the bacterium is poorly supported in the atrophic postmenopausal endometrium.31 Bilateral involvement of the fallopian tubes is usual, resulting in infertility.32 480

Diagnosis relies on a high index of suspicion in women at risk for TB. Investigations include full blood examination, chest X-ray, tuberculin skin testing (Mantoux), QuantiFERON gold, CT, MRI and ultrasound imaging, laparoscopy and hysteroscopy. (QuantiFERON gold testing may be a false negative with acute TB.) The definitive diagnosis is isolation of TB from the genital tract (culture or PCR). The sample can be obtained by biopsy or swabs. The presence of granuloma on histo­ pathology often gives a presumptive diagnosis. Standard anti-TB chemotherapy is usually effective and, in the absence of tubo-ovarian abscess, surgery is seldom required. REFERENCES 1) Wira CR, Grant-Tschudy KS, Crane-Godreau MA. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol 2005;53:65–76. 2) Wira CR, Fahey JV, Sentman CL, et al. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev 2005;206:306–35. 3) Franklin RD, Kutteh WH. Characterization of immunoglobulins and cytokines in human cervical mucus: influence of exogenous and endogenous hormones. J Reprod Immunol 1999;42:93–106. 4) Wira CR, Fahey JV, Ghosh M, et al. Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 2010;63:544–65. 5) Antonio MA, Hawes SE, Hillier SL. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J Infect Dis 1999;180:1950–6. 6) Venereology Society of Victoria Incorporated. National management guidelines for sexually transmissible infection. April 2002;5–7. Online. Available: . 7) Denham I. Laboratory approach to the diagnosis of sexually transmitted infections. In: Russell D, Bradford D, Fairley D, editors. Sexual health medicine. Melbourne: IP Communications; 2005. p. 49–56. 8) Centers for Disease Control and Prevention. 2010 STD treatment guidelines, 2010. Online. Available: . 9) Melbourne Sexual Health Centre. Treatment guidelines. HSV infection. June 2012. Online. Available: .

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10) Lee A, Bar-Zeev N, Walker SP, et al. In utero herpes simplex encephalitis. Obstet Gynecol 2003;102(5 Pt 2):1197–9. 11) Ahmed SH. Human papillomavirus organismspecific therapy. Medscape. Online. Available: . 12) Hillier SL, Marrazzo JM, Holmes KK. Bacterial vaginosis. In: Holmes KK, Sparling PF, Mardh PA, et al., editors. Sexually transmitted disease. 4th ed. New York: McGraw-Hill; 2008. p. 737–68. 13) Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74(1):14–2. 14) Marazzo JM. Interpreting the epidemiology and natural history of bacterial vaginosis: are we still confused? Anaerobe 2011;17(4):186–90. 15) Melbourne Sexual Health Centre. Treatment guidelines. Bacterial vaginosis. June 2012. Online. Available: . 16) Sobel JD. Vulvovaginal candidiasis. In: Holmes KK, Mardh PM, Sparling PF, et al., editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hill; 1999. p. 629–39. 17) Sobel JD. Candida vulvovaginitis. Semin Dermatol 1996;15(1):17–18. 18) Huppert JS. Trichomoniasis in teens: an update. Curr Opin Obstet Gynecol 2009;21:371–8. 19) Gulmezoglu AM, Azhar M. Interventions for trichomoniasis in pregnancy. Cochrane Database Syst Rev 2011;5. 20) Schachter J. Chlamydia infections. N Engl J Med 1978;298:428, 490, 540. 21) Melbourne Sexual Health Centre. Treatment guidelines. Chlamydia. June 2012. Online. Available: .

22) Lewis DA. The Gonococcus fights back: is this time a knock out? Sex Transm Infect 2010;86(6): 415–21. 23) Bolan GA, Sparling PF, Wasserheit JN. The emerging threat of untreatable gonococcal infection. N Engl J Med 2012;366(6):485–7. 24) Melbourne Sexual Health Centre. Treatment guidelines. Gonococcal infection. June 2012. Online. Available: . 25) Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol 2002;186:929. 26) Schnee DM. Pelvic inflammatory disease. J Pediatr Adolesc Gynecol 2009;22(6):387–9. 27) Sexual Health Society of Victoria. National management guidelines for sexually transmitted diseases, 2008. Online. Available: . 28) Ashok PW, Kidd A, Flett GMM, et al. A randomized comparison of medical abortion and surgical acuum aspiration at 10–13 weeks gestation. Hum Reprod 2002;17(1):92–8. 29) Nirmala M, Mahmood TA. Preventing infective complications relating to induced abortion. Best Pract Res Clin Obstet Gy 2010;24(4):539–49. 30) Arora VK. Relevance of DOTS strategy in female genital tuberculosis. Obstet Gynecol Today 2002;7:179–83. 31) Maestre MA, Manzano CD, Lopez RM. Postmenopausal endometrial tuberculosis. Int J Gynecol Obstet 2004;86:405–6. 32) Neonakis IK, Spandidos DA, Petinaki E. Female genital tuberculosis: a review. Scand J Infect Dis 2011;43:564–72.

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Section 3.7 UROGYNAECOLOGY Chapter 55

Pelvic organ prolapse

Chapter 56

Urinary incontinence

Chapter 55  PELVIC ORGAN PROLAPSE Julio Alvarez and Peter Dwyer

KEY POINTS Pelvic organ prolapse is a multifactorial condition where female pelvic organs herniate into the vaginal canal or, in more severe cases, through the vaginal introitus. The pelvic organs that can prolapse through the vagina are the uterus and cervix (uterocervical) or vaginal cuff post-hysterectomy, bladder (cystocele), rectum (rectocele) or pouch of Douglas and small bowel (enterocele). Pelvic organ prolapse is caused by a weakness in supporting ligaments, fascia and musculature of the pelvic floor, which in turn has been caused by one or more of the following: birth trauma, hormonal deficiency, increased intra-abdominal pressure, denervation and connective tissue modification. Minor degrees of pelvic organ prolapse do not require treatment, but symptomatic prolapse can be managed with non-surgical measures including pelvic floor exercises and vaginal pessaries or by surgical procedures that repair specific defects in vaginal and uterine supports and restore normal anatomy.

RELEVANT ANATOMY

LEVEL 1: APEX

Normal support of female pelvic organs is created by the dynamic interaction between connective tissue throughout the pelvis known as the endopelvic fascia and the pelvic floor muscles, specifically the levator ani. The endopelvic fascia is a web-like structure composed of collagen, elastin, adipose tissue, nerves, smooth muscle and blood vessels which loosely attach the pelvic organs to the muscles and bones of the pelvic girdle. Where the endopelvic fascia comes into contact with parietal fascia, a condensation of connective tissue known as the arcus tendinous is formed. The arcus tendineus, along with the endopelvic fascia and uterine ligaments, give support to the uterus, vagina, bladder and rectum and three distinct levels can be determined as described by DeLancey.1 The anatomical position of these three levels is crucial for understanding the aetiology and surgical repairs of pelvic organ prolapse. Figure 55.1 describes these three levels.

Level 1 supports the upper vagina and the uterine cervix to the latero-posterior pelvis. The cardinal ligaments and the uterosacral ligaments are a condensation of fibrous and connective tissue which arise from the lateral cervix and upper vagina (paracolpium) to attach to the pelvic sidewall over the sacroiliac joint.2 When these support structures fail, utero-cervical or vault prolapse occurs.

LEVEL 2: PARACOLPOS The vagina, as well as much of the muscular pelvic floor (levator ani), is surrounded and supported by a web-like structure known as the endopelvic fascia. The endopelvic fascia is composed of fibrous, muscular, connective, vascular, lymphatic and nervous tissues. The mid-portion of the vagina is supported laterally and attached to the levator ani muscle by the endopelvic fascia. The endo­ pelvic fascia condenses at the junction with the muscle,

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Cervix Level l Uterosacral/cardial ligament complex

To arcus tendinous fascia pelvis

Level ll

To arcus tendinous rectovaginalis Level lll

Obturator foramen Perineal membrane

Perineal membrane External anal sphincter

Arcus tendinous rectovaginalis

Superficial transverse perineal muscle

Urethra

Vagina Arcus tendinous fascia pelvis

Arcus tendinous levator ani

Perineal body

External anal sphincter

FIGURE 55.1 

The three levels of support of the cervix, vagina and perineum.

Source: Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2007-2015. All Rights Reserved.

creating a line known as the endopelvic tendinous arch or white line. Condensations of connective tissue anteriorly and posteriorly are known as the pubocervical and rectovaginal fascia respectively.

LEVEL 3: THE PERINEAL BODY   AND THE LEVATOR PLATE The vaginal introitus is attached anteriorly to the urethra and posteriorly to the perineal body. The perineal body is a thick, dense structure at the centre of the pelvic dia484

phragm created by the confluence of fascia from the puborectalis, bulbocavernosus and deep transverse muscles. Connective and fibrous tissue continue to condense posteriorly to the perineal body from the levator ani muscle creating the levator plate, which has an important role in the maintenance of urinary and faecal continence (Fig 55.2). Even though these three levels of support are described separately, in reality they are a continuum and all the structures work together to provide proper support.

Chapter 55  Pelvic Organ Prolapse

Piriformis

Rectum

Ischio-coccygeus

Vagina

Iliococcygeus

Urethra

Pubococcygeus

Pubic bone

BOX 55.1  Predisposing factors for   pelvic organ prolapse. Birth trauma (long labour or second stage, large baby, instrumental birth, levator ani injury) Increased abdominal pressure (obesity, constipation, chronic cough, heavy lifting) Denervation (compression injury during birth, spina bifida) Connective tissue disorders (Ehlers-Danlos syndrome) Ageing and oestrogen deficiency

FIGURE 55.2 

Cadaveric section of the pelvic floor muscles showing the relationship between muscles and pelvic organs.

Source: Gosling JA, Dixon J, Humpherson JA. Functional Anatomy of the Urinary Tract. An Integrated Text and Colour Atlas. London: Gower Medical Publishing, 1983.

AETIOLOGY Pelvic organ prolapse has been a health issue for over 3000 years and despite recent medical advances, little is known about its pathophysiology.3 Parity and childbirth play a major role in prolapse. Recent studies using MRI and 3D ultrasound have found a relationship between levator ani muscle injury and the presence of pelvic organ prolapse.4,5,6,7,8 These studies suggest that a woman is twice as likely to develop a pelvic organ prolapse if levator ani avulsion is present as well, and it is twice as likely that a pelvic organ prolapse will recur following surgery. Most epidemiological studies suggest that the prevalence of pelvic organ prolapse increases with age. The Women’s Health Initiative study showed a 20% increase in the odds ratio of pelvic organ prolapse per decade of life.9 Oestrogen deficiency undoubtedly makes a contribution to the impact of advancing age. Urogenital mucosal atrophy has been associated with prolapse. This could be by a direct effect of hormones on the connective tissue as well as a steady decrease in the blood supply to the support structure after menopause. Epidemiological studies also link obesity with pelvic organ prolapse. Some associate the increase in abdominal pressure with pelvic organ prolapse while others suggest that the quality of connective tissue could be poorer in obese women. Box 55.1 summarises most of the known risk factors for pelvic organ prolapse.

CLINICAL PRESENTATION Pelvic organ prolapse is frequently asymptomatic, with approximately 50% of parous women having descent of the anterior vaginal wall into the lower vagina. Pelvic organ prolapse can be associated with a wide array of

symptoms that vary depending on the compartment involved and the severity. The most common symptom is a ‘bulge’ or a dragging sensation. Some patients report that during a straining they can see a bulge or lump come through the vagina. Urinary tract symptoms may include urinary stress or urge incontinence, frequency, hesitancy, poor urinary stream or a sensation of incomplete emptying when passing urine (caused by urethral kinking). Women may report discomfort during intercourse or feel that a lump gets in the way. Surgical treatment of pelvic organ prolapse will frequently improve these symptoms but can also cause painful intercourse (dyspareunia) from scarring or vaginal narrowing and is a common cause of dissatisfaction after surgery. A rectocele may cause difficulty with defecation and the need to support the perineum or rectocele during straining in order to accomplish defecation. The presence of pelvic organ prolapse (especially when associated with other symptoms such as lower urinary tract symptoms and faecal incontinence) can have a large impact on women’s quality of life. These symptoms can cause a woman to feel insecure and embarrassed, lose self-confidence and ultimately retract from family and social activities.

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•

PHYSICAL EXAMINATION Patients with pelvic organ prolapse and lower urinary tract symptoms have to be examined in a well-lit and comfortable setting. Patients can be examined for pelvic organ prolapse in either the dorsal or lateral position with the knees bent forward. The perineum should be inspected at rest. Lack of perianal rugae between 11 to 1 o’clock is called the ‘dovetail’ sign and is associated with damage to the anal sphincter complex (Fig 55.3). The patient is asked to ‘push’ for at least 5 seconds to see if vaginal prolapse becomes evident.10 During this procedure it is important to be 485

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FIGURE 55.3 

Dove-tail sign (the lack of rugae around the anal sphincter between 11 and 1 o’clock usually) suggests damage to the anal sphincter complex.

make sure that the patient is not contracting the levator muscle to avoid flatus or urinary incontinence as this will impede the full protrusion of the prolapse. If the patient is unable to perform a Valsalva manoeuvre, coughing may be helpful. If a pelvic organ prolapse is present, the examiner should ascertain what is prolapsing (e.g. bladder [cystocele] or bowel [enterocele]) and the degree of descent. This is accomplished by using a Sims’ speculum and placing it inside the vagina to support either the anterior or posterior wall during the Valsalva manoeuvre. Finally, a bimanual examination must be performed to evaluate the prolapse, determine uterine size and position, and identify the presence of pelvic masses (Figs 55.4 to 55.6).

FIGURE 55.4 

Anterior compartment prolapse (cystocele) with Sims’ speculum retracting the posterior vaginal wall.

MANAGEMENT Classification Some system of grading the degree of prolapse is important to accurately record the degree of prolapse and document any change over time with or without treatment. Many systems have been used in the past; more recently, the POP-Q system gained popularity due to the use of objective measures and good inter- and intra-observer reliability.

POP-Q terminology The Pelvic Organ Prolapse Quantification (POP-Q) system is based on a nine-point grid system (Fig 55.7). All measurements are in centimetres proximal (negative) or distal (positive) relative to the hymen (0). There are nine defined points to be measured: six mobile points are measured at maximum Valsalva (Aa, Ba, C, D, Ap, Bp) and three fixed points at rest (GH, TVL, PB).11,12 Aa. This point is fixed at 3 cm proximal to the hymen anteriorly.

•

486

FIGURE 55.5 

Apical compartment prolapse (uterocervical prolapse). In the operating theatre with retraction by vulsellum forceps.

• • •

Ba. This point is defined as the lowest points of the prolapse between Aa anteriorly and point C. C. This point represents the cervix or the vaginal cuff in post-hysterectomy patients. Ap. This point is fixed at 3 cm proximal to the hymen posteriorly.

Chapter 55  Pelvic Organ Prolapse

• • •

Bp. This point is the lowest aspect of the prolapse posteriorly between the apex and the hymen. D. This point represents the pouch of Douglas or the posterior vaginal fornix. GH. Genital hiatus is the distance between the urethral meatus to the posterior aspect of the hymenal ring. PB. Perineal body is the distance between the posterior aspect of the hymenal ring and the middle of the anal canal. TVL. Total vaginal length is the maximum distance between the hymenal ring and point D in patients with a uterus or Point C in post hysterectomy patients. The terminology avoids assigning a specific label, such as cystocele or rectocele, to the prolapsing part of the vagina, acknowledging that the actual organ(s) above the prolapse cannot always be determined by a physical examination.

• • •

FIGURE 55.6 

Posterior compartment prolapse (rectocele).

Severity Once a proper assessment has been made of the prolapsed compartment, a stage of severity of the prolapse can be assigned. This goes from stages 1 to 4. Stage 1. The most distal point descends to less than –1 cm from the hymen. Stage 2. Maximum descent sits anywhere between –1 to and 1 cm from the hymen. Stage 3. Maximum descends protrudes through the hymen beyond +1 cm yet less than TVL. Stage 4. Maximum point of protrusion equals the TVL.

• • • •

EVALUATION/WORK-UP Recently advances in ultrasound and MRI imaging have provided a 3D evaluation of the pelvic organ prolapse. These images have helped to better understand what is behind the bulge. For example, these images can provide detailed information in the posterior compartment allowing us to see if behind the bulge sit an enterocele, rectocele or an intussusception. Transperineal ultrasound also has the ability to diagnose puborectalis avulsion and measure increased genital hiatus area; both are now considered risk factors for recurrence of pelvic organ prolapse.13,14 Assessment should provide the severity of the pelvic organ prolapse and a clear understanding of how it affects the patient’s quality of life. The patient’s expectations and what she can and would like to achieve through treatment need to be discussed. Patients may sometimes have inappropriately high expectations about prolapse surgery, thinking surgery will treat their depression and pelvic pain, or improve their sexual life. Expectations and treatment should be discussed, including both conservative measures and reconstructive pelvic surgery.

POP-Q Examination

D

Genital hiatus

Aa

ph

tvl

Ba Perineal body

gh

Bp Ap gh

Anterior wall

Aa

C

Ba

3 cm

Anterior wall

Posterior wall Ap

pb Posterior wall Bp

Cervix or cuff C Total vaginal length tvl Posterior fornix D

FIGURE 55.7 

POP-Q system, nine-point grid.

Source: Bump RC, The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10.

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CONSERVATIVE MEASURES Improving the patient’s overall health with lifestyle changes such as exercise, a balanced diet and weight reduction (especially in obese patients), treating respiratory problems, stopping or reducing smoking, and avoiding heavy lifting will frequently improve prolapse symptoms and avoid further deterioration. Exercises to strengthen pelvic floor muscles are beneficial in mild to moderate prolapse.

Vaginal pessaries Vaginal pessaries come in various shapes and sizes, with the most frequently used pessary being the ring pessary (Fig 55.8). Pessaries act as a wedge that is placed inside the vagina to impede descent and prevent the prolapse from protruding through the genital hiatus. The pessary should be fitted so the patient does not feel pain or find the pessary uncomfortable. Patients can usually be taught to self-remove, clean and reinsert the pessary, although many older women will not want to or be able to do this. Regular removal can help avoid more common complications such as bleeding or infection. Risk factors for an unsuccessful trial of the pessary are previous hysterectomy, rectocele and a large genital hiatus, usually above 5 cm. If the patient is unable to retain the pessary, a different-shaped pessary can be used such as the Gellhorn or the cube. These pessaries create a light vacuum between the pessary and the vaginal apex, which helps retention but can make removal more difficult, requiring the help of a trained health professional and the use of sponge forceps. Patients who have a pelvic organ prolapse and symptoms of stress incontinence can be offered an antiincontinence pessary; usually this is a ring pessary with an extension placed underneath the urethra to offer extra support during sneezing or coughing. Unfortunately, these pessaries move within the vagina and rarely provide good urinary control.15,16

SURGERY Pelvic reconstructive surgery for pelvic organ prolapse aims to improve both the anatomy and function of the pelvic floor, thus improving the patient’s quality of life. Surgery for pelvic organ prolapse can be performed abdominally (either open or laparoscopically) or via the vagina. Currently, abdominal procedures for apical repairs have better anatomical success; however, they are associated with longer operative time and morbidity. Vaginal surgery is better tolerated by patients and allows a quicker convalescence. Surgery should always be tailored to the type of prolapse and the patient’s needs.17

Surgery for the anterior compartment Anterior compartment prolapse involving the bladder (cystocele) and urethra (urethrocele) are the most common types of pelvic organ prolapse. Anterior vaginal wall 488

prolapse may be secondary to a weakness or a tear in the pubocervical fascia in the anterior compartment or secondary to the pubocervical fascia being detached from the apical support structures (level 1). Central defects from a tear in the pubocervical fascia will respond adequately to an anterior midline fascial plication; however, detachment from the apical support structures would most likely recur if the apical supports of the lateral cervical/uterosacral ligaments are not re­ attached to the vagina or cervix at level 1. Apical supports can be assessed on the examination couch or in theatre under anaesthesia.

Anterior midline plication The anterior midline plications first described by Kelly consist of dissecting the vaginal mucosa from the pubocervical fascia with blunt and sharp dissection. Once the lateral dissection has been performed reaching to the pubic rami, midline plication interrupted sutures are carefully placed in a horizontal superficial manner, avoiding the bladder and the ureters. A delay absorbable suture material is used. Finally, the pubocervical fascia is reattached to the apical support. The vaginal epithelium is closed usually with a running reabsorbable suture. Some trimming of the excessive vaginal mucosa might be required.

Posterior vaginal repair The surgical repair of the posterior compartment follows in a similar manner. A midline incision is made along the posterior aspect of the vagina; bilateral dissection of the vaginal mucosa from the rectovaginal fascia is performed. However, the posterior compartment offers a peculiar challenge: the rectovaginal fascia or the rectovaginal septum only extends about 3 to 5 cm from the perineal body towards the apex. Plication or site-specific correction of this fascia will only repair rectocele (rectum protruding though a weakening or tear in the septum), so beyond the edge of the rectovaginal septum, surgeons must dissect further laterally to find fascia to plicate the vaginal muscularis or plicate the levator ani in a procedure known as levator-plasty. This procedure can be performed in the presence of an enterocele, which may contain the small or large bowel, or the omentum. Caution is needed to avoid over-reducing the vaginal calibre when performing anterior or posterior repairs.

Apex (level 1) Repairing the apical supports when defective is essential for a good anatomical result and to prevent the recurrence of pelvic organ prolapse. The apical defects can be repaired vaginally or abdominally.

Transvaginal repair

Manchester repair In the early 1900s Fothergill and Donald from Manchester described a technique that became known as the Manchester-Fothergill procedure. It is now more commonly described as a ‘Manchester repair’. The surgery

Chapter 55  Pelvic Organ Prolapse

Support pessaries Ring pessary

Gehrung pessary

Hodge pessary

First- and second-degree uterovaginal prolapses The most common pessary, and the easiest to use

Cystoceles and rectoceles, with or without uterine collapse Can be manually moulded. It rests along the anterior vaginal wall to straddle the bladder, and the lateral bars straddle the rectum, providing support via the levator sling

Mild cystoceles in women with a narrow pubic arch, and for correcting a retroverted uterus

Cube pessary

Donut pessary

Gellhorn pessary

Third-degree uterovaginal prolapse Maintains its position by creating suction between itself and the vaginal wall. Has an area for drainage and has to be removed nightly

Third-degree uterovaginal prolapse Remains in place by having a larger diameter than the genital hiatus. Usually latex, but an inflatable version allows for easy insertion and removal and an individualised fitting

Third-degree uterovaginal prolapse with decreased perineal support Concave surface fits against the cervix or vaginal cuff. Stem should be positioned just behind the introitus, so perineum must be intact

Space-occupying pessaries

FIGURE 55.8 

This figure shows the variety in shape and sizes of some of the pessaries available.

Source: Springer and Int Urogynecol J, 2006, pp. 170–175, The history and evolution of pessaries for pelvic organ prolapse, Shah SM, Sultan AH and Thakar R; © 2006 International Urogynecology Journal, with kind permission from Springer Science and Business Media.

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involves dissecting the bladder off the anterior aspect of the cervix, clamping the lateral cervical/uterosacral ligaments and amputating the cervix, and attaching these ligaments anteriorly to the cervical remnant, thus shortening the support structures and ‘lifting’ the cervical remnant. This is followed by an anterior and posterior vaginal repair. This procedure is performed in women with significant uterocervical prolapse who wish to retain their uterus and finish having children. Sacrospinous fixation Sacrospinous ligament fixation was popularised in the 1980s by Nicholls.18 The sacrospinous ligament is a ligamentous structure covered by coccygeus muscle which extends from the lower portion of the sacrum to the ischial spines bilaterally. This procedure can be performed through the anterior or posterior vaginal walls with dissection towards the ischial spine, either unilaterally or bilaterally. Once the spine has been reached, careful dissection must be performed to free the ligament from surrounding tissue. A suture is placed two to three fingerbreadths medially to the spine and on the lower half of the ligament to avoid nerve or vascular damage. To place this suture, you may use a Miya hook or other instruments specially designed for this purpose, such as the Capio device (by Boston Scientific).19,20 The suture is then placed in the vaginal apex or uterine cervix to properly support the apical compartment. If permanent sutures are used, they must be carefully placed underneath the vaginal mucosa at the apex to avoid vaginal discharge, pain or dyspareunia. McCall culdoplasty In 1957, McCall described a technique to support the vaginal vault and to decrease the chance of an enterocele following a vaginal hysterectomy. This technique closes the posterior fornix by stitching the posterior edge of the vaginal mucosa to the peritoneum and the uterosacral ligament bilaterally. This stitch will plicate the ligaments in the midline and give support to the apical compartment.21,22 High uterosacral vault suspension This procedure anchors the vaginal cuff to the remnants of the uterosacral ligaments in women with significant post-hysterectomy vaginal vault prolapse.23 This can be performed as an intraperitoneal or extraperitoneal procedure.24 Two permanent or delayed absorbable sutures are placed bilaterally through the vaginal wall to the uterosacral ligaments at the level of the spine. Palpation of the remnants of the uterosacral ligament is facilitated by placing the ligament under tension. The placement of these sutures has the potential of injuring or kinking the ureters, so intraoperative cystoscopy and the visualisation of indigo-carmine from both ureteric orifices to confirm ureteric patency is necessary. Once the sutures are tied in the vaginal lumen, the uterosacral ligament acts as a pulley raising and supporting the vaginal cuff. 490

LeFort colpocleisis Colpocleisis is the complete or partial closure of the vagina to treat pelvic organ prolapse. This procedure is reserved for patients who are no longer sexually active and are medically unfit to undergo a more prolonged reconstructive surgery. This procedure has low morbidity, but loss of coital function and urinary problems post­ operatively can be a concern. The procedure consists of dissecting two rectangles off from the vaginal mucosa, one anterior and one posterior. Then both raw areas are sutured together on the edges to bring the anterior and posterior wall of the vagina together.

Abdominal procedure The main abdominal procedure is the abdominal sacrocolpopexy, first described in 1960s. This procedure consists of suspending the vaginal cuff or uterus to the sacrum along the longitudinal ligament at S2 to S3 with polypropylene synthetic mesh. The mesh is placed over the anterior and posterior vaginal wall to support the anterior posterior and vaginal cuff. The uterus and cervix can be preserved for future pregnancies by attaching the mesh to the posterior of the cervix in a procedure known as sacral hysteropexy. This procedure has a high anatomical success rate but has longer surgical time and higher morbidity. It can be performed as an open or laparoscopic procedure.25

Mesh in vaginal surgery In an effort to reduce the recurrence of pelvic organ prolapse, synthetic mesh has been used for reinforcement, especially of the anterior compartment, similar to abdominal wall hernia repairs. A recent randomised control trial has found a better anatomical outcome for the anterior compartment; however, this is associated with higher rates of complications. The use of mesh in vaginal surgery is associated with an increased risk of complications such as mesh exposure, pelvic pain and dyspareunia so at this stage it should only be used in women with a high risk of prolapse recurrence. Mesh exposure can be surgically excised and repaired, but total removal is difficult and does not always relieve all patient symptoms.26,27

CONCLUSIONS Pelvic organ prolapse, especially in the ageing population, continues to be a challenge. Its pathophysiology is not completely understood; however, we know congenital and environmental factors as well as birth trauma play an important role. Assessment requires careful evaluation of the patient’s symptoms, expectations and needs, followed by a detailed physical and gynaecological examination. Conservative and surgical options should be discussed with the patient and treatment tailored to the clinical situation.

Chapter 55  Pelvic Organ Prolapse

REFERENCES 1) DeLancey JO. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992;166(6 Pt 1):1717–24, discussion 1724–8. 2) Ramanah R, Berger MB, Parratte BM, et al. Anatomy and histology of apical support: a literature review concerning cardinal and uterosacral ligaments. Int Urogynecol J 2012;23(11):1483–94. 3) Downing KT. Uterine prolapse: from antiquity to today. Obstet Gynecol Int 2012;2012:649459. 4) Leffler KS, Thompson JR, Cundiff GW, et al. Attachment of the rectovaginal septum to the pelvic sidewall. Am J Obstet Gynecol 2001;185(1):41–3. 5) DeLancey JO. Structural anatomy of the posterior pelvic compartment as it relates to rectocele. Am J Obstet Gynecol 1999;180(4):815–23. 6) Boreham MK, Wai CY, Miller RT, et al. Morphometric properties of the posterior vaginal wall in women with pelvic organ prolapse. Am J Obstet Gynecol 2002;187(6):1501–8, discussion 8–9. 7) Tulikangas PK. Defect theory of pelvic organ prolapse. Clin Obstet Gynecol 2005;48(3):662–7. 8) Dietz HP. Pelvic floor trauma following vaginal delivery. Curr Opin Obstet Gynecol 2006;18(5):528–37. 9) Hendrix SL, Clark A, Nygaard I, et al. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol 2002;186(6):1160–6. 10) Orejuela FJ, Shek KL, Dietz HP. The time factor in the assessment of prolapse and levator ballooning. Int Urogynecol J 2012;23(2):175–8. 11) Manonai J, Mouritsen L, Palma P, et al. The inter-system association between the simplified pelvic organ prolapse quantification system (S-POP) and the standard pelvic organ prolapse quantification system (POPQ) in describing pelvic organ prolapse. Int Urogynecol J 2011;22(3):347–52. 12) Swift S, Morris S, McKinnie V, et al. Validation of a simplified technique for using the POPQ pelvic organ prolapse classification system. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(6):615–20. 13) Dietz HP, Beer-Gabel M. Ultrasound in the investigation of posterior compartment vaginal prolapse and obstructed defecation. Ultrasound Obstet Gynecol 2012;40(1):14–27. 14) Gupta S, Sharma JB, Hari S, et al. Study of dynamic magnetic resonance imaging in diagnosis

15) 16) 17) 18) 19) 20)

21)

22) 23)

24)

25) 26)

27)

of pelvic organ prolapse. Arch Gynecol Obstet 2012;286(4):953–8. Atnip S, O’Dell K. Vaginal support pessaries: indications for use and fitting strategies. Urol Nurs 2012;32(3):114–24, quiz 25. O’Dell K, Atnip S. Pessary care: follow up and management of complications. Urol Nurs 2012;32(3):126–36, 145, quiz 37. Umoh UE, Arya LA. Surgery in urogynecology. Minerva Med 2012;103(1):23–36. Nichols DH. Sacrospinous fixation for massive eversion of the vagina. Am J Obstet Gynecol 1982;142(7):901–4. Miyazaki FS. Miya Hook ligature carrier for sacrospinous ligament suspension. Obstet Gynecol 1987;70(2):286–8. Ouzaid I, Ben Rhouma S, de Tayrac R, et al. [Mini-invasive posterior sacrospinous ligament fixation using the CAPIO needle driver: an anatomical study]. Prog Urol 2010;20(7):515–19 [French]. Chene G, Tardieu AS, Savary D, et al. Anatomical and functional results of McCall culdoplasty in the prevention of enteroceles and vaginal vault prolapse after vaginal hysterectomy. Int Urogynecol J Pelvic Floor Dysfunct 2008;19(7):1007–11. Park AJ, Paraiso MF. Surgical management of uterine prolapse. Minerva Ginecol 2008;60(6):493–507. Shull BL, Bachofen C, Coates KW, et al. A transvaginal approach to repair of apical and other associated sites of pelvic organ prolapse with uterosacral ligaments. Am J Obstet Gynecol 2000;183(6):1365–73, discussion 73–4. Dwyer PL, Fatton B. Bilateral extraperitoneal uterosacral suspension: a new approach to correct posthysterectomy vaginal vault prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2008;19(2):283–92. Nygaard IE, McCreery R, Brubaker L, et al. Abdominal sacrocolpopexy: a comprehensive review. Obstet Gynecol 2004;104(4):805–23. Withagen MI, Vierhout ME, Hendriks JC, et al. Risk factors for exposure, pain, and dyspareunia after tension-free vaginal mesh procedure. Obstet Gynecol 2011;118(3):629–36. Skala CE, Renezeder K, Albrich S, et al. Mesh complications following prolapse surgery: management and outcome. Eur J Obstet Gynecol Reprod Biol 2011;159(2):453–6.

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Chapter 56  URINARY INCONTINENCE Kristina Cvach and Peter Dwyer

KEY POINTS Urinary incontinence (UI) is defined as the complaint of any involuntary loss of urine. Female urinary incontinence is a common disorder with worldwide prevalence estimated at 27.6%, rising with age.1 UI is a physical inconvenience which adversely affects quality of life. Women often do not seek help for their incontinence problems due to a sense of embarrassment. In order for women to access the help they need, medical practitioners must actively seek information about UI from their patients. UI is classified according to the presenting symptoms, or more objectively by diagnosis following assessment with urodynamic studies, imaging or cystourethroscopy. Women can present with symptoms of stress incontinence, urgency incontinence or mixed urinary incontinence. Objective assessment may confirm a diagnosis of urodynamic stress incontinence, detrusor overactivity, urinary retention with overflow and anatomical causes of urine leakage (fistula, urethral diverticulum). Careful evaluation with history, examination and selective investigations is required to make the diagnosis. Management is usually initially conservative, with measures such as advice on fluid management, lifestyle modification, continence aids, anticholinergic medication and pelvic floor physiotherapy. When first-line management fails to improve or cure the patient’s symptoms, further investigation with urodynamic studies, cystourethroscopy and imaging may be required before instigating surgical treatment.

ANATOMY OF THE LOWER URINARY TRACT The bladder is an extraperitoneal structure. It lies in close proximity to the symphysis pubis anteriorly and the vagina and cervix posteriorly. It is supported by its attachment to the anterior vaginal wall as well as the tonic contraction of the levator ani muscles that comprise the pelvic floor. The bladder is lined by transitional cell epithelium beneath which lies the detrusor smooth muscle fibres. The dome of the bladder is covered by adventitia and serosa. The triangular area bounded by the two ureteric orifices and the internal urethral opening is termed

the trigone of the bladder. The mucosa of the trigone often has areas of stratified squamous epithelium known commonly as squamous metaplasia. The anatomy of the bladder is shown in Figure 56.1. The female urethra extends below the bladder and measures approximately 3 to 4 cm in length. The lining of the urethra is a mix of transitional epithelium arising from the trigone and stratified squamous epithelium arising from skin and external urethral meatus. The lower third of the urethra fuses with the perineal membrane and is fixed while the upper two-thirds lies adjacent to the anterior vaginal wall, supported by the pubourethral ligaments, and has some degree of mobility. The intrinsic urethral sphincter is formed by two layers of smooth

Chapter 56  Urinary Incontinence

Ureters Trigone Base Superior surface Median umbilical ligament

Apex Inferolateral surfaces

A

Urethra Ureters

Opening of ureters

Trigone

B

Urethra

Internal urethral origice

FIGURE 56.1 

Bladder. A Superolateral view. B The trigone. Anterior view with the anterior part of the bladder cut away. Source: Drake RL, Vogl W, Mitchell AWM, Gray H. Gray’s Anatomy for Students. 2nd edn. Philadelphia: Churchill-Livingstone, 2009. Copyright © 2008 Churchill Livingstone, An Imprint of Elsevier. Figure 5.40.

muscle, an outer circular layer and an inner longitudinal layer continuous with the trigonal detrusor muscle. The intrinsic sphincter, along with the submucosal vasculature, is responsible for the coaptation of the urethra at the level of the bladder neck and is a vital component of the continence mechanism. The external urethral sphincter is comprised of slow-twitch striated muscle and, with the levator ani muscles of the pelvic floor, is responsible for voluntary control of urine flow.

NEUROPHYSIOLOGY OF THE LOWER URINARY TRACT The bladder has two main functions: storage and elimination of urine. Both the sympathetic and parasympathetic autonomic systems, as well as the somatic motor and sensory nervous systems, are involved in this complex function (Figs 56.2 and 56.3). Storage is facilitated by the sympathetic nervous system via the hypogastric nerve originating from T10 to L2. Relaxation of the detrusor muscle is via beta-adrenergic receptors and contraction of the smooth muscle of the bladder neck occurs via alpha-adrenergic receptors. Elimination is facilitated by the parasympathetic nervous system with contraction of the detrusor muscle via M2 and M3 muscarinic receptors. The somatic pudendal nerve, arising from S2 to S4, innervates the striated muscle of the external urethral sphincter via nicotinic receptors. Bladder afferents respond primarily to stretch or contraction and travel with both the sympathetic and parasympathetic nerves. Overall control of micturition relies on the interplay between cortical and subcortical centres. The pontine micturition centre (PMC) is situated in the mid pons and acts as the switch between bladder storage and elimination. Stimulation of the PMC results in stimulation of the sympathetic efferents, inhibition of the parasympathetic efferents and stimulation of pudendal efferents, with resultant storage. Conversely, inhibition of the PMC results in inhibition of sympathetic efferents, stimulation of parasympathetic efferents and inhibition of pudendal efferents, leading to relaxation of the external urethral sphincter, detrusor muscle contraction and urine elimination. Bladder function in the infant is under the control of the spinal reflex arc and results in involuntary voiding. During bladder filling, detrusor stretch receptors relay neural messages along both sympathetic and parasympathetic afferent pathways, terminating in the thoracolumbar and sacral spinal segments respectively. At this early stage, no coherent input comes from the cognisant brain, so the reflex arc results in stimulation of parasympathetic efferent outflow and inhibition of the pudendal nerve. This results in detrusor muscle contraction and relaxation of the extrinsic sphincter with resultant bladder emptying. As the brain develops, this reflex arc then comes under the control of the PMC and the periaqueductal grey (PAG) region in the midbrain. Sensory input from the bladder is relayed up the spinal cord, through the PMC and registered in the PAG. If it is not convenient to void at that time, the excitatory signals from the PMC to the spinal arc continue, facilitating ongoing urine storage. At a time when voiding is desired, the excitatory signals switch to inhibitory ones and this allows micturition to occur. Therefore, neurological disorders can greatly impact bladder function, depending on the level at which the pathology occurs, resulting in the re-emergence of reflex micturition. 493

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Bladder relaxation (sympathetic input) and Bladder contraction (parasympathetic input)

Sympathetic autonomic pathway (hypogastric nerve) Alpha Hypogastric nerve and plexus

Beta

T10 T11 T12 L1 L2 Onuf’s nucleus

Paraympathetic autonomic pathway (pelvic nerve)

S2 S3 S4 Somatic pathway (pudendal nerve)

Pelvic nerve and plexus

Pudendal nerve

External urethral sphincter (striated muscle)

FIGURE 56.2 

Neurourology of bladder storage and elimination. 1. Sympathetic nerves exit the spinal cord between levels T1 and L2. They synapse in the paravertebral ganglion, and postganglionic fibres travel to the bladder via the hypogastric nerve. 2. Parasympathetic nerves exit the spinal cord via S2 to S4. Preganglionic fibres travel to the bladder via the pelvic nerve and synapse close to the bladder, and then send short postganglionic fibres to the bladder. 3. The external urethral sphincter is innervated by motor neurons that originate in Onuf’s nucleus and travel via the pudendal nerve. Source: Walters MD, Karram MM. Urogynecology and Reconstructive Pelvic Surgery. 3rd edn. Edinburgh: Mosby, 2006. Copyright © 2006 Mosby, An Imprint of Elsevier. Figure 28.3.

CLASSIFICATION AND AETIOLOGY OF URINARY INCONTINENCE The classification of female lower urinary tract disorders has been based on symptoms, function (storage and 494

emptying), bladder and outlet activity, neurological activity or urodynamic findings. The most common classification of UI used in clinical practice is that based on patient symptoms. The International Urogynecological Association (IUGA) and the International Continence Society (ICS) have provided guidance on terminology.2

Chapter 56  Urinary Incontinence

PAG Storage

+

Voiding Pontine storage centre

Hypogastric nerve

Pontine micturition centre

+

Hypogastric nerve

-

bladder + Contracts outlet

–

Inhibits detruser Pelvic nerve

+ A

Pelvic nerve

+ + +

Pudendal nerve

External sphincter

B

External sphincter

+

-

detruser +– Contracts Inhibits bladder outlet Pudendal nerve

FIGURE 56.3 

Schematic representation of storage and voiding reflexes. A During bladder storage, distension of the bladder causes afferent signals that, in turn, cause efferent signals via the hypogastric nerve (sympathetic system, relaxation) and the pudendal nerve (increased tone of the striated sphincter). B During bladder elimination, increased afferent activity via the pudendal nerve travels through the periaqueductal grey matter (PAG) through the pontine micturition centre and, ultimately, sympathetic outflow (relaxation) and pudendal outflow (urethral tone) while increasing parasympathetic outflow (contraction). Source: Walters MD, Karram MM. Urogynecology and Reconstructive Pelvic Surgery. 3rd edn. Edinburgh: Mosby, 2006. Copyright © 2006 Mosby, An Imprint of Elsevier. Figure 28.5.

STRESS URINARY INCONTINENCE

URGENCY URINARY INCONTINENCE

Stress urinary incontinence (SUI) is the complaint of urinary incontinence occurring with coughing, sneezing, laughing or physical exertion. It occurs when the bladder neck and urethra are unable to remain closed in the presence of raised intra-abdominal pressures. This is a result of urethral hypermobility whereby the urethra is no longer supported by its connective tissue and/or the intrinsic sphincter fails to maintain closure. SUI is the most common cause of UI, accounting for 50%.1 The aetiology of SUI is multifactorial, with pregnancy and childbirth recognised as the most common. Ageing, obesity, genetic and lifestyle factors including heavy lifting, and drugs (e.g. alpha adrenergic blockers [prazosin]) are also aetiological factors.

Urgency urinary incontinence (UUI) occurs in the presence of urgency (defined as a sudden, compelling desire to pass urine) which is difficult to defer. Overactive bladder syndrome (OAB) is the term used to describe patients who experience urinary frequency, nocturia (nighttime voiding) and urgency with or without UUI. OAB is present in 12% of women in communitybased studies.3 Prevalence increases with age and is the most common cause of UI in the elderly population. OAB can be classified as neurogenic when secondary to a neurological condition (stroke, Parkinson’s disease, multiple sclerosis, spinal cord injury) and non-neurogenic (idiopathic, outlet obstruction). 495

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MIXED URINARY INCONTINENCE It is common for women to have symptoms of both SUI and UUI—this is termed mixed urinary incontinence (MUI). It is important to differentiate between the two types of UI in counselling patients about management strategies and expectations of treatment. The patient who continues to have UUI after a mid-urethral sling for her SUI will be very disappointed if she was not counselled about this possibility preoperatively.

VOIDING DYSFUNCTION AND OVERFLOW INCONTINENCE Voiding dysfunction (VD) refers to the inability to adequately empty the bladder and is generally a urodynamic diagnosis. Patients may complain of poor stream, straining to void, or a feeling of incomplete emptying. Voiding symptoms have been shown to poorly correlate with bladder emptying, so a screening post-void residual (PVR) or uroflow should be performed in patients with lower urinary tract symptoms (LUTS). Urinary retention, when severe, can result in overflow incontinence. Impaired bladder emptying can be secondary to abnormal bladder or urethral function or a loss of coordination between both. Possible causes include neurological disease, urethral obstruction secondary to a tight midurethral sling or urethral stricture, ageing or drugs (anticholinergics). In one study of women presenting with urinary symptoms for investigation, voiding dysfunction was present in 14% of the women, 5% had residual urine volumes over 150 mL and 0.6% had urinary retention with overflow.4

OTHER ANATOMICAL CAUSES OF UI A urethral diverticulum (UD) is an outpouching of the urethral mucosa. Aetiology can be varied; it may arise from infection in a para-urethral gland, be a result of urethral trauma or be congenital. UD can mimic many other lower urinary tract disorders, with the most frequent presentations being those of frequency, urgency, recurrent UTI and incontinence. Post-void dribble results from pooling of urine in the diverticular sac, which then passes out when the patient stands. An anterior vaginal wall mass may be present on examination, with pressure on the mass resulting in passage of fluid or purulent material from the urethra. Management of symptomatic UD is usually surgical excision.

UROGENITAL FISTULA Urogenital fistulae are abnormal communications between the urinary and genital tracts and can result in urinary incontinence. Causes of fistula are a congenital abnormality of development (ectopic ureter) or injury to the urinary tract during pelvic surgery, by radiation or by trauma (sometimes self-inflicted). In the developed 496

world, the most common cause is gynaecological surgery. In the developing world, the most common cause is prolonged obstructed labour with pressure necrosis, which can result in large, complex fistulae involving the urethra, bladder and rectum. Fistulae into the vagina can involve the bladder (vesicovaginal), urethra (urethrovaginal) and the ureters (ureterovaginal). Patients present with continual urine loss, usually on a background of recent pelvic surgery. Careful examination of the vagina will usually reveal the fistula tract opening, which is leaking urine. Cystourethroscopy, ultrasound or computerised tomography (CT) scan are performed prior to surgical repair, which can be performed through the vagina (preferred for vesico- or urethrovaginal fistulae) or abdominally. Occasionally small vesicovaginal fistulae may close spontaneously with continuous bladder drainage for 1 month.

CLINICAL EVALUATION A summary of the approach to the clinical evaluation of incontinence is shown in Table 56.1.

HISTORY A detailed history, with an emphasis on LUTS, should be taken from the patient. Open-ended questions asking about the most troublesome bladder symptom, its duration and whether the patient has sought medical attention in the past can provide an excellent basis for subsequent focused questioning. These questions should cover both storage (daytime and nocturnal urinary frequency, urgency, urge urinary incontinence, stress urinary incontinence) and voiding (quality of stream, straining to void) symptoms. If the patient is sexually active, coital incontinence either with penetration or orgasm should be enquired about. The number of incontinence episodes per day, number of pads used and activities the patient no longer engages in provide an indication of the impact her symptoms have on her daily life. A history of bladder pain on filling, haematuria or recurrent urinary tract infections requires further investigation to exclude underlying bladder pathology (bladder cancer, calculus). An estimation of fluid intake is made as patients may either drink excessively or have markedly reduced their oral intake in an effort to avoid their symptoms. Genital prolapse may be associated with LUTS and therefore symptoms related to prolapse, such as bulge or protrusion, should be enquired about. Constipation may exacerbate LUTS and therefore questioning about bowel function is imperative. This is also an excellent opportunity to enquire about anal incontinence (faecal and/or flatal) as this is very rarely offered by the patient without prompting. Past obstetric history including parity, mode of delivery, episiotomy/perineal tears and the use of postpartum

Chapter 56  Urinary Incontinence

TABLE 56.1  CLINICAL EVALUATION. History

Examination

Investigations Initial

Frequency: • daytime < 8 • nocturnal < 2

General: • cognitive impairment • mobility

Midstream urine specimen: • intercurrent UTI • microscopic haematuria

Incontinence type: • stress • urge • mixed • coital • number of episodes • use of pads

Abdominal: • scars • masses • palpable bladder

Post-void residual volume: • normal < 100 mL

Voiding symptoms: • stream • straining to void

Vulval/perineal skin integrity

Validated symptom and quality-of-life questionnaires: • UDI-6/IIQ-7 • Kings Health Questionnaire (optional)

Bladder pain: • haematuria • recurrent UTIs

Urethra • caruncle • prolapse

Bladder diary

Oral intake

Stress urinary incontinence

Prolapse symptoms: • protruding lump • pelvic heaviness

Prolapse assessment • POP-Q • Baden-Walker Subsequent

Bowel symptoms: • constipation • anal incontinence

Bimanual: • uterine size • adnexal masses

Urodynamic studies

Past obstetric history

Anterior vaginal wall mass, tenderness

Cystourethroscopy

Past gynaecologic history: • previous incontinence or prolapse surgery Past surgical history

Pelvic floor muscle strength— modified Oxford scale (0 to 5): • 0 = no contraction • 1 = flicker • 2 = weak squeeze, no lift • 3 = fair squeeze, definite lift • 4 = good squeeze with lift • 5 = strong squeeze with a lift

Imaging: • ultrasound • CT scan • MRI

Current medical history: • diabetes • neurological disorders • spinal injury/surgery • glaucoma

+/– rectal examination if relevant

Medications

Screening neurological examination: • lower limb/perineal sensation (S2, 3, 4) and reflexes

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physiotherapy for pelvic floor exercises is important to determine. Past gynaecological or surgical history including previous incontinence or prolapse surgery may have an impact on the patient’s current symptomatology. The patient’s menopausal status and use of oestrogens (oral or topical) should be documented. A history of diabetes, neurological disease (stroke, multiple sclerosis, Parkinson’s disease), spinal injury or surgery is noted. A history of narrow-angle glaucoma may preclude the use of anticholinergic medication and therefore this history must be obtained. A full sexual history including associated problems such as pain, urinary incontinence, poor lubrication, loss of arousal and libido should be taken. This can change for the better or worse with surgical treatment but is a frequent source of complaint postoperatively. A current list of medications should be documented, as agents such as diuretics, antihypertensives and antidepressants may contribute to LUTS.

EXAMINATION General examination includes an assessment of cognitive ability (often gleaned during history taking) and physical mobility. Abdominal examination provides information on previous surgery (not infrequently forgotten by the elderly patient), abdominal masses or the presence of a palpable bladder (uncommon). Pelvic examination includes an assessment of vulval/ perineal skin integrity as patients with incontinence frequently have excoriated skin. Parting the labia exposes the urethral meatus and vaginal introitus. Asking the patient to cough or Valsalva at this point may reveal stress incontinence and possibly concurrent prolapse. A formal assessment of prolapse with staging according to the Pelvic Organ Prolapse Quantification (POP-Q) system5 or Baden-Walker halfway system6 should be performed. Next, a bimanual examination assessing uterine size and adnexal masses as well as the presence of anterior vaginal wall fullness or tenderness (suggestive of a urethral diverticulum or vaginal cyst) is performed. An assessment of pelvic floor muscle strength is made. This is performed with the examining finger in the vagina while the patient is asked to perform a pelvic floor muscle contraction (‘squeeze as if you are trying to stop flatus’). This is graded according to the modified Oxford scale of 1 (no contraction ) to 5 (excellent). A rectal examination is performed if relevant to assess the strength of the anal sphincters and the presence of a rectocele. A screening neurological examination focusing on the distribution of S2, S3 and S4 is performed. This involves lower limb reflexes, perineal sensation and bulbocavernosus reflexes.

INVESTIGATIONS A midstream urine sample is obtained for microscopy and culture to detect microscopic haematuria and any UTI. An assessment of post-void residual volume (PVR), 498

either with a bladder scanner or in-out catheter, should be performed at the initial visit to screen for voiding dysfunction. A number of validated symptom and quality-of-life questionnaires have been developed for patients with LUTS, and these may be useful in the clinical setting— assessing symptom severity and response to treatment— as well as providing standardised data for research purposes (e.g. urogenital distress inventory/incontinence impact questionnaire—short forms,7 Kings Health Questionnaire8). A bladder diary is a useful tool to aid in the evaluation of LUTS (Fig 56.4). Patients may be unreliable in their own estimation of frequency, particularly daytime frequency, as well as the number of incontinence episodes and their oral intake. The diary is used to record the time and amount of each void, occurrence of incontinence episodes and the events surrounding the episode (i.e. cough, laugh, run, urgency, key-in-the-door), as well as the type and amount of oral intake. This can be done over 24 hours to 3 days and provides objective evidence of the patient’s bladder function during their normal daily activities. In patients with uncomplicated LUTS, this clinical assessment is usually all that is required prior to the commencement of a management plan. Those patients who have complicated LUTS (i.e. those with persistent or recurrent symptoms following surgery), recurrent UTIs, haematuria or failed conservative/medical management require more detailed evaluation which may include urodynamics, cystourethroscopy and/or imaging with ultrasound, CT scan or MRI. Multichannel urodynamics proceeds through three phases: 1. initial uninstrumented free uroflow; 2. subtracted filling cystometry; and 3. voiding pressure-flow study. Patients are asked to present with a comfortably full bladder and void while sitting on a commode. Urine is collected to measure voided volume and urine flow rate; a post-void residual measurement completes the uroflow phase, and this can be used as a screening assessment for voiding dysfunction. Next, a 7 French dual-lumen (pressure transducer and filling lumen) catheter is passed into the bladder and a pressure transducer is passed into the rectum or vagina. In this fashion, both abdominal and vesical pressures are recorded, and isolated detrusor pressure is then calculated by subtracting abdominal from vesical pressures (Fig 56.5). Maximum urethral closure pressure (MUCP) is determined by gradually withdrawing the catheter through the length of the urethra at a uniform rate, and recording the highest pressure obtained. This correlates with the ability of the urethra to remain closed via coaptation and is thought to reflect the function of the intrinsic sphincter. When the urethral closure pressure is very low (MUCP < 20 cm H2O) this is defined as intrinsic sphincter deficiency (ISD). Filling of the bladder proceeds at a uniform rate with the patient in the supine or standing position,

Chapter 56  Urinary Incontinence

DATE: Time Amt

DATE: Wet

Comment

Daily fluid intake (milliliters)

Time Amt Wet

DATE: Comment

Daily fluid intake (milliliters)

DATE:

Time Amt Wet

Comment

Daily fluid intake (milliliters)

Time Amt

DATE: Wet Comment Time Amt Wet

Daily fluid intake (milliliters)

Comment

Daily fluid intake (milliliters)

*Please bring your diary into the urodynamic appointment.

FIGURE 56.4 

An example of a bladder diary documenting daytime and nocturnal frequency, voided volumes, incontinence episodes and total daily oral intake.

and is usually stopped at 500 mL or at the patient’s bladder urgency or discomfort, whichever is the least. The patient is also asked to state sensations of first urge and urgency. Involuntary rises in detrusor pressure signal detrusor overactivity (DO), and may be accompanied by a leak. The pressure at which the leak occurs is termed detrusor leak point pressure (DLPP). This is particularly important in patients who have neurogenic bladders. High DLPPs (> 40 cm H2O) associated with poor compliance may result in vesico-ureteric reflux which, over time, can lead to renal impairment. Patients are asked to cough and Valsalva to elicit stress incontinence. The pressure at which the leak occurs is termed abdominal leak point pressure (ALPP). Low ALPP below 60 cm H2O is also indicative of intrinsic sphincter deficiency (Table 56.2). The patient is then asked to void with the catheters in situ while sitting on the commode and a repeat uroflow is obtained, providing information on voiding detrusor pressure. Voiding pressures in the female are usually below 50 cm H2O; pressures higher than this suggest

bladder outlet obstruction, either anatomical or functional (non-relaxing external sphincter or levator ani). Video urodynamics is performed with radio-opaque contrast as the instillation fluid with fluoroscopy. It is used predominantly in the setting of patients with neurogenic bladders to assess for the presence of vesicoureteric reflux as well as for identifying anatomical bladder outlet obstruction. Cystourethroscopy can be performed in the out­ patient setting using lignocaine lubricant or under anaesthesia as a stand-alone procedure or with other surgery. It is an essential tool for gynaecologists in the investigation and treatment of the lower urinary tract and pelvic pathology (e.g. women with haematuria or recurrent UTI, previous surgery with suspicion of a bladder/ urethral foreign body [suture, mesh], LUT fistula or urethral diverticula). Visualisation of the bladder can be performed using a flexible cystoscope or a 30-degree or 70-degree rigid cystoscope. In order to obtain circumferential views of the urethra, a 0-degree cystoscope is necessary. 499

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1:15 1:30 1:45 2:00 2:15 2:30 2:45 3:00 3:15 3:30 3:45 4:00 4:15 4:30 4:45 5:00 5:15 5:30 5:45 6:00 6:15 6:30 6:45 7:00 PSt St fi Ur Le Ur StSt St 45 49 49 50 45 57 70 121 122 143 150

Pves 44

51

60

43 40

43 42

60

36 30

34

0 150

cm H2O Pabd 34

8

10

14 30

78 80 82

10 10

11

0 150

cm H2O Pdet 10

0

0

0

0

0

4

3

0 0

0

0 25

cm H2O Flow 10

75 75

Digital Volume mL

107.8 243.9^

Pump mL/min

75

75 76

120

0 600

mL/s VH2O

0.0

135

29.9^

0

mL

FIGURE 56.5 

Detrusor overactivity trace. Bladder pressure is plotted in blue, rectal pressure in red, detrusor pressure in purple, flow in orange and filling in light brown. This is a filling cystometry, so the presence of flow signifies incontinence. Incontinence in this individual is seen as a consequence of a phasic rise in detrusor pressure, at a comparatively low bladder volume. Source: Wein AJ, Kavoussi LR, Novick AC, et al. Campbell-Walsh Urology. 10th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 66-7.

TABLE 56.2  URODYNAMIC PARAMETERS. Uroflow

Filling cystometry

Pressure flow

Voided volume > 150 mL

Compliance < 10 cm H2O rise at capacity

Voided volume

Maximum flow rate (Qmax) > 14 mL/sec

Capacity 400 to 500 mL

Maximum flow rate (Qmax) > 14 mL/sec

Postvoid residual (PVR) < 100 mL

First urge, urgency

Detrusor pressure at peak flow (PdetQmax) < 50 cm H2O

Detrusor overactivity—detrusor leak point pressure

PVR < 100 mL

Urodynamic stress incontinence—abdominal leak point pressure (< 60 cm H2O suggests ISD) Maximum urethral closure pressure (< 20 cm H2O suggests ISD)

500

Chapter 56  Urinary Incontinence

Imaging is useful in the assessment of structural abnormalities of the upper and lower urinary tract. Ultrasound can be used to assess for urethral diverticulae and vesicovaginal fistulae, and check upper tract normality. CT intravenous pyelogram (IVP) is used to assess for ureterovaginal and vesicovaginal fistulae. MRI is particularly useful in assessing the number, size and orientation of urethral diverticulae when planning for surgical correction (Figure 56.6).

MANAGEMENT Management of urinary incontinence should proceed in a stepwise fashion, commencing with simple conservative measures that target the most bothersome symptom and then offering more complex or invasive therapies to those patients whose symptoms do not respond.

ADVICE ON FLUID MANAGEMENT, CONTINENCE AIDS AND FURTHER INFORMATION Patients with LUTS should avoid excessive fluid intake (over 1500 mL), caffeine and alcohol. Good bowel habits are also encouraged with the use of fibre supplements and stool softeners as first-line management of constipation. Patients with poor vulval/perineal skin integrity may find zinc-based barrier creams useful. National continence societies (e.g. the Continence Foundation of

Australia, http://www.continence.org.au) provide valuable patient-oriented information and contacts for support groups. Information regarding the availability of continence aids (pads, bed protection) should be provided. There may also be funding available to help patients with the financial cost of these products (e.g. the Continence Aids Payment Scheme [CAPS] in Australia). If available, a trained continence nurse can provide this information and coordinate care.

PELVIC FLOOR PHYSIOTHERAPY Pelvic floor muscle exercises have been shown to be effective in the management of women with SUI. A structured exercise program under the direction of a dedicated pelvic floor physiotherapist has been shown to result in improvement or cure in mild to moderate SUI in up to 90% in the short term.9 The key to success of any exercise program is realistic goal-setting to maintain the patient’s motivation. Patients need to be aware that results can take some months to achieve. Pelvic floor physiotherapy is also useful in patients with OAB. These patients have often resorted to defensive toileting, going ‘just in case’ to avoid leakage episodes. Over time, this may result in a small capacity bladder. Bladder retraining focuses on lengthening the interval between voids, aiming for at least 2 hours. By deferring the urge to void using distraction techniques (quick pelvic floor muscle contraction, wiggling the toes, counting backwards from 100) and gradually increasing the time between voids, bladder capacity can be increased, resulting in decreased urinary frequency. In patients with voiding dysfunction related to high pelvic floor tone, physiotherapy can help with re-learning relaxation with the aid of biofeedback.

MEDICATION

FIGURE 56.6 

MRI with coronal view of urethral diverticulum with large ‘saddlebag’ appearance and extensions into lateral periurethral space. Source: Walters MD, Karram MM. Urogynecology and Reconstructive Pelvic Surgery. 3rd edn. Edinburgh: Mosby, 2006. Copyright © 2006 Mosby, An Imprint of Elsevier. Figure 36.1.

Anticholinergic medication has a role in the control of both neurogenic and non-neurogenic OAB/DO (Table 56.3). In OAB/DO patients, patchy denervation results in lowlevel ‘leak’ of acetylcholine, leading to heightened activity in afferent nerves (both C- and Aδ-fibres) and resulting in initiation of the micturition reflex at low levels of bladder filling. Anticholinergics act during the storage phase by decreasing the activity in these afferent nerves, resulting in decreased urgency and increasing bladder capacity. Anticholinergics in therapeutically recommended doses can inhibit the effects of these low concentrations of acetylcholine, but not of the high concentrations necessary for generating the voiding contraction (requiring efferent nerve activity), and therefore rarely cause urinary retention. Common side effects include those of dry eyes, dry mouth and constipation, which may result in discontinuation rates as high as 30%, depending on the agent. The β-3 adrenoreceptor agonist mirabegron has recently been approved for use in OAB. This class of drug increases bladder capacity via activation of adenylate cyclase and 501

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TABLE 56.3  ANTICHOLINERGIC AGENTS. Generic name

Trade name

Dose

Mechanism of action

Oxybutynin 5 mg

Ditropan

2.5 to 5 mg orally, three times a day

Non-selective antimuscarinic

Oxybutynin 3.9 mg/day patch

Oxytrol

One patch twice a week

Non-selective antimuscarinic

Tolterodine tartrate IR (1 or 2 mg)

Detrusitol

IR: 1 to 2 mg twice a day

Non-selective antimuscarinic

Solifenacin 5 or 10 mg

Vesicare

5 or 10 mg daily

M3 specific

Darifenacin 7.5 or 15 mg

Enablex

7.5 or 15 mg daily

M3 specific

Abbreviations: IR = immediate release, ER = extended release.

formation of cAMP. Studies have shown no effect on voiding parameters and minimal side effects, providing an alternative medication option for women in whom anticholinergics are contraindicated or not tolerated.10,11 Botulinum toxin A is one of seven serotypes of the purified toxin derived from Clostridium botulinum. It acts on both afferent and efferent pathways, decreasing ACH release and down-regulating purigenic and capsaicin receptors. It is injected into the detrusor muscle under cystoscopic vision. OnanotulinumtoxinA (Botox) has Australian Therapeutic Goods Administration (TGA) approval for use in neurogenic detrusor overactivity (NDO), where doses of 200 to 300 IU are used and for idiopathic detrusor overactivity (IDO) at a dose of 100 IU.12 The main effect of Botox is a reduction in urgency and UUI, with smaller reductions in urinary frequency. This effect commences 1 to 2 weeks following injection and has been shown to last for 6 to 9 months, with a gradual return to baseline parameters. Repeat procedures appear to be safe and retain efficacy. Complications such as procedure-related UTI and voiding dysfunction (10 to 15%) are common. VD may require self-catheterisation until the effect begins to wear off. The other, more serious, complications of Botox such as distant muscle paralysis and general malaise seen when larger concentrations are injected for muscle spasticity in children and adults do not appear to be of concern when used in the bladder (particularly in the IDO group).

NEUROMODULATION Sacral neuromodulation (InterStim™, Medtronic) is a percutaneous two-staged procedure performed under local anaesthesia involving the placement of an electrode in the S3 foramen with a pulse generator placed subcutaneously into the buttock. It is TGA-approved for patients with urge incontinence, urgency/frequency, and nonobstructive urinary retention. It has been shown to be effective in approximately 70% of patients. 502

SURGERY FOR STRESS URINARY INCONTINENCE Mid-urethral sling (MUS) surgery using synthetic polypropylene mesh is currently the gold standard surgery for SUI (Fig 56.7). It provides support to the hypermobile urethra and facilitates urethral closure in the presence of intrinsic sphincter deficiency. The sling is inserted through a small anterior vaginal wall incision roughly 1 to 1.5 cm proximal to the urethral meatus (i.e. at the level of the mid-urethra), then passed either retropubically or through the obturator foramen to exit through the skin, and sits tension-free under the urethra. Cure rates are in the order of 85 to 90%, with 11-year data for the retropubic MUS showing excellent duration of effect.13 Comparable results for the transobturator MUS have been obtained but patients with intrinsic sphincter deficiency have higher success with retropubic MUS.14 Complications include those of bladder perforation (5%), UTI (10%), voiding dysfunction (7%) and mesh exposure (< 1%). Vascular or bowel complications are rare but seen more often with retropubic MUS. Single-incision slings have no exit point and rely on fixation devices at each end of the sling to anchor it into the obturator internus fascia/muscle. Currently, there is minimal data available on efficacy and durability of effect. Overall, the single-incision slings are associated with lower patient-reported and objective cure rates.15 Prior to the MUS, the Burch colposuspension and the pubovaginal sling were the most successful procedures for SUI. Colposuspension is an abdominal procedure, placing bilateral permanent sutures into the para-urethral tissue and anchoring these into Cooper’s ligament running along the superior pubic ramus. This elevates the bladder neck, providing closure during raised intra-abdominal pressure. It has comparable efficacy to the MUS.16 Pubovaginal slings require both vaginal and abdominal incisions and use autologous fascia (rectus sheath, fascia lata) to create a sling, which is passed retropubically from below. The sling ends are sutured to the rectus sheath.

Chapter 56  Urinary Incontinence

A

B

FIGURE 56.7 

Mid-urethral slings. A The retropubic sling. B The transobturator sling.

Source: Ridgeway B, Barber MD. Midurethral slings for stress urinary incontinence: a urogynecology perspective. Urol Clin North Am. 2012 Aug;39(3):289–97. Copyright © 2012 Elsevier Inc. (Courtesy of Cleveland Clinic Foundation; with permission.)

REFERENCES 1) Minassian VA, Drutz HP, Al-Badr A. Urinary incontinence as a worldwide problem. Int J Gynaecol Obstet 2003;82:327–38. 2) Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J 2010;21:5–26. 3) Irwin DE, Milsom I, Hunskaar S, et al. Populationbased survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 2006;50:1306–14, discussion 14–15. 4) Dwyer PL, Desmedt E. Impaired bladder emptying in women. Aust N Z J Obstet Gynaecol 1994;34:73–8. 5) Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10–17. 6) Baden WF, Walker TA, Lindsey JH. The vaginal profile. Tex Med 1968;64:56–8. 7) Uebersax JS, Wyman JF, Shumaker SA, et al. Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for Women Research Group. Neurourol Urodyn 1995;14:131–9. 8) Kelleher CJ, Cardozo LD, Khullar V, et al. A new questionnaire to assess the quality of life of urinary incontinent women. Br J Obstet Gynaecol 1997;104:1374–9. 9) Bo K, Kvarstein B, Nygaard I. Lower urinary tract symptoms and pelvic floor muscle exercise

10)

11)

12) 13)

14)

15)

16)

adherence after 15 years. Obstet Gynecol 2005;105:999–1005. Khullar V, Amarenco G, Angulo JC, et al. Efficacy and tolerability of mirabegron, a beta(3)adrenoceptor agonist, in patients with overactive bladder: results from a randomised EuropeanAustralian phase 3 trial. Eur Urol 2013;63:283–95. Chapple CR, Kaplan SA, Mitcheson D, et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a beta(3)-adrenoceptor agonist, in overactive bladder. Eur Urol 2013;63:296–305. Tincello DG. Botulinum toxin treatment for overactive bladder and detrusor overactivity in adults. World J Urol 2012;30:451–6. Nilsson CG, Palva K, Rezapour M, et al. Eleven years prospective follow-up of the tension-free vaginal tape procedure for treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2008;19:1043–7. Schierlitz L, Dwyer PL, Rosamilia A, et al. Three-year follow-up of tension-free vaginal tape compared with transobturator tape in women with stress urinary incontinence and intrinsic sphincter deficiency. Obstet Gynecol 2012;119: 321–7. Abdel-Fattah M, Ford JA, Lim CP. et al. Singleincision mini-slings versus standard midurethral slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications. Eur Urol 2011;60:468–80. Ward K, Hilton P. Prospective multicentre randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence. BMJ 2002;325:67. 503

Section 3.8 PELVIC PAIN AND ENDOMETRIOSIS Chapter 57

Pelvic pain

Chapter 58

Endometriosis

Chapter 57  PELVIC PAIN Lenore Ellett and Peter Maher

KEY POINTS Pelvic pain is a common symptom in women, being responsible for approximately 10% of visits to gynaecologists, up to 40% of gynaecologic laparoscopies and around 20% of hysterectomies. Localisation to the organ of origin is not always straightforward, since the pain may originate outside the pelvis and be referred there. Alternatively, the disturbance may arise in a pelvic visceral structure and be felt over the corresponding dermatome. Common gynaecological causes of acute pelvic pain include early pregnancy disturbance, complications of ovarian cysts, pain associated with the menstrual cycle, mittelschmerz or dysmenorrhoea. It is important to distinguish those women in whom surgery is indicated. Chronic pelvic pain refers to pain of at least 6 months’ duration, below the umbilicus and severe enough to require treatment or cause functional disability. There are many possible causes but over half of these women will be found to have endometriosis. . Laparoscopy can be helpful in the investigation of chronic pelvic pain and management is often best when there is a multidisciplinary team approach.

THE PHYSIOLOGY OF PAIN

ONWARD PATHWAY

Pain is caused by excitation of the free, unspecialised endings of fast-conducting myelinated A delta and unmyelinated C nerve fibres. The former are distributed particularly in the skin and mucous membranes; the pain is felt immediately, the activating stimuli being of a highintensity mechanical nature (pinprick, squeezing). The latter are unmyelinated, slower conducting and widely distributed (including viscera); the pain is delayed, diffuse and less sharp, the fibres responding particularly to chemical irritation and heat, and less to high-intensity mechanical change such as distension and torsion. Smooth muscles are supplied with pain receptors, which respond to distension or, if there is a block to emptying, to isometric contraction.

Small pain fibres pass to the opposite side and ascend to the brain as part of the spinothalamic and spinomesencephalic tracts. Inhibitory fibres come from two sources: 1. collaterals from other large incoming sensory A beta fibres (hence the effectiveness of treatments such as acupuncture and transcutaneous electric nerve stimulation [TENS]); and 2. descending fibres from the tectal periventricular area (activated by opiates and stimulation of certain midbrain areas).

NERVE PATHWAYS Gynaecological pain may be somatic: muscles of the pelvic floor and vulval skin are innervated by the

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pudendal nerves (S2, S3 and S4). The mons and labia also receive sensory innervation from L1 and L2 via the ilioinguinal and genitofemoral nerves. Pain may also be visceral: from the uterus, fallopian tubes, ovaries and visceral peritoneum and transmitted by the sympathetic nervous system (T10 to L1). The principal afferent pathways and areas of referred pain are shown in Table 57.1. The relatively wide distribution of referred pain is explained by the embryonic origin of the gonad and Müllerian duct, as high as the 10th thoracic somite. The nerve supply and areas of referred pain of the bladder and rectum are similar to those of the lower uterus and upper vagina (Figs 57.1 and 57.2). The skin and skeletal muscle of the pelvis are innervated by the somatic division of the peripheral nervous system. Muscle innervation is derived from the ventral rami of the sacral (L4 to S4) and coccygeal plexus. Somatic afferents convey pain, touch and temperature from the skin, skeletal muscle and joints via nerves from these plexuses to the same relative spinal cord levels. Innervation of the internal genitalia and pelvic viscera is by sympathetic and parasympathetic nerves from the autonomic nervous system passing through the pelvic ganglia (Fig 57.2). Pain passes via sensory visceral afferent fibres from the uterus, inner fallopian tube, rectum, vagina, bladder and vestibular bulb to the paracervical plexus, to inferior and superior hypogastric plexuses, to the sympathetic chain (L2, L3), thence via the grey rami of T11 and T12 to the lateral spinothalamic tract to the thalamus and the cerebral cortex. Sympathetic nerves from the ovary, outer fallopian tube and broad ligament peritoneum pass directly to the aortic plexus at the level of L1 along the ovarian artery. The parasympathetic nerves leave the spinal cord with the anterior roots of S2, S3 and S4, and enter the inferior hypogastric plexus and

pass along the course of the blood vessels to the pelvic viscera. The nerves to and from the uterus pass along the uterosacral ligaments. Pain has two main functions: 1. to indicate impending or actual tissue damage (to minimise injury); and 2. to indicate the need for rest to aid healing. The unpleasant body sensation that characterises pain can makes it an emotional experience. The nervous system responds dynamically to pain. After an initial noxious stimulus, less input is required to trigger second-order neurons in the dorsal horn of the spinal cord (peripheral sensitisation). The biological purpose of this ‘wind-up’ is to increase the likelihood that the area will be protected from re-injury. It is this ability of the nervous system to adapt that is the foundation for chronic pain. Central sensitisation is largely mediated by wide dynamic range (WDR) neurons of the spinothalamic tract. The WDR neurons can develop abnormal synapses, sprouting into other areas of the dorsal horn, and can start to discharge spontaneously, even in the absence of the noxious stimulus. Both peripheral and central sensitisation can enhance and distort pain.

PAIN CHARACTERISTICS Visceral pain is diffuse, poorly localised, and dull and aching in character; this is because of the fewer visceral nerve fibres and smaller cortical representation. It tends to cause depression and nausea. The precipitating causes are overdistension, spasm and ischaemia of smooth muscle, stretching of associated connective tissue and blood vessels, and direct involvement of nerves (e.g. by cancer and infection) (Box 57.1 and Fig 57.3). With hollow viscera, the pain is often spasmodic or colicky.

TABLE 57.1  INNERVATION AND SITE OF REFERRED PAIN OF PELVIC VISCERA. Structure

Afferent nerves

Site of referred pain

Cervix, lower uterus, bladder neck, rectum

S2, S3, S4

Sacral area of the back, buttocks, back of legs

Bladder

T12, L1

Suprapubic, iliac fossae

Uterine body

Superior and inferior sympathetic plexuses T10, T11 T12, L1

Iliac fossae

Fallopian tube

Superior hypogastric plexus (T10, T11, T12, L1) and ovarian sympathetic fibres

Iliac fossae

Ovaries

Sympathetic fibres, T10

Anterior abdominal wall, lateral to and below umbilicus

Vagina

Upper: similar to cervix Lower: internal pudendal and parasympathetic, S2, S3, S4

Hypogastrium, lower back Perineum, lower back, buttocks

Vulva

L1, L2, S2, S3, S4

Sacrum, buttocks, back of legs

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Chapter 57  Pelvic Pain

Abdominal aorta

Sympathetic trunk and L2 ganglion White and grey rami communicantes Lumbar splanchnic nerves (sympathetics)

Intermesenteric (aortic) plexus Ovarian artery and plexus

Grey rami communicantes

Superior hypogastric plexus

Right hypogastric nerve (cut)

Common iliac artery and plexus Ureter Internal iliac artery and plexus

Right and le sacral sympathetic trunks and ganglia

Piriformis muscle

S2

Sacral splanchnic nerves (sympathetic) Pudendal nerve

S1

S3 S4

External iliac artery and plexus

Le hypogastric nerve Inferior hypogastric (pelvic) plexus

S5

Uterine (fallopian) tube Ovary

Pelvic splanchnic nerves (parasympathetic)

Urinary bladder Vesical plexus

Coccygeus (ischiococcygeus) muscle

Uterovaginal plexus Uterus (retracted)

Rectal plexus Rectum (retracted)

FIGURE 57.1 

Nerves of the pelvic cavity.

Source: Netter FH. Atlas of Human Anatomy. 6th edn, Philadelphia: Saunders, 2014. Copyright © 2014 Saunders, An Imprint of Elsevier. Plate 390.

BOX 57.1  Mechanisms of pelvic pain. Spasm of smooth muscle: uterine polyp, ectopic pregnancy, abortion, bowel pain, dysmenorrhoea Stretching of or pressure on ligaments: prolapse, endometriosis Disturbed circulation: congestion, ischaemia Irritation or stretching of peritoneum: bleeding, torsion of ovarian cyst, appendicitis Injury to nerves: carcinomatous infiltration Irritation or pressure on mucosal surfaces: IUD in uterus, stone in bladder

Pain from somatic structures (muscles, skin and bone) is usually well localised (the patient can point to the spot), sharp and continuous, and is felt as being more superficial than visceral pain. It tends to alert and activate the individual.

The difference between visceral and somatic pain can be illustrated by the sequence in acute appendicitis. The pain is initially visceral in type (i.e. related to the appendix itself) and is felt in the central abdomen, this being the area of somatic referral for the gut. With extension of the inflammatory process to the parietal peritoneum and overlying somatic structures (muscles and fascia), the pain then becomes localised to the right iliac fossa.

CLINICAL ASPECTS OF PAIN HISTORY When considering pelvic pain, the first task is to determine if it is an acute or chronic problem. If acute, one should rule out pregnancy and then determine if it cyclical or non-cyclical. The differential diagnoses in the assessment of acute pelvic pain are listed in Box 57.2 and for chronic pelvic pain in Table 57.2. A checklist to aid with history taking in the woman with chronic pelvic pain is given in Box 57.3. The six 507

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L1 First and second lumbar splanchnic nerves

L2

Superior hypogastric plexus

Lumbar part of spinal cord

Sympathetic trunk Inferior hypogastric (pelvic) plexus

Hypogastric nerves

Sacral part of spinal cord

Sympathetic Parasympathetic Somatic efferent Afferent

S2

S3

Sacral splanchnic nerves from sacral sympathetic trunk to inferior hypogastric (pelvic) plexus

S4

Sacral plexus

Pelvic splanchnic nerves

Pudendal nerve

FIGURE 57.2 

Innervation of the female genitalia. Schema of the spinal cord, the abdominal aorta and the female internal and external genitalia (the pelvic plexus is commonly referred to as the inferior hypogastric plexus). Source: Rees PM, Fowler CJ, Maas CP. Sexual function in men and women with neurological disorders. Lancet 2007 Feb 10;369(9560): 512–5. Copyright © 2007 Elsevier Ltd. Figure 3.

TABLE 57.2  DIFFERENTIAL DIAGNOSIS OF CHRONIC PELVIC PAIN. Location

Condition

Gynaecological

Adenomyosis, adhesions, endometriosis, intrauterine device (IUD), mittelschmerz, neoplasia, ovarian cyst or cyst complication (torsion, haemorrhage, rupture), pelvic congestion, pelvic inflammatory disease, postoperative peritoneal cysts, residual ovary/ovarian remnant syndrome, salpingitis

Bladder, ureter

Endometriosis, interstitial cystitis/painful bladder syndrome, neoplasia, recurrent urinary tract infection, renal stone

Bowel

Chronic constipation, coeliac disease, endometriosis, irritable bowel syndrome, inflammatory bowel disease, diverticulitis, neoplasia

Musculoskeletal

Coccygodynia, fibromyalgia, hernia, pelvic instability, pelvic floor myalgia, myofascial pain

Neurological

Abdominal migraine, neuralgia (e.g. pudendal, ilioinguinal, genitofemoral), neoplasia, neuropathic pain

Mental health

Depression, physical and sexual abuse, sleep disorders, somatisation, substance abuse

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Chapter 57  Pelvic Pain

BOX 57.2  Differential diagnosis of acute pelvic pain. Gynaecologic disease or dysfunction Pregnancy complication: ✚ Ectopic pregnancy ✚ Threatened or incomplete abortion ✚ Red degeneration of fibroid Ovarian pathology: ✚ Haemorrhagic functional ovarian cyst ✚ Ovarian torsion ✚ Rupture of ovarian cyst Infection: ✚ Endometritis ✚ Acute pelvic inflammatory disease ✚ Tubo-ovarian abscess Pain related to menstrual cycle: ✚ Mittelschmerz ✚ Dysmenorrhoea Gastrointestinal Appendicitis Bowel obstruction Diverticulitis Inflammatory bowel disease Genitourinary Cystitis Pyelonephritis Renal calculus Musculoskeletal Hernia

A

B FIGURE 57.3 

A Laparoscopy demonstrating a frozen pelvis in a woman with chronic pelvic pain. The cause was adenomyosis and endometriosis which had been complicated by infection after oocyte pick-up. The pouch of Douglas and adnexae are not visible due to severe adhesions. B Perihepatic adhesions or Fitz-Hugh-Curtis syndrome secondary to pelvic inflammatory disease seen in the same patient.

major sources of pelvic pain should be considered: gastrointestinal, urological, gynaecological, psychological, musculoskeletal and neurological. The International Pelvic Pain Society has developed a detailed history and examination form, which is freely available as a handout (http://www.pelvicpain.org/docs/patients/Patient-EducationBrochure.aspx). The characteristics of the pain should be noted (Box 57.3). A record of the patient’s pain intensity level should be obtained and repeat assessments of pain intensity using the same scale can help monitor treatment

responses. Visual analog scales plus the impact on activities of daily living are useful. The following features in the history (Box 57.3) may be useful. Colicky stabbing pain suggests muscle contraction such as a ureter expelling a calculus or the intestine overcoming obstruction. Cyclical pelvic pain associated with severe dysmenorrhoea is more likely to be hormonally mediated, such as endometriosis or adenomyosis. Pain that develops during pregnancy or immediately postpartum may have a musculoskeletal aetiology— pelvic instability. Nerve entrapment pain is often described as hot, burning or like electric shocks. Low central pain associated with a full bladder and urinary frequency should lead to consideration of interstitial cystitis/painful bladder syndrome. Pelvic pain exacerbated by prolonged standing associated with menorrhagia, deep dyspareunia and post­ coital ache may be due to pelvic congestion syndrome.

• • • • • •

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BOX 57.3  Pelvic pain: history. History of pain ✚ Characteristics of the pain ◗ location and radiation ◗ intensity, including with menstruation, micturition, defecation, physical activity ✚ Timing (e.g. dysmenorrhoea or dyspareunia) ✚ Quality ✚ Aggravating and relieving factors ✚ Associated features: ◗ nausea ◗ vomiting ◗ dysuria ◗ frequency ◗ diarrhoea Review of other systems with attention to symptoms of: ✚ Endometriosis ✚ Pelvic inflammatory disease ✚ Gastrointestinal disease (e.g. irritable bowel syndrome) ✚ Musculoskeletal disease ✚ Psychiatric disease—screen for depression: ◗ ‘During the past month, have you felt down, depressed or hopeless?’ ◗ ‘During the past month, have you felt little interest or pleasure in doing things?’ Obstetrics history Surgical history Gynaecological history: ✚ Menstrual ✚ Contraceptive ✚ Sexual ✚ Obstetric Pain history: ✚ Previous investigations ✚ Treatments ✚ Response to therapy Social history: ✚ History of domestic violence ✚ History of sexual or physical abuse: ‘Have you ever been touched against your will?’ ✚ Drugs and alcohol ✚ Past medications (pain and other) ✚ History of substance abuse Family history including: ✚ Fibromyalgia ✚ Chronic pelvic pain ✚ Irritable bowel syndrome ✚ Depression ✚ Interstitial cystitis ✚ Endometriosis ✚ Cancer

510

•

Chronic, relapsing abdominopelvic pain associated with constipation and/or diarrhoea, relieved by defecation, may be irritable bowel syndrome. The special features of pain in different gynaecological conditions are discussed elsewhere under those headings. The following points should be kept in mind: pain can be associated with disordered or even ‘normal’ function of the pelvic viscera and observed pathology in the pelvis (fibroid, ovarian cyst, endometriosis) may not be the cause of the pain. Endometriosis can be asymptomatic, and women with chronic pelvic pain may harbour endometriosis together with other causes for their symptoms. This may be one explanation for therapeutic failure and the persistence of chronic pelvic pain despite hysterectomy and bilateral salpingo-oophorectomy. There is evidence that a substantial proportion of women with chronic pelvic pain have non-gynaecological causes for their symptoms; up to half may have a history of current and/or previous physical or sexual abuse. Drug overuse and polysurgery are often prominent in the history of the woman with chronic pain.

EXAMINATION The woman with chronic pelvic pain may find physical examination difficult and anxiety provoking. One should always proceed slowly and respectfully. A complete gynaecologic and targeted physical examination should be conducted considering both gynaecological and nongynaecological causes of pain, as well as the concepts of referred pain and the existence of trigger points. General inspection. Note the woman’s posture and gait. Musculoskeletal dysfunction that enhances the lordotic curve can create pelvic muscle tenderness. Abdominal examination. Look for scars, masses, tenderness, hernias, presence or absence of distension, location of symptoms and whether tenderness is present. Pelvic examination. Focus on tenderness and its location, nodularity (particularly on uterosacral ligaments and pouch of Douglas), size, shape and mobility of pelvic organs. Take note of pelvic floor tenderness by applying pressure with one finger over the muscles of the pelvic floor. Vulva and perineum examination. Vestibulodynia is characterised by severe pain with light touch or tenderness to pressure. Straight leg-raising test. Ask the patient to lift both legs off the bed while you palpate the tender area in the abdomen. Pain will increase if it is from a musculoskeletal source (Carnett’s sign: entrapped nerve, hernia and myositis). True visceral sources are usually less tender.

• • •

• •

INVESTIGATIONS Appropriate history taking and physical examination should lead the gynaecologist towards the appropriate

Chapter 57  Pelvic Pain

investigations. Baseline tests may be useful to exclude some conditions: full blood examination erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as markers of inflammation β-hCG urinalysis, culture swab/first-pass urine for Chlamydia and gonorrhoea PCR pelvic ultrasound with an appropriately trained gynaecological ultrasonologist—ultrasound can be helpful to diagnose adnexal masses/cysts, hydrosalpinges and adenomyosis; transvaginal power Doppler imaging can detect low flow rates in the pelvic veins and help select those patients in whom venography is indicated MRI may be helpful for deep infiltrating endometriosis, adenomyosis. Other investigations that may be appropriate are: nerve conduction studies (e.g. pudendal nerve) pelvic venography for pelvic congestion syndrome— an abnormal venogram demonstrates dilated ovarian veins > 10 mm diameter, reflux and congestion of the ovarian venous plexus, uterine venous engorgement and filling of pelvic veins across the midline.

• • • • • •

• • •

Laparoscopic surgery Laparoscopy can be helpful and should be performed by a gynaecologist who is competent to diagnose and treat the causes of pelvic pain. In approximately two-thirds of patients with chronic pelvic pain, pathology will be found (Table 57.3). When the laparoscopy is normal, effective postoperative counselling is critical. The woman should

TABLE 57.3  LAPAROSCOPIC FINDINGS IN WOMEN WITH CHRONIC PELVIC PAIN. Diagnosis

Incidence (%)

No visible pathology

35

Endometriosis

33

Adhesions

24

Chronic pelvic inflammatory disease

5

Ovarian cysts

3

Pelvic varicosities

95% when used with image guidance. Core biopsy has a very low false-positive rate (almost zero) and can differentiate between invasive and in situ disease (Fig 59.7). Open biopsy is now rarely required. Remember that any breast mass or localised nodul­ arity needs a ‘triple assessment’: clinical examination (clearly documented with diagrams), breast imaging (mammography +/− ultrasound if ≥ 35 years of age and US alone if < 35 years old) and histology (FNA and/or core biopsy). This will determine whether a solid mass needs to be excised.

BENIGN BREAST DISEASE FIBROADENOMA Fibroadenomas can be considered variations of normal breast development as they are extremely common and 525

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FIGURE 59.7 

Core biopsy of a benign fibroadenoma. This can be unequivocally diagnosed as benign and will explain a clinical or radiologic well-defined mass in the breast.

Source: O’Malley FP, Pinder SE, Mulligan AM. Breast Pathology. 2nd edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 3.2.

under the same hormonal control as the rest of the breast (Fig 59.8). They account for 10 to 15% of all symptomatic breast lumps but 60% of breast lumps in women ≤ 20 years of age. Fibroadenomas are categorised into common, giant (> 5 cm) or juvenile (occurring in adolescents). Fibro­ adenomas tend to calcify and 20% of women will have more than one fibroadenoma of the breast. Over a 2-year period, 25% will increase, 50% will involute or disappear completely and 25% will remain unchanged.7 All fibroadenomas are managed in a similar fashion. Cytology is appropriate in small fibroadenomas in young woman but anything larger requires several core biopsies. Any rapidly growing fibroma or a fibroma > 4 cm should be excised to ensure it is not a phyllodes tumour, which has a malignant potential and is difficult to differentiate clinically from a fibroadenoma.

BREAST CYSTS Breast cysts form from a lobule distension and comprise 15% of breast lumps; they are commonly found in perimenopausal women. They have a characteristic imaging appearance and can be diagnosed and treated by a FNA. Up to 3% of woman with breast cysts will be found to have a breast cancer; however, the majority are incidental findings from breast imaging, unrelated to the underlying cyst.

SCLEROSIS Stromal aberration can cause sclerosis, which can mimic the appearance of breast cancer in mammography. 526

FIGURE 59.8 

A benign fibroadenoma; note the circumscribed outline and a lobulated cut surface.

Source: Fletcher CDM. Diagnostic Histopathology of Tumors. 4th edn. Philadelphia: Saunders, 2013. Copyright © 2013 Saunders, An Imprint of Elsevier. Figure 16.4.

Excisional biopsy is often needed. Pathologically, this group of lesions can be divided into sclerosing adenosis, radial scars and complex sclerosing lesions.

EPITHELIAL HYPERPLASIA Epithelial hyperplasia refers to an increase in the cells lining the duct lobule unit. This is the only benign breast condition associated with an increased risk of breast cancer if the cells show atypia (relative risk up to fivefold).8

DUCT ECTASIA Duct ectasia or dilation increases as a woman ages and with progressive ductal shortening the nipple is often inverted into a slit-like retraction (versus entire nipple retraction due to breast cancer). Duct ectasia can be associated with a cheesy discharge and a palpable doughy mass but surgery would only be instigated at the patient’s request. Other benign breast disease includes duct papillomas (associated with blood-stained nipple discharge), nipple adenomas (nipple ulceration requiring surgical excision), para areola cysts (seen in puberty), lipomas (soft

Chapter 59  Breast Disorders

lobulated growths visible on mammography), hamartomas (fibroadenolipomas) and, rarely, sarcoidosis.

BREAST SYMPTOMS NIPPLE DISCHARGE Physiological nipple discharge in the premenstrual female population is quite common and the colour can range from white, green, yellow to blue and black (obviously distressing to the patient!). All women with nipple discharge should have a careful clinical examination and mammography if > 35 years of age. If the discharge is from a single duct, it should be checked for haemoglobin as up to 10% of these patients with moderate to large amounts of blood in their nipple discharge will have an underlying malignancy.9 Most bloody nipple discharge is due to a papilloma or other non-malignant condition. If a woman desires preservation of breastfeeding ability then localised (versus total) duct excision should be considered. Galactorrhoea describes lactation in a non-pregnant population. Prolactin level should be checked and if > 1000 IU/L, cranial imaging to rule out a pituitary tumour is recommended. A careful drug history is needed, as many agents can cause hyperprolactinaemia.

MASTALGIA Cyclical breast pain is extremely common premenstrually but must be differentiated from non-cyclical or unilateral persistent mastalgia, which should be investigated with imaging as outlined earlier and any lesions found then biopsied. It is also common that pain experienced in the breast is actually referred pain from the chest wall and it is important to differentiate the two as they are managed differently. Chest wall pain is managed with reassurance, NSAIDSs and, in severe cases, precise infiltration with local anaesthetic and a steroid depot injection. Note that breast pain with normal clinical examination and imaging is actually a very rare symptom of breast cancer.10 Symptoms suggestive of referred breast pain include: reproduction of pain with pressure on the chest wall due to tender costochondral junctions (Tietze’s syndrome) unilateral pain pain induced by exercise pain positioned very lateral or medial on the breast. True mastalgia (pain in the breast tissue itself) is thought to be due to hormonal modulation and there are different theories as to the cause (oestrogen or prolactin excess, progesterone deficiency or increased breast hormone receptor sensitivity). Treatment involves reassurance, simple analgesics and a supportive fitting bra. Caffeine reduction, while a popular anecdotal

• • • •

recommendation, has no high-quality evidence to support it. Low-fat diets, progesterone, evening primrose oil and γ-linoleic acid have contradicting or poor-quality evidence to support their use in managing mastalgia. Bromocriptine, a dopamine agonist, is no longer recommended due to its significant side effect profile (including headaches and vertigo). Luteal phase danazol is superior to placebo but obviously has androgenic side effects. Luteal phase tamoxifen is also effective but at the cost of menopausal side effects. Topical tamoxifen is under investigation. SSRIs have also been shown to be more effective than a placebo in randomised controlled trials (RCTs).11

BREAST INFECTION Breast infections can be divided into neonatal (usually S. aureus), lactation associated (S. aureus, S. epidermidis and streptococci) and non-lactating (S. aureus, enterococci, anaerobic streptococci, Bacteroides spp.). All breast infections should be managed with anti­ biotics (initially oral but intravenous if systemically unwell) and any clinical signs of an abscess should be confirmed with US and then aspirated (preferably US-guided drainage). Repeat procedures can include repeated aspiration under US guidance or incision and drainage. General or specialist breast surgeons should be appropriately involved. In lactating women, ongoing expressing or breastfeeding from the affected breast should be strongly encouraged, with adequate lactational support. Breast milk culture will frequently grow contaminants. If the infection persists despite adequate treatment with flucloxacillin, culture from aspiration or drainage is likely to be helpful. Non-lactating breast infection includes the following. Periareolar infection occurs in women in their third decade and is strongly associated with smoking. Central breast pain, nipple discharge, a mass and nipple retraction to the side of the infection are common features. This can be complicated by abscess formation. Treatment is with antibiotics and aspiration/ incision and drainage; however, up to one-third of women will experience a fistula (as the underlying diseased duct has not been removed). These women should be referred to an experienced breast surgeon. Peripheral non-lactating breast abscesses are rare and the patient may be immunosuppressed. They tend to recur so extensive surgery should be avoided. Rarely, non-lactating breast infections can be associated with ductal carcinoma in situ, hence mammography is recommended after symptom resolution in women > 35 years of age. Other breast infections include skin-associated infections (such as cellulitis post-mastectomy or radiation treatment), infected sebaceous cysts, hidradenitis suppurativa, tuberculosis, and self-inflicted trauma and consequent infection.

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BREAST CANCER Breast cancer has a 12.5% incidence by 85 years of age and an incidence near 2% in women under 50 years of age.2

BREAST CANCER HISTOPATHOLOGY Breast cancers arise from the epithelial cells that line the duct lobular breast unit. Ductal carcinoma in situ (DCIS) describes malignant cells that have not invaded past the basement membrane. Older terminology divides cancers into ductal and lobular; however, better understanding shows that all breast cancers arise from the duct lobular unit and so this terminology, while still in use, has been largely superseded.

CLASSIFICATION AND STAGING Breast cancer can be classified by physical findings, histology, tumour grade, stage of disease and receptor status. Special types of breast cancer are: tubular mucinous cribriform papillary medullary classic lobular. No special type (NST; also known as NOS [not otherwise specified]) tumours are graded depending on nuclear atypia and degree of mitosis from grade I, II and III on the Bloom and Richardson scale. Grade is linked to survival. Occasionally lymphomas or sarcomas occur in the breast as well as phyllodes tumours (rare fibroepithelial tumours that range from benign to malignant). Other important prognostic factors used in classification include hormone receptor status (oestrogen [ER], progesterone [PR], erb-B2 or HER2 positive/negative) and lymph vascular space invasion (LVSI). Breast cancer staging uses the clinical tumour node metastases (TNM) system but this is challenging as it relies on accurate assessment of lymph node status. It can be converted into a clinical stage of 0 to 4 based largely on tumour size and axillary lymph node status. All patients should have a full blood examination and liver function test in addition to imaging. If these bloods are abnormal or if there is more advanced primary disease at presentation, the patient should have liver and bone imaging for any metastases that would alter primary management.

• • • • • •

DUCTAL CARCINOMA IN SITU Ductal carcinoma in situ (DCIS) is the most common form of non-invasive cancer, comprising up to 4% of symptomatic cancers and up to 25% of malignancies detected through screening (usually microcalcifications). 528

Lobular carcinoma in situ (LCIS) is rare. DCIS is usually classified by its histological grade. DCIS can express oestrogen receptor positivity as well as HER2 positivity. The natural history if left untreated is heterogeneous; however, approximately 40% of DCIS will progress to invasive cancer over three decades. Treatment options involve wide local excision +/− radiotherapy if < 4 cm affected area or mastectomy if > 4 cm. Survival rates are equivalent; however, conservative surgery has a higher recurrence rate. Tamoxifen reduces the recurrence risk without demonstrating a survival benefit.12 High-grade DCIS has a 1% chance of axillary nodal involvement and so should have nodal assessment.

PAGET’S DISEASE OF THE BREAST OR MAMMARY PAGET DISEASE Paget’s disease of the breast (PDB) describes an eczemalike appearance of the nipple with yellow discharge that is associated with breast malignancy (Fig 59.9). Breast cancer (in situ or invasive) is present in 80% of cases. Approximately 50% of these women will have an associated breast mass, which is likely to be carcinoma, 20% will have a mammographic abnormality and 25% will have occult DCIS.13 Paget’s needs to be differentiated from nipple eczema (which frequently involves the areola) on punch biopsy of the affected skin. Any mass lesion should be treated by surgery with axillary assessment. If there is no mass lesion, wide local excision and postoperative radiotherapy is recommended.

FIGURE 59.9 

Paget’s disease of the breast.

Source: Jacobs L, Finlayson C, Yang SC. Early Diagnosis and Treatment of Cancer. London: Elsevier, 2011. Figure 11.8.

Chapter 59  Breast Disorders

RISK FACTORS Risk factors associated with only a modest increase (< 3 times) require no specific action by patient or practitioner. Risk factors for breast cancer include the following. Older age. Risk doubles every decade until menopause, when it slows; however, 40% of all breast cancers are still found in women > 70 years of age. Geography. Breast cancer risk is lower in eastern Asian countries but an immigrant’s children rapidly acquire the host country’s risk profile, suggesting that genetics are not as important as the geography. High oestrogen exposure. Undergoing menopause > 55 years of age doubles the risk of breast cancer compared to a woman who underwent menopause at 45 years of age. Nulliparous women have a 1.7-fold increased relative risk of breast cancer compared to parous women. Breast cancer risk is also doubled in women who have their first child after 30 years of age versus 20 years of age.14 Each year of breastfeeding reduces a woman’s risk of breast cancer by 4%. Postmenopausal obesity doubles a woman’s risk of breast cancer, likely related to increased oestrogen from peripheral aromatisation. Chest wall radiotherapy. This is particularly relevant to young women treated with radiotherapy for lymphoma. Atypical epithelial hyperplasia. This is associated with a fivefold increase in a women’s risk of breast cancer (roughly 15% risk over 15 years).15 Complex fibroadenomas, duct papillomas and other benign breast conditions are associated with a slight but not clinically relevant increased breast cancer risk. Hormone therapy. Hormone replacement therapy (HRT) and the link to breast cancer remains a significant issue to many women. Essentially, for every year of HRT use, the relative risk of breast cancer is increased by 1.023.16 The type, mode and dose of oestrogen or progesterone don’t seem to alter the risk. HRT does increase breast density and so reduces the sensitivity and specificity of screening. Conflicting data exists on whether breast cancers found in HRT users are earlier or more likely to be node positive. Family history. A woman’s risk of breast cancer is increased if a first-degree relative develops breast cancer < 50 years of age (but not significantly increased if the relative is over 50 years of age). Genetic factors. It is estimated that 10% of breast cancers are due to a genetic syndrome. While the genes are usually autosomal dominant, variable penetrance means that family members may carry the affected gene without developing cancer. BRCA 1 (chromosome 17) carries a 55 to 85% lifetime risk of breast cancer and BRCA 2 (chromosome 13) carries a 35 to 85% lifetime risk (Table 59.1).

TABLE 59.1  RISK OF CANCER TO AGE 70 IN BRCA 1 AND BRCA 2 CARRIERS

• • •

• •

•

• •

Cancer type

BRCA 1 %

BRCA 2 %

General population %

Breast

40–75

40–75

7

Contralateral breast

65

50

1/year after diagnosis

Ovarian

40

15

5 cm or cancer that involves the skin (ulceration, induration,

Chapter 59  Breast Disorders

oedema or peau d’orange) or chest wall, and is commonly seen in inflammatory breast cancers (Fig 59.11). Five-year survival is only 50% and patient neglect plays a significant part, as symptoms may have been present for months or years prior to hospital attendance. Primary treatment is adjuvant or neoadjuvant chemotherapy then radiotherapy, as mastectomy has a high local recurrence rate, although successful neoadjuvant therapy sometimes facilitates surgery months later.

METASTATIC BREAST CANCER Metastatic disease behaves heterogeneously and 10% of women will have evidence of this at the time of presentation. Metastatic breast cancer is not curable but treatment can prolong life. The average period of survival after metastasis is 18 to 24 months; however, aggressive hormone-negative tumours are associated with much shorter survival times.28 All patients should receive systemic therapy that includes hormonal therapy, chemotherapy or use of the newer biologic agents. Surgery and radiotherapy may have a role for localised symptomatic disease. Metastatic hormone sensitive tumours may be kept indolent by various anti oestrogen regimes. Overall, 70% of patients respond to hormone treatment if tumours are ER and PR positive, 40% respond if the tumour is positive for one hormone receptor and < 10% respond if the tumour is ER and PR negative.29,30 Interestingly, oestrogenresistant tumours can become oestrogen sensitive if oestrogen stimulation is stopped. HER2-positive metastatic tumours should receive trastuzumab. Chemotherapy is recommended for symptomatic patients only, as there is no evidence that treating asymptomatic metastatic disease increases survival.

FIGURE 59.11 

Inflammatory breast cancer.

Source: Jacobs L, Finlayson C, Yang SC. Early Diagnosis and Treatment of Cancer. London: Elsevier, 2011. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 11.9.

First-line chemotherapy achieves response rates of approximately 50% with symptom palliation and improved quality of life. Sequential single-agent chemotherapy, usually preferred as combination chemotherapy, has higher toxicity and does not show a survival advantage.31 Bisphosphonates are recommended for boney metastasis as their use can reduce the need of palliative radiotherapy. Bone pain is managed with NSAIDSs and opiates. Marrow infiltration may reduce any of the blood progenitor cell lines and chemotherapy is recommended. Malignant pleural effusions are common and most will re-accumulate if simply aspirated, hence pleurodesis is preferred. The potentially fatal complication of hypercalcaemia is treated with intravenous hydration and bisphosphonates. Central nervous system metastases are common and isolated brain involvement may be treated with high-dose steroids, surgical excision and radiotherapy. It goes without saying that these patients have a significant psychological burden and are best managed by a multidisciplinary team. REFERENCES 1) Breast Cancer Care. Online. Available: . 2) Australian Institute of Health and Welfare, Cancer Australia. Breast cancer in Australia: an overview. Cancer series no. 71. Cat no. CAN 67. Canberra: AIHW; 2012. 3) Lanng C, Hoffmann J, Galatius H, et al. Assessment of clinical palpation of the axilla as a criterion for performing the sentinel node procedure in breast cancer. Eur J Surg Oncol 2007;33(3):281. 4) Fletcher SW, Black W, Harris R, et al. Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 1993;85(20):1644. 5) Nelson HD, Tyne K, Naik A, et al. Screening for breast cancer: an update for the US Preventive Services Task Force. Ann Intern Med 2009;151(10):727. 6) Masood S. Fine needle aspiration biopsy of nonpalpable breast lesions. In: Schmidt W, editor. Cytopathology annual 1993. Baltimore: Williams and Wilkins; 1994. 7) Dent DM. Fibroadenoma. World J Surg 1989;13(6):706–10. 8) Hartmann LC. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353(3):229. 9) Murad TM, Contesso G, Mouriesse H. Nipple discharge from the breast. Ann Surg 1982;195(3):259. 10) Duijm Le, Guit GL, Hendricks JH, et al. Value of breast imaging in women with painful breast: observational follow up study. BMJ 1998;317(7171):1492. 11) Brown J, O’Brien PM, Marjoribanks J, et al. Selective serotonin reuptake inhibitors for 533

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

12) 13) 14)

15)

16)

17)

18) 19)

20)

21)

premenstrual syndrome. Cochrane Database Syst Rev 2009;(2):CD001396. Staley H, McCallum I, Bruce J. Postoperative tamoxifen for ductal carcinoma in situ. Cochrane Database Syst Rev 2012;(10):CD007847. Ikeda DM, Helvie MA, Frank TS, et al. Paget disease of the nipple: radiologic-pathologic correlation. Radiology 1993;189(1):89. Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: the Nurses’ Health Study. Am J Epidemiol 1994;139(8):819. Degnim AC, Visscher DW, Berman HK, et al. Stratification of breast cancer risk on women with atypia: a Mayo cohort study. J Clin Oncol 2007;25(19):2671. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data form 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 1997;350(9084):1047. Rivadeneira DE, Simmons RM, Christos PJ, et al. Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients. J Am Coll Surg 2000;191(1):1. Veronesi U. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg 2010;251(4):595. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 2005;366(9503):2087. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92(14):1143. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effect of radiotherapy after breastconserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of

534

22) 23)

24) 25)

26)

27)

28) 29)

30)

31)

individual patient data for 10 801 women in 17 randomised trials. Lancet 2011;378(9804):1707–16. Moja L, Tagliabue L, Balduzzi S. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012;(4):CD006243. Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 2005;365:1687–717. Department of Health, Australian Government. Cancer screening. . Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA 1 and BRCA 2 mutation carriers: the PROSE Study Group. J Clin Oncol 2004;22(6): 1055. Finch A, Beiner M, Lubinski J, et al. Salpingooophorectomy and the risk of ovarian, fallopian tube and peritoneal cancers in women with a BRCA 1 or BRCA 2 mutation. JAMA 2006;296(2):185. Kroman N, Jensen MB, Wohlfahrt J, et al. Pregnancy after treatment of breast cancer—a population based study on behalf of Danish Breast Cancer Cooperative Group. Acta Oncol 2008;47(4):545–9. Vogel CL, Azevedo S, Hilsenbeck S, et al. Survival after first recurrence of breast cancer. The Miami experience. Cancer 1992;70(1):129. Osborne CK, Yochmowitz MG, Knight WA 3rd, et al. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980;46(12 Suppl.):2884. Bloom ND, Tobin EH, Schreibman B, et al. The role of progesterone receptors in the management of advanced breast cancer. Cancer 1980;45(12):2992. Sledge GW, Neuberg D, Bernardo P, et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 2003;21(4):588.

Section 3.10 NEOPLASIA AND OTHER LUMPS Chapter 60

Benign and malignant disorders of the vulva and vagina

Chapter 61

Benign and malignant disorders of the cervix

Chapter 62

Benign and malignant disorders of the uterus, and the pelvic mass

Chapter 63

Benign and malignant disorders of the ovary and the fallopian tube

Chapter 60  BENIGN AND MALIGNANT DISORDERS OF THE VULVA AND VAGINA Ross Pagano

KEY POINTS Dermatoses and fungal diseases are the most common conditions of the vulva. They may cause severe pruritus. Vulvar pain in association with an essentially normal-appearing vulva is termed vulvodynia. Vulvar intraepithelial neoplasia can be classified into HPV-related and dermatosis-related. Both have a malignant potential and treatment is recommended. Vulvar cancer is less common than other genital tract cancers. The mainstay of treatment is surgery.

BENIGN VULVA DISORDERS CHANGES IN NOMENCLATURE The following changes in nomenclature have been endorsed by the International Society for the Study of Vulvovaginal Disease (ISSVD). When the word vulva is used as an adjective, the preferred term is ‘vulvar’ and not ‘vulval’. Vulval dystrophy has been replaced by ‘vulvar dermatosis’. Lichen sclerosus et atrophicus has been replaced by just ‘lichen sclerosus’. Vulvar vestibulitis (or vestibular) syndrome has been replaced by ‘vestibulodynia’. The most common causes of pruritus vulvae are the dermatoses and fungal infections of the vagina and vulva. Premalignant conditions such as vulvar intraepithelial neoplasia (VIN) and extramammary Paget’s disease can also cause chronic pruritus which is often focal. The most common acute painful conditions of the vulva are herpes infections, Bartholin’s duct abscesses, acute ulceration (usually aphthous) and infections such as intertrigo, folliculitis or even cellulitis. The most common causes of chronic vulvar pain are the dermatoses where severe

• • • •

scratching can cause skin splitting or where the dermatosis is characterised by pain (e.g. lichen planus) and the eruptive bullous disorders (e.g. pemphigus). When there is vulvar pain with no obvious cause evident and the vulva looks essentially normal, this is called vulvodynia and is a common cause of entry dyspareunia and even apareunia.

VULVAR DERMATOSES The most common dermatoses of the vulva are lichen sclerosus, lichen simplex chronicus and lichen planus. Other dermatoses that occur elsewhere on the body can also occur on the vulva such as psoriasis, herpetiform lesions and fixed-drug eruptions and these are managed along the usual lines.

Lichen sclerosus Lichen sclerosus (LS) is the most common condition seen in a vulvar disorders clinic and presents with chronic pruritus vulvae. However, up to 20% of women may be asymptomatic and the diagnosis is usually suspected due to the characteristic appearance of the vulva. It occurs in 1 in 80 women and usually affects older women (peri and postmenopausal), although it is important to realise that it can occur at any age, even in children and infants.

Chapter 60  Benign and Malignant Disorders of the Vulva and Vagina

LS is now regarded as an autoimmune disorder which is familial and primarily affects the vulva, although it can also affect other areas of the body. This condition does not affect the vagina. The condition often extends to include the perianal skin resulting in pruritus ani. The vulva has a characteristic whitish appearance called ‘leukoplakia’ and this is due to the dermis being acellular and thickened due to deposition of collagen. With time, the collagen fibres contract resulting in fibrosis and anatomical distortion. This results in fusion of the labia minora to the labia majora with obliteration of the interlabial space (labial resorption), introital stenosis making sexual penetration difficult or even impossible, and burying of the clitoris resulting in reduced sensation. The epidermis is usually very thin, giving an atrophic and superficially ulcerated appearance, hence the old nomenclature of ‘lichen sclerosus et atrophicus’. This term is no longer used as the epidermis is not atrophic at all and actually has a high cell turnover. In the early phase of the condition, the patient experiences episodes of pruritus which often resolve spontaneously after 1 to 2 weeks. In young women, it is often mistakenly diagnosed as Candida infection as the pruritic episodes will often resolve when anti-Candida therapy is used, but this is just coincidental. Ignoring the condition in children and young women can lead to significant vulvar scarring and permanent introital stenosis. The condition is lifelong, and in the advanced stages the vulva is distorted with loss of the labia minora and clitoris, and introital stenosis and patchy pigmentation throughout. Management consists of avoidance of local irritants and the application of a high-potency corticosteroid preparation, usually as an ointment. This should be used frequently until the symptoms are brought under control and then used on a prophylactic basis to prevent further flare-ups. If introital stenosis occurs, this can be relieved surgically. The overall risk of progression of LS to invasive squamous cell carcinoma is 5% although this may just be a result of long-term scratching and trauma (Fig 60.1). With aggressive use of topical corticosteroids to eliminate pruritus, this risk should be reduced. However, these patients require long-term follow-up for the development of VIN (differentiated type) and these lesions usually present with unresponsive focal pruritus and hyperkeratosis. Occasionally, in the advanced stages, LS fails to respond to topical steroids and so injectable intralesional or even oral steroids have to be used.

Lichen simplex chronicus Lichen simplex chronicus (LSC) is the second most common form of dermatitis seen on the vulva and usually results from chronic irritation (contact dermatitis) or emotional stress (Fig 60.2). LSC tends to affect primarily the labia majora and tends to spare the non-hair-bearing areas, whereas lichen sclerosus tends mostly to affect the medial non-hair-bearing areas of the vulva. It is usually bilateral, although it can be focal and, if so, definitely requires biopsy. Lichenification (exaggeration of the skin

FIGURE 60.1 

Lichen sclerosis with areas of vulvar carcinoma.

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 17.9.

creases due to dermal oedema) is usually evident clinically. The condition usually responds to the removal of irritant factors (soaps, pads, panty liners, deodorants, etc.) and responds well to short courses of topical steroids, usually of mid-strength potency. This condition is generally not regarded as premalignant.

Lichen planus Lichen planus (LP) is far less common than lichen sclerosus and usually presents with vulvar pain and ulceration (Fig 60.3). It is also regarded as an autoimmune disorder and is a lifelong condition. LP often affects the vagina and can be a cause of chronic vaginal discharge, not responding to antifungal and antibiotic treatment. Rustcoloured patches are seen both on the vulva and in the vagina, occasionally with ulceration, and these are extremely tender. It can be associated with LP of the mouth and often responds poorly to topical steroids. If the condition is confined to the vagina, the resultant discharge may be helped with the long-term application of hydrocortisone cream per vaginam, although this condition often requires systemic corticosteroids to bring it under control and then high-potency topical cortico­ steroids to maintain control. In refractory cases, oral methotrexate or azathioprine are required for control. LP has the same risk of development of vulvar carcinoma as LS (5%). 537

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Other dermatoses Psoriasis of the vulva usually occurs in patients who have psoriatic lesions elsewhere. On the vulva, the lesions are well demarcated with a distinct border and are usually quite erythematous in colour but often lack the scaliness that is seen in lesions elsewhere. The condition often affects the natal cleft. Treatment is similar to that given for lesions elsewhere.

PAINFUL CONDITIONS OF THE VULVA Bartholin’s duct abscess

FIGURE 60.2 

Lichen simplex chronicus.

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 17.5.

This occurs when there is a blockage of the opening of the Bartholin’s gland duct at the vulvar vestibule. The cause of the blockage is unknown, probably due to trauma, and results in a cystic swelling just lateral to the vaginal introitus at either 4 or 8 o’clock. The fluid within the cyst is sexual lubricant produced by the gland on that side and if it doesn’t drain spontaneously, it will inevitably become infected and result in an abscess. The average length of the duct is 2.5 cm and the abscess is in the duct, not in the Bartholin’s gland itself. The abscess can be as large as an egg. Originally described as often occurring in patients with gonorrhoea, this association is now extremely rare. The preferred management is surgery (under general anaesthetic) and this involves draining the abscess and creating a new permanent opening using the technique of marsupialisation. Draining the abscess alone will never cure the problem. It is best to perform the marsupialisation when the cyst is not infected.

Herpes genitalis This is the most common cause of recurring painful lesions on the vulva. The lesions usually present with clusters of painful vesicles, always in the same location, and then form superficial ulcers. They are acquired by sexual contact and respond well to a short course of oral antiviral therapy. If they are recurrent, then long-term prophylaxis against further outbreaks is achieved by continuous low-dose oral antiviral therapy.

Lichen planus This is a potent cause of vulvar pain and has been discussed in the previous section.

Plasma cell (Zoon’s) vulvitis FIGURE 60.3 

Vulvar lichen planus.

Source: Lentz GM, Lobo RA, Gershenson DM, Katz, VL. Comprehensive Gynecology. 6th edn. St Louis: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 18.14.

This condition is less common than lichen planus but has a very similar clinical presentation. Patients present with painful erythematous lesions scattered throughout the vulva and vagina. It is regarded as an autoimmune disorder and the characteristic histological feature is a heavy infiltration of plasma cells. Treatment involves topical vulvar and intravaginal high-potency cortico­ steroid creams.

Cicatricial pemphigoid This is an immunobullous eruption causing multiple painful superficial (epidermal) blisters throughout the 538

Chapter 60  Benign and Malignant Disorders of the Vulva and Vagina

entire vulva and usually requires hospitalisation for pain relief. Systemic steroid therapy is the main line of therapy.

VULVAR ULCERS, FISSURES AND ABSCESSES Apart from herpetic ulcers, the most common painful ulcers on the vulva are aphthous ulcers. These are similar to mouth ulcers, do not necessarily occur in conjunction with mouth ulcers and usually occur at times of stress. They respond well to topical high-potency corticosteroid cream, as do mouth ulcers. Occasionally they can become chronic and, due to fibrosis at the base, they never heal. These require surgical excision. Traumatic ulcers can occur due to sexual practices, tight clothes and sporting pursuits. Behçet’s disease may present with a large, solitary, painful vulvar ulcer and is always associated with concomitant oral ulcers. It may involve the eyes (uveitis), the skin on the legs (erythema nodosum) or both. It is predominantly a generalised vasculitis and usually requires admission to hospital for analgesia and systemic steroid therapy as well as colchicine or azathioprine. Chronic deep vulvar fissures are often related to associated large bowel disorders such as Crohn’s disease and treatment involves adequate control of the underlying condition. Superficial vulvar ulcers often occur as a result of chronic vulvar candidiasis and will be discussed in the section on infections. Hidradenitis suppurativa is an uncommon disorder in Australia as it is most commonly seen in AfricanAmericans. It is caused by blockage of the apocrine sweat glands resulting in large, painful abscesses and fissures in the axilla and on the vulva. Conservative therapy with long-term antibiotics, retinoids and spironolactone can help, although treatment predominantly involves surgical drainage of the abscesses and excision of chronic fissures.

VULVODYNIA Vulvodynia is a chronic vulvar disorder which is defined by the ISSVD as ‘vulvar discomfort, most often described as burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable neurologic disorder’. This is where the patient has significant symptoms, especially pain, and yet there is no obvious cause and the vulva looks essentially normal. It should not be regarded as a primary psychological disorder but a condition that can lead to secondary psychosexual problems. A differential diagnosis of the causes of vulvar pain is given in Box 60.1. Provoked vestibulodynia (previously called ‘vulvar vestibulitis syndrome’) causing significant entry dyspareunia is the most common clinical presentation of vulvodynia in young women and unprovoked generalised vulvodynia and clitorodynia are the most common presentations in postmenopausal women. The incidence of

BOX 60.1  ISSVD terminology and classification of vulvar pain (2003). I

Vulvar pain related to a specific disorder 1 Infectious (e.g. candidiasis, herpes) 2 Inflammatory (e.g. lichen planus, immunobullous disorders) 3 Neoplastic (e.g. Paget’s disease, squamous cell carcinoma) 4 Neurologic (e.g. herpes neuralgia, spinal nerve compression) II Vulvodynia 1 Generalised a Provoked (sexual, non-sexual or both) b Unprovoked c Mixed (provoked and unprovoked) 2 Localised (e.g. vestibulodynia, clitorodynia, hemivulvodynia) a Provoked (sexual, non-sexual or both) b Unprovoked c Mixed (provoked and unprovoked)

provoked vestibulodynia of varying degree has been reported to be as high as 15% of the female population. However, the true incidence of significant dyspareunia due to vulvodynia is unknown, although our clinical impression is that it would not be greater than 1 to 2% of sexually active females.

Aetiology The aetiology of vulvodynia is unknown. Women with provoked vestibulodynia have a higher concentration of nerve fibres (type C) within the vulvar vestibule (probably congenital) and if these are damaged due to some triggering factor, they will then respond by transmitting all sensation as pain. Possible triggering factors are chronic candidiasis, trauma during intercourse due to inadequate lubrication, sexual abuse and vaginal delivery.

Clinical presentation Clinical presentation of patients with provoked vestibulodynia is usually entry dyspareunia, often resulting in complete apareunia. There is marked pinpoint tenderness confined to the vulvar vestibule. The vulva looks normal except for patchy erythema within the vestibule at the sites of tenderness. There is usually a secondary vaginismus due to involuntary introital muscle spasm.

Management Management of vulvodynia requires a multidisciplinary approach. Most importantly, it gives the patient a diagnosis, an explanation of her condition and a therapeutic plan. Modalities used are drug therapy, physiotherapy, psychosexual counselling and surgery. 539

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Drug therapy involves neuromodulators such as tricyclic antidepressants (e.g. amitriptyline orally or as a topical cream [currently being evaluated]) or anti­ epileptic agents (e.g. pregabalin). Physiotherapy involves active relaxation of the introital muscles and surgery involves excision of the vulvar vestibule with vaginal advancement.

diethylstilboestrol (DES) in utero (given to the mothers to supposedly prevent miscarriage), the incidence is 40% and has been associated with the development of clear cell adenocarcinoma of the vagina.

VULVAR OEDEMA

The most common infection involving both the vagina and the vulva is fungal and is caused by Candida albicans. This results in a heavy vaginal discharge, often with an appearance similar to cottage cheese, and can cause intense pruritus of the vulva with erythema and swelling. The vaginal pH is usually normal. Other less common strains of Candida such as C. glabrata and C. krusei tend to cause more drug-resistant infections. However, up to 20% of women have C. albicans on vaginal culture without any symptoms or signs of infection. Treatment of an acute vaginal candidiasis involves use of an azole preparation either as a cream or pessary intravaginally for up to 6 days or a single dose of oral fluconazole 150 mg, or both. Recurrent vulvovaginal candidiasis (RVVC) is defined as four or more episodes of candidiasis in a 12-month period. This often occurs as a result of being on long-term broad-spectrum antibiotics, diabetes, oestrogen therapy (e.g. the pill, hormone replacement therapy) and stress. Management involves correcting the causative factor (e.g. optimal diabetes control), diet modification (reduced sugar and yeast intake) and long-term therapy with oral fluconazole 150 mg weekly continuously for up to 6 months, depending on the duration of symptoms. Intravaginal boric acid capsules were often used historically in resistant cases. Although boric acid may be difficult to access, it is still sometimes used in short courses where other treatments fail, especially those caused by C. glabrata. Chronic vulvar candidiasis is where the Candida infection is expressed clinically primarily in the vulva; the vagina is often normal in appearance and can be negative on culture. The main symptoms are burning and irritation rather than pruritus. The symptoms are cyclical, with flare-ups occurring predominantly in the week premenstrually and complete relief of symptoms during menstruation. The vulva has a chronic brick-red colour, often with superficial skin splitting, particularly in the interlabial sulci. Satellite red spots are often seen outside the main area of erythema, looking similar to a nappy rash. Management involves substituting the oral con­ traceptive pill with a progesterone-only contraceptive, ceasing hormone replacement therapy and undertaking long-term oral fluconazole therapy. Oral probiotics have little beneficial effect on this condition. An important point to stress is that candidiasis is very uncommon in low-oestrogenic states. Children (once out of nappies) and postmenopausal women not on hormone replacement therapy very rarely get candidiasis unless they are diabetic or on long-term antibiotics. Thus, it is

Acute swelling of the vulva can occur during a flare-up of any of the dermatoses or infections, including candidiasis. It can also occur as an urticarial reaction to any topical agent (very rarely to sperm) and also to trauma. Chronic oedema is usually due to lymphatic obstruction and this may result in the development of chronic wartlike vesicular eruptions referred to as lymphangiectasia. This usually requires surgical excision or laser ablation.

VULVOVAGINAL DISORDERS CONGENITAL DISORDERS Complete duplication of the vagina can occur either de novo or associated with complete duplication of the entire genital tract. As one vaginal canal assumes dominance once sexual activity commences, the patient is often not aware of her condition. Menstruation is usually normal and fertility is not affected unless there is an associated disparity in uterine cavity sizes leading to miscarriage if implantation occurs in the smaller horn. Vaginal agenesis is very rare and only occasionally is there a functioning uterus present. Usually it is associated with complete lack of development of the entire genital tract. An artificial vagina can be created by opening a space between the bladder and rectum, with a skin graft covering a suitable mould inserted into this space. Imperforate hymen is usually diagnosed following puberty when amenorrhoea occurs with severe cyclical pain due to distension of the vagina by menstrual fluid. Sexual intercourse is impossible and the condition is easily corrected by surgical division of the hymen. Congenital cysts of the vagina are usually painless, discovered accidentally and can vary in size up to that of an egg. They usually are a remnant of the male reproductive system and are called Gartner’s duct cysts. The ducts run down from the paraovarian space, along the sides of the uterus, down the anterolateral corners of the vagina and onto the vulva. Distension can occur anywhere along this route and excision is performed only if they are symptomatic. Vaginal adenosis is where columnar epithelium replaces squamous epithelium. It may be an extension of the cervical columnar tissue but it may arise de novo in the vagina. It usually appears as a dull red patch which can bleed when touched and can cause heavy physiological discharge. It occurs in 2% of the normal population. In patients who were exposed to the drug 540

INFECTIONS Candidiasis

Chapter 60  Benign and Malignant Disorders of the Vulva and Vagina

vital to exclude other causes of pruritus before assuming it is due to candidiasis. Tinea of the vulva usually extends into the groins and presents with an itchy, well-circumscribed erythematous rash with central clearing (as opposed to psoriasis where the erythema is uniform). Topical terbinafine or clotrimazole creams are used, often for many weeks. Intertrigo refers to tinea occurring in areas of the body where there is constant skin-to-skin contact (e.g. submammary, abdominal and groin skin folds in obese women). Treatment is similar to that for tinea but weight loss is actively encouraged.

Trichomonal vaginitis (vulvitis) Trichomonal vaginitis (vulvitis) is an uncommon cause of vaginitis. It is caused by Trichomonas vaginalis and is often seen following frequent sexual activity. A profuse frothy discharge occurs with a typical ‘fishy’ odour and this may irritate the vulva. The vagina and particularly the cervix are inflamed and multiple petechiae can be seen, giving the cervix a strawberry-like appearance. Treatment is with oral (or intravaginal) metronidazole.

Condylomata (warts) Vulvar warts are the result of infection with the human papilloma virus (HPV) type 6 and 11 and are usually the result of sexual contact. Vaginal and cervical warts are less common than vulvar warts but it is imperative that the entire genital tract is assessed and a cervical Pap smear is taken. Warts are usually in small crops with a central stalk and treatment consists of cryotherapy (an office procedure), diathermy or laser ablation (under general anaesthetic). For widespread and recurrent lesions or where the above treatments could be harmful (e.g. peri-clitorally), topical imiquimod cream (usually for 16 weeks) is an effective alternative.

Bacterial vaginosis Bacterial vaginosis (BV) is not strictly speaking an infection but rather an overgrowth of the natural bacteria in the vagina with a loss of lactobacilli (and hence loss of natural acidity). The patient often complains of a heavy, yellow/ green, malodorous vaginal discharge, and BV often occurs following frequent intercourse. On examination, the vagina does not look inflamed and the vaginal pH is elevated. Microscopy reveals ‘clue cells’, which are epithelial cells covered by a proliferation of bacteria. BV usually responds to a course of intravaginal clindamycin cream or metronidazole (oral or vaginal). Regular acidic gels inserted per vaginam can protect against recurrences.

Sexually transmitted infections (STIs) This topic has been covered more extensively earlier in this book (especially Ch 54). Persistent offensive vaginal discharge not responding to topical therapies, vulvovaginitis and symptoms of urethritis are the usual clinical presentations of infection with Neisseria gonorrhoea or Chlamydia. However, it is important to note that many

women can have these genital infections and yet have no clinical symptoms or physical signs. Thus, if suspected, swabs are mandatory.

Other conditions Atrophic vaginitis Inflammation of the vagina due to low oestrogen levels occurs commonly in peri- and postmenopausal women and to a lesser extent in lactating women. Due to the low oestrogen levels altering the flora of the vagina, resulting in a lack of lactobacilli and acidity, bacterial superinfection occurs with increased discharge and symptoms of burning, irritation and even pain. This occurs mostly in sexually active women but can also occur without sexual activity. The vagina is often inflamed looking with the features of atrophy (thin vaginal skin with loss of rugosity). There is often a thin yellow discharge, which may have an offensive odour. The vulva is also often inflamed, particularly around the vaginal introitus. Treatment consists of inserting topical oestrogen into the vagina, either as a cream or pessary, usually twice per week on a long-term basis. Women taking systemic hormone replacement therapy often still have atrophic vaginitis and require supplementary topical therapy as well. Even though the vulva can be inflamed, topical oestrogen cream purely to the vulva is ineffective as the vulva has very few oestrogen receptors. As the vulvitis is usually due to irritation from the vaginal discharge in these women, correcting the vaginal atrophy will usually result in improving both the vaginal and vulvar symptoms. It is very uncommon for postmenopausal women to get vulvovaginal candidiasis unless they are taking hormone replacement therapy (either topical or systemic), are diabetic or are on long-term antibiotics.

Foreign bodies Never forget the presence of a foreign body in the vagina as a cause of intractable offensive vaginal discharge. This problem highlights the importance of examining the patient! The most common foreign body found is a tampon that has been forgotten. Sex toys and condoms are also often found. However, a large uterine polyp (e.g. a submucous fibroid) extruded through the cervix can have the same effect as it is often partly necrotic. In children, the most common foreign body seen is a concretion of toilet paper and is usually found under anaesthesia.

Inflammatory conditions Desquamative inflammatory vaginitis Desquamative inflammatory vaginitis (DIV) presents with intractable vaginal discharge. It occurs most commonly in the peri- and early postmenopausal years. The main complaint is a profuse, purulent, non-malodorous vaginal discharge which fails to respond to topical oestrogen or antifungal agents. Culture is usually negative and the pH is always elevated. The vagina is usually inflamed 541

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and petechiae are often seen throughout. It is thought to be an autoimmune disorder and responds well to long-term intravaginal anti-inflammatory creams such as clindamycin (an antibiotic with powerful antiinflammatory effects) or hydrocortisone.

PAEDIATRIC VULVOVAGINAL DISORDERS The following are considerations when dealing with vulvovaginal disorders in the neonate or child. Neonatal labial fusion can occasionally be seen at birth and responds well to topical oestrogen cream, with complete resolution in most cases. Vaginal discharge usually requires an examination under anaesthesia to make a diagnosis. Usually you are dealing with a foreign body such as toilet paper concretions, small beads and so on. Sexual abuse must always be kept in mind and STI swabs are mandatory if there is no obvious cause. Pruritus vulvae usually occurs as a result of an irritant contact or a vulvar dermatitis. The most common vulvar dermatitis is psoriasis, with the erythematous rash often affecting skin between the buttocks as well. Atopic dermatitis is common but is usually associated with other atopies. Lichen sclerosus is a rare (1 in 800 children) but very important cause of chronic pruritus as it can cause significant and permanent scarring if left untreated. The condition often resolves at puberty. In the past, doctors have mistaken it for sexual abuse (because of trauma from chronic scratching) leading to wrongful and distressing accusations. Topical corticosteroids (of effective potency) is the main treatment for these conditions. It is important to emphasise that candidiasis is very rare in children once they are out of nappies. Also, there is no place for the application of topical oestrogen in children except for neonatal labial fusion. Vulvar soreness can be caused by primary bacterial infections (from trauma) or from scratching dermatitic skin resulting in secondary infection. Bacteria involved are usually Group A streptococci, Group B streptococci and Staphylococcus aureus. Rarely, the immunobullous disorders can become secondarily infected, as well as aphthous ulcers. Never forget fixed drug eruption (reaction to a particular drug) manifested as a focal vulvar eruption. Oral erythromycin is a good antibiotic for paediatric vulvitis as it also has a potent anti-inflammatory effect.

• •

•

•

VULVAR CANCER AND PRECANCER Carcinoma of the vulva is uncommon, accounting for under 1% of all cancers affecting women. It accounts for 3% of all female genital tract cancers and is diagnosed in 542

2 women per 100 000 each year. It is most common in the postmenopausal years (55 to 75) although it can also occur in younger women, particularly when related to HPV. Like in the cervix, all invasive vulvar cancers most probably pass through a precancerous phase (vulvar intraepithelial neoplasia). Early detection and treatment of vulvar intraepithelial neoplasia theoretically should significantly reduce the incidence, surgical morbidity and mortality of vulvar cancer. Vulvar cancer is significantly more common in smokers, particularly when it is HPV related. This cancer is far more common in Australian Indigenous women.

VULVAR INTRAEPITHELIAL NEOPLASIA (VIN) Vulvar intraepithelial neoplasia (VIN) occurs in the vulva in two distinct clinical and pathological forms. Originally it was classified as a single entity but it became apparent that it has two distinct presentations, a HPV-related lesion in younger women with a low malignant potential and a dermatosis-related lesion in older women with a much higher malignant potential. To differentiate the two distinctly different clinical presentations, the condition has been subclassified into: 1. VIN usual type (HPV-related); and 2. VIN differentiated (dermatosis-related). The original terminology of grading VIN into grades I, II and III has been discarded and the term VIN I eliminated (now referred to as HPV atypia or minor atypia only). VIN grades II and III have been combined into a single highgrade lesion and are now referred to as purely VIN. As already stated, this is then classified as ‘VIN usual type’ (i.e. HPV-related) or ‘VIN differentiated’ (i.e. LS-related); in rare cases, where the pathologist cannot determine the type, it is called ‘VIN unclassified’. VIN usual type is HPV-related (usually type 16) and occurs much more commonly in smokers. This usually presents in younger women and at least 10% of patients presenting with this have an associated high-grade cervical intraepithelial neoplasia (CIN), and thus colposcopy of the entire genital tract is recommended. It is subclassified into three types depending on the appearance; namely, ‘warty’, ‘basaloid’ and ‘papillary’. These lesions are usually multiple, symptomatic (pruritus) and cosmetically unacceptable. Even though these lesions can resolve spontaneously, especially in young women, treatment to eliminate these lesions is recommended both for symptomatic control and prevention of malignancy. The overall risk of malignant change is 4%. VIN differentiated always develops in an area of dermatosis, usually lichen sclerosus, although the other dermatoses are also involved to a lesser extent. The role that chronic scratching has in the development of VIN and cancer in an area of untreated dermatosis is yet to be evaluated but active treatment of the dermatosis should reduce the risk of malignant change. In this type of VIN, the lesions are often solitary and the usual presentation is focal pruritus not responding to topical steroids. The

Chapter 60  Benign and Malignant Disorders of the Vulva and Vagina

malignant potential of these untreated lesions is very high, probably 100%. The three clinical features of VIN lesions (of both types) are: 1. distinct borders 2. lesion is raised above surrounding skin 3. irregular surface contour. Patchy pigmentation occurs occasionally and irregular vessels are sometimes seen on colposcopy. The ideal treatment of all types of VIN is surgical excision with a clear margin. If the lesion is not re-sectable (e.g. is multifocal, on the anal margin), laser ablation is acceptable. Where this is not possible (e.g. on the clitoris or urethra), topical imiquimod cream for 16 weeks and careful follow-up is a promising alternative. Recurrences (up to 20%) can occur within the first 5 years. Long-term follow-up is mandatory.

CARCINOMA OF THE VULVA The majority of vulvar cancers are squamous cell carcinomas, either related to an existing vulvar dermatosis or secondary to wart virus (HPV) activity. It usually presents as a persistent raised lump or chronic ulcer with raised edges. It is usually painless but if it is large, it can cause pain from rubbing against adjacent skin. The diagnosis is made on biopsy, preferably at the edge of the lesion and including some surrounding normal unaffected skin. If the depth of invasion is < 1 mm, the risk of local node spread is nil. If > 5 mm depth of invasion, the incidence of groin node involvement is > 35%. To plan treatment, staging of the cancer is mandatory. Stage 1A: tumour confined to vulva/perineum, < 2 cm in diameter and < 1 mm invasion. Stage 1B: tumour confined to vulva > 2cm in diameter or > 1mm invasion, negative nodes. Stage 2: tumour with adjacent spread (1/3 lower urethra or anus, 1/3 lower vagina) with negative nodes. Stage 3: tumour of any size with positive inguinofemoral lymph nodes. Stage 4A: tumour deeply invades regional structures (2/3 upper urethra, 2/3 upper vagina), rectal/bladder mucosa or fixed to pelvic bone; ulcerated inguinal nodes. Stage 4B: any distant metastasis, including pelvic lymph nodes. Nodal spread is closely related to depth of invasion. This is usually ipsilateral unless the tumour is involving central structures such as the clitoris or anterior labia minora, in which case both groins are at risk. If groin nodes are negative, survival rates are very high. To assess the risk of nodal spread before embarking on a complete groin dissection, the technique of sentinel groin node biopsy has been developed, as it is used in breast cancer

• • • • • •

management. The technique involves injecting Technetium 99-labelled albumin with a blue dye around the lesion and then using a gamma scan to find the firstdraining lymph node and excising it. It is only used if the tumour is smaller than 4 cm in diameter and the inguinal nodes are not clinically involved. Surgery remains the main treatment modality for early vulvar cancer. For stage 1A, excision of the tumour with a 1 cm margin and dissecting down to the inferior fascia of the urogenital diaphragm is adequate (100% 5-year survival). For stage 1B, ipsilateral (or bilateral) groin node dissection is the standard management if the nodes are not clinically involved. It is in this group that sentinel node biopsy is currently being evaluated to see if the radical groin dissection can be avoided. Adjuvant radiotherapy to the vulva and groins is employed if more than two inguinal nodes have metastases or if there is any extracapsular spread of tumour in any node (50% 5-year survival). If pelvic nodes have metastases, the prognosis is very poor (10% 5-year survival).

OTHER VULVAR TUMOURS Vulvar Paget’s disease (extramammary Paget’s) This is an uncommon condition usually occurring in postmenopausal women. It is usually unilateral, mostly affects the labia majora and presents with a chronic itchy, scaly rash. Usually, it is a primary cutaneous lesion that arises from the apocrine glands and is non-invasive. In 15% of primary Paget’s, there is evidence of an associated invasive lesion, usually a skin appendage adenocarcinoma. Secondary vulvar Paget’s disease usually arises from an underlying anal or rectal adenocarcinoma. Treatment of primary Paget’s disease is wide local excision, although one-third of patients have local recurrences despite clear margins. Thus, long-term follow-up is mandatory. For recalcitrant cases, topical imiquimod has been used successfully, although the mechanism of action is unclear as the aetiology is not thought to be viral.

Cancer of the Bartholin’s gland This type of cancer is rare but must be kept in mind when a patient presents with a painless lump in the region of the ischiorectal fossa. Radical excision and lymphadenectomy is required. In women, 5% of malignant melanomas occur on the vulva and yet the vulva accounts for only 1% of the total skin area. Benign pigmented lesions are common on the vulva but any change requires immediate investigation. Colposcopy is an excellent diagnostic tool and any pigmented lesion that is raised or has internal pigment variation requires excision. A benign condition called melanosis vulvae can occur in women in their 20s and 30s where a number of discrete pigmented lesions develop within the labia minora. Once confirmed on 543

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histology, they have little risk of turning malignant. They often disappear as women approach menopause. Remember that patchy benign pigmentation surrounding the vaginal introitus can also occur in patients with lichen sclerosus. FURTHER READING Australian Institute of Health and Welfare, Australasian Association of Cancer Registries. Cancer in Australia: an overview, 2012. Cancer series no. 74. Cat. no. CAN 70. Canberra: AIHW; 2012. Australian Institute of Health and Welfare, Cancer Australia. Gynaecological cancers in Australia: an overview. Cancer series no. 70. Cat. no. CAN 66. Canberra: AIHW; 2012. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 2008;26(35):5802–12. Dennerstein G, Scurry J, Brennan J, et al. The vulva and vaginal manual. Melbourne: Gynederm Publishing; 2005.

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Edwards L. Genital dermatology atlas. Philadelphia: Lippincott Williams & Wilkins; 2004. Edwards L. The diagnosis and treatment of infectious vaginitis. Dermatol Ther 2004;17(1):102–10. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131(10):2349–59. Kaufman R, Faro S, Brown D. Benign diseases of the vulva and vagina. 5th ed. St Louis: Mosby; 2004. Ridley CM, Neill S. The vulva. 2nd ed. London: Blackwell Science; 1999. Wilkinson EJ, Stone IK. Atlas of vulvar pathology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2012. Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva, Switzerland: World Health Organisation; 1968. Public Health Papers No. 34. Online. Available: .

Chapter 61  BENIGN AND MALIGNANT DISORDERS OF THE CERVIX Jeffrey Tan

KEY POINTS Cervical ectropion, cervical polyp and nabothian cysts are common benign conditions of the cervix. Cervical cancer is the third most common cancer in females worldwide and remains a major problem in resource-poor nations. It usually arises as pre-invasive disease at the ‘transformation zone’, the junction between the squamous and columnar epithelium. Metaplasia of the columnar epithelium under the influence of human papillomavirus (HPV) results in malignant potential. Malignant potential arises when HPV enters into basement cells and becomes integrated in the cell genome. Screening for cervical cancer has dramatically reduced the incidence of cervical cancer in well-resourced nations. In 2014, recommendations have been made to move to 5-yearly screening based primarily on HPV testing from the age of 25 years. In Australia and New Zealand, most cervical cancer presents in stage 1, is managed surgically and has a 5-year survival rate of about 90%. The introduction of the HPV vaccine is expected to significantly further reduce the incidence of cervical cancer. The current vaccine has efficacy against types 16 and 18 which are responsible for 70% of cervical cancer.

BENIGN DISORDERS OF THE CERVIX The cervix has the same embryonic origin as the uterine body. It is exposed to the acid vaginal milieu at puberty and the everted endocervical columnar epithelium undergoes metaplasia. It is this area, known as the transformation zone, that when subjected to microtrauma allows the human papillomavirus (HPV) DNA to become integrated in the cell genome and lead to squamous intraepithelial lesions. A variety of other infections can occur but most inflammatory changes leading to cervicitis do not have any specific microbes detected. During reproductive life, the passage of spermatozoa is facilitated at mid-cycle as a result of the effect of peak oestrogen levels on the cervical mucus. This role in conception can be disturbed by the physiological changes during the menstrual cycle, infection, surgery and contraception.

CONGENITAL ABNORMALITIES The cervix develops from the Müllerian ducts, as do the fallopian tubes, uterus and upper two-thirds of vagina.1 Complete failure of fusion of the Müllerian ducts results in duplication of the upper vagina, cervix and uterine body (‘uterus didelphys’). Gynaecological problems are surprisingly uncommon unless there is incomplete development of one side, sometimes resulting in unilateral obstruction to menstrual flow.

EVERSION AND NABOTHIAN CYSTS The cervix consists of the ectocervix, a stratified squamous epithelium, and the endocervix, a single layer of columnar epithelium. At puberty, with increasing oestrogen influence, the cervix undergoes eversion and the columnar epithelium becomes exposed to the acidic environment (Fig 61.1). Squamous epithelium grows over the exposed

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

NC

Mucus

FIGURE 61.2 

Cervical nabothian cyst.

Source: Pfenninger JL, Fowler GC. Pfenninger and Fowler's Procedures for Primary Care. 3rd edn. Philadelphia: Saunders, 2010. Copyright © 2010 Saunders, An Imprint of Elsevier. Figure 137.2.

FIGURE 61.1 

Cervical ectropion.

Source: Reproduced with permission from Oncoserve Systems.

columnar epithelium and glands and this benign process is called metaplasia. This area of change is called the transformation zone and is often the key area where micro­ organisms can cause infections. HPV enters the basement cells through micro-abrasions of this area and persistent infection can then lead to cervical intraepithelial neoplasia and eventually cancer if untreated. Size of cervical eversion (or ectropion) can increase with increasing parity or the use of the contraceptive pill. Treatment by cauterisation or cryotherapy is often unnecessary unless there is problematic vaginal discharge or postcoital bleeding. It is recommended that colposcopy be done first for persistent postcoital bleeding prior to considering any treatment. Nabothian cysts are benign retention cysts from obstruction of the crypts of the endocervical clefts by overlying squamous epithelium. They can be located in the ectocervix or endocervix and, if they are present in multiples or are sufficiently large, can lead to cervical hypertrophy. They often resolve spontaneously and do not require incision or cauterisation (Fig 61.2).

CERVICITIS Cervicitis is an inflammatory finding often reported on Pap smears without the women reporting any symptoms. However, if there is profuse, discoloured or malodorous vaginal discharge and/or postcoital bleeding, genital swabs should be taken for microbiological examination and a Pap smear taken if there are clinical concerns, even if the woman is not due for routine Pap screening. Microbiological tests should also include Chlamydia trachomatis, Neisseria gonorrhoea, Mycobacterium genitalis and, in cases with obvious blisters, herpes virus as well. 546

Although pelvic discomfort and dyspareunia are uncommon, these symptoms could allude to accompanying pelvic infections. Treatment is not necessary for asymptomatic cervicitis. Prescription of antibiotics or antifungal treatment should be confined to specific infections confirmed on tests rather than for all reported vaginal discharge.

BENIGN TUMOURS Endocervical polyps Endocervical polyps are often found during routine Pap screening. There are often no signs or symptoms of their presence, but occasionally they can present as contact bleeding. The most common type is adenomatous with endocervical-glandular elements set in a vascular stroma. Other tissues may predominate or co-exist, such as fibrous or fibromyomatous types (Figs 61.3 and 61.4). These polyps can sometimes be an extension from the endometrial cavity, protruding through the cervical os. Cervical intraepithelial neoplasia can also be found on the surface of the polyp. However, malignant changes are extremely rare. As most polyps are small (< 1 cm) and single, they can be removed with the polyp forcep in an office setting with minimal discomfort. The polyp is grasped with the sponge-holding forcep and twisted until the stalk comes off; the polyp is sent for histological examination. The base can be treated with a swab stick containing Monsel’s paste (ferric subsulphate) or coated with silver nitrate. If the polyp is large or multiple, it can be removed under general anaesthesia and a curettage done at same time to exclude endometrial polyps, especially if there has been abnormal bleeding.2 For the postmenopausal woman with an endocervical polyp, it will be worthwhile to get a pelvic ultrasound to exclude any co-existing endometrial pathology.

Chapter 61  Benign and Malignant Disorders of the Cervix

Papillomas There are two main papillomatous lesions of the cervix: the true squamous cell papilloma and the condyloma acuminatum. Condylomas (or warts) are often irregular, multiple and can co-exist with vaginal and vulvar warts. They are due to HPV infection, and often Pap smears can be abnormal at the same time (Fig 61.5). These can be treated with cautery or laser ablation; single lesions can

resolve spontaneously. Genital warts are on the decrease since the introduction of HPV vaccination.

Leiomyomas Leiomyomas are smooth muscle tumours similar to their uterine counterparts. Protruded fibroids through cervical os could originate from the uterine cavity and may need hysteroscopic resection or, in cases of large protruding necrotic fibroid, may need hysterectomy (Figs 61.6 and 61.7).3 Very rarely, they may have malignant sarcomatous changes.

FIGURE 61.3 

Cervical polyp.

Source: Reproduced with permission from Oncoserve Systems.

FIGURE 61.5 

Cervical condyloma.

Source: Reproduced with permission from Oncoserve Systems.

Cervical fibroid

FIGURE 61.4 

Cervical polyp. The stroma is fibromuscular and the base contains thick-walled blood vessels. Endocervical crypts, some dilated, are present within the polyp.

Source: Anderson MC, Robboy SJ, Russell P, Morse A. The cervix—benign and non-neoplastic conditions. In: Robboy SJ, Anderson MC, Russell P eds. Pathology of the Female Reproductive Tract. Edinburgh: Churchill Livingstone, 2002. Copyright © 2002 Churchill Livingstone, An Imprint of Elsevier.

Another fibroid arising from fundus and body of uterus

FIGURE 61.6 

Cervical fibroid.

Source: Courtesy of Dr Pradeep Saxena.

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A

B

FIGURE 61.7 

A A pedunculated fibroid is seen to be prolapsed into the cervix. B The pedicle is highlighted by colour Doppler, seen here in monochrome. Source: Allan PLP, Baxter GM, Weston, MJ. Clinical Ultrasound. 3rd edn. Edinburg: Churchill Livingston, 2011. Copyright © 2011 Churchill Livingston, An Imprint of Elsevier. Figure 36.60A and B.

PREMALIGNANT AND MALIGNANT DISORDERS OF THE CERVIX The beginning of the end of the cervical cancer legacy can now be written in this chapter. HPV is now accepted as a necessary cause of cervical cancer. The HPV vaccination is available for primary prevention, and mostly given to young adolescents. Cervical screening is still necessary through utilising HPV testing and cytology, by conventional Pap or by liquid-based technology. With our understanding of low-grade abnormality on cytology as being mainly a transient HPV infection, the role of colposcopy in the management of screened abnormalities is more targeted towards women with a higher likelihood of having a high-grade abnormality. Management algorithms have been introduced for various combinations of results of screening tests. Treatment of pre-invasive abnormalities is also likely to be favoured for those with high-grade abnormalities as there is a high chance of spontaneous resolution of low-grade abnormalities. Screening also allows for diagnosis of earlier stages of invasive cancer, with uterine-sparing surgery to preserve fertility. Microinvasive disease (stage 1A1) can be treated with cone biopsy and stage 1A2 to small lesion stage 1B1 could be treated with trachelectomy. Most stage 1A2 to stage 2A cancer will require hysterectomy, simple or radical, and some with pelvic lymphadenectomy as well. For more advanced invasive disease, the addition of chemotherapy to radiotherapy has improved outcomes for long-term survival. Despite all the advancement in the last decade, sadly, many less-developed countries still do not have the ability or capacity to embrace some or all of these preventive 548

tools and women still suffer and succumb to this largely preventable disease.

INCIDENCE Cervical cancer is the third most common cancer in women and the seventh overall, with an estimated 530 000 new cases in 2008. More than 85% of the global burden occurs in developing countries, where it accounts for 13% of all female cancers (Fig 61.8A). High-risk regions are Africa, South-Central Asia and South America, where agestandardised rates (ASRs) are above 20 per 100 000, and lowest in western Asia, Northern America and Australia/ New Zealand (ASRs less than 6 per 100 000). Cervical cancer was responsible for 275 000 deaths in 2008, about 88% of which occurred in developing countries (Fig 61.8B).4 Cervical cancer is the 12th most common cancer affecting Australian women, with 7 new cases of cervical cancer diagnosed per 100 000 women in the population in 2009. It is also the 19th most common cause of cancer-related death, with 2 deaths per 100 000 women in 2010. Cervical cancer incidence and mortality are both higher in Aboriginal and Torres Strait Islander women, with an incidence more than twice, and mortality five times, that of non-Indigenous women.5

AETIOLOGY AND PATHOGENESIS The cervix is the lowest aspect of the uterus, where it joins the inner end of the vagina. Cancer of the cervix may originate from the mucosa of the surface of the cervix (squamous cell origin) or from within the canal (columnar cell origin). The initial abnormality mostly arises as pre-invasive disease at the transformation zone, the junction between the squamous and columnar

Chapter 61  Benign and Malignant Disorders of the Cervix

Incidence ASR Female

Cervix uteri cancer 30.2+ 20.6–30.2 13.6–20.6 7.9–13.6 < 7.9 No Data

A Mortality ASR Female

Cervix uteri cancer 17.5+ 9.8–17.5 5.8–9.8 2.4–5.8 < 2.4

B

No Data

FIGURE 61.8 

Cervical cancer incidence. Estimates of A the incidence and B mortality from cervical cancer on a country by country basis in 2012. These are taken from the GLOBOCAN project, which provides contemporary estimates of the incidence of, mortality and prevalence from major types of cancer, at a national level, for 184 countries. Reproduced with permission from Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 16 March 2015.

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epithelium (Fig 61.9). Squamous cell carcinoma accounts for 75% of cervical cancers and the rest are mainly adenocarcinomas and adenosquamous carcinomas (Fig 61.10). We now know that persistent HPV is necessary but insufficient alone to cause cervical cancer.6 Approximately 70% of cervical cancers worldwide are associated with oncogenic HPV types 16 and 18 (Fig 61.11).7 Other factors are associated with the development of cervical cancer following oncogenic HPV infection:8 environmental (e.g. smoking) sexual exposure (e.g. parity, multiple partners, early onset of sex) hormonal (e.g. long-term use of oral contraceptives) immunosuppressive (e.g. HIV, transplant recipients) long-term systemic steroid users. Although these co-factors are well described, it is still not possible to predict who will develop cervical cancer.

• • • • •

HPV genotypes

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Cumulative percentage 53.5

53.5

16 18 45 31 33 52 58 35

17.2 6.7 2.9

70.7 77.4 80.3

82.9 2.6 85.2 2.3 87.4 2.2 1.4 88.8 10 20 30 40 50 60 70 80 90 100 Cervical cancer cases aributed to the most frequent HPV genotypes, %

0

FIGURE 61.11 

HPV types in cervical cancer worldwide.

Source: Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJLM. (2004), Against which human papillomavirus types shall we vaccinate and screen? the international perspective. Int. J. Cancer, 111: 278–285. Copyright © 2004 Wiley-Liss, Inc.

Columnar epithelium

Stratified squamous epithelium

A

B

C

FIGURE 61.9 

Carcinoma arising from transformation zone.

Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Other carcinoma

Squamous cell carcinoma

Adenocarcinoma Other carcinoma

1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Number of new cases per 100 000 women 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 Adenosquamous carcinoma 1 0

FIGURE 61.10 

ASR for cervical cancer.

Source: Based on Australian Institute of Health and Welfare material from Australian Cancer Database, Fig 6.3. This material is licensed under Creative Commons BY 3.0 (CC-BY 3.0) license, http://creativecommons.org/licenses/by/3.0/au/.

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Chapter 61  Benign and Malignant Disorders of the Cervix

PRE-INVASIVE DISEASE OF THE CERVIX CLASSIFICATION Cytology Australia uses a modified Bethesda system of classification (AMBS2004). It is essentially similar to the Bethesda System (TBS2001), which is used worldwide (Table 61.1).9 There are two components, consisting of squamous and glandular abnormalities. For the pre-invasive abnormalities, the low-grade (Figs 61.12 and 61.13) and high-grade squamous intraepithelial lesions (Figs 61.14 and 61.15) are further divided into their respective possible

abnormalities. Glandular abnormalities are stratified by their increasing abnormal features: atypical endocervical or glandular cells of undetermined significance, possible high-grade glandular lesion, endocervical adenocarcinoma in situ and adenocarcinoma (Fig 61.16).

Histology The terminology for HPV-associated cervical lesions has gone through a long history of disparate diagnostic terms, using terminologies like dysplasia and carcinoma in situ. Currently, Australia utilises the cervical intraepithelial neoplasia (CIN) classification. CIN 1 corresponds to low-grade abnormality and CIN 2 and CIN 3 are considered high-grade abnormalities.

TABLE 61.1  AUSTRALIAN MODIFIED BETHESDA SYSTEM. AMBS 2004

Australian NHMRC-endorsed terminology 1994

TBS 2001

Incorporates

Possible low-grade squamous intraepithelial lesion

Low-grade epithelial abnormality

Atypical squamous cells, undetermined significance (ASC-US)

Non-specific minor squamous cell changes. Changes that suggest, but fall short of, HPV/CIN 1

Low-grade squamous intraepithelial lesion

Low-grade epithelial abnormality

Low-grade squamous intraepithelial lesion

HPV effect, CIN 1

Possible high-grade squamous lesion

Inconclusive, possible high-grade squamous abnormality

Atypical squamous cells, possible high-grade lesion (ASC-H)

Changes that suggest, but fall short of, CIN 2, CIN 3 or SCC

High-grade squamous intraepithelial lesion

High-grade epithelial abnormality

High-grade squamous intraepithelial lesion

CIN 2, CIN 3

Squamous cell carcinoma

High-grade epithelial abnormality

Squamous cell carcinoma

Squamous cell carcinoma

Atypical endocervical cells of undetermined significance

Low-grade epithelial abnormality

Atypical endocervical cells, undetermined significance

Non-specific minor cell changes in endocervical cells

Atypical glandular cells of undetermined significance

Low-grade epithelial abnormality

Atypical glandular cells, undetermined significance

Non-specific minor cell changes in glandular cells

Possible high-grade glandular lesion

Inconclusive, possible high-grade glandular abnormality

Atypical endocervical cells, possibly neoplastic

Changes that suggest, but fall short of, AIS or adenocarcinoma

Endocervical adenocarcinoma in situ

High-grade epithelial abnormality

Endocervical adenocarcinoma in situ

Adenocarcinoma in situ

Adenocarcinoma

High-grade epithelial abnormality

Adenocarcinoma

Adenocarcinoma

Squamous abnormalities

Glandular abnormalities

Source: National Health and Medical Research Council. Licensed under Creative Commons Attribution 3.0 Australia License, http://creativecommons.org/licenses/by/3.0/au/

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Progression* Months

Time

Normal HPV infection CIN 1 epithelium koilocytosis Low-grade squamous intraepithelial lesion (ASCUS/LSIL)

Years

CIN 2

CIN 3

Invasive carcinoma High-grade squamous intraepithelial lesion (HSIL)

Regression

FIGURE 61.12 

Progression of cervical disease. *With increasing probability of viral DNA integration. Abbreviations: CIN = cervical intraepithelial neoplasia: ASCUS = atypical squamous cells of undetermined significance.

Source: Adapted from Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003;16:1–17; and Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287(16):2114–9.

FIGURE 61.14  FIGURE 61.13 

Low-grade abnormal Pap cytology.

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 4.3-9.

CERVICAL SCREENING The progressive development of cellular changes from HPV infection to cervical cancer generally takes 10 to 20 years (Fig 61.12). This forms the basis of cervical screening, to detect and manage screened abnormalities before they become cancer. The Papanicolaou or smear 552

High-grade Pap abnormality (conventional Pap).

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 4.2-5.

test is still the most common utilised test in cervical screening program. HPV testing for high-risk HPV types are being introduced into primary screening, usually for women over 30 years of age. The National Cervical Screening Program (NCSP) in Australia recommends the following: Pap tests for all women 18 to 70 years of age who have ever had sex and have not had a hysterectomy

•

Chapter 61  Benign and Malignant Disorders of the Cervix

•

women should start having Pap tests every 2 years from 18 to 20 years of age, or 1 to 2 years after sexual activity commences.10 Australia is planning to establish a new cervical screening program in 2017, with primary HPV screening replacing cytology (Pap smear). The Medical Services Advisory Committee (MSAC) has recommended that from May 2017 public funding in the NSCP should be for:11 5-yearly cervical screening using a primary HPV test with partial HPV genotyping and reflex liquid-based

•

cytology (LBC) triage, for HPV-vaccinated and unvaccinated women 25 to 69 years of age, with exit testing of women up to 74 years of age self-collection of an HPV sample, for an underscreened or never-screened woman, which has been facilitated by a medical or nurse practitioner (or on behalf of a medical practitioner) who also offers mainstream cervical screening invitations and reminders to be sent to women 25 to 69 years of age, and exit communications to be sent to women 70 to 74 years of age, to ensure the effectiveness of the program. These recommendations are expected to be implemented in Australia in May 2017.

• •

Screening methods Cytology Cytology can be collected with conventional glass slides or in a liquid medium (Fig 61.17). Exfoliated cells are collected from the cervix and examined under the microscope after suitable preparation by trained screening personnel, cytologist or cytopathologist. Liquid-based samples can be placed on slides and examined by an automated computerised imager that highlights areas of abnormalities, which are then confirmed by screeners. To begin with, it is important to adequately explain to the woman what steps are involved before and during the procedure. Privacy and minimal discomfort should be FIGURE 61.15 

High-grade Pap abnormality (ThinPrep Pap).

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 4.3-6.

FIGURE 61.17 

FIGURE 61.16 

Glandular Pap abnormality.

Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 4.2-3.

Comparison of the appearance of conventional Pap smear versus a machine-made thin-layer preparation. Note the uniformity in the distribution of cells throughout the machine-made slide (bottom) compared with the streaking and aggregating of cellular material seen in the conventional Pap smear (top). Source: Apgar BS, Brotzman GL, Spitzer M. Colposcopy: Principles and Practice. 2nd edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 4.3-4.

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The cervical sample placed in liquid for liquid-based cervical cytology can be used to test for high-risk HPV, with partial HPV genotyping capacity to identify HPV 16 and HPV 18. Further identification of other pathogenic genotypes (e.g. HPV 45, HPV 31, HPV 33) can similarly be performed with some cost increase. Such is the superior performance of HPV testing that it is planned to replace cervical cytology as the primary screening technique.

Cytovrush

Wooden spatulas

Plastic broom

FIGURE 61.18 

Cervical samplers.

70+

65–69

55–59

60–64

45–49

35–39

40–44

25–29

High-grade abnormalities Per cent 12 10 8 6 4 2 0

50–54

Source: Dehn RW, Asprey DP. Essential clinical procedures. 3rd edn. Philadelphia: Saunders, 2011. Copyright © 2002, 2007, 2013 Saunders, An Imprint of Elsevier. Figure 18.9.

30–34

70+

65–69

55–59

Age group (years)

60–64

45–49

35–39

40–44

25–29

30–34

< 20

20–24

Low-grade abnormalities Per cent 12 10 8 6 4 2 0

50–54

Australia useds a modified Bethesda system of classification (AMBS2004). More than 2 million cytology tests were performed in 2011 in the NCSP. For those women tested aged 20 to 69, 2.1% of cytology tests were unsatisfactory and 92.3% of cytology tests were negative. A definite or possible high-grade abnormality was reported in 1.5% of cytology tests. An abnormality was reported in 5.6% of cytology tests, most of which were in the low-grade category. While not a true result per se, unsatisfactory cytology means that due to the unsatisfactory nature of the cells sampled, the pathologist is unable to determine a clear result. This may be due to either too few or too many cells, or the presence of blood or other factors obscuring the cells, or to poor staining or preservation. Abnormalities are most common in younger women, due to HPV infections that occur frequently after sexual debut. Lowgrade abnormalities are highest in women under 20 and in those aged 20 to 24, while high-grade abnormalities are relatively low in women under 20 and peak in women aged 20 to 29 (Fig 61.19). Detection of both low-grade and high-grade abnormalities then decreases with increasing age, only increasing slightly in women aged 70 or over. Participation in the NCSP was steady at 59% for all 2-year periods from 2004–2005 to 2008–2009, before a slight decrease to 58% in 2009–2010, and to 57% in the latest reporting period 2010–2011.10 Participation tends to be lower at both ends of the spectrum of age range, in women of lower socioeconomic status and in the Indigenous population. Much effort is needed to target women in these lower-screened groups as participation rate is the most important factor in reducing cancer in screening program. There are algorithms in the NCSP for various

HPV testing

< 20

Reporting and incidence

screened abnormalities. Women with low-grade abnormalities can have a Pap smear repeated in a year. Highgrade abnormalities including possible invasive/invasive disease and glandular abnormalities are usually managed with colposcopy in the first instance.12

20–24

ensured. Many types of samplers are used but the aim is to ensure collection of cells from the ectocervix as well as the endocervical canal, utilising a single or a combination of samplers. When utilising liquid medium, the cervix sampler or a plastic spatula is preferable. One should not use the Cytobrush in pregnant women (Fig 61.18).

Age group (years)

FIGURE 61.19 

Cervical abnormalities detected by cytology by age.

Source: Screening to Prevent Cervical Cancer: Guidelines for the Management of Asymptomatic Women with Screen Detected Abnormalities, © Commonwealth of Australia 2005 National Health and Medical Research Council, http://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/wh39. pdf. Creative Commons Attribution 3.0 Australia license.

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Chapter 61  Benign and Malignant Disorders of the Cervix

Management of screened abnormalities in the current cytology-based program are outlined in Figure 61.20.

Colposcopy A colposcope (an instrument that magnifies the cells of the cervix) gives a closer view of the cervix to check the extent and nature of the screened abnormality. The cervix is inspected before and after application of 3 to 6% acetic acid (with or without the use of the green filter for display of the angioarchitecture) and finally inspection after the application of Lugol’s iodine (Schiller’s test). The detection of CIN is based on the surface changes at inspection. Punch biopsy is then taken from the most abnormal area(s). Findings at colposcopy had been classified in the past as CIN1 (low-grade abnormality) and CIN2, CIN3 (high-grade abnormality) (Figs 61.21, 61.22 and 61.23). The new International Federation for Cervical Pathology and Colposcopy (IFCPC) nomenclature 2011 simplifies the grading of colposcopic abnormality to grade 1 (minor) or grade 2 (major).13 General principles are identifying: the location of the lesion the size of the lesion the grade of the lesion ■ grade 1 (minor): fine mosaic; fine punctuation; thin acetowhite epithelium; irregular, geographic border ■ grade 2 (major): sharp border; inner border sign; ridge sign; dense acetowhite epithelium; coarse mosaic; coarse punctuation; rapid appearance of acetowhitening; cuffed crypt (gland) openings; Lugol’s staining (Schiller’s test) stained brown in normal epithelium due to presence of glycogen.

TREATMENT The aim of treatment is to eradicate the CIN lesion around the cervical os with minimal removal of surrounding normal tissue. Low-grade abnormality, CIN 1, is not usually treated as it is considered to be a transient HPV infection with a high resolution rate. However, women with CIN 1 abnormalities need yearly follow-up until their Pap smears remain normal over 2 years before returning them to the normal screening interval. High-grade abnormalities, CIN 2 and CIN 3, are usually treated by ablation or excisional techniques. There is no

• • •

Normal

FIGURE 61.21 

Colposcopy image of CIN 1.

Source: Reproduced with permission from Oncoserve Systems.

Repeat cytology at 2 years

LSIL

Cervical cytology

Repeat cytology at 1 year HSIL

Normal, HPV, CIN 1 Repeat cytology at 12 months

Colposcopy +/– target biopsy

CIN 2, CIN 3

Ablative or excisional therapy

AdenoCIS

Excisional therapy

Invasive disease Refer to gynaecological oncologist

FIGURE 61.20 

An algorithm for the management of abnormal cervical cytology. 555

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obvious superior surgical technique for treating CIN in terms of treatment failures or operative morbidity.14 The residual or recurrence rate after treatment for high-grade CIN should be not more than 5%. Suspicion of microinvasive or glandular disease always requires excisional techniques, with some favouring cold knife cone biopsy to loop excision, but the choice ultimately depends on the surgeon’s competence in the treatment modality.

Ablative techniques Laser ablation is used in some centres that have laser facility, although this is not common now due to the high cost of equipment. Cryotherapy and cold coagulation are also used, more often in less-developed countries. Radical

pin and ball cautery was popular in the 1970s but has fallen out of favour. Complications include infection, secondary haemorrhage and cervical stenosis.

Excisional techniques Loop excision of cervix (known as LEEP or LLETZ) utilises a wire loop to excise the abnormal area around the cervical os. The base of the cervix is then cauterised with a ball probe (Fig 61.24). This is the most common method of treatment for high-grade CIN. Complications are as per ablative treatment, with additional concern being raised about the risk of obstetric complications with premature rupture of membrane or premature labour.15 It would appear that this risk is related more to the amount of tissue removed at treatment than to the modality of treatment. Cold knife conisation, when utilised, is usually for women with suspicion of microinvasive or glandular disease. As there is a need to excise more length of the cervix in these two conditions, there is an increased risk of cervical incompetence in pregnancy (Fig 61.25). Women with high-grade CIN during pregnancy are usually not treated unless there are concerns with invasive disease. They may need repeat colposcopy during the pregnancy but are usually assessed again 3 months postpartum.

ADENOCARCINOMA IN SITU

FIGURE 61.22 

Colposcopy image of CIN 2.

Source: Reproduced with permission from Oncoserve Systems.

Cervical cytology reports suggesting a glandular abnormality are rare, constituting well under 1% of all reports. Squamous CIN are often present, together with this premalignant glandular abnormality. However, cervical Cervix

Electrosurgical loop

FIGURE 61.23 

Colposcopy image of CIN 3.

Source: Reproduced with permission from Oncoserve Systems.

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Speculum

FIGURE 61.24 

Loop excision of cervix.

Source: Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2007-2015. All Rights Reserved.

Chapter 61  Benign and Malignant Disorders of the Cervix

Knife angled toward endocervical canal

FIGURE 61.25 

Cold knife conisation.

Source: Baggish MS, Karram MM. Atlas of Pelvic Anatomy and Gynecologic Surgery. 3rd ed. St Louis: Mosby; 2011. Copyright © 2011, 2006, 2001.

screening is less effective at preventing cervical adenocarcinoma compared to squamous carcinoma, and the incidence of cervical adenocarcinomas has remained stable. This probably results from a number of factors, including the anatomical situation of glandular lesions, sampling deficiencies at the time of smear taking and difficulties with cytological interpretation. Colposcopy is still important but much less reliable in the assessment of glandular lesions than it is for squamous lesions. Excisional biopsy, usually with cold knife cone or loop excision, is indicated for the further assessment and treatment of a woman with a cytology report predicting adenocarcinoma in situ (Fig 61.26).12

VAGINAL INTRAEPITHELIAL NEOPLASIA This is less common and can co-exist with CIN or present in women who have had a hysterectomy with a history of CIN. Colposcopy is indicated and excision is often required for high-grade VAIN. Ablative methods can also be used, though usually for persistent low-grade abnormality. More difficult and persistent VAIN may be treated with local application of 5-fluorouracil ointment or irradiation, though rarely.

THE DIETHYLSTILBOESTROL (DES) SYNDROME Diethylstilboestrol (DES) was given to pregnant women between 1940 and 1970 to provide luteal support to those

FIGURE 61.26 

Colposcopic image of adenocarcinoma in situ (AIS). Source: Reproduced with permission from Oncoserve Systems.

with a previous poor pregnancy outcome. Although DES exposure in utero rarely leads to vaginal adenocarcinoma, vaginal adenosis occurs in 45% of these women and structural abnormalities (transverse vaginal septum, cervical collar, anterior cervical ridge, cervical hypoplasia) are present in 25%. Women exposed to DES need regular review by a clinician experienced in colposcopy of the lower genital tract.12 557

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INVASIVE CERVICAL CANCER Early changes in cervical cells rarely cause symptoms. If early cell changes develop into cervical cancer, the most common signs include bleeding or pain after intercourse, unusual vaginal discharge, vaginal bleeding after menopause, leg pain or swelling and lower back pain.

DIAGNOSIS The affected area is usually obvious, with a raised, irregular, sometimes ulcerated and reddened lesion which bleeds with contact. When the lesion is small or in the cervical canal, a histological diagnosis may be made with cone biopsy, large loop excision of the transformation zone or colposcopy with target biopsy.

Staging The International Federation of Gynecology and Obstetrics (FIGO) staging is based on clinical examination. The FIGO staging guidelines were most recently updated in 2009 (Table 61.2).16 A thorough pelvic examination is mandatory to provide information for FIGO staging, and this rarely requires anaesthesia. When there is doubt as to which stage a particular cancer should be allocated, the earlier stage is mandatory. The following examinations are permitted for the determination of FIGO staging, as indicated by the presenting characteristics of palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous pyelography, and X-ray examination of the lungs and skeleton. Blood tests should include full blood count and renal and liver functions. CT and/or MRI and/or positron emission tomography (PET) may provide information on nodal status or systemic spread, but are not mandatory.17

The second dimension, the horizontal spread, must not exceed 7 mm. Vascular space involvement, either venous or lymphatic, should not alter the staging, but should be specifically recorded because it may affect treatment decisions. In a screened population like Australia, microinvasive carcinoma accounts for about 20% of cervical cancer.

Stage IA1 The recommended management is hysterectomy, whether by abdominal, vaginal or laparoscopic approach. The risk of lymph nodes spreading is less than 1%. If fertility is desired, observation after excisional biopsy is appropriate, provided the margins are clear and there is no lymphovascular space invasion. Women with stage IA1 cancer need regular follow-up with Pap smears, at least annually for 5 years.

Stage IA2 There is an increased risk of lymph node metastasis of 6 to 8 % with stage IA2 disease. The recommended treatment is modified radical hysterectomy and pelvic lymphadenectomy. If fertility is desired, an option would be large cold knife cone biopsy or radical trachelectomy with extraperitoneal or laparoscopic pelvic lymphadenectomy (Fig 61.27).18

CLINICALLY INVASIVE CARCINOMA Stages IB1–IIA1 Treatment is usually by modified radical or radical abdominal hysterectomy and pelvic lymphadenectomy

MANAGEMENT Management involves the following: 1. clinicopathological assessment 2. counselling of patient 3. pre-therapy assessment 4. treatment. In each of the above steps, the woman and immediate family (with permission from the patient) should be involved in the management process, with adequate time provided for discussion. A multidisciplinary approach is now the norm to ensure the best physical and psychological outcome.

Microinvasive carcinoma (stage 1A) Both stage IA1 and IA2 are diagnosed after excisional biopsy, usually with a cold knife cone, and subject to microscopic examination of removed tissue, which must include the entire lesion. The depth of invasion should not be > 5 mm taken from the base of the epithelium. 558

FIGURE 61.27 

Vaginal radical trachelectomy.

Source: Einstein MH, Park KJ, Soonda Y, et al. Radical vaginal versus abdominal trachelectomy for stage IB1 cervical cancer: a comparison of surgical and pathologic outcomes. Gynecol Oncol 2009;112:73. Figure 3.29.

Chapter 61  Benign and Malignant Disorders of the Cervix

TABLE 61.2  CANCER OF THE CERVIX UTERI.a Stage

Description

I

The carcinoma is strictly confined to the cervix (extension to the uterine corpus should be disregarded).

  IA

Invasive cancer identified only microscopically. (All gross lesions even with superficial invasion are stage IB cancers.) Invasion is limited to measured stromal invasion with a maximum depth of 5 mmb and no wider than 7 mm. IA1 Measured invasion of stroma ≤ 3 mm in depth and ≤ 7 mm width. IA2 Measured invasion of stroma > 3 mm and < 5 mm in depth and ≤ 7 mm width.

  IB

Clinical lesions confined to the cervix, or preclinical lesions greater than stage IA. IB1: Clinical lesions no greater than 4 cm in size. IB2: Clinical lesions > 4 cm in size.

II

The carcinoma extends beyond the uterus, but has not extended onto the pelvic wall or to the lower third of vagina.

  IIA

Involvement of up to the upper two-thirds of the vagina. No obvious parametrial involvement. IIA1: Clinically visible lesion ≤ 4 cm. IIA2: Clinically visible lesion > 4 cm.

  IIB

Obvious parametrial involvement but not onto the pelvic sidewall.

III

The carcinoma has extended onto the pelvic sidewall. On rectal examination, there is no cancer-free space between the tumor and pelvic sidewall. The tumor involves the lower third of the vagina. All cases of hydronephrosis or non-functioning kidney should be included unless they are known to be due to other causes.

  IIIA

Involvement of the lower vagina but no extension onto the pelvic sidewall.

  IIIB

Extension onto the pelvic sidewall, or hydronephrosis non-functioning kidney.

IV

The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder and/or rectum.

  IVA

Spread to adjacent pelvic organs.

  IVB

Spread to distant organs.

a

Adapted from FIGO Committee on Gynecologic Oncology. The depth of invasion should not be more than 5 mm taken from the base of the epithelium, either surface or glandular, from which it originates. Vascular space invasion should not alter the staging. Source: Wiebe E, Denny L, Thomas G. Int J Gynecol Obstet 2012;119(S2):S100–9, Table 1. b

with or without adjuvant therapy. Primary radiation therapy can also be utilised instead. Standard radiation treatment of cervical carcinoma is external pelvic irradiation plus brachytherapy. Suggested doses of external beam radiation are 45 to 50 Gy in 180 to 200 cGy per fraction. Brachytherapy is usually intracavitary caesium utilising uterine tube and upper vagina ovoids. Both surgical and irradiation results are comparable, although toxicity profiles vary.19 Patients should be informed regarding therapeutic options, associated toxicities and expected outcomes. There is an increased utilisation of laparoscopy for radical hysterectomy and pelvic lymphadenectomy,

compared with the traditional open approach (laparotomy).20 The use of robotic surgery for laparoscopy is also being introduced. This may assist in the nerve-planesparing radical hysterectomy, which could reduce complications that affect the bladder function.21

Stages IB-IVA The use of concurrent platinum-based chemotherapy with radiotherapy should be considered standard-of-care treatment for FIGO stages IIB and higher, and also for most patients with stage IB2, to optimise local control and survival (Figs 61.28 and 61.29).22 559

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FIGURE 61.28 

Extended field radiotherapy simulation portals.

Source: Allen D, Narayan K. Managing advanced-stage cervical cancer. Best Pract Res Clin Obstet Gynaecol Aug 2005;19(4):591–609. Figure 3.

A

B

FIGURE 61.29 

Brachytherapy. A Pretreatment cervical tumour expanding the cervix and extending into the lower part of the corpus uteri. The tumour/normal tissue interface is clearly visible. B The same tumour as in A after 40 Gy external beam chemoradiotherapy at first brachytherapy insertion. Source: Allen D, Narayan K. Managing advanced-stage cervical cancer. Best Pract Res Clin Obstet Gynaecol Aug 2005;19(4):591–609. Figure 4.

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Chapter 61  Benign and Malignant Disorders of the Cervix

PROGNOSIS Approximate 5-year survival figures are as follows: stage IB: 85 to 90% stage II: 70 to 75% stage III: 30 to 40% stage IV: 10 to 20%. The major advantages of surgery are more accurate assessment of tumour (including lymphatic) spread. If the pelvic lymph nodes are positive, the pelvis and para-aortic areas can be irradiated in an attempt to eradicate residual or microscopic disease. Complications of surgery include bladder morbidity due to partial denervation, haemorrhage, infection, fistula formation and thromboembolism. The major problems with radiotherapy are posttreatment ischaemia of the pelvis, involving the vagina (causing sexual dysfunction), but also the bladder (cystitis), small bowel (obstruction, perforation) and rectum (proctitis). Early reactions (malaise, nausea, anorexia, diarrhoea) usually subside soon after completion of radiotherapy.

• • • •

POST-TREATMENT FOLLOW-UP Follow-up is more frequent in the first 5 years and annual thereafter. Recurrent disease may be pelvic, para-aortic, distant or a combination of these. The majority of recurrences occur within 2 years of diagnosis, and the prognosis is poor. Treatment decisions should be based on the performance status of the patient, the site of recurrence and/or metastases, the extent of metastatic disease, and prior treatment. Relapse in the pelvis following primary surgery may be treated by either radical chemoradiation or pelvic exenteration. Pelvic exenteration may be a feasible treatment option in selected patients after previous surgery or pelvic radiation if there is no evidence of intraperitoneal or extrapelvic spread, and in those who have a tumour-free space along the pelvic sidewall.

CERVICAL CANCER DURING PREGNANCY Decisions about management should involve the obstetrician and neonatologist as well as the woman (and preferably her partner), and her wishes must be respected. Diagnoses made before weeks 16 to 20 of pregnancy are generally treated without delay, with either surgery or chemoradiation, owing to concerns about the possible detriment to the patient’s survival if treatment is delayed. If the diagnosis is made after 20 weeks’ gestation, treatment delay appears to be an option for stages IA2 and IB1. Treatment consists of classical caesarean delivery and radical hysterectomy when a balance is reached between competing maternal and fetal health risks, usually at not later than 34 weeks’ gestation. For more advanced disease, it is not known whether treatment delay will affect survival.21

THE CERVICAL CANCER VACCINE Over 100 types of HPV have been identified, with more than 30 types associated with sexual activity and at least 14 types associated with the ultimate development of cancer, including oropharyngeal cancers, vulvar cancers, cervical cancers and anal cancers.23,24 At the time of publication of this book, two vaccines have been developed: 1. a vaccine containing viral-like proteins (VLPs) of HPV 16,18, 6 and 11, the latter two being responsible for genital warts; and 2. a vaccine against 16 and 18 alone.25,26 Initial trials have shown substantial protection against the development of high-grade dysplasia (which is a surrogate for invasive cancer) and already we are seeing a dramatic fall in the incidence of genital warts in the community. Under the National Immunisation Program, the vaccine against types 16, 18, 6 and 11 is administered to 12- to 13-year-old girls and boys in a school-based program. However, because not all HPV types which cause cancer of the cervix are covered by this vaccine, it is mandatory that the cervical screening program continue in the ‘post-vaccine’ era. REFERENCES 1) Roberts CP. Surgical methods in the treatment of congenital anomalies of the uterine cervix. Curr Opin Obstet Gynecol 2011;23(4):251–7. 2) Esim Buyukbayrak E. Cervical polyps: evaluation of routine removal and need for accompanying D&C. Arch Gynecol Obstet 2011;283(3):581–4. 3) Khan AM. Prolapse of a large necrotic cervical fibroid. J Obstet Gynaecol 2011;31(7):671. 4) Globocan. 2008. Online. Available: . 5) Australian and Institute of Health and Welfare, American Association for Cancer Research. Cancer in Australia An overview 2012. Canberra. 6) Bosch FX, Lorincz A, Muñoz N, et al. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55(4):244–65. 7) Muñoz N, Bosch FX, Castellsagué X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004;111(2):278–85. 8) Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin Virol 2005;32(Suppl. 1):S16–24. 9) Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287(16):2114–19. 10) Australian and Institute of Health and Welfare. Cervical Screening in Australia 2011–2012. Cancer series no. 82. Cat. no. CAN 79. Canberra: AIHW. Online. Available: . 11) Hammond I. NCSP renewal: 2016. RANZCOG O&G Magazine 2014;16(3):26. 561

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12) NHMRC. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: National Health and Medical Research Council; 9 June 2005. Online. Available: . 13) Bornstein J, Bentley J, Bösze P, et al. 2011 colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy. Obstet Gynecol 2012;120(1):166–72. 14) Martin-Hirsch PP, Paraskevaidis E, Bryant A, et al. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2010;(6):CD001318. 15) Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006;367(9509):489–98. 16) Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obstet 2009;105(2):103–4. 17) Wiebe E, Denny L, Thomas G. Cancer of the cervix uteri. Int J Gynecol Obstet 2012;119(Suppl. 2):S100–9. 18) Shepherd JH, Spencer C, Herod J, et al. Radical vaginal trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer–cumulative pregnancy rate in a series of 123 women. BJOG 2006;113(6):719–24.

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19) Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997;350(9077):535–40. 20) Park JY, Kim DY, Kim JH, et al. Laparoscopic compared with open radical hysterectomy in obese women with early-stage cervical cancer. Obstet Gynecol 2012;119(6):1201–9. 21) Fujii S, Takakura K, Matsumura N, et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol 2007;107(1):4–13. 22) Chemoradiotherapy for Cervical Cancer MetaAnalysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 2008;26(35):5802–12. 23) Hildesheim A. Human papillomavirus variants: implications for natural history studies and vaccine development efforts. J Natl Cancer Inst 1997;89(11):752–3. 24) de Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses. Virology 2004;324(1):17–27. 25) Frazer IH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 2004;4(1):46–54. 26) Stanley M. Immune responses to human papillomavirus. Vaccine 2006;24(Suppl. 1):S16–22.

Chapter 62  BENIGN AND MALIGNANT DISORDERS OF THE UTERUS, AND THE PELVIC MASS Michael Quinn and Adam Pendlebury

KEY POINTS Fibromyomas (uterine leiomyomas) are common benign tumours of the uterus affecting approximately 20% of women. The most common clinical presentations are menorrhagia or the incidental finding of a pelvic mass. Initial treatment is largely symptomatic but surgical or radiological removal of the fibromyoma may become necessary. Adenomyosis is endometrial tissue in the myometrium of the uterus. Unlike endometriosis, it is more common in women with children. Clinical features include menorrhagia, dysmenorrhoea and dyspareunia. Hysterectomy is indicated if symptomatic therapy is not successful. Endometrial hyperplasia is largely the consequence of ‘unopposed oestrogen’. It is therefore more common in obese women with persistent anovulation—typical of the polycystic ovary syndrome. In women who wish to retain their childbearing ability or are otherwise not suitable for surgery, sustained medical therapy with progestogens is likely to be successful, but repeated biopsy is necessary to confirm resolution. Endometrial cancer is increasing in incidence as a consequence of the obesity epidemic. Hysterectomy with bilateral salpingo-oophorectomy is the mainstay of therapy, with supplementary radiotherapy indicated in those with adverse prognostic features but local disease. The pelvic mass is best viewed in terms of the possible organ of origin. Detailed clinical assessment is imperative prior to imaging.

BENIGN DISORDERS OF THE UTERINE BODY FIBROMYOMAS Epidemiology Fibromyomas (also known as leiomyomas or fibroids) are very common benign tumours of the myometrium occurring in approximately 20% of women. They are almost always benign. They develop and grow during the reproductive years, becoming more common as the menopause approaches. Postmenopausally, atrophy occurs following withdrawal of oestrogens and progesto-

gens but the tumours may remain quite large. Relative to the incidence in Caucasians, fibromyomas are more common in Africans and less common in Asians. Long-term oral contraceptive pill users appear to be less likely to develop uterine fibromyomas, although the evidence is inconclusive.

Pathology Fibroids may be intramural (within the uterine wall) or they may project from the myometrium into the uterine cavity (submucosal), the peritoneal cavity (subserosal) or the broad ligament (intraligamentous). They may also occur in the uterine cervix, although this is rare. The attachment to the myometrium of subserosal,

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submucosal or intraligamentous fibroids may be broad (sessile) or narrow (pedunculated). Fibroids are white and the cut surface has a ‘whorled’ appearance with smooth muscle cells interlacing with connective tissue (Fig 62.1).

Subfertility and recurrent miscarriage

Clinical features

Differentiating fibromyomas from leiomyosarcoma

Menorrhagia Heavy periods are more common as a result of the increased endometrial surface area and also abnormal vessels supplying the endometrium overlying the fibroid, as they have to course around the tumour. Menorrhagia will not be a feature of subserosal fibroids.

Pelvic mass This is probably the most common presentation and a fibromyomatous uterus may resemble a pregnancy— occasionally extending well above the umbilicus.

Incarceration with urinary retention Occasionally the fibroid will grow in the hollow of the sacrum and, as it enlarges, press the urethra forwards against the back of the symphysis pubis. Eventually, this will produce acute urinary retention.

Extrusion of a submucous fibromyoma through the cervix A pedunculated submucous fibroid may be ‘expelled’ by the uterus down through the cervix, even so far as causing a uterine inversion. Clinical features include postcoital bleeding and colicky uterine pain. Infection is more likely to occur if the tumour is submucous and/or the woman is puerperal.

Fibroids that are submucosal in location may distort the uterine cavity and lead to problems with either conception or recurrent miscarriage. This is not a feature of subserosal or intramural fibroids.

There are no reliable clinical or imaging predictors to differentiate benign fibromyomas from malignant leiomyosarcomas. A uterine sarcoma may occasionally be diagnosed on endometrial biopsy in the work-up of abnormal bleeding. However, a normal endometrial biopsy does not exclude uterine sarcoma. Approximately 1 in 500 cases undergoing surgery with uterine fibroids have a histological diagnosis of leiomyosarcoma.

Obstetric sequelae The following are potential complications that may occur as a consequence of a fibromyoma in a pregnant woman. Acute pain from red degeneration commonly occurs in pregnancy and is due to acute infarction of the fibroid as it seems to outgrow its blood supply. It is important in the differential diagnosis of acute abdominal pain in pregnancy. No therapy is needed and the pain resolves within days. Red degeneration may also follow GnRH analogue administration and be associated with a high fever and general systemic toxicity if the fibroid was large and leaking considerable products of fibroid necrosis into the woman’s circulation. Malpresentation becomes more likely if the cavity is distorted in shape, resulting in a breech presentation or a transverse or oblique lie. Obstructed labour may develop if there is a cervical fibroid or a pedunculated subserous fibroid low in the hollow of the sacrum and pouch of Douglas. Infection may occur in conjunction with puerperal sepsis but is rare otherwise.

•

• • •

Diagnosis Examination The fibroid is usually firm, smooth and non-tender when assessed on abdominal or vaginal examination. Multiple tumours can give the impression of an irregular mass. At the time of red degeneration, the fibroid will be acutely tender. An intramural fibroid may give the impression of uniform uterine enlargement but a subserous fibroid can often be distinguished from the uterus. FIGURE 62.1 

Broad-based leiomyoma arising from the lateral uterine wall.

Source: Bradley LD, Falcone T. Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. St Louis: Mosby. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 10.20.

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Investigations The diagnosis may already have been confirmed by direct inspection at the time of a laparoscopy or laparotomy (e.g. caesarean section). Ultrasound should be diagnostic where there is any doubt. In the postmenopausal woman, calcium may be seen consequent on calcific degeneration of the fibroid.

Chapter 62  Benign and Malignant Disorders of the Uterus, and the Pelvic Mass

Treatment Initially, anaemia may require correction by iron therapy or rarely by transfusion. The options are to observe only with reassurance, pharmacological therapy, ablation, myomectomy or hysterectomy.

Observation only Fibroids of less than 8 cm diameter do not require removal if they are asymptomatic. An annual assessment of growth would be made up until the menopause in the extremely unlikely event that the fibroid underwent malignant change. If a pregnancy is planned, clinicians are divided on the role of prophylactic myomectomy of large fibroids. On one side, myomectomy will reduce the likelihood of the obstetric complications mentioned previously. On the other side, most women with fibroids in pregnancy don’t have complications and the uterine scar may rupture during labour. A caesarean section would generally be recommended if a full-thickness uterine scar was present.

Medical treatment Anti-fibrinolytic (e.g. tranexamic acid) non-steroidal antiinflammatory drugs (NSAIDs) (e.g. mefenamic acid, naproxen or ibuprofen) or the oral contraceptive pill can reduce menstrual loss. The levonorgestrel-releasing intrauterine system (LNG-IUS) (e.g. Mirena) has also been effective in reducing menstrual loss in women with fibromyomas. GnRH analogues will reduce fibroid size with a concomitant reduction in menstrual blood loss. However, on discontinuation of therapy there is usually a rapid return to pre-therapy fibroid size and symptoms. GnRH analogues may be used selectively for preoperative downsizing of fibroids when considering myomectomy or hysterectomy to reduce operative complications.

Procedural therapy

Radiological myomectomy Embolisation of the vessel supplying the fibroid will reduce symptoms in about 90% of carefully selected cases. Infection of the necrotic fibroid is a recognised complication. Some women are suitable for magnetic resonance-guided focused ultrasound (MRgFUS). Surgical myomectomy Myomectomy can be performed abdominally (open or laparoscopic) or vaginally (hysteroscopic). Bleeding of significant degree is common and a blood transfusion required in up to 5% of cases. Hysterectomy is the preferred procedure, and surgical myomectomy is reserved for those who want their childbearing capacity retained. Hysterectomy Hysterectomy is a much more straightforward operation for large, symptomatic fibroids than surgical myomectomy. Very large or cervical fibroids may impinge on adjacent structures, making hysterectomy more difficult.

ADENOMYOSIS Epidemiology Adenomyosis is a condition where endometrial glands extend into the myometrium. It is found in about onethird of women. Like fibroids, adenomyosis is more common in women over 40 years of age than in younger women, and atrophies postmenopausally. Unlike endometriosis and fibroids, adenomyosis is more common in the multiparous rather than in women who have not had children.

Pathology Sections of the myometrium reveal endometrial glands within the myometrial substance. These may form discrete lumps of endometrial tissue (adenomyomas).

Clinical features The most common symptom of adenomyosis is heavy and painful periods. Dysmenorrhoea arises from menstruation within the myometrium. Menorrhagia may occur as a result of the same inflammatory process within the myometrium having an impact on the adjacent endometrial shedding. Up to one-third of women will be asymptomatic and the diagnosis only made on histopathological review when a hysterectomy is performed for other reasons.

Diagnosis Examination may reveal a tender, bulky uterus on bimanual examination, but there may be no specific findings. Imaging may be diagnostic if there is substantive adenomyosis.

Treatment As for fibroids, adenomyosis can be managed observationally, pharmacologically or procedurally. The combined oral contraceptive pill or LNG-IUS may be beneficial. Surgical removal is difficult with uterine conservation as the planes are less clear between the adenomyoma and the uterus than is the case for a fibroid. As for fibroids, hysterectomy is preferred if symptoms are not responsive to pharmacological therapy and childbearing is complete.

ENDOMETRIAL POLYPS Endometrial polyps are relatively common causes of menorrhagia. They are mostly benign but may occur in endometrial hyperplasia or endometrial cancer. Clinical presentation is usually with menorrhagia or intermenstrual bleeding. Diagnosis is made when an ultrasound or outpatient hysteroscopy reveals the endometrial polyp. Treatment involves removal using polyp forceps and twisting until separation occurs. Usually there is minimal bleeding. Larger polyps may be resected hysteroscopically with an electrosurgical loop. 565

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PYOMETRA OR HAEMATOMETRA These conditions occur as a result of obstruction to the cervical canal. In pyometra, the obstruction is followed by infection. Aetiology includes a complication of surgery (e.g. Manchester repair), cervical or endometrial cancer, congenital atresia of the cervix or a vaginal septum (which may be unilateral, causing obstruction on one side while the other side is menstruating normally. Treatment is by relieving the obstruction, prescribing antibiotics and treating any underlying cause. It is important to exclude malignancy in the postmenopausal patient with pyometra, and hysterectomy should be performed in this situation if the condition is not resolving.

UTERINE PERFORATION This means an instrumental breach of the uterine wall. It most commonly occurs at dilatation and curettage for infected retained products of conception, when the uterine wall is particularly soft. It can also occur during abortion or insertion of an intrauterine contraceptive device. Immediate complications include haemorrhage from the uterine wound but this is mostly not severe unless perforation occurs laterally. More concerning is damage to the bowel if the procedure has continued for a time before the perforation is recognised. In this event, a laparoscopic assessment is prudent to diagnose any obvious visceral damage or excessive bleeding. If there is any risk of bowel injury, the patient must be observed intensively postoperatively. If the bowel has definitely been grasped, a laparotomy is needed and the whole bowel should be inspected for injury and repaired as needed. Failure to do so may lead to a potentially fatal faeculent peritonitis in the days after surgery. Late complications include uterine rupture from the site of perforation during a subsequent labour.

INTRAUTERINE SYNECHIAE (ASHERMAN’S SYNDROME) (See Chapter 48.)

ENDOMETRIAL HYPERPLASIA Pathology Endometrial hyperplasia may occur with or without cytological atypia, which in turn reflects the likelihood of associated or future endometrial carcinoma. The glandular structures are ‘simple’ or ‘complex’ (branching) but this has less impact on the likelihood of cancer (Fig 62.2).

Predisposing factors Endometrial hyperplasia is most often the product of unopposed oestrogen; that is, oestrogen in the absence of sufficient progestogen to inhibit ‘oestrogen-induced’ 566

endometrial proliferation. Common causes are listed in Box 62.1.

Clinical features The most common presentation of endometrial hyperplasia is with menorrhagia or intermenstrual bleeding. Ultrasound or hysteroscopy will show increased endometrial thickness and the diagnosis is confirmed on endometrial biopsy.

Management A dilatation and curettage should be performed to exclude concurrent endometrial cancer. Treatment is usually with progestogen therapy, either oral medroxyprogesterone acetate or the LNG-IUS. Following an initial response to hormone therapy, ongoing surveillance is required, particularly as the source of the unopposed oestrogen (usually obesity) persists. If childbearing is complete and atypical features are present, a hysterectomy is preferred to minimise risks of current or future endometrial cancer.

MALIGNANT DISORDERS OF THE UTERINE BODY ENDOMETRIAL CANCER Epidemiology Endometrial carcinoma is the gynaecological cancer that is increasing in incidence most rapidly—a change that is almost certainly related to the obesity epidemic. Childbearing, the combined oral contraceptive pill and hormone replacement therapy that includes progestogen will both reduce the likelihood of future endometrial cancer.

Pathology Endometrioid, papillary serous and clear cell are the most common cell types in endometrial adenocarcinoma. The last two are associated with a worse prognosis. Endometrioid cancers are graded 1 to 3 but papillary serous and clear cell carcinomas are high grade by definition. The cancer is staged as per Box 62.2.

Type 1 and type 2 endometrial carcinoma Type 1 endometrial cancers are usually well differentiated and of endometrioid type. They are associated with obesity, delayed menopause, diabetes, hypertension and unopposed oestrogen exposure, as in oestrogen-secreting tumours and polycystic ovarian syndrome. Tamoxifen doubles the risk. It has long been recognised that prescribing oestrogens without a progestogen in women with an intact uterus for hormone replacement therapy in the menopause is associated with the substantial increase in these cancers. These cancers are almost invariably ER/PR positive. In contrast, type 2 endometrial cancers are usually a high-grade (poorly differentiated), clear-cell or serous

Chapter 62  Benign and Malignant Disorders of the Uterus, and the Pelvic Mass

A

B

C

D

FIGURE 62.2 

Spectrum of endometrial hyperplasia. A Simple hyperplasia consisting of crowded proliferative glands with simple tubular profiles. B Complex non-atypical hyperplasia with crowded, branched proliferative glands. C Higher-power view of complex non-atypical hyperplasia. Note that the polarity of the nuclei is maintained, as is their elongate, uniform appearance. D Complex atypical hyperplasia. Contrast the architectural and cytologic features with the uninvolved glands on the right. In atypical areas, note the nuclear crowding, nuclear overlap, enlarged rounded nuclei, prominent nucleoli and increased eosinophilic cytoplasm. Source: Weidner N, Cote RJ, Suster S, Weiss LM. Modern Surgical Pathology. 2nd edn. Philadelphia: Saunders/Elsevier, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 37.9.

type and the prognosis is considerably worse. These cancers are usually steroid-receptor negative. The mutational landscape of endometrial cancer is complex, with mutations in the same pathway and different permutations of co-existing pathways. Microsatellite instability is present in 20 to 45% of type 1 cancers but in only up to 15% of type 2 cancers, with PTEN mutation also found in a vast majority of type 1 cancers but rarely in type 2, whereas alterations in the PIK3CA pathway is seen in about half the cases of type 1 and a third of the cases of type 2 cancers.

Screening for endometrial cancer No test has yet been developed to screen for women with endometrial malignancy. Nonetheless, patients often present early with localised disease due to symptoms occurring early in the course of the disease.

Clinical presentation The traditional presentation of endometrial cancer is with postmenopausal bleeding. Diagnosis is made on hysteroscopy with endometrial biopsy. Increasingly, the 567

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BOX 62.1  Causes of unopposed oestrogen leading to endometrial hyperplasia and endometrial cancer. Obesity High oestrogen chronic anovulation (e.g. polycystic ovarian syndrome) Granulosa cell tumour Oestrogen-only hormone replacement therapy or Tamoxifen

BOX 62.2  Stages of endometrial cancer. Stage IA: Endometrium only or less than halfway through the myometrium Stage IB: Halfway or more into the myometrium Stage II: Cervix but has not spread outside the uterus Stage III: Cancer has spread beyond the uterus and cervix, but has not spread beyond the pelvis Stage IIIA: Serosa of the uterus and/or to the fallopian tubes, ovaries and ligaments of the uterus Stage IIIB: Vagina and/or parametrium Stage IIIC: Lymph nodes in the pelvis and/or para-aorta Stage IVA: Bladder and/or bowel wall Stage IVB: Outside pelvis (e.g. abdominal lymph nodes other than para-aortic, peritoneal disease, liver metastases)

diagnosis is suspected on screening ultrasound of women at increased risk of endometrial cancer. An endometrial thickness ≥ 5 mm should prompt endometrial biopsy in at-risk postmenopausal women. In a premenopausal woman with abnormal menstrual bleeding that is resistant to therapy, or with risk factors for endometrial cancer, an endometrial biopsy should be performed because premenopausal women may also develop endometrial cancer.

Management Assessment requires staging and assessment of suitability for surgery. Treatment centres on hysterectomy and bilateral salpingo-oophorectomy (Fig 62.3). Pelvic and paraaortic node sampling/clearance is sometimes indicated, based on the preoperative and intraoperative assessment of the likelihood of extra-uterine disease. Lymph node status can be used to guide further treatment. Radiotherapy is the most common adjuvant therapy used in endometrial cancer. Histopathological and clinical factors are used to determine the need for adjuvant 568

FIGURE 62.3 

Total abdominal hysterectomy (TAH) and bilateral salpingooophorectomy (BSO) showing large polypoid adenocarcinoma of the endometrium with deep myometrial invasion. Source: DiSaia PJ, Creasman WT. Clinical Gynecologic Oncology. 8th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An imprint of Elsevier. Figure 5.12.

radiation, which reduces recurrence rates in selected patients. Brachytherapy is more commonly used than external radiotherapy. The role of chemotherapy remains uncertain and clinical trials are being conducted to address this issue. Where patients are unfit for surgery, consideration may be given to hormonal therapy or primary radiotherapy. The long-term efficacy of these treatments is less well established.

UTERINE SARCOMA Uterine sarcoma is very rare. The most common form is a leiomyosarcoma, which is highly malignant. Other types are carcinosarcoma, endometrial stromal sarcoma and the mixed Müllerian tumour. A rare form that may occur in the vagina in young patients is sarcoma botryoides, named after its grape-like structures. Presentation is usually with abnormal bleeding and a pelvic mass. Treatment is hysterectomy for localised disease, sometimes supplemented with radiotherapy or chemotherapy, although evidence for these approaches is limited.

THE PELVIC MASS DIFFERENTIAL DIAGNOSIS In considering the origin of the pelvic mass, an appreciation of the likely organs from which such a mass could emanate makes categorisation simple and straightforward, as shown in Table 62.1.

Chapter 62  Benign and Malignant Disorders of the Uterus, and the Pelvic Mass

TABLE 62.1  ORIGINS OF THE PELVIC MASS. Bowel

Bladder

Uterus

Ovary

Fallopian tube

Other

Diverticular abscess

Large bladder diverticulum

Pregnancy

Ovarian cyst (simple)

Hydrosalpinx

Tumours arising from soft tissues including pelvic floor muscles and nerves

Malignant bowel tumour

Urinary retention

Uterine fibroids

Ovarian tumour (benign or malignant)

Adenomyosis

Tubo-ovarian abscess

Crohn’s disease

Uterine sarcoma Haematometra Hydrometra

Once the origin of a pelvic mass has been considered, the next step is to have a transvaginal ultrasound performed with the basic aim of excluding malignancy. When a pelvic mass is suspected following history and physical examination, the management needs to be based on the age of the patient, her menopausal status, the urgency of the presenting symptoms and the location of the mass, together with other findings on clinical examination. For instance, if a nodule is present around the umbilicus (a Sister Joseph’s nodule, named after a theatre nurse who diagnosed her own metastatic ovarian cancer), there is a suspicious supraclavicular node (Troisier’s sign), or there is nodularity in the pouch of Douglas or ascites present, then malignancy is much more likely.

Features of malignancy on ultrasound The following features of malignancy may be visible with ultrasound: bilaterality solid areas presence of ascites presence of surface papillae or excrescences obvious extra ovarian spread (e.g. to omentum) reduced vascular resistance on Doppler studies. Ultrasound findings will readily dictate the next step. This may be to do nothing, order a CA 125, order a CEA level (for mucinous tumours) or order a repeat ultrasound if considered a ‘simple’ cyst, which is less than 10 cm in premenopausal women and 5 cm in postmenopausal women. Recent studies have given excellent insight into the prevalence of simple cysts in both pre- and postmenopausal women. For instance in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial in the United States, simple cysts were seen in 14% of women

• • • • • •

the first time their ovaries were visualised. New cysts occurred in 8% of women within 12 months and of those women with a simple cyst, in half the cyst persisted and in a third the cyst resolved spontaneously. Interestingly, 15% of those women with the cyst at the first screen had two cysts present and 7% had three cysts present. In only 1% of cases did a cyst grow in the year following this screening ultrasound where none was present previously. Importantly, women with one or more simple cysts were not at a significantly increased risk of subsequently developing an ovarian malignancy compared to those women without a cyst.1 Likewise, in the ovarian cancer screening program from Kentucky more than 1000 women were identified as having complex cystic ovarian tumours with septations, with over 70% of women being postmenopausal. Almost 40% of these septated cystic tumours resolved spontaneously but 60% persisted over the year of follow-up; in only one case was a cancer subsequently found and, indeed, this was in the opposite ovary.2 The most important issue is around solid nodules; when there are such nodules present within cysts then the risk of malignancy is considerably higher, particularly if there is abnormal blood flow within these solid areas. The combination of a complex cyst and raised CA 125 in a postmenopausal woman means at least a 90% chance of malignancy being present (Fig 62.4). Where there is a clinical suspicion of malignancy based on a fixed nodular mass in a perimenopausal or postmenopausal patient, an abdominopelvic CT scan is useful to assess for extrauterine disease or a possible primary tumour causing ovarian metastases: so-called Krukenberg tumours. Figure 62.5 is a useful algorithm in assessing the patient with a pelvic mass. For the premenopausal patient, adding a test for HE4 to the CA 125 will add a major degree of sensitivity and specificity. 569

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A

B

FIGURE 62.4 

Ovarian cancer. Female, age 57 years, with a pelvic mass. Axial contrast-enhanced images at the level of the kidneys (A) and pelvis (B) show an obstructed right kidney (white arrow) and bilateral pelvic masses with cystic and solid components (black arrows). Upon resection, this mass was found to consist of bilateral ovarian cystadenocarcinomas.

Source: Gunderson LL, Tepper JE, Bogart JA. Clinical Radiation Oncology. 3rd edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 9.10. Pelvic mass

Ultrasound (U/S)

Simple cyst < 6 cm

Premenopausal

Suspicious for malignancy

Non-ovarian lesion

Consider CA 125

Consider CA 125

Appropriate evaluation (CT or MRI of pelvis, laparoscopy)

Gynaecologic referral Consideration of laparoscopy

Gynaecologic oncology referral Laparotomy

Postmenopausal

Repeat examination and U/S in 1–3 months

Resolution of cyst

Cyst > 6–8 cm or size < 6 cm with any equivocal U/S findings

Persistent cyst

? CA 125

Oral contraceptive pill

Repeat U/S

FIGURE 62.5 

Approach to the patient with a pelvic mass.

Source: (Modified from Carlson KJ et al: Primary care of women, ed 2, St Louis, 2002, Mosby.).

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Chapter 62  Benign and Malignant Disorders of the Uterus, and the Pelvic Mass

THE PELVIC MASS IN YOUNG WOMEN Germ cell tumours of the ovary occur at a median age of 19 years and, because of this, the young woman who presents with pelvic pain and is found to have a large abdominopelvic mass should be considered as having a malignant germ cell tumour until this is safely excluded. Tumour markers, including alpha feta protein, HCG and LDH, should be undertaken and the ultrasound will inevitably show a solid and cystic tumour; this should be followed by an MRI or CT scan if available to delineate spread of disease. REFERENCES 1) Greenlee RT, Kessel B, Williams CR, et al. Prevalence, incidence, and natural history of simple ovarian cysts among women > 55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010;202(4):373.e1–9. 2) Saunders BA, Podzielinski I, Ware RA, et al. Risk of malignancy in sonographically confirmed septated cystic ovarian tumors. Gynecol Oncol 2010;118(3):278–82.

FURTHER READING Chandavarkar U, Kuperman JM, Muderspach LI, et al. Endometrial echo complex thickness in postmenopausal endometrial cancer. Gynecol Oncol 2013;131(1):109–12. Kriplani A, Awasthi D, Kulshrestha V, et al. Efficacy of the levonorgestrel-releasing intrauterine system in uterine leiomyoma. Int J Gynaecol Obstet 2012;116(1):35–8. Schindler EA. Non-contraceptive benefits of oral hormonal contraceptives. Int J Endocrinol Metab 2013;11(1):41–7. Zhang J, Feng L, Zhang B, et al. Ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroid treatment—a clinical study. Int J Hyperthermia 2011;27(5):510–16. Zhou XD, Ren XL, Zhang J, et al. Therapeutic response assessment of high intensity focused ultrasound therapy for uterine fibroid: utility of contrastenhanced ultrasonography. Eur J Radiol 2007;62(2):289–94.

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Chapter 63  BENIGN AND MALIGNANT DISORDERS OF THE OVARY AND THE FALLOPIAN TUBE Vivek Arora

KEY POINTS Ovarian tumours are classified according to the cell of origin: epithelial, stromal, sex-cord stromal or germ cell tumours. Epithelial ovarian tumours can be further divided into benign, borderline and malignant, based on histology. The possibility of ovarian cancer should always be considered in differential diagnosis of a complex ovarian mass due to paucity of clinical signs and symptoms. Germ cell tumours are seen in adolescent girls and young adults while epithelial ovarian cancers are the predominant form of ovarian malignancy in the postmenopausal age group. There is no effective screening test for ovarian cancer.

INTRODUCTION Ovarian pathology poses a unique diagnostic challenge to the gynaecologist due to the relative inaccessibility of the primary organ and myriad presentations. An understanding of the embryological development of the ovary, its physiology and its anatomical relationships is essential in order to understand the pathogenesis and clinical presentation of ovarian tumours. The ovarian cells arise from three possible origins: epithelial, germ cell and stromal. Tumours arising from the epithelial and stromal cell lines constitute the majority (70 to 80% and 10 to 15% respectively), with germ cell tumours and others constituting the remainder.

DIAGNOSTIC WORK-UP PRESENTATION Ovarian tumours, unless they have undergone an acute event like torsion, rupture or haemorrhage, are notoriously asymptomatic. Pain, peritonism and fever are symptoms of an acute event involving an ovarian tumour.

Due to the close proximity of gastrointestinal and genitourinary structures, symptoms of ovarian pathology are often misinterpreted as those arising from these structures leading to delayed diagnosis. Symptoms may include urinary frequency or urgency, abdominal distension, altered bowel habits and a feeling of upper abdominal fullness. Some ovarian tumours, both benign and malignant, may be hormonally active and present with dysfunctional uterine bleeding (DUB) or postmenopausal bleeding (PMB). Hormone-producing tumours in a young girl may present with isosexual precocity.

HISTORY Assessment of a woman presenting with an ovarian cyst/ tumour includes a detailed history including symptoms, age, parity, desire for future fertility and previous history of ovarian pathology. The age of the patient gives an indication of the likelihood of malignancy. Borderline ovarian tumours tend to present at a younger age than malignant ovarian tumours (35 to 55 years). Epithelial ovarian cancers are more common in postmenopausal women while germ cell

Chapter 63  Benign and Malignant Disorders of the Ovary and the Fallopian Tube

tumours are the predominant form of malignancy in adolescent girls and young adults. Parous women who have breastfed have a lower risk of developing ovarian cancer. A family history of breast and ovarian cancer as well as a personal history of breast cancer increase the risk of ovarian cancer in the presence of a suspicious ovarian mass even in the absence of known familial hereditary cancer syndromes.

Chapter 62) (Fig 63.2). Large ovarian masses are more difficult to evaluate by ultrasonography alone and the use of computed tomography scan (CT scan) or magnetic resonance imaging (MRI) may contribute additional information, especially in evaluation of the peritoneal cavity and the regional lymph nodes.

EXAMINATION

CA 125 is the most important tumour marker used in the evaluation of adnexal masses. It is a glycoprotein derived from both coelomic and Müllerian epithelium. It is commonly raised in most epithelial ovarian cancers (except mucinous ovarian cancer), with high levels indicating an advanced stage at presentation. CA 125 is also used for monitoring response to treatment in women with advanced ovarian cancer. CA 125 levels may be raised in some physiological and benign conditions such as pregnancy, fibroids, menstruation and peritoneal irritation from other benign pathology. Mucinous ovarian cancers are usually associated with raised levels of carcinoembryonic antigen (CEA).

General examination should focus on the general state of nutrition. Supraclavicular lymphadenopathy may indicate visceral malignancy. Pedal oedema would indicate poor nutrition, low serum albumin, deep vein thrombosis, a mass effect in the pelvis causing venous engorgement or a combination thereof. Abdominal examination would reveal ascites or a palpable mass if any, the size, character and mobility of which should be noted (Fig 63.1). In cases with acute presentation, rule out peritonism associated with intraabdominal bleeding or infection. Pelvic examination would reveal signs of pelvic peritonism in the form of tenderness and cervical excitation in cases of benign pathology, like torsion. If an ovarian mass is felt, its character and mobility should be noted. Nodularity in the pouch of Douglas may indicate towards endometriosis or malignancy.

IMAGING FOR OVARIAN TUMOURS

TUMOUR MARKERS

FUNCTIONAL CYSTS OF THE OVARY Before considering serious ovarian pathology, it is important to mention the functional enlargements of the ovary. These are usually found in premenopausal women and

Ultrasonography is the single most effective investigation for the evaluation of ovarian masses and has been the mainstay of diagnostic evaluation (see Pelvic Mass in

FIGURE 63.1 

Abdominal distension, a common presentation of ovarian cancer. Source: Saleha MA, Dabbousb HM, El Missiria AM. Percutaneous intervention averted the need for liver transplantation. Egyptian Heart Journal 2012 Dec;64:255–8. Figure 3.

FIGURE 63.2 

A complex ovarian mass with solid areas in a cyst as seen on ultrasonography. 573

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may be symptomatic, often leading to a clinical diagnosis of ‘cyst accident’—an unhelpful term to be strictly avoided in clinical practice.

FOLLICULAR CYST A follicular cyst results from an overdistended, unruptured Graafian follicle. It is usually under 5 cm in diameter and rarely grows to more than 8 cm. Ultrasonography shows a unilocular cyst with no internal septations or echogenicity. Follicular cysts are usually asymptomatic; however, a haemorrhage inside the cyst or torsion usually presents as acute pelvic pain. A follow-up pelvic ultrasound examination of asymptomatic follicular cysts in 3 months, in immediate postmenstrual phase, would reveal a resolution in as many as 80% of the cases. Ovarian torsion is a surgical emergency akin to testicular torsion and the possibility should always be considered in a premenopausal woman presenting with acute onset pelvic pain and signs of lower abdominal peritonism. Torsion of a normal ovary is rare but possible. It more commonly occurs in the setting of a dermoid cyst, a follicular cyst or a paraovarian cyst. An ultrasound of the pelvis may show an ovarian cyst with or without restricted blood flow on colour Doppler. Differential diagnosis includes a cyst rupture, cyst haemorrhage, ectopic pregnancy, pelvic inflammatory disease (PID) and appendicitis. A diagnostic laparoscopy may be needed to confirm the diagnosis. The effects of interrupted blood flow to the ovary may be reversible if diagnosis is made early. A delay in diagnosis in a case of ovarian torsion usually results in ovarian necrosis, requiring extirpation of the affected gonad. The serum levels of CA 125 may be elevated.

CORPUS LUTEUM CYST Another common incidental diagnosis in women of the reproductive age group is usually picked up on ultrasonography carried out for an unrelated indication. The appearance on sonography may suggest a complex cyst with a solid area. A small corpus luteum cyst usually regresses with conservative management. A corpus luteum cyst can occasionally rupture and present with a haemoperitoneum. A diagnostic laparoscopy is often needed to confirm the diagnosis and to remove the cyst wall, which is the usual source of bleeding in these cases.

THECA LUTEIN CYSTS Theca lutein cysts are a result of hyperstimulation of the atretic follicles in the ovary as a result of excessive stimulation from high levels of human chorionic gonadotrophin (hCG) hormone, as occurs in cases of hydatidiform mole and ovarian hyperstimulation syndrome following administration of ovulation induction medicines. These cysts usually regress with conservative management following the treatment of molar pregnancy or cessation of ovulation-inducing drugs. 574

EPITHELIAL OVARIAN TUMOURS PATHOLOGY Epithelial ovarian tumours are derived from Müllerian epithelium. It is important to understand the embryological development of the ovary and the female genital structures in order to explain the Müllerian origin of epithelial ovarian neoplasms. The ovary develops from the primordial germ cells and the surrounding surface epithelium while the fallopian tubes, uterus and upper vagina develop from the Müllerian (paramesonephric) duct. Müllerian epithelium may get incorporated as inclusions in the ovarian cortex during development, be acquired during reproductive years from the fallopian tube and the uterus or be explained by an older theory of Müllerian metaplasia of the ovarian surface epithelium. Benign, borderline, well-differentiated epithelial neoplasms (serous, endometrioid and mucinous) and clear cell cancers of the ovary almost always arise from the Müllerian epithelium of the ovarian surface or cortical inclusions. Most of the highgrade serous and endometrioid ovarian cancers are now believed to arise from the Müllerian epithelium of the fallopian tubes and the peritoneal surfaces. In addition, foci of endometriosis may act as a precursor to endometrioid and clear cell carcinomas. Epithelial ovarian tumours are lined by cells of Müllerian origin that have differentiated into epithelium resembling the mucosa of fallopian tube (serous), intestinal or endocervical mucin-secreting epithelium (mucinous), endometrium (endometrioid and clear cell) or transitional cell lining of the urinary tract (Brenner tumour). High-grade cancers that do not resemble any of the above are termed ‘undifferentiated carcinomas’ and tend to behave aggressively. Benign ovarian tumours are characterised by welldifferentiated cells in a single layer lining the cyst wall in the absence of cytological or nuclear atypia, solid areas and extra-ovarian spread. A borderline ovarian tumour is a pathological diagnosis. The term is used only for tumours of epithelial origin. Borderline tumours are characterised by cellular atypia, layering of abnormal cells and cellular tufting but in the absence of stromal invasion on histology. They share some features of malignant ovarian tumours, such as the possibility of non-invasive or invasive implants and the risk of recurrence, but tend to run an indolent course. They can recur as invasive malignancy in 1 to 2% of cases. Malignant epithelial ovarian tumours show worsening histological abnormality in the form of increasingly abnormal cells, with abnormal nuclei and frequent mitoses indicating rapid proliferation. There is stromal invasion through the basement membrane indicating aggressiveness and a propensity to spread. This manifests itself as distant metastases or invasive peritoneal implants typical of ovarian cancer at diagnosis.

Chapter 63  Benign and Malignant Disorders of the Ovary and the Fallopian Tube

On gross examination, borderline and invasive epithelial ovarian tumours tend to present as solid-cystic tumours. Papillary excrescences macroscopically and foci of stromal calcification are common features of border­ line and well-differentiated serous tumours (Fig 63.3). Foci of calcification present as psammoma bodies seen in borderline serous ovarian tumours and well-differentiated serous carcinomas. High-grade, poorly differentiated serous tumours tend to lack psammoma bodies and have a more solid appearance, with areas of haemorrhage and necrosis. Serous ovarian tumours are composed of tissue that resembles the mucosal architecture of the fallopian tube epithelium. Accounting for the vast majority of ovarian neoplasms, 60% of serous tumours are benign, 10% are borderline and 30% are malignant at diagnosis. Serous borderline and invasive tumours are more likely to be bilateral (25 to 50%) and to have extra-ovarian disease at presentation (25 to 30%). Serum levels of CA 125 are a useful tumour marker for advanced stage borderline and malignant serous ovarian tumours. Mucinous ovarian tumours are characterised by mucin-containing epithelial cells resembling the columnar epithelium of the endocervical canal or the intestinal epithelium. Mucinous ovarian tumours are benign in 80%, borderline in 10% and malignant in 10% of cases. All varieties of mucinous tumours tend to occur in a younger population as compared to serous types. Borderline and invasive mucinous tumours tend to be unilateral in the majority of cases (90 to 95%), are less likely to present with extra-ovarian disease (5 to 10%) and tend to present as large masses. Endometrioid ovarian tumours tend to be associated with foci of endometriosis in most cases. Endometrioid

FIGURE 63.3 

Papillary excrescences in an ovarian cyst.

ovarian cancer is now considered to be the second most common variety after serous ovarian cancers. Microscopically, the architecture is similar to endometrial lining of the uterus. The degree of associated cellular abnormality and presence of invasion further dictates their classification as borderline or invasive. Clear cell tumours are so called because of the presence of glycogen or mucin-filled cells causing cytoplasmic clearing. Clear cell carcinomas of the ovary tend to arise in foci of endometriosis and are usually associated with endometrioid cancer of ovary.

PRINCIPLES OF SURGICAL MANAGEMENT OF OVARIAN TUMOURS Benign ovarian tumours The choice of surgical procedure for benign ovarian pathology depends on the size of the neoplasm, ability to identify normal ovarian tissue, age of the patient and index of suspicion for malignancy. It is usually not necessary to remove the whole ovary for benign pathology; an ovarian cystectomy will usually suffice. The choice of surgical approach between laparoscopy and laparotomy will depend on the size of the neoplasm and skill of the surgeon. If there is any doubt regarding the nature of the neoplasm, the procedure carried out should minimise the risk of tumour rupture and intraoperative spillage. The tumour should be sent for a frozen section intra­ operatively to confirm the diagnosis and complete surgical staging if necessary.

Borderline and malignant ovarian tumours Staging of borderline and malignant ovarian tumours is based on surgico-pathological principles that involve removal of the primary tumour (Box 63.1). In the absence of obvious metastatic disease, the aim of the surgery is to identify occult metastatic disease by sampling peritoneal surfaces and retroperitoneal lymphatic tissue. Surgery should be carried out through a generous midline incision that allows thorough inspection of the peritoneal cavity. The peritoneal cavity should be explored for obvious signs of metastatic disease, including palpation of the retroperitoneum to exclude obvious lymphatic involvement. The affected adnexa is removed first and sent for frozen section to confirm the diagnosis. Surgical staging involves sampling of ascitic fluid or peritoneal washings; hysterectomy; bilateral salpingo-oophorectomy; omental biopsy; random peritoneal biopsies from the culde-sac, para-colic gutters and diaphragmatic surfaces; and lymph node sampling from pelvic and para-aortic nodal groups. Surgical staging dictates prognosis, adjuvant treatment and surveillance by identifying occult metastatic disease. The extent of surgery is dependent on disease spread and desire for fertility preservation. 575

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BOX 63.1  FIGO 2014 Staging of borderline and malignant ovarian tumours. Stage I Tumour limited to ovaries IA Tumour limited to one ovary (capsule intact) or fallopian tube, no tumour on ovarian or fallopian tube surface. No malignant cells in ascites or peritoneal washings. IB Tumour limited to both ovaries or fallopian tubes; capsules intact, no tumour on ovarian or fallopian tube surface. No malignant cells in ascites or peritoneal washings. IC Tumour limited to one or both ovaries or fallopian tubes with any of the following: IC1 Surgical spill intra-operatively IC2 Capsule ruptured before surgery or tumour on ovarian or fallopian tube surface IC3 Malignant cells in ascites or peritoneal washings. Stage II Tumour involves one or both ovaries or fallopian tubes with pelvic extension below pelvic brim or peritoneal cancer (Tp) IIA Extension and/or implants on uterus and/or tube(s) and/or ovaries. IIB Extension to and/or implants on other pelvic tissues. Stage III Tumour involves one or both ovaries, or fallopian tubes or primary peritoneal cancer, with cytologically or histologically confirmed spread to peritoneum

outside the pelvis and/or metastases to the retroperitoneal lymph nodes IIIA Metastases to retroperitoneal lymph nodes with or without microscopic peritoneal metastasis beyond pelvis (no macroscopic tumour). IIIA1 Positive retroperitoneal lymph nodes only (cytologically or histologically proven). IIIA1(i) Metastases < 10 mm in greatest dimension (note this is the tumour dimension and not the lymph node dimension). IIIA(ii) Metastases > 10 mm in greatest dimension. IIIA2 Microscopic extrapelvic (above the pelvic brim) peritoneal involvement, with or without retroperitoneal lymph node involvement. IIIB Macroscopic peritoneal metastasis beyond pelvic brim 2 cm or less in greatest dimension, with or without retroperitoneal lymph node involvement. IIIC Peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension, with or without regional lymph node metastasis. Stage IV Distant metastases (excludes peritoneal metastases) IVA Pleural effusion with positive cytology. IVB Metastases to extra-abdominal organs including extra-abdominal lymph nodes.

Source: Information reproduced with permission granted by FIGO, from Prat et al. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet 2014;124(1):1–5.

Cytoreductive (debulking) surgery is carried out for advanced disease with obvious metastatic transperitoneal spread (Fig 63.4). The aim of cytoreductive surgery is to leave behind minimal residual disease in order to allow maximal benefit from the adjuvant chemotherapy. Optimal cytoreduction is defined as no macroscopic residual disease. There is evidence to suggest a longer survival following adjuvant chemotherapy in women with minimal residual disease as compared to those with bulky residual disease. For malignant tumours localised to the ovary, a hysterectomy, bilateral salpingo-oophorectomy and surgical staging is the standard management if childbearing is complete. A fertility-sparing staging can be carried out in young women who desire future fertility. This usually involves carrying out a unilateral salpingo-oophorectomy and surgical staging. If the contralateral ovary appears normal, it should be left alone. If the other ovary is abnormal, a cystectomy or biopsy may be carried out. If malignant disease is identified in the other ovary, it should be removed as well. The uterus may still be preserved if 576

grossly normal to allow for future childbearing using a donor oocyte.

BENIGN EPITHELIAL TUMOURS Cystadenomas Ovarian cystadenomas are cystic tumours arising from the epithelial lining of the ovary. Cystadenomas can be serous or mucinous based on the histology of the epithelial lining and the character of the fluid contained in them. They can be uniloculated or multiloculated and can grow to a significant size before becoming clinically apparent. Serous cystadenomas are more common and may be associated with fibromas (see later this chapter), while mucinous tumours tend to be multiloculated and present as large masses in young women. Ovarian cystectomy is the standard management in younger patients with smaller cystadenomas. A laparoscopic approach is standard for smaller cysts (up to 15 cm); however, a laparotomy or mini-laparotomy will be required for larger cysts.

Chapter 63  Benign and Malignant Disorders of the Ovary and the Fallopian Tube

BORDERLINE OVARIAN TUMOURS

FIGURE 63.4 

Metastatic spread of ovarian cancer to the omentum.

Brenner tumour Brenner tumours are derived from squamous epithelial cells that resemble transitional cells of urinary tract. Brenner tumours are almost always benign. Borderline and malignant Brenner tumours are exceedingly rare. The Brenner tumour is unilateral in over 90% of the cases. The gross appearance is that of a solid or solidcystic tumour, and the cut section is hard and gritty due to foci of calcification. Histologically, the tumour is characterised by a background of fibrous tissue interspersed with nests of transitional cell epithelium (Walthard cell rests). The treatment of a benign Brenner tumour is unilateral salpingo-oophorectomy.

Ovarian endometrioma The ovaries are a common site for the formation of endometriomas (Ch 58). Endometriomas or ‘chocolate cysts’ are formed by repeated episodes of bleeding from the endometriotic lining and the characteristic cyst fluid has a ‘ground glass’ appearance on ultrasonography. Clinical signs and symptoms are those of associated endometriosis: pelvic pain, dysmenorrhoea, dyspareunia or incidentally diagnosed on investigation for subfertility. CA 125 is raised in over half of the patients with endometriosis, although the levels seldom rise over 200 IU/ml. Management usually involves a laparoscopic cystectomy and excision of any associated pelvic endometriosis. Ovarian endometriomas tend to recur, hence long-term surveillance is necessary.

Borderline ovarian tumours or ovarian neoplasms of low malignant potential (LMP) account for 10 to 20% of all epithelial ovarian tumours. They tend to occur in younger women (35 to 55 years) as compared to malignant tumours and are thus encountered more often in women who desire future fertility. Serous and mucinous borderline ovarian tumours are the most commonly described types. Endometrioid, clear cell and transitional cell (Brenner) borderline tumours have been described in the past but constitute a very small percentage of LMP ovarian tumours. The presentation of LMP tumours is similar to that of other ovarian masses, either as an incidental finding on imaging for an unrelated indication or presenting with non-specific symptoms related to size and site. Imaging usually reveals a complex ovarian mass with solid and cystic components, a solid area or a ‘mural nodule’ in a largely cystic ovarian mass, or even a unilocular cyst in as many as 20% of the cases. CA 125 is normal in half of the cases and only mildly elevated (usually less than 100 units/mL) in another quarter. Gross examination of the ovary may reveal a smooth surface with a solid area in the cyst. Papillary excrescences are common but areas of haemorrhage and necrosis in the solid part are usually absent (Fig 63.3). Papillary excrescences may also be seen externally on the ovarian surface. Peritoneal implants may be invasive or noninvasive (a pathological diagnosis). Staging of LMP tumours is along the lines of malignant ovarian tumours and is based on principles of surgico-pathological staging. Standard surgical management of LMP tumours includes total hysterectomy, bilateral salpingo-oophorectomy, and peritoneal and omental biopsies. A fertility-sparing staging procedure may be carried out by limiting the pelvic surgery to removal of affected adnexa only in women with no obvious metastatic disease. In the presence of peritoneal metastatic disease, an attempt should be made to remove all macroscopic disease. An ovarian cystectomy should be avoided where possible as a sole management because of the high rates of recurrence (20 to 30%). Appendectomy is usually carried out as well in cases of mucinous ovarian tumours, as some of these apparently ovarian tumours are of gastrointestinal origin, most commonly arising in the appendix. Follow-up should include long-term surveillance in women who have undergone a fertility-sparing procedure (recurrence risk 5 to 7% following unilateral salpingooophorectomy) and those with peritoneal metastatic disease at presentation. The condition recurs as invasive malignancy in 1 to 2% of cases. Overall, the survival rate following the diagnosis of an LMP ovarian tumour is excellent even in advanced stages: 92 to 95% in stages I to II and 70% in advanced stages with invasive peritoneal implants. Chemotherapy is not recommended even in cases with invasive or 577

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non-invasive implants because of poor response rates to chemotherapeutic agents. Spontaneous regression of metastatic implants is known to occur.

EPITHELIAL OVARIAN CANCER Following the success of cervical screening programs, ovarian cancer is now the second most common gynaecologic cancer in the Western world but accounts for the highest proportion of deaths related to gynaecologic cancer. Epithelial ovarian cancers account for 95% of malignancies arising in the ovary. Although an uncommon cancer with a lifetime risk of 1.4%, the average age-specific incidence of ovarian cancer rises from approximately 2 per 100 000 at 20 years of age and 25 per 100 000 at 50 years to 50 per 100 000 at 70 years or more. The significance of these numbers lies in increasing risk with age. Epithelial ovarian cancers may be divided into two groups based on the site of origin: those arising from the Müllerian epithelium on the ovary as well as the cortical inclusions (see earlier this chapter), and those arising from the Müllerian epithelium of the fallopian tube (fallopian tube carcinoma) and the peritoneal cavity (primary peritoneal carcinoma). They are collectively termed ‘ovarian cancer’ or ‘ovarian-like cancer’ because their biological behaviour and principles of management are similar. Likely precursor lesions in the fallopian tube have been identified in a proportion of high-grade serous ovarian cancers that have their origin in the fallopian tube. These are described as serous tubal intraepithelial lesions (STILs). However, the likelihood of developing serous ovarian cancer in the background of these lesions is as yet undetermined. We have gained considerable insight into the common mutations found in different types of ovarian cancers. The extent of the role of various mutations in ovarian cancer initiation, progression and any possible role in targeted treatments is still a topic for ongoing research. The predominant mutations seen in high-grade serous adenocarcinoma of the ovary are those involving TP 53 gene, while the mutations of KRAS or BRAF genes are more common in mucinous adenocarcinomas and lowgrade serous carcinomas.

Presentation Ovarian cancer causes few symptoms in early stages and has been termed the ‘silent killer’. The symptoms, when present, are vague and include abdominal fullness, bloating, reduced appetite due to upper abdominal fullness, urinary urgency or frequency and abdominopelvic pain. The symptoms do not point to a specific problem and hence are ignored by the patient or the care provider, for as long as 6 months or more in a third of patients according to one study. The poor prognosis of the condition is in part related to late stage at presentation: over 70% of women will present with disseminated peritoneal disease. New-onset abdominal symptoms that are persistent and 578

affecting activities of daily living require further investigation and a prompt referral to a specialist. Examination will usually reveal an abdominopelvic mass with or without clinical ascites. Serum levels of CA 125 are raised in most cases of advanced stage ovarian cancer. Mucinous tumours are usually associated with a rise in serum levels of CEA.

Risk factors Advancing age is the most important risk factor for developing ovarian cancer. Nulliparity and a history of infertility are associated with increased risk, probably related to the theory of incessant ovulation. Increased risk of endometrioid and clear cell ovarian cancer has been noted in the presence of endometriosis. An increased risk in women on postmenopausal hormone replacement therapy has been suggested. Obesity has been linked to an increased risk of mucinous tumours. Women with mutations in BRCA genes are at a high lifetime risk of developing ovarian cancer. Carriers of the BRCA 1 gene have a 40% lifetime risk while carriers of the BRCA 2 gene have a 20% lifetime risk of developing serous ovarian cancer. Women with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) have approximately a 10% lifetime risk of developing ovarian cancer and around a 50% lifetime risk of developing endometrial cancer. Other cancers which may develop include right-sided colon cancer and, rarely, cancers of the urinary and biliary tracts. Ovarian cancers developing in women with genetic predisposition tend to occur at a younger age than in the general population.

Screening for epithelial ovarian cancer No test or combination of tests has been validated as costeffective in screening the asymptomatic woman for ovarian cancer, although future studies in the United Kingdom and in the United States may provide more insight into the value of ultrasound +/− CA 125 testing in both the general population and those who are at high risk due to mutation carriage.

Protective factors Multiparity, breastfeeding and the use of oral contraceptives tend to confer some degree of protection against developing ovarian cancer, lending credence to the incessant ovulation theory of causation. Carrying out bilateral salpingo-oophorectomy will prevent 98% of ovarian cancers arising from the ovarian surface epithelium and the fallopian tube. It will not prevent a small proportion of tumours arising from the Müllerian epithelium on the peritoneal surface (the primary peritoneal carcinomas). Hysterectomy without the removal of ovaries and tubal ligation seems to confer a moderate degree of protection against the development of ovarian cancer.

Pathology The World Health Organisation classification of epithelial ovarian cancer includes: serous, mucinous, endometrioid,

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clear cell and transitional cell (Brenner and non-Brenner) carcinomas. Serous histology accounts for the vast majority of epithelial ovarian cancers (> 75%), followed by mucinous (5 to 10%), and endometrioid (5 to 10%), with others (including clear cell cancers, Brenner tumours and metastatic tumours) making up the rest.

Management of epithelial ovarian cancers Routine blood work, including full blood count, renal and liver function tests, is necessary for pre-treatment fitness and to rule out significant anaemia that may be associated with malignancy or may result from intraperitoneal and vaginal bleeding. Serum levels of tumour markers CA 125 and CEA should be requested. The latter helps in differentiating a small proportion of metastatic tumours from the bowel and is also a useful tumour marker for mucinous ovarian cancers. Imaging should include a CT scan or MRI of abdomen and pelvis in addition to a chest X-ray to rule out metastatic disease to the chest, regional lymph nodes and general peritoneal cavity. Surgery is usually required to confirm the diagnosis, for staging and to decrease the tumour burden in advanced stage disease. Surgical staging and/or cyto­ reduction are carried out based on the principles described in this chapter. One-fourth of patients have disease confined to the ovary or the pelvis (stages I and II) at diagnosis, with the remaining 75% presenting with advanced stage disease, mostly with peritoneal metastatic disease. Adjuvant treatment with platinum-based chemotherapy is required for most patients except a few stage I patients. Carboplatin and paclitaxel are the usual combination for most patients. The response rates are good, with 70 to 80% of women achieving ‘remission’, defined as the absence of any evidence of disease. However, the disease tends to recur in the majority, requiring further courses of chemotherapy. Follow-up of women after treatment of ovarian cancer involves regular clinical review and examination to rule out recurrence. Serum levels of CA 125 are used in post-treatment surveillance. Recurrences are usually associated with rising levels. Imaging studies are carried out if indicated by the presence of symptoms or rising CA 125. Despite the advances in chemotherapy and surgical management of ovarian cancer over the last two decades, the survival rates of women diagnosed with ovarian cancer remain poor. Women with disease limited to an ovary at diagnosis have a 5-year survival rate of 80 to 90%. However, a large proportion of patients with stage III disease at diagnosis have a 5-year survival rate of 35 to 45%.

PSEUDOMYXOMA PERITONEI Pseudomyxoma peritonei is a unique and rare condition characterised by large intra-abdominal collections of gelatinous material (jelly belly), causing distortion of abdominal anatomy and inevitably progressing to

intestinal obstruction. The source of gelatinous material was thought to be ovarian mucinous tumours but these are now known to originate from the appendix. Treatment includes extensive resection of peritoneal surfaces followed by adjuvant chemotherapy.

RISK-REDUCING BILATERAL SALPINGO-OOPHORECTOMY There is no reliable screening test available for ovarian cancer. Investigators have tried using clinical examination, monitoring tumour marker CA 125 and pelvic ultrasound alone or in combination without achieving reasonable accuracy. This brings the focus to measures that can reduce the risk of developing ovarian cancer, especially in women who are at a risk significantly higher than the general population. As mentioned earlier, women who are carriers of BRCA 1 and 2 mutations and those with Lynch syndrome have a lifetime risk ranging from 10 to 40%. Use of the combined oral contraceptive pill during reproductive years confers up to a 50% reduction in the risk of ovarian cancer but may be associated with a slight increase in the risk of breast cancer during current use in carriers of BRCA mutations. Use of the combined oral contraceptive pill for any duration is associated with a reduced risk. Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is the other major intervention available to reduce the risk of ovarian cancer developing in women. The procedure should only be considered in women who have a significantly higher risk for developing ovarian cancer in view of the operative risks and risks associated with premature menopause. The procedure can be carried out by a laparoscopic approach with low operative morbidity. The entire fallopian tube should be removed along with the ovary. Intraepithelial lesions in the fallopian tube are identified in 1 to 3% of women undergoing rrBSO, which are now believed to be the precursor lesions for a proportion of ovarian cancers.

SEX-CORD STROMAL TUMOURS Sex-cord stromal tumours develop from the cells derived from sex-cords and supportive stroma derived from coelomic epithelium and cells of genital ridge that develop into hormone-producing theca cells and granulosa cells. These cells are derived from the tissue that surrounds the primordial germ cells. Sex-cord stromal tumours can be benign (fibromas and thecomas) or malignant (granulosa cell tumour and Sertoli-Leydig cell tumours). Sex-cord stromal tumours can present in any age group. Juvenile granulosa cell tumours and SertoliLeydig cell tumours tend to predominate in premenarchal girls and young adults. Fibromas, thecomas and adult granulosa cell tumours tend to present in the third to sixth decades of life. 579

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FIBROMAS Fibromas are the most common benign sex-cord stromal tumours arising from the supportive stroma of the ovary. They present as oval, hard and fibrous masses, and are sometimes associated with a cystic component, which is when they are termed ‘cystadenofibromas’ or ‘adenofibromas’. Fibromas are usually unilateral, are not hormonally active, can occur at any age and tend to be diagnosed later in life as they are usually asymptomatic. They rarely grow to more than 10 to 15 cm in size. Fibromas can present with ascites and right-sided hydrothorax, which promptly resolves after removal of the primary tumour. This presentation is known as Meigs’ syndrome. Management usually involves removal of the affected adnexa. A hysterectomy is not required unless indicated for other reasons.

THECOMAS Thecomas are solid neoplasms arising from ovarian stroma; they are similar to fibromas, but tend to be hormonally active as they are derived from theca cells. Thecomas are usually unilateral and tend to present in postmenopausal women. They produce oestrogen and tend to be associated with endometrial cancer in 20% of cases at presentation. Thecomas are almost always benign. Hysterectomy and bilateral salpingo-oophorectomy is the recommended management for thecomas due to the risk of associated endometrial malignancy.

SERTOLI-LEYDIG CELL TUMOURS Sertoli-Leydig cell tumours show differentiation similar to epithelial and interstitial tissues of testis. Therefore, not surprisingly, they are associated with the production of male hormones and signs of virilisation in the third decade of life.

GRANULOSA CELL TUMOURS Granulosa cell tumours (GCTs) of the ovary is the most common potentially malignant sex-cord stromal tumour of the ovary, comprising 2 to 5% of all ovarian malignancies. There are two subtypes: the adult subtype, which comprises 95% of all GCTs and is seen commonly in adults (median age 50 to 54 years); and the juvenile subtype, which tends to present in the peri-pubertal age group. Both subtypes are hormonally active.

Clinical features The clinical presentation may be related to the mass or to the hormonal activity. Granulosa cell tumours produce oestradiol and women may present with postmenopausal bleeding or dysfunctional uterine bleeding related to oestrogen excess. Associated endometrial pathology is not uncommon, with approximately 25% of women presenting with endometrial hyperplasia and approximately 5% being diagnosed with endometrial carcinoma related to oestrogenic stimulation at presentation. Haemorrhage 580

into the tumour is not uncommon, occasionally resulting in an acute presentation in a perimenopausal woman. Juvenile GCTs tend to present with isosexual precocity. Adult GCTs are usually unilateral and tend to present as solid cystic masses of varying size. Imaging will usually reveal a complex mass of moderate size. The cut surface tends to be yellowish in colour due to the presence of intracytoplasmic lipids. Histologically, the round pale cells of adult GCTs are arranged in a rosette around a central cavity, mimicking a primordial follicle. This arrangement is called the Call-Exner bodies, and is typically seen in adult GCTs. The nuclei of these cells tend to have a longitudinal groove giving them a ‘coffee bean’ appearance. Inhibin is also a useful tumour marker for post-treatment follow-up.

Management GCTs are surgically staged according to the guidelines for ovarian cancer staging. (Box 63.1). A total hysterectomy, bilateral salpingo-oophorectomy, omental and peritoneal biopsies are recommended for those women who have completed childbearing. Fertility-sparing staging surgery involving unilateral salpingo-oophorectomy and peritoneal biopsies may be carried out in younger women with disease limited to the ovary and who desire future fertility. An endometrial biopsy is a must for these women to rule out co-existing endometrial pathology induced by the excess hormonal activity. The rate of long-term survival is over 90% for women with disease limited to the ovary, and surgery alone is the accepted treatment. Adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) is recommended for women presenting with advanced stage disease. Recurrences of GCTs are infrequent but tend to occur late, often presenting 8 to 12 years after the primary treatment. The most common site of recurrence is in the pelvis and abdominal cavity.

GERM CELL TUMOURS Ovarian germ cell neoplasms arise from the primordial germ cell of the ovary and may be benign (97%) or malignant (3%). Malignant germ cell tumours tend to present in young women (10 to 30 years of age, with peak incidence at 15 to 19 years) and form 70% of all the malignant ovarian neoplasms in this age group. Teratomas and dysgerminomas are the most common germ cell tumours diagnosed in pregnancy and puerperium. The classification of ovarian germ cell tumours is based on the differentiation of the proliferating cells. Dysgerminomas, the most common types of germ cell tumours, are the undifferentiated neoplasms comprised of immature germ cells and are similar to the seminomas seen in males. The differentiated neoplasms may develop into a tissue similar to the embryo (teratomas with their derivatives from the primitive germ cell layers) or into extraembryonic tissues (tissue resembling the placenta: embryonal carcinoma, choriocarcinoma and endodermal sinus tumour). Germ

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cell tumours can develop in extra-gonadal sites such as the mediastinum. The clinical presentation of germ cell tumours may relate to their size, since these tumours tend to grow quickly and often present as large masses in young adults. Abdominal pain, a relatively common presenting symptom, may be related to rapid growth, haemorrhage, tumour rupture or torsion. Acute pain related to haemorrhage or rupture may be misdiagnosed as appendicitis or ruptured ectopic pregnancy. These tumours may cause isosexual precocity or symptoms of pregnancy due to the production of hormones such as human chorionic gonadotrophin (hCG). Diagnostic work-up includes imaging, which may reveal a solid or solid cystic mass (usually unilateral) and may be accompanied by signs of haemorrhage in the mass. There may be associated ascites related to torsion, but the tumours are usually confined to one ovary at presentation. Young women presenting with a suspicious ovarian mass should have serum levels of hCG, alpha fetoprotein (AFP) and lactate dehydrogenase (LDH). The tumours with extraembryonal derivatives (yolk sac tumour and embryonal carcinoma) tend to produce AFP, while LDH production is a feature of dysgerminomas. The production of hCG is related to the presence of placental tissue in embryonal carcinoma and non-gestational choriocarcinoma.

DERMOID CYST OF OVARY (MATURE TERATOMA) Ovarian dermoids are the most common germ cell tumours of the ovary in women of reproductive age. Dermoids make up around 15% of all ovarian tumours and are bilateral in approximately 10% of women. The peak incidence is in the 25 to 35 age group, and dermoids are the most common ovarian tumours diagnosed in pregnancy. Usually uniloculated, dermoids have a smooth surface. Multiple dermoids are known to occur in a single ovary and may be associated with mucinous cystadenomas. Dermoids arise from the totipotent cells and tend to contain structures derived from all three primitive germ layers: ectoderm, mesoderm and endoderm (Fig 63.5). The ectodermal elements such as hair, skin, skin appendages and teeth are most commonly seen. Neural tissues, cartilage, respiratory epithelium and gastrointestinal tissue are also seen variably. Struma ovarii is a dermoid cyst that contains thyroid-like tissue capable of producing thyroxine. Dermoids have a propensity to undergo torsion. They are almost always benign, although malignant transformation has been reported in up to 1% of mature teratomas. Squamous cell carcinoma arising in the lining of the dermoid is the most commonly reported malignant transformation. Dermoids have a typical appearance on ultrasonography due to their fat content and foci of calcification. Management involves laparoscopic cystectomy and an attempt to preserve as much normal ovarian tissue as possible. A mini-laparotomy may be needed for larger dermoids.

FIGURE 63.5 

Dermoid cyst of the ovary.

Source: Spencer RJ, Kurek KC, Laufer MR. Ovarian dermoid cyst super-infected with methicillin-sensitive Staphylococcus aureus leading to the misdiagnosis of appendicitis in an adolescent. J Pediatr and Adolesc Gynecol April 2011; 24(2)e25–e28. © 2011 North American Society for Pediatric and Adolescent Gynecology.

MALIGNANT OVARIAN GERM CELL TUMOURS Dysgerminomas Dysgerminoma is the most common germ cell tumour of the ovary, accounting for one-third of malignant ovarian germ cell tumours (MOGCTs). Dysgerminomas can occur at any age but most often tend to present in adolescents and young adults. A dysgerminoma is the most common malignant tumour of the ovary diagnosed in pregnancy. Histologically, the neoplasm is made up of undifferentiated germ cells seen as sheets of large vesicular cells with clear cytoplasm and central nuclei (‘fried egg’ appearance) interspersed with linear stroma containing plentiful lymphocytes. Dysgerminomas are bilateral in 10 to 20% of cases—the only germ cell tumour with a significant chance of occurring bilaterally at presentation.

Gonadoblastomas Gonadoblastomas are rare tumours that are histologically made up of a germ cell element similar to dysgerminoma and a stromal cell element similar to a granulosa cell or Sertoli cell tumour. They tend to arise in dysgenetic gonads related to an abnormal karyotype (45,X or 46,XY). Phenotypic females, constituting 80% of patients with gonadal dysgenesis, tend to have non-functional streak gonads. A karyotype is recommended in presence of streak gonads. In view of the high incidence and aggressive nature of the tumour and high risk of developing malignancy in the contralateral ovary, removal of the contralateral ovary is recommended in cases of gonadal dysgenesis. 581

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Immature teratomas While immature teratomas or malignant teratomas comprise only 1% of all malignant ovarian tumours, they are the second most common malignant germ cell tumours of the ovary. Histologically, they are comprised of tissues from the three germ cells in immature form. The presence of immature neural tissue (representing the ectodermal tissue) is a characteristic of immature teratoma.

Endodermal sinus tumour (yolk sac tumour) Endodermal sinus (or yolk sac) tumours constitute a fourth of all MOGCTs. These aggressive tumours tend to metastasise early and spread intra-abdominally. Lymphatic involvement is also commonly seen. Raised serum AFP is commonly a useful tumour marker in these tumours. Histologically, perivascular formations of cuboidal cells and reticular stroma around a central capillary (called Schiller-Duval bodies) are a characteristic diagnostic feature of yolk sac tumours.

Embryonal carcinoma Embryonal carcinoma is one of the most malignant tumours arising from the ovary. It tends to occur in even younger age groups than other malignant germ cell tumours (median age of 15 years). The tumour produces AFP from cells with yolk sac differentiation and hCG from cells differentiating into syncytiotrophoblastic giant cells.

Non-gestational choriocarcinoma Non-gestational choriocarcinoma is an extremely rare but highly malignant tumour associated with raised serum hCG levels at presentation. These tumours usually present in pre-menarcheal girls and young adults. Presenting symptoms may include isosexual precocity, irregular vaginal bleeding, amenorrhea or symptoms suggestive of ectopic pregnancy depending on the age at presentation. In most cases, the tumour presents as a mixed germ cell tumour, confirming its non-gestational origins.

Treatment Surgery for ovarian germ cell tumours is required for diagnosis, staging and treatment, and should be carried

582

out along the International Federation of Gynecology and Obstetrics (FIGO) guidelines for staging of epithelial ovarian cancers (Box 63.1). However, there are certain factors that dictate the extent of surgical management of malignant ovarian germ cell tumours: they tend to occur in young women who will be desirous of retaining future fertility; although presenting as large masses, 60% tend to be localised to the ovary at diagnosis; they are unilateral in vast majority of cases; and they tend to be exquisitely sensitive to adjuvant platinum-based chemotherapy. In most cases, surgery is limited to unilateral salpingooophorectomy, peritoneal biopsies and sampling of pelvic and para-aortic lymph nodes. Therefore, a fertility-sparing procedure that involves removal of the affected adnexa only, peritoneal biopsies and lymph node sampling is the norm in young girls. Adjuvant therapy with platinum-based chemotherapeutic regimens for MOGCTs has been a major advance in management of these tumours. Treatment with bleomycin, etoposide and cisplatin (BEP) has been the standard adjuvant treatment for advanced stage germ cell tumours for the past two decades due to the exquisite chemosensitivity of these tumours to these agents. Adjuvant chemotherapy is usually advised for most ovarian germ cell tumours except stage IA dysgerminomas and stage IA low-grade immature teratomas. Other germ cell tumours are aggressive enough to require adjuvant chemotherapy even when diagnosed early. Although the literature is limited in numbers, over 80% of women treated with this regimen go on to resume menstruation and a significant proportion achieve successful pregnancies. Surveillance following treatment for malignant ovarian germ cell tumours involves clinical examination, measurement of tumour markers and imaging, as guided by patient symptoms and abnormal physical findings. FURTHER READING Reade CJ, McVey RM, Tone AA, et al. The fallopian tube as the origin of high grade serous ovarian cancer: review of a paradigm shift. J Obstet Gynaecol Can 2014;36(2):133–40.

Section 4 NEONATOLOGY Chapter 64

Neonatal physiology: adaptation and resuscitation

Chapter 65

Routine neonatal care

Chapter 66

Assessment of the neonate

Chapter 67

Neonatal feeding and nutrition

Chapter 68

Neonatal jaundice

Chapter 69

Neonatal neurological presentations

Chapter 70

Neonatal respiratory distress

Chapter 71

The small for gestational age and large for gestational age neonate

Chapter 72

Neonatal infection

Chapter 73

Congenital malformations

Chapter 74

Neonatal haematology

Chapter 75

The preterm neonate and perinatal transport

Chapter 64  NEONATAL PHYSIOLOGY: ADAPTATION AND RESUSCITATION Kypros Kyprianou

KEY POINTS At birth the fetus makes a transition from an in utero environment (in which gas exchange, nutrition and thermoregulation are largely taken care of) to being an independent, air-breathing neonate in a much more variable and demanding environment. The fetus is adapted to survival in an in utero environment that has a relatively low partial pressure of oxygen. As such, the newborn has the ability to withstand periods of hypoxia during the transition period that would result in organ damage in the adult. In order to understand this natural transition to extrauterine life, an appreciation of fetal and neonatal circulatory anatomy, as well as an understanding of the fetal and neonatal respiratory system, is required. Most newborns transition to extrauterine life aided only by innate reflexes and physiological mechanisms that ensure respiration is promptly established. Resuscitation is required when there is failure of this natural transition to extrauterine life and there is evidence of cardiorespiratory and/or neurological depression at birth. Often newborns that will require resuscitation appear pale, floppy and/or apnoeic. Positive pressure ventilation may be necessary until spontaneous respiration becomes established. Algorithms of neonatal resuscitation exist; using air (as opposed to 100% oxygen) is now near universal for the term neonate requiring resuscitation.

THE CARDIOPULMONARY SYSTEM IN TRANSITION The essential features of the fetal and neonatal cardio­ pulmonary system are shown in Figure 64.1.

FETUS In the placenta, oxygen diffuses down a concentration gradient from the maternal to the fetal side of the pla­ centa. From the placenta, blood returns to the fetus via the umbilical vein. The PaO2 of the oxygenated fetal blood in the umbilical vein is 2.7 to 3.3 kPa (20 to 25 mmHg). In the fetus, the highest oxygen concentration in the body occurs in a vein, the umbilical vein, just as it does in the

adult in the pulmonary veins. Figure 64.1 (prenatal circu­ lation) shows oxygenated blood in the umbilical vein returning to the fetal heart (the right atrium) via the ductus venosus and then the inferior vena cava. A key difference in fetal circulation is that of ‘lung bypass’. As already mentioned, blood is oxygenated by the placenta, not the lungs. As such, blood flow to the lungs is, in a sense, not required and hence ‘diverted’. The ductus arteriosus and the foramen ovale allow blood to bypass the lungs. 1. The ductus arteriosus connects the main pulmonary artery to the arch of the aorta. The pulmonary vascu­ lature is constricted and the pressure necessary to pump blood from the right ventricle to this highresistance pulmonary vascular bed is greater than

Chapter 64  Neonatal Physiology: Adaptation and Resuscitation

Prenatal circulation Ligamentum arteriosum (obliterated ductus arteriosus)

Aorta Pulmonary trunk Superior vena cava Right pulmonary artery

Ductus arteriosus Le pulmonary artery Le pulmonary vein

Right pulmonary vein Foramen ovale

Inferior vena cava

Hepatic vein

Aorta

Ductus venosus Liver Hepatic portal vein Umbilical vein

Celiac trunk Superior mesenteric artery Kidney Gut

Umbilical arteries

Fossa ovalis (obliterated foramen ovale) Ligamentum venosum (obliterated ductus venosus) Ligamentum teres (round ligament) of liver (obliterated umbilical vein)

Medial umbilical ligaments (occluded part of umbilical arteries) Postnatal circulation

Figure 64.1 

Anatomy of fetal circulation: pre- and postnatal circulation.

Source: Florin TA, Ludwig S, Aronson PL, et al. Netter’s Pediatrics. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 106.2.

that required to pump blood to the systemic circula­ tion. A large proportion (nearly 90%) of right ven­ tricular outflow blood is hence directed to the systemic circulation via the ductus arteriosus. 2. Some blood returning from the placenta to the right atrium crosses the foramen ovale, passing directly to the left atrium and into the systemic circulation.

NEONATE The heart and lungs There are two sudden changes in the cardiopulmonary system at the time of birth. The lungs become filled with air, and coincident with this is a large reduction in the pulmonary artery resistance and hence pressure. The oxygen in air acts as a pulmonary vasodilator. Other vaso­ active mediators (such as bradykinin and nitric oxide) are released in response to the oxygenated lung. These medi­ ators act as further pulmonary vasodilators. Hence, in the minutes after birth, blood flow to the lungs can increase by a factor of 10.

The second change is the removal of the placental circulation (commonly via cord clamping) that results in an increase in the systemic vascular resistance and an increase in the left atrial and ventricular pressures. These changes (reduced pulmonary vascular resistance and increased systemic vascular resistance) together have two important effects: 1. a resultant reduction in the right-to-left shunt of blood through the patent foramen ovale, and 2. almost complete cessation of blood flow within the ductus arteriosus. Subsequently, over the ensuing few days the muscu­ lar wall of the ductus arteriosus constricts. Direct oxygen exposure and withdrawal of dinoprost (prostaglandin E2)-induced relaxation are thought to be key factors in this closure. The ductus arteriosus normally closes in the 24 to 48 hours after birth. Several weeks later, the ductus arteriosus becomes anatomically obliterated. The fetus begins to make breathing movements from late in the first trimester, and by term the fetus makes intermittent breathing movements about 60% of the time. The lung is a secretory organ prior to birth, with 585

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

approximately 100 to 150 mL/kg body weight of fluid being produced in the lungs of a healthy fetus. Amniotic fluid consists primarily of fetal lung fluid and fetal urine. The large volume of fluid present in the lungs must be cleared at the time of birth, with the first breaths. This is achieved by: 1. a cessation of fluid secretion from the lungs 2. extrusion of some fluid as the chest is compressed during the birth process 3. resorption of the fluid via the lung interstitium into pulmonary capillaries and lymphatics. This final point, resorption, is the main process by which the newborn eradicates intraluminal lung fluid. If the resorption of lung fluid is delayed, then the condition of transient tachypnoea of the newborn occurs (described in Chapter 70). While changes in the cardiopulmonary system are the most dramatic and sudden during transition, there are other systems that undergo important and major physiological adaptations.

Other organs and behaviour In utero, the fetal kidneys have a very limited capacity to concentrate urine. This ability is achieved gradually over the neonatal and early infant period, reaching a glomerular filtration rate (GFR) of 20 mL/min/1.73 m2 by 1 month of age (compared to a normal adult GFR of 120 to 130 mL/min/1.73 m2). During the first days after birth, the newborn may be faced with a limited caloric intake during a period of high energy requirement. There are several important mecha­ nisms in place to meet these energy demands. In the third trimester, glycogen stores are laid down, chiefly in the fetal liver. Glycogen can be converted to glucose in times of need; this is particularly important as glucose is a key energy substrate for the newborn brain. Brown fat deposits are also laid down at this time, mainly between the scapulae. Brown fat is an efficient source of energy for thermogenesis; it is particularly important that the newborn be able to generate heat to maintain thermal equilibrium. There are characteristic behavioural changes during the normal transition from the intra- to extrauterine environment in the term newborn. After delivery, the healthy newborn is alert and vigorous. This period of alertness lasts 15 to 30 minutes and is followed by a period of quiet alertness. In this state, the newborn can follow a face, turn to sound and at times may imitate facial expressions.

NEONATAL RESUSCITATION INTRODUCTION While neonatal resuscitation is a relatively rare event, and irrespective of the clinical setting in which birth is 586

taking place, the birth attendant present at the delivery should be competent and confident in the resuscitation of the newborn. A newborn has the innate, reflex ability to naturally establish spontaneous respiration. There are a number of conditions that may lead to ‘neonatal respiratory depres­ sion’ (sometimes referred to as ‘birth depression’) where there is a failure to establish spontaneous respiration and external assistance—neonatal resuscitation—is required. Impaired delivery of oxygen to the fetus during labour is one such cause and is termed ‘birth asphyxia’. Other causes of neonatal respiratory depression are listed in Box 64.1. The term ‘birth asphyxia’ is sometimes avoided because of concerns that it may have medico-legal conse­ quences; that is, a legal team may infer an element of preventability if the child is later found to have a longterm disability. This is incorrect on two grounds. First, the presence of birth asphyxia does not necessarily imply that subsequent disability is causally related. For example, conditions such as cerebral palsy can occur in the absence of birth asphyxia, hence any association may be coinci­ dental in any given case. Second, birth asphyxia occurs from time to time in well-managed cases and prevent­ ability should not be assumed. Many events occur sud­ denly and catastrophically with little possibility of avoiding birth asphyxia and its subsequent sequelae (see Chapter 69). In determining whether respiratory depression at birth was due to hypoxia, a number of factors will be considered. At birth these parameters include, but are not limited to, the Apgar scores, the duration of resuscitation, and the presence and degree of neonatal hypoxaemia and acidosis. In the early neonatal period, factors that will be considered include a detailed neurological assessment, the presence or absence of neonatal encephalopathy,

BOX 64.1  Causes of neonatal respiratory depression. Maternal sedation (e.g. benzodiazepine) or narcotic administration (e.g. morphine or pethidine) Intrapartum hypoxia Antenatal hypoxic event (e.g. an episode of sustained maternal hypotension, acute or chronic placental insufficiency, cord complication, vasa praevia haemorrhage) Infections (e.g. cytomegalovirus [CMV], bacterial chorioamnionitis) Congenital malformations, genetic or chromosomal anomalies Intracranial haemorrhage or infarction (e.g. fetal stroke, haemorrhage in relation to severe fetal thrombocytopenia)

Chapter 64  Neonatal Physiology: Adaptation and Resuscitation

multi-organ failure (e.g. cardiac, renal), electroencepha­ lography (EEG) and/or MRI changes and the promptness or degree of recovery. It is often—but not always—possible to anticipate those newborns who have a high risk of potential birth depression. In this case, someone proficient at newborn resuscitation (other than the birth attendant) should be present to care for the newborn baby. Conditions which place the newborn at increased risk of asphyxia, and hence likely to require neonatal resuscitation, are listed in Box 64.2. Approximately 1 in 10 newborns require some resus­ citative assistance to help establish breathing at birth. A smaller number of newborns (approximately 1%) require more extensive neonatal resuscitation. Recognition of the newborn that requires resus­ citation is important; often newborns that will require resuscitation appear pale, floppy and/or apnoeic. Most newborns establish spontaneous respirations by 60 seconds after delivery but if spontaneous respirations are not established within this time, active intervention is required.

NEONATAL RESUSCITATION ALGORITHM The general appearance, colour, tone and breathing efforts are all examined en mass in the first few seconds of birth. Along with an assessment of the heart rate (via palpation of the pulsating cord or auscultation of the praecordium), these assessment measures guide the attendant down the neonatal life support pathway. Various national and international neonatal resuscitation algorithms exist. They all share similarities with some minor variations. The algorithm presented in Figure 64.2 is the current recommended Neonatal Life Support Resuscitation Algorithm from the Australian Resuscita­ tion Council (ARC) and the New Zealand Resuscitation Council (NZRC). Fundamentals including optimising a

BOX 64.2  Factors placing a fetus at risk of asphyxia. Antepartum haemorrhage: placental abruption or placenta praevia Umbilical cord prolapse Fetal heart rate abnormalities Thick meconium staining of the liquor Suspected severe intrauterine growth restriction Suspected large-for-gestational-age newborn Haemolytic disease of the newborn Major congenital malformation Severe maternal infection or suspected neonatal sepsis Prematurity, especially < 35 weeks Multiple births

patent airway, ensuring adequate ventilation and recog­ nising the variation in normal with respect to targeted oxygen saturations are the key features of the ARC algo­ rithm. The equipment required for neonatal resuscitation is listed in Figure 64.3. As mentioned earlier, predicting which newborns will require resuscitation may not always be possible; as such the equipment should be prechecked and ready at hand.

THE BIRTH OF A NEWBORN: THE FIRST MINUTES OF LIFE If neonatal resuscitation is required, it should proceed promptly. The baby may be lying on the mother’s abdomen, placed there as the cord is being cut. Alterna­ tively, at a caesarean section delivery the baby is handed to a midwife or paediatrician as soon as the newborn is delivered and the cord is clamped and cut. From this point, a step-by-step approach to neonatal resuscitation is suggested. 1. Place the newborn on a flat, firm surface at a suitable working height. A light source and radiant heater should be overhead. 2. Dry the newborn with a warm towel. This minimises the heat lost from evaporation and provides the nec­ essary tactile stimulation, which—if the child is in primary apnoea—will facilitate the reflex response to start spontaneous respiration (Box 64.3). Slapping the

BOX 64.3  Primary and secondary apnoea. Early animal studies explored periods of apnoea in the newborn mammal. These were traditionally labelled primary and secondary apnoeas. During the course of asphyxia there is an apnoeic period during which, with appropriate general measures such as tactile stimulation, the newborn will spontaneously commence respiration. This is called the period of primary apnoea. If the asphyxia has been more prolonged or severe, such measures will never be effective in causing spontaneous respirations to commence: the so-called secondary apnoea. In this case, only after assisted respiration (resuscitation) has been provided and hypoxia and acidosis reversed will spontaneous respirations commence. Importantly, there is no way of knowing in advance (or during resuscitation) whether the newborn is in a period of primary or secondary apnoea. These definitions, while assisting in animal and scientific explanations of asphyxia, do not assist in the real-world delivery room. Hence, any apnoea should be treated as significant, with resuscitation provided as per the algorithm shown in Figure 64.2. 587

Beischer & MacKay’s: Obstetrics, Gynaecology and the Newborn

Newborn Life Support Term gestation? Breathing or crying? Good tone?

At all stages ask: do you need help?

No Prevent heat loss Ensure open airway Stimulate HR below 100? Gasping or apnoea? Yes Positive pressure ventilation SpO2 monitoring HR below 100?

Yes Stay with mother

Routine care: Prevent heat loss Ongoing evaluation

No No

Laboured breathing or persistent cyanosis? Yes

No

Ensure open airway SpO2 monitoring Consider CPAP

Yes Ensure open airway Reduce leaks Consider increasing pressure & oxygen HR below 60? Yes Add chest compressions 3 compressions to each breath 100% oxygen Consider intubation or LIMA

Post-resuscitation care

Targeted pre-ductal SpO2 a˜er birth 1 min 2 min 3 min 4 min 5 min 10 min

60—70% 65—85% 70—90% 75—90% 80—90% 85—90%

HR below 60? Yes Venous access, adrenaline Consider volume expansion

Adrenaline IV 10—30 mcg/kg (0.1—0.3 mL/kg of 1:10,000 solution)

Figure 64.2 

Neonatal resuscitation algorithm.

Source: Australian Resuscitation Council, New Zealand Resuscitation Council. Neonatal Resuscitation Algorithm.

soles of the feet is an outdated practice that is not required because it may be deleterious to provide a painful stimulus and distracts from appropriate resuscitation. 3. Most babies who do not require active resuscitation will achieve a clear airway unaided. Routine suction is not recommended although excessive oral secre­ tions may be suctioned under visualisation. Pro­ longed or vigorous suction may cause bradycardia, by stimulating pharyngeal vagal receptors. 4. If the baby has not commenced adequate spontane­ ous respirations (remains apnoeic or has slow, gasping or weak self-ventilatory efforts), commence assisted ventilation (positive pressure ventilation). This is most commonly achieved with the use of a tight-fitting mouth-and-nose mask, attached to one of the follow­ ing devices: 588

a. a self-inflating bag-valve-mask apparatus, or b. a device to deliver positive pressure ventilation (e.g. NeoPuff, Fig 64.4), or c. an anaesthetic bag and mask. Airway adjuncts (e.g. Guedel airway or laryngeal mask) are rarely necessary and prompt improvement in cardiorespiratory function nearly always ensures with adequate ventilation with one of these three devices. Irrespective of which device is used, the primary aim is to achieve adequate ventilation of the lungs. Adequate lung ventilation is assessed by visual inspection of the chest wall movement, which should match that which would occur with normal neonatal respirations. The pressure necessary to achieve this is usually around 30 cm H2O. Higher pressures are sometimes required; however, this may result in

Chapter 64  Neonatal Physiology: Adaptation and Resuscitation

General equipment • Firm, padded resuscitation surface • Overhead warmer • Light for the area • Clock with timer in seconds • Warmed towels or similar covering • Polyethylene bag or sheet, big enough for a baby less than 1500 g birthweight • Stethoscope, neonatal size preferred • Pulse oximeter plus neonatal probe. Equipment for airway management • Suction apparatus and suction catheters (Size 6 French [Fr], 8 Fr and either 10 Fr or 12 Fr) • Oropharyngeal airways (sizes 0 and 00) • Intubation equipment: o Laryngoscopes with infant blades (00, 0, 1) o Spare bulbs, and baŠeries o Endotracheal tubes (sizes 2.5, 3, 3.5 and 4 mm, uncuffed) o Endotracheal stylet or introducer o Supplies for fixing endotracheal tubes (e.g. scissors, tape, ties) • End-tidal carbon dioxide detector (to confirm intubation) (e.g. Pedi-Cap) • Meconium suction device (to apply suction directly to endotracheal tube) • MagiII forceps, neonatal size (optional) • Laryngeal mask airway, size 1 Equipment for supporting breathing • Face masks (range of sizes suitable for premature and term infants) • Positive-pressure ventilation device, either: o T-piece device (e.g. NeoPuff), or o Flow-inflating bag with a pressure safety valve and manometer and o Self-inflating bag (approximately 240 mL) with a removable oxygen reservoir • Medical gases: o Source of medical oxygen (reticulated and/or cylinder, allowing flow rate of up to 10 L/min) with flow meter and tubing o Source of medical air o Air/oxygen blender • Feeding tubes for gastric decompression (e.g. size 6 Fr and 8 Fr) Equipment for supporting the circulation • Umbilical venous catheter (UVC) kit (including UVC size 5 Fr) • Peripheral IV cannulation kit • Skin preparation solution suitable for newborn skin • Tapes/devices to secure UVC/IV cannula • Syringes and needles (assorted sizes) • Intraosseous needles, 50 mm length Drugs and fluids • Adrenaline: 1:10 000 concentration (0.1 mg/mL) • Volume expanders o Normal saline o Blood suitable for emergency neonatal transfusion needs to be readily available for a profoundly anaemic baby Documentation • Resuscitation record sheet Figure 64.3 

Neonatal equipment checklist.

Source: Australian Resuscitation Council, New Zealand Resuscitation Council. Guideline 13.1: Introduction to resuscitation of the newborn infant. December 2010. Online. Available: http://resus.org.au/download/section_13/guideline-13-1dec10.pdf

iatrogenic pneumothorax. Ventilation is provided at a rate of 40 to 60 breaths per minute. Given that respiratory depression is often the primary issue being treated, adequate ventilation is central to neonatal resuscitation. Direct airway, and hence lung ventilation, can be achieved with the use of a laryngeal airway mask

or via an endotracheal tube. The devices listed previ­ ously can then be attached directly to the laryngeal airway or endotracheal tube to assist in ventilation. However, intubation is rarely required if one appro­ priately uses a mask and one of the devices listed. 5. In the term neonate requiring assisted ventilation, the inspired oxygen concentration is initially 21%; that is, 589

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difference (higher ventilatory rates) again highlights the principle that adequate ventilation is a key com­ ponent of neonatal resuscitation. Cardiac compres­ sions are given at a rate of 100 per minute. 7. Failure of adequate cardiorespiratory function at this point often relates to issues around potential airway obstruction or inadequate ventilation. Adrenaline is the only drug recommended in neonatal resuscitation, although it is rarely required. Adrenaline should only be considered if clear attention, reassessment and establishment of adequate ventilation and chest com­ pressions do not result in an increase in heart rate. It should be administered via central access (e.g. a promptly inserted umbilical vein catheter). Endo­ tracheal administration of adrenalin (one requires a tenfold dose) is a further option, but remains controversial. The role of fluids in neonatal resuscitation remains less clear-cut. For example, fluid volume expansion may be considered, especially if one sus­ pects that severe shock is due to fetal blood loss. This may necessitate—in the first instance—the adminis­ tration of a crystalloid volume expander; that is, 0.9% normal saline (initial bolus of 10 to 20 mL/kg). Impor­ tantly, in the absence of severe blood loss, some animal studies have shown deleterious effects of fluid-bolus when used in neonatal resuscitation. Figure 64.4 

A demonstration of the NeoPuff device. Source: Fisher & Paykel.

ventilatory resuscitation commences in air. The use of peripheral oxygen monitoring is recommended, espe­ cially in the context of laboured breathing and/or when resuscitating a newborn requires assisted ventilation. The use of air/oxygen mixtures allows for the titration of inspired oxygen in order to avoid overoxygenation. Initial resuscitation in 100% oxygen is not recommended; adverse outcomes including delay to establish normal respiratory state have been shown. A range of acceptable tissue oxygen saturation mea­ surements over the first few minutes of life is shown in the Neonatal Resuscitation Algorithm (see the table Targeted pre-ductal SpO2 after birth in Fig 64.2). Importantly, the ability to use air/oxygen mixtures during the resuscitation is now almost universal. 6. Very occasionally, when the heart rate remains < 60 bpm, and despite adequate assisted ventilation, chest compressions are then required. The ratio of compressions to ventilatory breaths in neonates differs from the ratios listed in resuscitation guide­ lines for infants, children and adults. The neonatal chest compression/ventilation rate is 3:1; that is, three compressions to one ‘ventilatory breath’. This 590

The Apgar score If present, the severity of birth depression can be ascer­ tained by a number of clinical methods. The Apgar score comprises assessment of five items: heart rate, respira­ tory effort, muscle tone, colour and reflex response. Each item is scored from 0 to 2 with a maximum possible score of 10 (Table 64.1). The Apgar score is based on the degree of cardiorespiratory and neurological depression present,

TABLE 64.1  APGAR SCORE.* Sign/score

0

1

2

Heart rate per minute

Absent

< 100

> 100

Respiratory effort

Absent

Weak

Strong

Muscle tone

Limp

Some flexion

Well flexed

Reflex response

None

Weak

Strong

Colour

Blue or pale

Body pink, extremities blue

Pink

*Five items receive a score between 0 and 2 for a maximum possible score of 10, which will be obtained by those newborns who are most vigorous at the time of birth. The Apgar score is usually recorded at 1 and 5 minutes after birth.

Chapter 64  Neonatal Physiology: Adaptation and Resuscitation

and is measured at 1 and 5 minutes after birth. It is com­ monly measured in all babies at birth regardless of whether or not birth depression is present. A normal Apgar score is 7 to 10; a score of 4 to 6 demonstrates moderate depression and a score of 0 to 3 demonstrates severe depression. The Apgar score is useful in assessing the adequacy of resuscitation and, in some studies, has been shown to have a degree of prognostic value. Approx­ imately 9% of babies with an Apgar score at 5 minutes or less than 7 will have some neurological disability com­ pared to around 2% in the remaining population.1 A more precise measure of birth depression is by measuring the degree of acidosis or hypoxia of fetal blood, via umbilical cord sampling. The umbilical artery pH best reflects the metabolic state of the fetus and a pH below 7.0 is indicative of significant birth depression, with a pH < 7.15 indicative of fetal compromise. While both Apgar scores and cord pH sampling have limitations in predicting long-term neurological outcome, in cases where birth depression is suspected both are often obtained and documented.

Response to resuscitation In the vast majority of cases of resuscitation, the newborn responds to adequate assisted ventilation and hence restoration of cardiorespiratory function. Subsequent increase in heart rate and improvement in cardiovascular status often ensures purely with effective ventilatory resuscitation. The Neonatal Resuscitation Algorithm shown in Figure 64.2 and the steps described in this chapter outline the current evidence base that guides neonatal resuscitat­ ing. Ongoing research, both in Australia and internation­ ally, occurs to better facilitate evidence-based resuscitation guidelines (see Box 64.4).

BOX 64.4  Online neonatal resources. In Australia, various states and territories offer neonatal resuscitation training. Additionally, the Australian Resuscitation Council updates and reviews neonatal (and other) resuscitation guidelines. Some useful resources can be found at: ✚ Australian Resuscitation Council (ARC): http://www.resus.org.au ✚ International Liaison Committee on Resuscitation (ILCOR): http://www.ilcor.org

BOX 64.5  Starting and stopping resuscitation. In situations where viability is an issue (e.g. extreme prematurity or known severe congenital anomalies), consideration for supportive, nonresuscitative care should be discussed and offered to the family, ideally before birth. In the event of a prolonged neonatal resuscitation, thought should be given to the cessation of resuscitation. Newborns can be resuscitated, and survive without disability, despite an Apgar score of 0 at 1 minute. General consensus is to consider ceasing resuscitation if the heart rate is undetected and remains so for 10 minutes.2 If heart rate is restored by 10 minutes but there is still no respiratory effort, the outcomes can remain favourable. Clear and open discussion among the resuscitation team, as well as with the family, should guide decisions regarding starting or ceasing resuscitation.

If there has been a significant hypoxic event and/or extensive neonatal resuscitation, clear guidelines exist to assess and offer treatment to these newborns in the immediate postnatal period. This includes postresuscitation therapeutic hypothermia, which is discussed in Chapter 69. Lastly, there may be situations where families choose not to resuscitate a newborn; for example, in extreme prematurity or in cases with known severe congenital anomalies. Conversely, lack of response to a prolonged resuscitation ultimately requires a decision to stop treat­ ment (see Box 64.5). REFERENCES 1) Ehrenstein V, Pedersen L, Grijota M, et al. Association of Apgar score at five minutes with long-term neurologic disability and cognitive function in a prevalence study of Danish conscripts. BMC Pregnancy Childbirth 2009;9:14. 2) Australian Resuscitation Council, New Zealand Resuscitation Council. Guideline 13.10: Ethical issues in resuscitation of the newborn infant. December 2010. Online. Available: .

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Chapter 65  ROUTINE NEONATAL CARE Kypros Kyprianou

KEY POINTS Monitoring the newborn in the immediate postnatal period is required to ensure normal transition to extrauterine life. Routine care should: ■ allow maternal–infant bonding ■ promptly detect illness or abnormality of the newborn ■ actively facilitate and support breastfeeding. Breastfeeding can be initiated in the delivery room, soon after birth. Newborns should be maintained in a thermal environment that is appropriately warm, while avoiding under- or overheating. Newborns who otherwise do not require specific medical intervention should be nursed in their mother’s room, in their own cot, whenever possible. The arrival of a new member into the family causes many changes that can be the source of both joy and stress. Education and support are necessary to enhance parenting skills.

CARE AFTER BIRTH Most newborns in the developed world are born in a hospital or healthcare facility. Most centres follow similar procedures. Immediately after vaginal delivery, the newborn is promptly placed onto the mother’s abdomen or chest. Vitamin K is often administered intramuscularly at this time in order to prevent haemorrhagic disease of the newborn (see Chapter 74). Immediately following delivery, the newborn remains in the labour ward until it has been established that transition to extrauterine life has occurred without problems. The newborn’s temperature should be normal (36.5 to 37.3°C). There should be comfortable respiratory efforts and a respiratory rate less than 60 breaths per minute, with no signs of increased work of breathing or excessive mucus secretions, nor of cyanosis. Identity labels are often attached to the

wrist and/or ankle of the newborn and verified against those of the mother. All of these assessments can easily be achieved while the newborn remains on their mother’s chest (Fig 65.1). The newborn should be weighed and the head circumference and length measured and documented. Newborn growth assessment is discussed in more detail in later chapters. Normal postpartum care is also discussed in Chapter 40.

GENERAL CARE Transition to extrauterine life begins prior to and during birth and continues in the minutes and hours after birth. Early recognition of abnormal transition is important. This includes being vigilant for respiratory distress or cardiovascular compromise. As such, close observation of the newborn is required, especially immediately after

Chapter 65  Routine Neonatal Care

FIGURE 65.1 

Immediate skin-to-skin contact soon after delivery.

Source: Eglash A, Montgomery A, Wood J. Breastfeeding. Disease-AMonth June 2008;54(6):337–412. Figure 5.

birth. Alertness, temperature, colour, heart rate and respiratory rate are routinely observed. Often respiratory rate and effort as well as heart rate are recorded as ‘observations’. Some centres advocate for regular observations (e.g. every 15 minutes to hourly) over the first few hours of life, then pre-feed observations (e.g. 4-hourly) until discharged. A temperature of < 36.0°C requires active treatment by nursing under a radiant warmer, or preferably, by skin-to-skin contact with a parent (Fig 65.2).

UMBILICAL CORD The umbilical cord stump should be checked for haemorrhage at the time of the first set of observations. It becomes necrotic and separates between approximately 1 week and 14 days after birth. Normal care involves keeping it clean using water at the time of routine bathing, and thoroughly drying it afterwards. Swabbing with alcohol, methylated spirits or antibiotic solution is unnecessary.

BATHING The newborn may be washed daily or every second day commencing 2 or 3 days after birth. Commercial baby soaps may be used sparingly. Care should be taken to prevent cross-infection by disinfection of communal equipment such as baths. Unless there is an outbreak of skin infection, there is no need to use an antiseptic solution at bath time. Bathing must not expose the newborn to cold stress.

URINE AND STOOLS Urine and stools are often passed in the first hours after birth. Meconium (the thick, sticky and black stool) is passed first and continues to be passed for several days. Meconium then gradually transitions to a looser, yellow

FIGURE 65.2 

Skin-to-skin contact or ‘kangaroo’ care.

Source: Lissauer T, Clayden G, Craft A. Illustrated Textbook of Paediatrics. 4th edn. Edinburgh: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 10.10a.

stool. Failure of a full-term newborn to pass meconium in the first 24 hours may indicate an anatomical or functional gut obstruction (e.g. anal atresia, Hirschsprung’s disease or meconium plug). Breastfed newborns have a variable pattern of passing stool: some pass a stool after each breastfeed (gastro-colic reflex) and some may not pass a stool for some days. Artificially fed newborns pass a stool one to two times per day. There are often normal changes in the colour, consistency and frequency of stooling that occur in the days and weeks after birth; parents should be made aware of this to avoid any unnecessary worry or investigations. The buttocks can be cleaned simply with water or a moist wipe. Any excoriation of the skin should be treated early with a barrier cream (e.g. zinc-based barrier creams). Urine output and frequency of wet nappies (at least two or three wet nappies per 24 hours over the first few days of life) should also be monitored in the immediate postnatal period. Nearly all newborns will pass urine sometime in the first 24 hours of life; failure to do so should be cause for concern. A failure to pass urine or reduced urine output may signal renal injury (most commonly from perinatal asphyxia—if severe enough to cause renal injury, one would expect other clinical parameters to be abnormal) or, rarely, urinary obstruction. 593

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WEIGHING The term newborn normally loses up to 10% of body weight by day 3 or 4 but is back to birth weight by days 7 to 10. This is normal and expected, and again parents should be made aware of this expectation. Until the birth weight is regained, it is customary to weigh the newborn every 2 to 3 days. For the first several weeks thereafter, the average weight increase is approximately 30 g/day. Neonates that remain below their birth weight at 2 weeks of age require prompt assessment. Test weighing before and after a feed, to estimate the amount of milk that a baby has taken, is rarely indicated. It tends to create high levels of anxiety without providing information which is not available in other ways. For example, dehydration is diagnosed by low urine output, poor feeding and decreased skin turgor, while inadequate nutrition is diagnosed by failure to gain weight over a period of 1 week or more. An experienced lactation consultant can provide breastfeeding support and assist in promoting milk supply, even in the context of weight loss or poor weight gain.

DOMICILE Rooming-in, where the baby is nursed in a cot by the mother’s bedside, is encouraged. This allows the mother to bond and begin to interpret her newborn baby’s cries and anticipate their needs. Similarly, with the newborn at the bedside, demand breastfeeding is readily possible and the risk of cross-infection is reduced. Co-sleeping and bed-sharing practices are important issues that are often discussed and explored with families in this rooming-in setting. Parents need to be aware of the risk of sudden infant death syndrome (SIDS) when newborns (and infants) co-sleep with adults. Co-sleeping should not be permitted in the immediate postnatal period as cases of unintentional smothering have occurred, likely due to the mother being less responsive to her infant because of exhaustion, narcotic analgesics and epidural analgesia. Various international and local policies and protocols exist to guide new mothers and clinical staff on current recommendations and practices. Issues around bonding, feeding, maternal fatigue and/or sedation, and other safety and culturally sensitive issues are important discussion points.

THERMAL ENVIRONMENT Long before the advent of modern newborn care, the importance of the thermal environment of the newborn was recognised. It is no accident that the ‘incubator’ (or isolette) has become synonymous with modern care of the newborn. Cold stress is deleterious to the newborn due to increased metabolic demand in attempting to restore normothermia; it is associated with increased mortality. Conversely, overheating should also be avoided. The axillary temperature range considered normothermic for a 594

newborn is 36.5 to 37.3°C. In a normal ‘room temperature’ environment (usually 20°C), the newborn may lose heat and hence is often dressed and swaddled in one or two blankets and placed into an open cot or bassinet. The head is a large proportion of the newborn’s body surface area and it is an importance source of heat loss. A hat may be used for a baby that has become hypothermic, but the hat should be removed once normothermia is reached. Similarly, a well-swaddled newborn that is normothermic should have their head uncovered to prevent overheating. As with co-sleeping, there is an association with overheating and SIDS. Skin-to-skin contact (also called ‘kangaroo care’) is when the baby is placed prone, naked except for a nappy, on the bare chest of a parent (Fig 65.2). The baby will become and remain normothermic due to heat conduction. A blanket should be placed over the baby, across the parent’s chest, to prevent heat loss by convection from the baby’s back. The baby’s head should not be covered. This form of temperature regulation is preferred over the use of overhead heat sources. As well as being a highly effective method of temperature regulation, skin-to-skin contact benefits bonding and breastfeeding. If an overhead heat source is used in the case of hypothermia, great care must be exercised if used in close proximity to the baby: burns may result.

BEHAVIOUR AND SLEEP The newborn has a wide range of innate and individual behavioural patterns. For example, the human face is preferred to objects, colours or patterns. Within several days, the newborn is able to track a parent’s face visually. Hearing, vision and smell are combined to enable a newborn to ‘recognise’ their own mother. By several weeks, it is thought that a newborn can visually discriminate between their mother and a stranger. The newborn can be comforted by cuddling and rocking movements or by very gentle patting. Similarly, skin-to-skin contact and swaddling can help in settling. The newborn reflex sucking motion is also naturally soothing. Sleep–wake cycles are often irregular, and in the early neonatal period can be reversed (i.e. more wakeful periods during the night and more sleep during the day). In the first few weeks after birth, the average total time spent sleeping is around 16 to 18 hours a day. Normal sleep–wake patterns, with more alert periods during the day and more settled sleep overnight, normally develop at around 4 to 8 weeks of age.

NEONATAL HEEL-PRICK SCREENING There are many genetic or metabolic diseases which, although rare, can present in the newborn period. Screening for these diseases may be useful if: 1. the presence of the disease is not obvious at birth; 2. the test can

Chapter 65  Routine Neonatal Care

reliably screen for the disease; and 3. treatment can be instituted which improves the outcome. Generally, blood is collected onto blotting paper (or Guthrie card) from a heel-prick, usually on the third to fifth postnatal day (Fig 65.3). The Guthrie test for phenylketonuria (PKU) was introduced over 40 years ago (see Box 65.1).

BOX 65.1  Neonatal screen: a brief history. Neonatal screening began in the 1960s with the work of American microbiologist Dr Robert Guthrie. The initial screening test was for PKU and utilised filter paper (known as the Guthrie card) for the collection and transport of newborn blood samples. Dr Guthrie’s screening technique for PKU used a bacterial inhibition assay: the Guthrie test. While the Guthrie card remains in widespread use, technological advances have resulted in a range of newer screening techniques (e.g. mass spectrometry, radio-immunoassays) to detect over 30 different genetic and metabolic conditions. Other diseases commonly screened for are congenital hypothyroidism (Fig 65.4), cystic fibrosis, galactosaemia, amino acid disorders and fatty acid oxidation disorders. Local jurisdictions govern which diseases are screened; this varies across states and internationally.

IMMUNISATION Immunisation for some diseases may commence in the newborn period. In some counties (e.g. Australia) the hepatitis B vaccine is routinely given soon after birth, and the tuberculosis vaccine bacille Calmette-Guérin (BCG) is given to high-risk groups such as the Australian Indigenous population. The first of the routine childhood immunisations (against rotavirus, B. pertussis, diphtheria, tetanus, polio, Haemophilus influenza, hepatitis B and pneumococcus) are routinely given in Australia at 6 to 8 weeks of age.

BONDING, FAMILY AND SIBLINGS The arrival of a new baby in a family imposes the need for a change in family dynamics. This can be stressful. This stress can be minimised by measures such as

FIGURE 65.4 

FIGURE 65.3 

The newborn screening test. A heel-prick blood sample is placed onto blotting card. The card is dried and sent to a central screening laboratory for testing. Correct age, date and time of birth as well as newborn and parental information needs to be clearly documented on the card.

Source: Gladding PA, Evans CA, Crawford J, et al. Posthumous diagnosis of long QT syndrome from neonatal screening cards. Heart Rhythm April 2010;7(4):481–486. Figure 1. Copyright © 2010 Heart Rhythm Society.

Congenital hypothyroidism (cretinism). This infant presented with hypothermia, lethargy and poor feeding. Examination revealed: a depressed nasal bridge; puffy eyelids; thick, dry and cold skin; coarse hair; large tongue; and abdominal distension. His cry was poor and hoarse. Because hypothyroid newborns may be asymptomatic, this and some other important conditions are screened for. (See Neonatal Heel-prick Screening). Untreated hypothyroidism can cause intellectual disability.

Source: Besser CM, Thorner MO. Comprehensive Clinical Endocrinology. 3rd edn. Edinburgh: Mosby, 2002. Copyright © 2002 Mosby, An Imprint of Elsevier.

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providing appropriate parenting education prenatally as well as adequate visiting opportunities and support for all the family in the hospital. If any concerns about parenting skills are recognised during the hospital stay, additional support of the family should be arranged through community maternal and child health services. When a preterm or sick newborn is separated from the parents and family for a long period, special attention is required to how this stress is handled. Opportunities for family members to have physical contact with their newborn should be maximised, such as the chance to

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handle the sick or very preterm baby as soon as the clinical condition allows. If the baby or outcome is different from parental expectation (such as occurs when there is illness, unexpected malformation or a death), there will be additional stress. Importantly, parental stress and anxiety exist in a sociocultural milieu, and sensitivity from the clinical team is paramount. The discrepancy between parental expectation and perceived setback (even if the issue is, medically speaking, ‘minor’) may still cause parents and families significant distress.

Chapter 66  ASSESSMENT OF THE NEONATE Kypros Kyprianou

KEY POINTS The purpose of the newborn examination is to assess for evidence of congenital malformations and illnesses. A systematic examination is essential if abnormal features are not to be missed. A newborn examination should be performed shortly after birth, is commonly repeated prior to the baby leaving hospital, and is performed again at 6 weeks of age. Of all neonatal deaths (i.e. deaths at age < 28 days), 75% occur in the first 24 hours after birth and are often due to obvious and/or significant malformations or disease. The remainder occur in the days to weeks following birth. An adequate examination will assist in identifying critical issues such as sepsis or congenital cardiac disease. Conditions detected as part of the newborn examination may not always be life-threatening, but nonetheless require detection to prevent morbidity, alleviate anxiety and allow for appropriate follow-up. At term the healthy newborn is visually alert, is attentive to the sound of the human voice, sucks, uses crying as a method of communicating various needs, and is self-aware and self-protective. Many of these features are altered in the presence of illness. To maximise the value of the examination, the newborn should be in a quiet but alert state and the parents should be present.

THE PHYSICAL EXAMINATION The newborn physical examination should be performed thoroughly and systematically to exclude malformations or disease processes, on the first postnatal day, prior to hospital discharge and at the age of 6 weeks. An appreciation of common normal variations is important to provide reassurance to the parents. Any pathology must be identified accurately so that a management plan can be developed; the early identification and treatment of abnormalities may reduce any associated morbidity. The initial part of the examination focuses on general issues. It should ideally be performed with at least the mother present. This allows:

1. the details of the history to be clarified 2. the family dynamics to be assessed 3. the interactions and attitude of the mother to her baby to be observed 4. an opportunity for the family to ask questions 5. the opportunity to demonstrate and explain features of the examination to the parents. The following features in the history should be noted. 1. Family history. Was there a family history of inherited, psychiatric and/or parenting disorders? 2. Gestational history. Was there any discrepancy between the dates and ultrasound assessment of

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gestational age? Were any of the following present: maternal medication, maternal drug abuse, fetal growth restriction, prematurity, maternal diabetes or other medical illness? Were there anatomical anomalies on antenatal ultrasound screening that warrant reassessment and evaluation in the newborn period? 3. Delivery history. Were any of the following present: asphyxia risk factors, trauma, instrumental delivery, low Apgar scores or need for resuscitation? 4. Neonatal history. Check the following: Has the newborn passed urine? Has there been any delay in the passage of meconium? Is the feeding history satisfactory? Is the newborn’s behaviour and alertness normal? The examination should be performed in a warm, draught-free environment. The examiner’s hands should be washed prior to the examination to reduce the risk of cross-infection.

MEASUREMENT The weight, length and head circumference must be recorded and checked against the appropriate percentile charts (Figs 66.1 and 66.2). Length is most accurately recorded using a neonatal measurement board: the baby’s crown is placed at one end, making sure that the hips and knees are held extended, with the ankle and foot at 90 degrees to the base of the measuring board (Fig 66.3). The weight of the naked newborn should be recorded using appropriate infant scales. The head circumference is the maximum measurement that encompasses the occipital protuberance, the parietal eminences and the forehead (Fig 66.4) It is sometimes referred to as the occipito-frontal circumference (OFC). Once documented, these newborn growth parameters should be compared against the population parameters by reference to growth charts. Such population growth charts are prepared in each community and reviewed regularly (e.g. every 10 years) to take into account progressive changes in birthweight. A diagnosis of small for gestational age (weight less than the 10th percentile on population data for a given age and sex) or microcephaly is made in this way. The growth charts shown in Figures 66.1 and 66.2 are useful as they show the normal variation in birth weights across gestational ages. For example, the 50th percentile for weight, length and head circumference is approximately 3.55  kg, 51  cm and 35  cm respectively for boys born at 40 weeks’ gestation. Growth significantly outside expected parameters may signify particular maternal or neonatal illness and hence dictate a variation in newborn management practices. The definition, assessment and management of newborns born small or large for gestational age are discussed in Chapter 71. 598

GENERAL OBSERVATION The newborn must be undressed for the examination. Often helpful parents would like to assist in the undressing, but if done competently and confidently by the examiner, much information can be gained. While undressing the newborn, and once the baby is exposed, the examiner is able to make an assessment of the general neurological state of the baby; neuromuscular tone and the degree of activity, irritability and lethargy. The presence of newborn reflexes, particularly the Moro and grasp reflexes, should be elicited. The following general observations should be made before the baby is unduly disturbed. 1. Respiratory rate. A respiratory rate > 60 breaths per minute defines tachypnoea in the newborn. The observation of laboured breathing (e.g. use of accessory muscles of respiration, subcostal and intercostal retractions) indicates that breathing is abnormal. 2. Colour. The presence of jaundice, pallor, marked plethora or cyanosis should be noted. A continued search for cyanosis should be made if the newborn becomes unsettled because cyanosis is usually most easily identified during a period of crying. Cyanosis can only be detected visually in the newborn when more than 5 g/dL of desaturated haemoglobin is present. Acrocyanosis is cyanosis of the extremities (e.g. hands and feet) without central cyanosis. It is quite common, normally observed during the first days of life (up to a week). 3. Dysmorphic features. Many syndromes in the newborn have characteristic dysmorphic features. The exact diagnosis may be the realm of the expert, but identification of dysmorphisms at the first examination is important. Particular attention should be placed on detection of facial dysmorphisms as well as that of limb, hand, feet, spinal, heart and genital anomalies. Down syndrome (trisomy 21) is one of the most common congenital syndromic diagnoses (Box 66.1). 4. Limitation of movement. This may suggest the possibility of a deep tissue injury such as a fractured clavicle or humerus. Neurological injury (e.g. brachial plexus injury) may also be heralded by a unilateral weak hand or arm. 5. Skin. The presence of any of the following should be noted. a. Vernix. This is a white substance often present on the skin at birth (Fig 66.5). Its role in the fetus is to prevent overhydration of the fetal skin. b. Lanugo. Fine downy hair covers the skin of the shoulders, upper arms and thighs (Fig 2.4). This is quite evident in premature babies but also found in term newborns. c. Petechiae. These small pin-point haemorrhagic skin lesions may be benign, occurring on the face

Chapter 66  Assessment of the Neonate

FIGURE 66.1 

Fetal–infant growth chart for newborn boys. This 2013 chart uses data from the World Health Organisation as well as data from growth registries in Australia, Germany, the United Kingdom, the United States, Canada, Scotland and Italy. Source: Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.

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FIGURE 66.2 

Fetal–infant growth chart for newborn girls. This 2013 chart uses data from the World Health Organisation as well as data from growth registries in Australia, Germany, the United Kingdom, the United States, Canada, Scotland and Italy. Source: Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.

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BOX 66.1  Down syndrome.

FIGURE 66.3 

Infant measurement of length on Measure Mat II®. Source: Hopkins Measure Mat II® ©2015 Hopkins Medical Products.

FIGURE 66.4 

Measuring the head circumference. Place the measuring tape around the largest circumference of the infant’s head, across the occiput and the forehead.

If Down syndrome is suspected, a search should be made for associated features. A striking feature is reduced neuromuscular tone, causing floppiness and marked head lag when pulled to the sitting position from supine. Other features include: ✚ bilateral single-palmar creases ✚ shortness and curvature of the fifth phalanx ✚ short, spade-like hands ✚ upward sloping (in the medial to lateral direction) palpebral fissures ✚ Brushfield’s spots (pale speckling of the periphery of the iris) ✚ brachycephaly ✚ a large tongue ✚ umbilical or inguinal hernias ✚ congenital heart disease ✚ a wide space between the first and second toe. Definitive diagnosis is by chromosome analysis, with rapid assays (Trisomy 21-specific fluorescence in situ hybridisation [FISH]) becoming increasingly available; results are often available within 24 hours. Awareness of parental anxiety and providing appropriate clinical support are key therapeutic issues when exploring a new and often unexpected diagnosis of Down syndrome. Down syndrome is discussed in more detail in Chapter 73.

Source: Ball J, Dains JE, Glynn JA, et al. Seidel’s Guide to Physical Examination. 8th edn. St Louis: Mosby, 2015. Copyright © 2015 Mosby, An Imprint of Elsevier. Figure 6.5.

due to suffusion during the birth process (Fig 66.6). If they occur on the trunk, they are much more likely to be associated with thrombocytopenia (Fig 66.7). Causes include neonatal alloimmune thrombocytopenia, secondary to chronic fetal hypoxia or marrow suppression due to congenital infection. The newer classifications of early-onset (< 72 hours) and late-onset (> 72 hours) thrombocytopenia are useful in that they help guide diagnostic investigations and hence management.1 The finding of petechiae should prompt a search for other signs of congenital infection: hepatosplenomegaly, cataracts, retinitis, microcephaly, limb abnormalities and heart disease. Lastly, given that the causes of petechiae can range from benign to significant, further paediatric opinion is often required to facilitate prompt diagnosis and guide management.

d. Milia. These occur particularly over the nose and are small sebaceous cysts (Fig 66.8). They disappear by several months of age. e. Erythema toxicum. This is a common newborn rash, manifesting as pustules with an erythematous base (Fig 66.9), which often has a widespread distribution. The site of the rash changes over a period of several hours. If there is any doubt about whether these are infected lesions, a rapid diagnosis can be made by microscopic examination of the contents of the vesicles; in erythema toxicum they contain eosinophils. f. Vesicles. These are uncommon but may be the first sign of infection with herpes simplex virus (HSV), which has a high mortality rate and requires early recognition and treatment. Luckily, in Australia, the florid presentation as shown in Figure 66.10 is becoming increasingly rare. Skin, eye and mouth (SEM) infection may present with localised clustering of vesicles with an erythematous base. This presentation accounts for 601

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FIGURE 66.6 

Petechiae in this newborn are localised to the face. This was likely due to a prolonged delivery, with impaction and/ or cord tightly around neck. Source: Courtesy of Prof. Norman Beischer.

FIGURE 66.5 

This newborn is being delivered via caesarean section, breech extraction. Vernix (the creamy white covering) on this newborn’s thighs, chest, neck and arms is clearly visible. Source: Courtesy of Prof. Norman Beischer.

FIGURE 66.7 

Widespread petechial rash is noted in this 24-hour-old infant. There are a number of important differential diagnoses to consider. In this case, this child had thrombocytopenia due to congenital rubella. Source: Courtesy of Prof. Norman Beischer.

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Chapter 66  Assessment of the Neonate

FIGURE 66.8 

FIGURE 66.9 

Source: Weston, WL, Lane, AT & Morelli, JG, Color Textbook of Pediatric Dermatology. 4th edn. Philadelphia: Mosby Elsevier, 2007. Figure 21.5. Copyright © 2007 Mosby, An Imprint of Elsevier.

Source: Courtesy of Prof. Norman Beischer.

Milia are noted on the tip of the nose. These spots may be mistaken for pustules.

This pustular-erythematous eruption on the face is consistent with the benign rash of erythema toxicum.

FIGURE 66.10 

The erythema, erosions and grouped vesicles seen in this newborn are consistent with congenital herpes infection. Prompt treatment with intravenous aciclovir is necessary.

Source: Koch LH, Fisher RG, Chen C, et al. Congenital herpes simplex virus infection: two unique cutaneous presentations associated with probable intrauterine transmission. J Am Acad Dermatol Feb 2009;60(2):312–5. Figure 2. Copyright © 2008 American Academy of Dermatology, Inc.

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approximately 50% of neonatal HSV. While it may appear benign initially, progression to central nervous system disease and/or disseminated (multi-organ) disease can occur. Other causes may be an inherited disorder of the epidermis (epidermolysis bullosa) which vesiculates prior to shedding of the skin (Fig 66.11). g. Pustules. Pustules may be present from birth in the condition of congenital candidal infection, or appear later particularly with Staphylococcus aureus skin infection. The differential diagnosis needs to include the much more common condition, erythema toxicum, which is described earlier. Another differential is pustular melanosis (Fig 66.12).

Congenital dermal melanocytosis (Mongolian spot) is the most frequently encountered newborn pigmented lesion. It presents as a large pigmented macule with indefinite borders, often distributed over the lower back. Such lesions are more

h. Hair. This is present on the head and body in variable amounts. Common cultural-genetic norms need to be recognised. i. Birth marks. Naevus simplex, also known as ‘stork bites’, are superficial vascular naevi found most commonly over the occiput and the eyelids or between the eyebrows (Fig 66.13). They fade over several months, disappearing in the second year of life.

FIGURE 66.12 

Neonatal pustular melanosis. Note the dark macules that underlay the pustules. Source: Brinster NK, Liu V, Diwan H, McKee PH. Dermatopathology: High-Yield Pathology. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 1.

FIGURE 66.13  FIGURE 66.11 

This newborn has a vesiculobullous rash that has now almost completely desquamated. A diagnosis of epidermolysis bullosa (EB) was made, with classic histopathological features of EB seen on skin biopsy. Source: Courtesy of Prof. Norman Beischer.

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Naevus simplex or ‘stork bite’ is present in up to 15% of newborns. It appears as a red area on the upper eyelids, root of nose, upper lip and/or nape of neck. These lesions are benign, often fade with time but nonetheless may case maternal anxiety. Source: Courtesy of Prof. Norman Beischer.

Chapter 66  Assessment of the Neonate

common in heavily pigmented individuals and tend to fade with time. The inexperienced observer may mistake them for bruises. A capillary malformation (port-wine stain or naevus flammeus) is a deep vascular naevus, usually found on the face, often in the distribution of a division of the trigeminal nerve. It does not fade and remains to become a cosmetic problem. Although commonly benign, there is a rare but important risk of associated neuroepileptic syndromes (e.g. Sturge-Weber syndrome) or ophthalmological issues. Infantile haemangioma (or strawberry naevus) is a raised ‘birthmark’ which may be present at birth or appear in the weeks after birth (Fig 66.14). It becomes larger for several months and then regresses spontaneously, usually by 3 years of age. Several may appear on the one individual. Treatment is necessary if the haemangioma distorts tissue such as the eyelid or airway. Occasionally, very large haemangioma leave redundant skin or scar tissue after regressing. Large haemangiomas (often separately classified) may be associated with platelet destruction and thrombocytopenia (Kasabach Merritt phenomenon).

(Congenital) melanocytic naevus is often familial and may be very large and hairy (Fig 66.15). Naevi are often heavily pigmented and well circumscribed. Depending on their distribution, they may become a cosmetic problem. No early treatment is effective; they tend to grow proportionally with the child. (Note: these are different to congenital dermal melanocytosis described earlier). Fat necrosis is an indurated area of skin where pressure has been applied over a protracted period. While not always warranted for the common and benign skin issues, a paediatric or dermatological opinion may assist families to decide on a desired course of action. Following this general examination, the systematic examination moves to the hands, followed by the arms, head, face, neck, thorax, abdomen, hips, legs and feet. This has the advantage that, unlike a systems-oriented approach to examination, there will be little need to backtrack during the examination. It can be accomplished in a relatively short time without undue disturbance to the newborn and it is unlikely that abnormalities will be missed. A caveat to this approach includes auscultation of the heart early in the examination (e.g. during or soon after undressing, prior to the infant becoming distressed from being exposed). In this instance, a more settled and quiet neonate will better facilitate cardiac auscultation. Remember: the system is hands to head, head to toe.

HANDS Polydactyly (an excessive number of digits) or syndactyly (fused digits), should alert the examiner to the possibility of other associated malformations. Extra digits can occur

FIGURE 66.14 

FIGURE 66.15 

Source: Courtesy of Prof. Norman Beischer.

Source: Courtesy of Prof. Norman Beischer.

This strawberry naevus above the left eyelid has grown since birth. It will regress with time. Treatment with oral propranolol (utilising the anti-angiogenesis effect of ß-agonists) is increasingly being administered.

A giant melanocytic naevus involving almost the entire anterior chest wall of this otherwise well newborn. These lesions do not regress. Serial excision and skin grafting can be performed when older.

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on both hands and feet (Fig 66.16). Often supernumerary digits are found joined to the ulnar side of the hand by a thin pedicle of tissue without bone (post-axial polydactyly). Ligature in the immediate newborn period is associated with complications and no longer recommended. Instead, referral for paediatric opinion and cosmetic correction is advised. Pre-axial (radial) polydactyl may be associated with syndrome diagnoses and warrants further assessment. A single palmar crease is present unilaterally in 5% of the ‘normal’ population.

ARMS Achondroplasia Short-limbed dwarfism (e.g. achondroplasia) is associated with a reduction in the length of the proximal segment of the limb relative to the distal segment (Fig 66.17).

Arthrogryposis

systematic examination. The cardiovascular examination, which is undertaken when the thorax is examined, may be initiated by palpation of the brachial artery during examination of the arm.

Grasp and Moro reflexes This is an opportune time to elicit the grasp and Moro reflexes and check head control when pulled from supine. The grasp reflex (Fig 66.18) is elicited by stroking the palms of the hands. Pulling the newborn from the wrists allows an assessment of head control to be made. The term newborn is almost able to keep the head in line with the trunk. The Moro reflex is elicited in a number of steps. 1. The newborn’s upper body is flexed with the trunk and head supported by the examiner’s open hand, raising the trunk to 30°. In this starting position, the lower back, buttocks and legs remain on the cot surface.

Arthrogryposis is restriction of the range of joint movement (e.g. inability to flex the elbow to 180°). This may suggest abnormalities of connective tissue, or be part of a syndromic diagnosis.

Acquired pathology Failure of normal spontaneous movement or failure to move symmetrically may suggest a fracture of the humerus or clavicle after a difficult delivery or the presence of a deep tissue or bone infection.

Cardiovascular examination If the newborn is quiet at this stage, it is an opportune time to undertake the only departure from the rigidly

FIGURE 66.17  FIGURE 66.16 

Extra digits can be due to autosomal dominant genetic defects. They can be isolated or part of a broader syndromic diagnosis example. Source: Courtesy of Prof. Norman Beischer.

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The proportionally shorter legs and arms seen in this infant are consistent with achondroplasia. This infant also has evidence of kyphosis.

Source: Canale ST, Beaty JH, Campbell WC. Campbell’s Operative Orthopaedics. 12th edn. St Louis: Mosby, 2013. Copyright © 2013 Mosby, An Imprint of Elsevier. Figure 41.231.

Chapter 66  Assessment of the Neonate

2. Abrupt releasing to allow the newborn to return back to the supine position (with forewarning given to family in attendance) causes the head and upper trunk to fall backwards, simulating a ‘fall’ and thus triggering the Moro reflex. 3. The resulting reflex is visualised as both arms extend upwards and outwards in response to the simulated ‘fall’. Opening of the palms with extension of the fingers is seen (Fig 66.19). This is then followed by a return to the (normal) flexed position. Failure of extension of arms and opening of the palm heralds an abnormal Moro. Abnormalities of the Moro reflex occur symmetrically if there is central nervous system depression or neuromuscular disease, or unilaterally in conditions such as fracture of the clavicle or a brachial plexus injury. Remember, a watchful mother is often nearby and reassurance and explanation is required prior to conducting the Moro assessment. Elicitation of these reflexes, along with a general appraisal of tone, strength, level of activity and alertness, form an appropriate neurological screening examination.

HEAD Size

congenital infections. The finding of macrocephaly, usually defined as a head circumference > 97th percentile for gestational age, requires that hydrocephalus be ruled out as a possible cause by cranial ultrasound imaging.

Shape and moulding A newborn cranial vault is made up of distinct separate bones or plates. There may be overlapping of the individual cranial vault bones due to moulding, facilitating movement through the birth canal. This moulding of the head during the birth process may result in a variable degree of elongation of the head (Fig. 35.8B) and settles quickly.

Fontanelles and sutures The diamond-shaped anterior fontanelle should be felt as a soft depression in the anterior part of the cranial vault (Fig 66.20). The triangle-shaped posterior fontanelle can often be hard to palpate in the immediate postnatal period (due to movement and moulding of the separate cranial vault bones). Often confusion may arise between overlapping sutures (normal) and premature fusion of sutures (abnormal, termed ‘craniosynostosis’). Plain X-ray confirmation is required for a formal diagnosis of craniosynostosis. However, appropriate paediatric follow-up over time may prevent unnecessary cranial radiation.

A non-stretch tape measure is used to measure the maximum occipitofrontal circumference. Microcephaly, usually defined as a head circumference < 3rd percentile for gestational age, may be associated with abnormalities of the brain such as occur with numerous syndromes and

FIGURE 66.19 

FIGURE 66.18 

The grasp reflex is elicited by gently stroking the palm of the newborn’s hand. Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 2.16.

Once released from the initial position, the Moro reflex occurs in response to the simulated ‘fall’. The newborn’s arms, hands and fingers are symmetrically extended, as in this image. Immediately following this, the newborn returns to a (normal) flexed posture. A ‘normal’ Moro is documented if the extension/flexion response is observed and symmetrical. Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 2.18B.

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Caput Cephalhematoma

Subgaleal haemorrhage Skin

Epicranial aponeurosis Periosteum Skull Dura

FIGURE 66.21 

Unlike a caput or cephalohaematoma, a sub-galeal haematoma can be life-threatening. FIGURE 66.20 

Palpation of the anterior fontanelle.

Source: Epstein O, Perkin GD, Cookson J, et al. Clinical Examination. 4th edn. Edinburgh: Mosby, 2008. Copyright © 2008 Mosby, An Imprint of Elsevier. Figure 12.25.

This allows for the moulding and sutures to ‘settle’, as well as for assessment of continued head growth and review of head shape.

Extra-cranial swellings or haematomas Classification of extra-cranial fluid collections or haematomas is important based on the various causes and blood-fluid collections that can occur along certain anatomical planes. Terms such as ‘chignon’ or ‘tissue haematoma’ are discouraged due to their ambiguity. An understanding of the anatomy, presentation and risk factors is important to allow for recognition of the most serious condition: a sub-galeal haemorrhage (Fig 66.21). A caput succedaneum (or simply ‘caput’) may occur spontaneously or following instrumental delivery. They can occur anywhere and may cross the suture lines (unlike cephalohaematomas; see Fig 66.21). Caputs are characterised by tissue oedema and are often associated with cranial vault moulding. They can be due to prolonged engagement in the birth canal or vacuum-assisted delivery. They often resolve in the first hours to days after birth. A cephalhaematoma occurs beneath the periosteum and thus the haematoma is confined to one cranial bony plate (usually over the parietal or occipital bone; see Fig 66.22). They are commonly associated with an instrument-assisted delivery (e.g. forceps or vacuum). Cephalohaematomas rarely expand after birth; they may completely resolve, or calcify leaving a minor convexity to the cranial vault. A subgaleal haemorrhage occurs due to shearing of blood vessels outside of the periosteum, below the epicranial aponeurosis (galea aponeurotica). This anatomical plane does not readily tamponade and persistent bleeding in this ‘space’ may cause severe,

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FIGURE 66.22 

Cephalhaematoma overlying the right parietal bone.

Source: Lissauer T, Clayden G, Craft A. Illustrated Textbook of Paediatrics. 4th edn. Edinburgh: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 10.5.

life-threatening blood loss. They present with diffuse, fluctuate swellings that may shift with palpation. They can occur spontaneously, but vacuum-assisted delivery increases the risk significantly. If a cranial swelling is evident, close observation is required, especially after an instrumental delivery. If a subgaleal haemorrhage is suspected, regular cardiovascular monitoring and prompt senior neonatal advice is required.

Encephalocele Failure of closure of the neural tube may result in an encephalocele being present in the midline on the head anywhere from the anterior face to the occiput. Spina bifida is a much more common type of neural tube defect

Chapter 66  Assessment of the Neonate

involving failure of fusion of the neural tube, usually the lower spine. Increasing awareness of the role that folate supplementation plays in preventing neural tube defects, including mandatory folate fortification of flour and bread (common in many jurisdictions around the world; commenced in Australia in 2009), has decreased the overall prevalence of neural tube defects.

FACE Ears The size, form and position of the ears are checked. Several syndromes are associated with underdevelopment of the auricle or a low positioning (low-set ears) of the auricle on the head. Low-set is defined as when the top of the ear helix falls below a horizontal line that is imaged through the middle of the eyes and outer canthus. The patency of the external auditory meatus should be visually established. Pre-auricular pits or skin tags may be benign, familial or associated with deficits of auditory acuity. Many centres now screen for congenital hearing impairment in all newborns prior to discharge (Fig 66.23).

Eyes Check that the eyes are present and of normal size. The red reflex should be routinely sought. Viewing the newborn’s pupil from a distance through an ophthalmoscope elicits the red reflex. If there is nothing abnormal between the light of the ophthalmoscope and the retina then a bright orange-red view is obtained through the pupil. (Think of a camera-flash-induced ‘red-eye’ phenomenon.) If cataracts (such as may occur with congenital infections) or retinoblastoma are present, the pupil appears white, dull or dark rather than red (Fig 66.24). Other uncommon syndromes may be associated with disorders of eye size (e.g. microphthalmia) or the distance between them (e.g. hypertelorism). Intermittent strabismus (squint) may be normal until 3 months of age. If the strabismus is always present or remains present beyond

3 months of age, referral for ophthalmologist opinion is required. Subconjunctival haemorrhages are not uncommon, especially after a difficult delivery (Fig 66.25). The haemorrhages resolve over a 2-week period. Unilateral tearing suggests a blocked tear duct, which almost always resolves spontaneously. The presence of conjunctivitis in a newborn warrants assessment for congenital gonococcal or chlamydial infection (Fig 66.26). Pupillary reflexes to light should be present and elicited (both directly and consensually) in the term newborn.

Lips A cleft lip is obvious (Fig 66.27); it may be unilateral or bilateral. The palate, including the soft palate, should be visualised and palpated. Bilateral cleft lip and palate may be associated with a more generalised midline defect with abnormalities of the brain and pituitary gland. A sucking blister is a normal variant and resolves spontaneously.

Mouth The mouth should be inspected using a torch. The roof of the mouth should be inspected to detect a cleft but must also be palpated to exclude a sub-mucosal defect of the palate. Excessive secretions should alert the examiner to the possibility of a problem with deglutition (inability to swallow): oesophageal atresia, central neurological depression or neuromuscular disease. Normal variants may include neonatal teeth. Removal may be advised since they are not well fixed and may be aspirated. Epulis is a hamartoma which arises from the alveolar ridge (Fig 66.28). It may require marsupialisation. A ranula presents as a mass beneath the tongue and is due to partial blockage of the submandibular duct. It usually resolves spontaneously. Epithelial inclusion cysts (‘Epstein’s pearls’) are commonly found on the palate and are benign. Other oral lesions are rare; however, if present they may warrant further expert opinion because they may be derived from the thyroid gland, be tumours or interfere with the patency of the airway.

FIGURE 66.24  FIGURE 66.23 

Newborn hearing screening assessment.

Source: Lissauer T, Clayden G, Craft A. Illustrated Textbook of Paediatrics. 4th edn. Edinburgh: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier.

Red reflex. Normal red reflex in the left eye and white reflex in the right eye. This patient was later diagnosed with retinoblastoma in the right eye. Source: Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin’s Neonatal-Perinatal Medicine. 10th edn. Philadelphia: Saunders, 2015. Copyright © 2015 Saunders, An Imprint of Elsevier. Figure 103.7.

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FIGURE 66.26  FIGURE 66.25 

Scleral haemorrhage is noted in this newborn. Provided the remainder of the examination is normal, this common finding is often attributable to a prolonged birth or difficult extraction.

Unilateral purulent discharge associated with erythema and swelling is noted in relation to this newborn’s right eye. Gonococcal and chlamydial infection needs to be excluded. Source: Courtesy of Prof. Norman Beischer.

Source: Courtesy of Prof. Norman Beischer.

The tongue may be large in Beckwith-Wiedemann syndrome, which may be associated with hypertrophy of limbs and organs as well as severe hypoglycaemia. Tethering of the tip of the tongue (‘tongue-tie’ or ankyloglossia) is a normal variant which has been implicated in shortterm (e.g. breastfeeding) and long-term (e.g. speech articulation) issues. However, the extent in which tongue-tie leads to clinically significant symptoms is not supported by high-quality evidence. This has lead to a diversity of opinion (and hence management practices) between professional groups such as midwives, lactation nurses, paediatricians, speech pathologist and surgeons. When counselling parents, this diversity in opinion, and hence management, should be acknowledged.

Nose Abnormalities of the nose are rare. The most serious is choanal atresia, which is an abnormal membranous cover in the nasopharynx which causes airway obstruction and respiratory distress. Since the neonate prefers to breathe through the nose, severe problems result if the choanal atresia is bilateral. The diagnosis is made if a neonatal airway suction catheter or feeding tube cannot be passed further than 1 to 2 cm through the affected nostril. 610

Skin It is normal for the active baby with long fingernails to have scratch marks on the face (Fig 66.29). Other skin features are described earlier in the chapter.

NECK Lateral masses Cystic hygromas (Fig 66.30) and branchial cysts are soft, fluctuant swellings which transilluminate. Surgical opinion should be sought.

Midline masses Midline masses are likely to be a goitre (Fig. 35.11).

Lateral fistulas Lateral fistulas may be a remnant of the branchial arch, are prone to infection and require surgery.

Sternomastoid tumour A sternomastoid tumour is due to a haematoma of the sternomastoid muscle and usually presents as a tendency for the newborn to favour head rotation towards the side of the tumour. The swelling in the body of the

Chapter 66  Assessment of the Neonate

FIGURE 66.29 

Facial scratch marks are self-inflicted in this newborn due to long fingernails. Source: Courtesy of Prof. Norman Beischer.

FIGURE 66.27 

A unilateral cleft was noted at birth in this 5-day-old infant. Assessment for the presence or absence of associated palatal defects is important. Source: Courtesy of Prof. Norman Beischer.

FIGURE 66.30 

Large neck mass consistent with a cystic hygroma. Airway compromise is the most immediate, life-threatening issue.

Source: Dhillon RS, East CA. Ear, Nose and Throat and Head and Neck Surgery. 4th edn. Edinburgh: Churchill-Livingstone, 2013. Copyright © 2013 Churchill-Livingstone, An Imprint of Elsevier. Elsevier 2013, Figure 4.16.

FIGURE 66.28 

Epulis of the left gum margin simulating a neonatal tooth. Source: Courtesy of Prof. Norman Beischer.

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sternomastoid muscle can be felt particularly as the head is rotated away from the side of the tumour and the muscle on that side is stretched. Physiotherapy by passive and active stretching of the muscle is indicated, although the majority will improve spontaneously.

THORAX Respiration

The newborn respiratory rate should be < 60 breaths per minute. Faster rates, which are often associated with sternal recession and use of the accessory muscles of respiration, define respiratory distress, which is discussed in Chapter 70. Stridor should not be present and suggests a laryngeal cause of airway obstruction.

Chest wall Variations in size, symmetry and shape of the chest may exist. Pectoral anomalies or masses may be present. Anomalies may be isolated findings or as part of a congenital syndrome.

Breasts Small, firm, discrete swellings below the nipples may signal newborn breast enlargement. This hormoneresponsive condition is common in the newborn, particularly initially and in some breastfed infants. Occasionally milk (in previous eras termed ‘witches milk’) may appear at the nipple but this, like enlargement, will resolve with the passage of time.

Nipples The nipples may be widely spaced in a number of congenital syndromes (e.g. Turner’s syndrome).

Cardiovascular examination The quality of the pulse should be palpated at the cubital fossa. A delay in the arrival of the femoral pulse compared with the brachial pulse (i.e. brachio-femoral delay) may signal a coarctation. More commonly, however, a weak or absent pulse in the lower limbs may be associated with coarctation of the aorta. Prompt detection of a critical coarctation prior to closure of the ductus arteriosus can be life-saving. The normal heart rate is usually between 100 and 170 bpm but may be lower if the newborn is in deep sleep or higher if crying. The praecordial impulse is palpated to determine that it is on the left side and of normal character with no thrills. The heart sounds are auscultated to exclude murmurs or other abnormalities. Pulse oximetry is increasingly being used as a ‘screen’ for congenital cardiac disease to improve detection.2,3

ABDOMEN Shape Distension suggests an intestinal obstruction. A scaphoid abdomen is seen in diaphragmatic hernia. Divarication of 612

the rectus abdominis muscles is not uncommon and causes a prominent bulge in the upper midline. It improves with age.

Hepatomegaly The normal liver edge can often be palpated in the newborn period, up to one or two finger-breadths below the right costal margin.

Splenomegaly The tip of the spleen can often be palpated. Enlargement may be associated with intrauterine infection or a haematological condition causing extramedullary haemopoiesis.

Umbilical cord The umbilical cord should be clean and contain three vessels: two small but thick-walled muscular arteries and one slightly larger but thin-walled vein. The site through which the umbilical vessels entered the abdomen in fetal life can be palpated as a defect in the linea alba. If an umbilical hernia is present, the bowel contents protrude through this defect, especially during crying or straining. Bowel strangulation does not occur and no treatment is necessary. Other abnormalities (gastroschisis, omphalocele) are discussed in later chapters. Two-vessel cords (one artery, one vein) are an anatomical variation. Provided antenatal ultrasounds are normal, and a postnatal assessment is otherwise unremarkable, no specific follow-up is required (although opinions differ as to whether or not postnatal renal assessment is warranted).

Inguinal hernia Inguinal hernia should be sought by visual inspection of asymmetry over the inguinal canal. In the male, the spermatic cord is no more than several millimetres in diameter and should be palpable below the external inguinal ring. If a hernia is palpated, an attempt should be made to reduce it through the inguinal canal. Inguinal hernias, unlike umbilical hernias, require prompt operative treatment due to the risk of bowel strangulation.

GENITALIA AND ANUS The site of the anus should be well away from the perineum and should be visually inspected to exclude imperforate anus (Fig 66.31).

Female external genitalia In the female, the labia minora are more prominent than later in life. Enlargement of the clitoris or ambiguous genitalia require close inspection and documentation as well as delicate discussions with the family. Prompt discussion with neonatal paediatricians, a neonatal surgeon and endocrinologists is required (Fig 66.32).

Chapter 66  Assessment of the Neonate

Hymenal skin tags are not uncommon and regress over several months. A mucoid vaginal discharge is common in the first several weeks.

Male external genitalia

FIGURE 66.31 

An imperforate anus was thought to exist on newborn assessment of this female neonate. On closer inspection, an anteriorly positioned anus was noted, in close proximity to the posterior vaginal opening. Surgical intervention is required. Source: Courtesy of Prof. Norman Beischer.

FIGURE 66.32 

Clitorimegaly is noted in this newborn; no testes are palpable bilaterally. Diagnoses such as partial androgen insensitivity or congenital adrenal hyperplasia are considerations. Assessment of internal organs as well as hormonal and chromosomal analysis guide diagnosis. Initial non-assignment of sex is an important first step in this complex socio-medical condition. Source: Courtesy of Prof. Norman Beischer.

The foreskin is normally adherent to the glans and cannot be retracted until 3 to 6 years of age. Forcible attempts to do this may result in scarring of the tissue at the tip of the foreskin, which may lead to phimosis later in life. Importantly, phimosis is rare and does not often occur in the early childhood years. It can be treated medically, with circumcision a seldom first-line option. With respect to male circumcision, various professional health bodies (e.g. the Royal Australasian College of Surgeons, the Royal Australasian College of Physicians) have conducted reviews and released position statements that are available to guide clinicians, midwives and families. This has occurred in response to changing cultural and societal norms with emerging contention around circumcision. Circumcision is now performed less commonly than previously. Many families often decide prenatally whether they wish circumcision to be performed. Reasons for this are based on cultural and religious expectations as well as personal preference and beliefs. Importantly, there are no medical indications for circumcision in the newborn period. If circumcision is considered, there are clear contraindications: 1. hypospadias; and 2. bleeding disorders. Complications post-circumcision include haemorrhage, infection, ulceration of the glans and rarely, surgical catastrophes. The procedure may be performed in the first weeks of life. Adequate procedural analgesia is necessary and post-procedure analgesia is highly encouraged. In the male, the urethral meatus should be identified at the tip of the penis. If it occurs on the underside (ventral aspect) of the penis then hypospadias is present which will often require corrective surgery (Fig 66.33). As mentioned, circumcision is contraindicated in the context of hypospadias, as the foreskin may be required in corrective surgery. The scrotum should be well developed and symmetrical. If it is not, then unilateral or bilateral undescended testes should be suspected. A red or tender scrotum suggests testicular torsion or strangulated inguinal hernia: both conditions are surgical emergencies. The testes should be palpable in the scrotum or in the inguinal canal and be able to be expressed well into the scrotum. They should be fully descended by 6 weeks of age. Both hydrocoele and inguinal hernia present as masses in the scrotum. Hydrocoeles transilluminate brightly, hernias do not. Hydrocoeles require no treatment while inguinal hernias require prompt surgical correction because of the risk of strangulation.

HIPS Dislocation Hip examination must be mastered if the tragic results of a missed dislocation of the hip are to be avoided. The 613

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FIGURE 66.33 

Hypospadias. An elongated urethral opening, extending to the scrotum, is noted in this newborn.

A

Source: Courtesy of Prof. Norman Beischer.

condition is now termed ‘developmental dysplasia of the hip’ (DDH), replacing the previous nomenclature of ‘congenital dislocation of the hip’. This highlights the developmental understanding of this condition and hence the importance of ongoing surveillance beyond the newborn period. Prompt early detection and treatment (with appropriate harness) can vastly eliminate any long-term morbidity from DDH. Adequate examination is not as difficult as it sounds and it is best learned after demonstration. First, the pelvis should be stabilised with one hand with the fingers posteriorly over the pelvis and sacrum and the thumb over the pubis. The other hand is used to grasp the femur: the middle finger over the greater trochanter and the thumb along the inner aspect of the femur. Then two manoeuvres are undertaken as shown in Figure 66.34. A. With the hip flexed to 90°, the femur is gently pushed posteriorly towards the cot mattress. If the hip is ‘dislocatable’, there will be a ‘clunk’ felt and sometimes heard as the femoral head is pushed out over the posterior acetabular rim. This is the so-called Barlow manoeuvre and is deemed positive if a posterior dislocation is elicited. B. In the case where the femur was already dislocated, no ‘clunk’ will be felt. However, it will be detected in the second manoeuvre, which is to abduct the femur with the middle finger elevating the femoral trochanter. If the hip is dislocated, then as the femur is 614

B FIGURE 66.34 

Tests for developmental dysplasia of the hip. A The Barlow manoeuvre. B Ortolani’s manoeuvre. Source: Herring JA, Tachdjian MO, Texas Scottish Rite Hospital for Children. Tachdjian’s Pediatric Orthopaedics. 5th edn. Philadelphia: Saunders, 2015. Copyright © 2015 Saunders, An Imprint of Elsevier. Figures 16.20A and B and 16.21A and B.

Chapter 66  Assessment of the Neonate

abducted it will reach a point where it suddenly relocates anteriorly, with the femoral head slipping back into the acetabulum; similarly, a ‘clunk’ is often felt in this instance. This second manoeuvre is referred to as Ortolani’s manoeuvre.

FEET Talipes Talipes is a positional deformity of the ankle and foot (Fig 66.35). There are four possible abnormal positions: calcaneovarus (foot up and in) calcaneovalgus (foot up and out) equinovarus (foot down and in), and equinovalgus (foot down and out). While it is important to use these descriptive terms correctly, of far more consequence is whether the deformity is positional or fixed. Positional deformities can be corrected to a normal position during active movement. Fixed deformities (often termed ‘club foot’) cannot be corrected even with passive movement. Fixed talipes requires physiotherapy, serial corrective plasters and sometimes surgery, which may need to be performed in the first 6 months for optimal results. Talipes is most often an isolated finding but may also occur with other abnormalities or in a variety of syndromes. One conceptual consideration for talipes is that of an in utero ‘packaging’ problem. Hence, its presence may alert the examiner to consider other ‘packaging’ problems including developmental dysplasia of the hips and assessment of the spine and neck (see Neck and Hips in this chapter).

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A

B

Supernumerary toes or absent toe The same rules apply as for supernumerary fingers (see the section on Hands earlier this chapter). Overriding toes often occur in families and do not require treatment.

Shape Abnormalities of ‘shape’ may occur in syndromes such as the rocker-bottom sole with overhanging of the heel in trisomy 18.

Tone and back The newborn is held in ventral suspension in the palm of the examiner’s hand to allow a determination of the newborn’s muscle tone as well as allowing a visual inspection to be made for back and spine anomalies. Evidence of overt spina bifida or encephalocele should be clearly seen. A sacral dimple may be evident as a midline dimple over the sacrum. Rarely, the base is not identifiable and it may be a fistula in communication with the spinal canal and predispose to meningitis. Other midline sacral anomalies (e.g. hypertrichosis, skin discolouration, lipoma, haemangioma) may herald underlying spina bifida occulta and requires further evaluation. This completes the examination.

C FIGURE 66.35 

Bilateral clubfoot. Treatment is with serial casting and/or the use of foot abduction orthoses.

Source: A Foster A, Davis N. Congenital talipes equinovarus (clubfoot). Surgery 2007;25(4). Figure 1. B Bass A. Update on club foot. J Paediatr Child Health 2011;22(6). Figure 8. C Bass, A, Update on club foot. J Paediatr Child Health 2011;22(6). Figure 7.

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COMPLETION If any abnormalities have been found, these need to be frankly discussed with the parents. Where there is uncertainty about a diagnosis or its implications, it is preferable that this be acknowledged at the time. The parents will appreciate an honest admission of uncertainty. In addition, an important part of the examination is the confirmation of abnormalities detected antenatally with ultrasonography. The presence or absence of such findings should be related to the obstetrician concerned, as should any finding of unsuspected abnormalities. A complete examination should be documented appropriately. Most infants are given a ‘child health’ book, which includes a section on the newborn exam. Any parenteral questions or concerns should be addressed. Further paediatric assessment and timely follow-up should be arranged, depending on any anomalies found. There are many variations of normal, which do not require treatment. These must be differentiated from pathological changes and appropriate advice and reassurance given to the parents. Prior to discharge, it must be established that the mother is competent in feeding and caring for her

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newborn. Educational programs on care of the baby and child rearing should be provided during the prenatal period and hospital stay. Arrangements are made for a check in the immediate post-discharge period through hospital or community-based midwife or child-health nurse domiciliary services. A thorough reassessment of the newborn at 6 weeks of age is universally recommended. Lastly, immunisation schedules should also be provided and the family doctor should be sent details of the delivery and the newborn. REFERENCES 1) Roberts I, Stanworth S, Murray NA. Thrombocytopenia in the neonate. Blood Rev 2008;22(4):173–86. 2) Paediatrics and Child Health Division, RACP. Position statement: examination of the newborn. March 2009. 3) Mahle WT, Martin GR, Beekman RH 3rd, et al. Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease. Pediatrics 2012;129(1):190–2.

Chapter 67  NEONATAL FEEDING AND NUTRITION Kypros Kyprianou

KEY POINTS The nutritional needs of the newborn can be met naturally (via breastmilk) or artificially (via formula). The advantages that breastfeeding provides include: 1. protection against infections; 2. a reduced risk of some diseases of adulthood; 3. the provision of hormones, growth factors and digestive enzymes; and 4. facilitation of mother–infant bonding. Breastfeeding is a natural process, with innate reflexes and responses (e.g. rooting reflex, sucking reflex) helping to initiate attachment and feeding. However, the technique and subsequent progression to established breastfeeding are not innate or inherited: they must be learned. Correct breastfeeding technique reduces the incidence of complications such as breast engorgement, pain, mastitis and cracked nipples, and promotes successful feeding. The practices of rooming-in, avoiding separation of the mother from her baby, early suckling in the labour ward, frequent suckling until feeding is well established, no supplementary feedings of formula (unless medically prescribed) and consistent advice have all been shown to be effective practices in promoting successful breastfeeding. For those who cannot or choose not to breastfeed, a substitute of cow’s-milk-based artificial formula can be offered. Newborns who are feeding well and are obtaining adequate nutrition will pass urine more than four times per day and their body weight will initially increase by 150 to 210 g per week. What defines ‘normal’ in terms of breastfeeding frequency and duration is extremely broad. The duration and frequency of feeding should not be regulated by the clock. Understanding the concepts behind demand feeding and reading the natural cues of neonates are an important part of education on breastfeeding. Regardless of the feeding method, there may be problems or concerns and the pathological must be distinguished from what is a variation of normal.

AN INTERNATIONAL PERSPECTIVE Breastfeeding is encouraged by international bodies such as the World Health Organisation (WHO) and UNICEF, by the training of lactation consultants to an international standard and by active groups of nursing mothers in many countries. In developing countries (with a high infant

mortality rate) there is a clear inverse association between breastfeeding and overall mortality. Artificially fed newborns in these countries demonstrate significantly higher mortality and morbidity associated with diarrhoeal illness, compared to breastfed infants. In particular, a WHO systematic review concluded that: ‘breastfeeding substantially protects against morbidity/ mortality from diarrhea and that such protection is higher among infants who are exclusively breastfed in the first 6 months of life’.1

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This same systematic review also showed that breastfeeding conferred morbidity and mortality protection (in both high- and low-income settings) against respiratory infections. A further WHO systematic review examined the long-term effects of breastfeeding.2 A small but clear protection of breastfeeding was noted, with evidence of lower overweight/obesity later in life, lower hypertension, lower type 2 diabetes (especially in adolescents) and higher IQ. (See Box 39.1.) Importantly, breastfeeding rates are increasing in both developed and developing countries.3

BREASTFEEDING Breastmilk is ideal for the term newborn. The functions of breastfeeding are to provide: nutrition immunological and antimicrobial protection hormonal influences (e.g. breastmilk hormones and growth factors) digestive enzymes (e.g. lipases) facilitation of mother–infant bonding. There is a reduced likelihood of infectious diseases such as gastroenteritis, middle ear infections and many nosocomial bacterial and viral infections in the breastfed infant compared with the artificially fed infant. As mentioned, in developing countries, this protection against infection, particularly against diarrhoea, translates into a distinct survival advantage. Epidemiological studies require randomisation to establish strong associations between interventions and outcomes, but it has often not been possible to do this in studies of breastfeeding. However, some well-conducted epidemiological studies suggest that breastfeeding may: protect against later diseases including diabetes mellitus, cancer, ischaemic heart disease, multiple sclerosis, coeliac disease and Crohn’s disease result in a higher cognitive performance reduce the risk of sudden infant death syndrome (SIDS) increase the success of maternal–infant bonding in the mother, reduce the risk of ovarian cancer and pre-menopausal breast cancer.

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ANATOMY OF THE BREAST

areola, which contains 18 to 20 sebaceous glands known as the Montgomery follicles.

INTERNAL STRUCTURE The glandular tissue is divided into 15 to 20 lobes. Each lobe radiates outwards from the areola like the spokes of a wheel. The lobes are divided into lobules, which are made up of milk-secreting units known as alveoli. The alveolar cells take up the substances they require from the maternal blood to form breastmilk. Internal cellular and para-cellular pathways synthesise and secrete the various components of human breastmilk: lactose, oligosaccharides, fats, proteins (e.g. casein, lactalbumin, IgA), electrolytes and cellular components (e.g. macrophages) into the alveolar lumen. The alveoli drain into intralobular ducts that unite to form lactiferous ducts. The lactiferous ducts dilate as they pass towards the nipple to form the lactiferous sinuses, which are situated at the base of the nipple. From these sinuses, the lactiferous ducts open onto the summit of the nipple. Extensive fibrous tissue and fat separate the lobes and support not only the glandular tissue but also the vessels, nerves and lymphatics.

Changes during pregnancy During pregnancy, changes occur in the breast, preparing it for the function of lactation. These changes are brought about by progesterone, which stimulates alveolar growth, and oestrogen, which in turn stimulates proliferation of the duct system. Changes include the following. Increased blood supply; the veins over the breast become noticeable. Enlargement of both the breast (proliferation of lactiferous ducts and alveolar growth) and the nipple occur. The areola enlarges and becomes more pigmented. Montgomery follicles, which are modified sebaceous glands in the areola, become more prominent; their secretion keeps the nipple soft and pliable during pregnancy. Colostrum can be expressed. Striae may appear during pregnancy and usually do so at the time of rapid enlargement of the breasts, often late in the first trimester. Striae do not occur with the rapid, and sometimes extreme, enlargement which occurs with the onset of lactation. More information on lactation and breast disorders can be found in Chapters 39 and 59.

• • • • • •

EXTERNAL STRUCTURE

PHYSIOLOGY OF LACTATION

The breast lies between the second and sixth rib and extends from the sternum, with a tail which extends to the axilla (the axillary tail of Spence). In the centre of the breast is an erectile structure, the nipple, the tip of which is indented by the openings of 15 to 20 lactiferous ducts. Surrounding the nipple is an area of pigmented skin, the

The process of lactation takes place in three stages: the production of milk in the alveoli, the flow of milk along the ducts to the lactiferous sinuses and the withdrawal of milk from the nipple by the baby. During pregnancy, the anterior lobe of the pituitary gland releases prolactin, but production of breastmilk is

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held in abeyance by inhibition of prolactin by the high blood oestrogen level. After delivery, the level of oestrogen falls, allowing prolactin to initiate lactation. Stimulation of local nerve endings by the baby sucking in turn induces secretion of more prolactin and thus more breastmilk. The ejection of milk is helped by the hormone oxytocin, which is released from the posterior lobe of the mother’s pituitary gland in response to suckling; this is the basis of the let-down or milk-ejection reflex. Oxytocin causes contraction of the myoepithelial cells in the mammary alveoli, forcing milk into the lactiferous ducts. Oxytocin also causes uterine muscle contraction and so uterine pain (‘afterpains’) may be initially experienced during breastfeeding.

COLOSTRUM For the first two to three days after the birth of the newborn, the secretion of the breast is colostrum, which differs from mature milk in both appearance and composition. It is yellow in colour, thicker in composition and usually formed in only small amounts. It has a high protein content and a low carbohydrate and fat content. It has high concentrations of immunoglobulins and immunocompetent cells.

‘COMING-IN’ OF THE MILK On the second to fourth day after birth, the composition of the breast secretion changes and milk volume increases. The breasts become full and sometimes tense and uncomfortable due to a combination of venous engorgement and milk engorgement: this is termed the ‘coming-in’ of the milk. To maintain successful lactation, the necessary requirements are: 1. an adequate and frequently repeated sucking stimulus to provide the neurohormonal reflex; 2. complete emptying of the breast; and 3. a mentally and physically healthy mother.

BREASTMILK Breastmilk varies in composition between each breast, between feeds, during each feed, diurnally and over the course of lactation. Four major constituents are listed. 1. Protein. The protein content of human milk is lower than that of other mammals. Whey (soluble protein) comprises 60 to 70% of the protein, with the remainder being casein (insoluble protein). IgA is also secreted in human breastmilk. 2. Fat. The fat content is highly variable, increasing markedly during the feed and being highest in the late morning and early afternoon. Fatty acid profiles are different from cow’s milk, but do vary in human milk depending on maternal diet.

3. Carbohydrate. The carbohydrate content of breastmilk is lactose, which is present in higher concentration in human milk than in cow’s milk. Lactose promotes calcium absorption and the growth of natural intestinal lactobacilli. 4. Micronutrients. Cow’s milk has higher mineral concentrations than human milk and, in particular, its high sodium concentration makes it unsuitable for use in the newborn. Breastmilk is an adequate sole source of nutrition until 4 to 6 months of age. The exceptions to this are the need for additional vitamin K to prevent haemorrhagic disease of the newborn. Additionally, iron and other micronutrients diminish in concentration over time; hence, supplementation (especially for premature infants born < 32 weeks’) is sometimes required.

ANTENATAL PREPARATION When the mother first visits the antenatal clinic, a history is taken of any previous breastfeeding experience. An examination of the breasts is made, noting in particular the presence of inversion or retraction of the nipple. The general health of the mother should be maintained at as high a level as possible and a balanced diet is very important. Maternal elimination diets (during pregnancy and breastfeeding) have not been shown to confer benefits to the newborn in terms of protection for atopic diseases. The advantages of breastfeeding are discussed with the parents, and the mother is encouraged to believe in her capacity to breastfeed. She is given instruction in the physiological process of lactation, so that she has some idea of what to expect after the birth of the baby. Knowledge of breastfeeding is acquired, not inherited. While knowledge of the benefits of breastfeeding is important, many women choose to breastfeed not so much because of the demonstrated benefits but because they regard it as a fulfilment of motherhood. Antenatal preparation of the breast and nipple such as rolling out the nipple is not necessary. If the nipple is inverted, wearing plastic nipple shields antenatally has not been demonstrated to be effective and may actually reduce the likelihood of successful breastfeeding by focusing attention on the nipple as a problem.

MANAGEMENT OF BREASTFEEDING Breastfeeding is a partnership between the mother and baby, the most important period being the first few days after the baby is born. The baby is put to the breast as soon after birth as possible. The mother may do this but if not, it should be suggested by the obstetrician or midwife and facilitated by the staff. The setting should be as tranquil as possible and measures may need to be 619

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taken to keep the newborn warm; skin-to-skin contact of the mother and baby with a sheet or blanket over the baby is often satisfactory. This early suckling stimulates the release of oxytocin and prolactin from the maternal pituitary gland, and facilitates both uterine involution and milk production by the mother. A joint statement by WHO and UNICEF describing 10 steps to successful breastfeeding (outlined in Box 39.2) was released in the late 1980s. In the decades following this statement, evidence of the efficacy of these steps mounted. In particular, antenatal education (step 3), showing mothers how to breastfeed (step 5) and continuing support after discharge (step 10) are proving to be cost-effective and robust health interventions, irrespective of resource limitation.4

TECHNIQUE OF BREASTFEEDING Attention to technique in the early stages may prevent many later problems. The principles are that the mother should be comfortable, the newborn should be brought to the breast rather than vice versa and help with repositioning on the second breast may be necessary. The mother adopts a position of comfort such as sitting up in bed with her back supported, lying on her side or sitting on a chair. The baby, awake and eager to feed, is held securely, close to the mother’s body and facing her. The baby’s back, neck and head should be straight and well supported. The baby’s mouth should be open. It may be necessary to stroke the corner of the mouth with the nipple to elicit the ‘rooting’ reflex in which the baby opens the mouth. The baby is brought to the breast rather than feeding the nipple and breast into the baby’s mouth. It is important that the baby attaches adequately by taking a good amount of the breast, including the nipple and much of the areola into the mouth (Fig 67.1). Failure to do this will mean that the nipple will be sucked on directly, causing nipple trauma and pain. When attached correctly, the gums will then lie over the lactiferous sinuses (Fig 39.2). If the baby is appropriately positioned, it is not necessary to depress the breast to ensure that the nose is unobstructed. Unnecessary depression of the breast may cause blockage of some of the alveolar ducts leading to breast engorgement and mastitis. Milk is then obtained from the breast mainly by the action of the whole mouth of the baby in compressing the lactiferous sinuses and less so by direct suction. During the first several minutes, the let-down reflex occurs and the baby obtains the greater part (90%) of the milk (the foremilk) at this time. The feed should be continued on one breast because the hindmilk which comes later in a feed is richer in fat. The other breast may be offered at the same feed depending on the interest of the baby, but it is not necessary for a baby to feed from both breasts at each feed. Help with the repositioning process is advisable to ensure that the mother is comfortable. 620

FIGURE 67.1 

This newborn is partially attached. Ideally, the nipple and much of the areola should be in the newborn’s mouth, often with the tip of the nose against the mother’s breast. Source: iStockphoto/onebluelight.

When the infant has finished feeding, the breast is often released spontaneously. This may be facilitated by gently pushing down on the jaw or placing a finger into the corner of the mouth and thus breaking the vacuum created by the sucking. There are no rules about either the time that the baby should stay at the breast or the time between feeds. This is an important area of parental education that needs to be reinforced. During or at the conclusion of feeding, the baby may be winded or burped. This is performed by holding the baby upright against the mother’s shoulder while she exerts gentle pressure on the back by rubbing or stroking. When ready, the infant is then placed on their back, in the cot. Immediate and longer-term signs of successful feeding are contentment, appropriate alert/sleep cycles, normal tissue turgor, at least four or five wet nappies per day and an adequate weight gain (150 g or more per week over the first 3 months). It is not necessary to provide supplementary feeds in the appropriately grown term newborn, even in the hottest climates.

BREASTFEEDING DIFFICULTIES The difficulties which may arise with breastfeeding have numerous causes (Fig 67.2). A careful history and examination of the mother, the baby and the feeding process will allow an accurate diagnosis to be made, which is a prelude to successful treatment. The difficulties may be general or local and may be in the mother, the baby, the caregiver or any combination of these. The problems may have a psychological, physiological or anatomical cause.

Chapter 67  Neonatal Feeding and Nutrition

Maternal difficulties Engorgement Engorgement commonly occurs on the third or fourth day (Fig 67.3). Hormonal activity causes an increase in blood flow to the breasts and a sudden increase in milk production. Tension in the breast increases, with Pain Anxiety, uncertainty, lack of interest

Pain

Hungry dissatisfied baby

Sore/cracked nipple

Poor let-down reflex

Bacterial infection

Breast engorgement

Mastitis

resulting obstruction to the venous and lymphatic vessels and interference with the flow of milk along ducts. Engorgement may also occur at any time during lactation when there is inadequate removal of milk from the breast. The condition may be treated and also largely prevented by allowing the baby unrestricted suckling. Milk may need to be expressed at the beginning of the feed so that an adequate amount of the breast can be taken into the baby’s mouth. Expression of milk between feeds may also be necessary. Analgesia may be necessary for a short period. Persistent pyrexia may signify infection, possibly mastitis.

Breast infection

Failure of lactation

FIGURE 67.2 

Interrelated factors which can result in breast engorgement, breast infection and failure of lactation. Source: Courtesy of Prof. Norman Beischer.

Mastitis Inflammation of the breasts is usually due to problems with milk flow such as may occur if the baby is not fed as often as usual. It may also follow breast engorgement and cracked nipples. The infecting organism is usually Staphylococcus aureus. The breast or breasts are inflamed, hard, reddened and painful, with enlarged glands in the axilla, pyrexia and often malaise. Prevention is by adequate breast emptying and the avoidance of cracked nipples. When mastitis has occurred, the breast should be emptied adequately, usually by allowing the baby to suckle, but by manual expression as well if necessary. Anti-staphylococcal antibiotics may be prescribed empirically. Definite isolation of causative organism is via breastmilk culture. Often there is no contraindication to breastfeeding during the period of antibiotic therapy. Breast abscess If mastitis is not treated adequately, an abscess may form (Fig 67.4). Diagnosis may be difficult because fluctuation is less easy to elicit than at other sites. If resolution does

FIGURE 67.4  FIGURE 67.3 

Engorgement of the breasts on day 5 of the puerperium. Source: Courtesy of Prof. Norman Beischer.

Breast abscess.

Source: Bland KI, Copeland EK. The Breast. 4th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 5.7A.

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not occur with appropriate antibiotics, incision and drainage is carried out. In difficult cases, ultrasound imaging may be useful in identifying a collection of pus.

that is necessary in the first few days. Very large nipples are uncommon and do not preclude breastfeeding.

Flat or inverted nipples The baby does not feed from the nipple, but rather from the breast. Very often, feeding will be successful despite a flat or inverted nipple. The initial expression of some milk to soften the breast may be useful. Evidence that the use of a nipple shield is effective in this situation is lacking, though such shields are often used.

A history is necessary to identify irritants such as soaps, solvents or perfumes as causes of dermatitis. Treatment is by attention to the correct technique of feeding to ensure good attachment and also by wiping milk on the nipple and areola at the conclusion of a feed. A topical cortisone cream and systemic analgesics may be necessary for a short period if the condition is severe.

Overabundance

Psychological difficulties

Overabundance of milk is uncommon once the milk has ‘come in’ and supply and demand have stabilised. It is recognised by rapid refilling of the breasts, constant leaking of milk, and vomiting, choking and rapid weight gain in the baby. Sometimes weight gain is poor because the newborn takes large volumes of foremilk, which is rich in lactose; this may be associated with frequent loose stools. Treatment is by expressing a small amount of milk prior to each feed and feeding from one breast only at each feed. In this way, each breast is stimulated to produce milk only at alternate feeds.

Insufficient supply Postnatal maternal illness (e.g. severe anaemia in a setting of postpartum haemorrhage) may interfere with milk supply. Alternatively, this problem is often seen where the mother is anxious, tense and/or apprehensive. The mother may have a poor knowledge of breastfeeding (supply and demand, overemphasis on ‘strict’ feeding times, attachment, let-down reflex and so on). The condition is recognised by: the baby crying frequently between feeds, although subsequently the baby may become lethargic weight loss or inadequate weight gain signs of dehydration (infrequent concentrated urine, loss of skin turgor, lethargy). Treatment is by checking that attachment and position are correct, encouraging frequent feeding, allowing adequate time for feeding and relieving fear, tension, pain or anxiety. If these measures are not effective, the newborn may be fed via a ‘supply line’ while suckling at the breast, which may improve the newborn’s sucking and can increase maternal milk supply. The antiemetic agent domperidone is sometimes used ‘off label’ to increase milk supply. It works by an antidopaminergic effect that increases prolactin release.5

• • •

Cracked nipples

The mental attitude of the mother plays a vital role in the success of breastfeeding. Fear of failure, anxiety to succeed, a poor self-image, misinformation and ignorance may all play a part in breastfeeding not being successful. These reasons must be distinguished from the others listed here. Encouragement and the fostering of a positive self-image may be required. Conflicting information from health professionals must be avoided. All clinical staff should be familiar with the contents of the breastfeeding information sheet, which should be provided to expectant mothers antenatally.

Neonatal difficulties Feeding characteristics vary a great deal between newborns. Some feed slowly, others quickly, some feed continuously, others take long rests during a feed. Because the range of normal is wide, it is important not to label a behaviour as abnormal when it is not. The astute health advocate emphasises this notion—that a wide range of normal exists—as it can explain and alleviate much maternal anxiety, not just about breastfeeding.

Inability to suck adequately This may occur in the preterm newborn, or in one with congenital malformation, neurological disease or acute systemic illness such as infection. The diagnosis should be made after physical examination. A strong and effective suck often develops from around 34 weeks’ gestation. If the cause is prematurity, the baby usually requires feeding by a gastric tube (orogastric or nasogastric).

Anatomical problems The baby with cleft lip and palate will have difficulty with breastfeeding, but may be successful with professional support. Expressed breastmilk can be fed using a special bottle and teat. Choanal atresia and micrognathia are other causes of difficulty.

Sore nipples

A sleepy or lethargic baby

The sensitivity of the nipple increases after birth. Nipple pain is common in the first week after delivery. Treatment consists of ensuring proper attachment (the baby should breastfeed, not nipple-feed), not applying proprietary compounds to the nipple, which increase the chance of dermatitis, and checking for signs of candidal infection of either the nipple or the baby. Reassurance may be all

The baby may not be ready for feeding. If persistent, or if this is a sudden change, examine the baby, looking for signs of illness such as congenital heart disease, a dysmorphic syndrome (e.g. Down syndrome), neuromuscular disease, cleft palate or sepsis. Sometimes none of these illnesses will be found, in which case the lethargy or sleepiness may be due to a difficult delivery, sedation

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from intrapartum drugs or drugs in the breastmilk. Importantly, a sleepy or lethargic baby warrants a prompt paediatric medical opinion.

Breast refusal Refusal of the breast by the baby is a demoralising experience for the mother. This is usually temporary and requires only perseverance. Early refusal is more likely to be caused by errors in technique such as inappropriate attachment, positioning or duration of feeding, while later refusal warrants seeking medical causes, particularly of the ear, nose and throat system, such as oral candidiasis. Neonatal–maternal interactions are also important considerations.

Difficulties created by caregivers When there are difficulties with breastfeeding, it is important that expert diagnosis of the problem and advice is given. It is not appropriate to simply recommend that a change to artificial feeding will solve the problem. In healthcare facilities where formula is conspicuous, where formula manufacturers’ leaflets imply that breastfeeding can be difficult and that artificial feeding is the obvious answer, the mother may receive an ambivalent message: the stated message being that ‘breast is best’, but the implied message being that ‘formula is equally good’. Training resources for health workers are available from various sourcess, including the WHO, UNICEF and established breastfeeding advocacy services (e.g. Lactation Consultants of Australia and New Zealand.)

BREAST EXPRESSION The methods of breast expression may be manual or mechanical, the latter being by means of a hand or electrical pump. Manual expression is the method of choice unless the expression is to be for a long duration, such as following the birth of a very preterm newborn. Manual expression. After washing the hands, the fingers are placed under the breast for support with the thumb on top. Compression is applied between the fingers and thumb rhythmically about 30 times per minute. Occasional pressure and stroking of the breast with the fingers and palm is helpful in forcing milk towards the nipple. Hand pump. The pump is held firmly over the nipple and the plunger withdrawn, applying suction to the breast. This is repeated until the breast feels empty. Electric pump. The pump is placed over the nipple and the power switched on. The pump withdraws milk into a container by applying intermittent suction (Fig 67.5).

•

• •

SUPPRESSION OF LACTATION The reasons why lactation may need to be suppressed are perinatal death, the mother does not wish to breastfeed,

FIGURE 67.5 

Electric pump being used to express breastmilk into a sterilised bottle. Source: Shutterstock/Gemenacom.

the baby is to be adopted, puerperal psychosis, to wean suddenly after breastfeeding or when breastfeeding is contraindicated. In the developed world, breastfeeding is contraindicated in infants of HIV-positive mothers and hence suppression may be required. However, in developing countries the risks of not breastfeeding may outweigh the risk of acquiring HIV infection and it may be safer to breastfeed. Indications for the suppression of lactation do not include babies who may not initially be able to breastfeed but may be able to later, such as the preterm or sick newborn. There is only a short list of maternal drugs which are contraindicated in breastfeeding. These are cytotoxic drugs, radioactive compounds and some psychoactive medications. Suppression is best achieved by avoidance of breast stimulation. Analgesia for temporary painful engorgement may be necessary. This is all that is required in the majority of cases. Cabergoline is used to suppress breastmilk via its dopamine agonist properties, thus decreasing prolactin secretion. A single dose of 1 mg cabergoline is given on the first day post-partum for lactation inhibition. Given that prolactin can act as a natural contraceptive, its inhibition may result in an earlier return to fertility.

RELACTATION For a number of reasons, such as sore nipples or separation of mother and baby, a mother may cease breastfeeding but then wish to resume lactation. This may be related to factors such as missing the closeness of the baby, or new information regarding the advantages of breastfeeding. Relactation will be successful in the majority of cases. 623

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The baby should be offered the breast frequently; until the supply has been established, it is necessary to ensure that adequate nutrition is provided.

Donor human breastmilk In the neonatal intensive care unit (NICU) setting, adequate awareness and practices concerning the nutrition of premature infants have contributed to improving neonatal outcomes. Artificial non-human (‘formula’) milk has been associated with increasing the risk of necrotising enterocolitis (NEC). As such, donor human breastmilk is being utilised in NICUs around Australia. From the 1940s to 1970s, local community hospitals did practice human milk sharing. Following trends from overseas, 2006 saw the first pasteurised donor human milk (PDHM) bank opening in Perth, Australia. PDHM banks are now present in a number of Australian states, although its implementation is not yet universal. The human breastmilk is pasteurised and offered as an alternative to artificial formula when the mother’s own milk is unavailable. Quality assurance, community education and donor screening are all important considerations. Various practices and protocols exist, though commonly PDHM is offered to newborns in intensive care who are < 32 weeks’ and are at risk of, or recovering from, NEC.

ARTIFICIAL FEEDING The indications for artificial feeding are maternal preference or, rarely, contraindications to breastfeeding (e.g. HIV-positive mother in the developed world, maternal medications). The purpose is to provide nutrition where a substitute for breastfeeding is required. Modern formulas (based on cow’s milk) meet the nutritional requirements of the newborn. Unmodified cow’s milk should not be used. It is important to be sensitive to the different reasons why mothers may choose to feed their babies a formula. Reasons include associations with others who have failed at breastfeeding and embarrassment at using the breast for feeding. The mother’s right must be respected and her choice supported. The process of bottle-feeding should be made as satisfying as possible for both herself and her newborn. However, she deserves warm, skilled support, not a cold assurance that failure does not matter. Any artificial feed must: be well tolerated by the newborn; provide sufficient calories; provide sufficient carbohydrate, protein and fat; provide sufficient water; and contain adequate minerals, salts and vitamins. Modern formulas based on cow’s milk are modified to attain a composition similar to that of breastmilk. Formulas are available in a powdered form which requires reconstitution with water that is boiled then cooled. Interestingly, despite a pro-breastfeeding ethos in most maternity hospitals, there is often a ready supply of ready-mixed formula. Each formula may have 624

a different method for reconstitution. The manufacturer’s instructions must be followed. Indeed, the safety of formula feedings is entirely dependent on reconstitution of the formula in the correct strength, the cleanliness of the water, the cleanliness of the apparatus (i.e. bottles, teats) and safe storage of the prepared feed. Hospital staff should ensure that the mother understands the importance of these issues. ‘Follow-on’ formulas are recommended for infants from about 6 to 12 months of age. Beyond 12 months of age, full-cream, store-bought cow’s milk is sufficient (if combined with a wideranging nutritious intake of ‘solids’).

METHOD OF FEEDING While the sense of intimacy fostered by breastfeeding is advantageous to mother and newborn, a loving mother feeding artificially can impart a sense of security to her newborn. To this end, the mother should simulate breastfeeding as closely as possible. Face-to-face contact is possible as the baby is held closely. Traditionally, the milk is warmed to body heat, but babies happily adjust to taking milk at room temperature. Formula should not be warmed in a microwave oven because of the danger of the feed being too hot. Babies should never be left unattended while bottle-feeding.

First feed The first feed can be given once the mother has been transferred to the postnatal ward. There is no advantage to early feeding as there is with breastfeeding. The first feed should be of full-strength formula when the newborn is awake and within the first 4 hours. The exception to this is the at-risk neonate; that is, if the newborn is small for gestational age, preterm or the infant of a diabetic mother. Hypoglycaemia may ensue and early feeding within the first 2 hours should be commenced if the newborn is well. Local protocols and policies exist to ensure neonatal hypoglycaemia (and the subsequent risk of seizures) is mitigated by adherence to feeding regimes/ protocols for at-risk newborns.

Frequency and duration of feeds Feeding should be on demand. Most babies settle into a pattern of feeding every 3 to 4 hours. As mentioned previously, the normal spectrum can be broad, with an appreciation that feeding outside these strict parameters may indeed still be normal. Feed volumes vary from feed to feed. Table 67.1 shows the approximate feed volumes taken in a 24-hour period for artificially fed newborns. The baby is fed until satisfied, with a limit of 30 minutes for each bottle. The baby should be ‘winded’ in the same way as the breastfed baby during and at the end of the feed.

Volume of feed The healthy breastfed term newborn drinks a variable amount ranging from about 100 to 180 mL/kg of body

Chapter 67  Neonatal Feeding and Nutrition

TABLE 67.1  APPROXIMATE FEED VOLUMES FOR ARTIFICIALLY FED NEWBORNS. Postnatal day

Fluid (mL/kg body weight/day)*

1

30–60

2

60–90

3

90–120†

4

120–140†

5–6

140–160†

Day 7 onwards

150–180†

*This table serves as a guide for artificial feeding volumes. Newborns who are breastfed often have significantly lower volumes of predominantly colostrum in the first 24 to 48 hours. †Babies requiring intravenous fluids have similar requirements over the first 1 to 3 days of life. Intravenous volumes rarely exceed 100 mL/kg/day from day 3 or 4 onwards.

weight per day, but averaging about 150 mL/kg/day by the end of the first week. A widely used regimen of fluid volumes in those receiving formula is shown in Table 67.1. Similar regimes or protocols exist to govern intravenous fluid administration in newborns that are nil-by-mouth.

Prior to hospital discharge Prior to hospital discharge, the following issues should be dealt with. Adequate instruction in an appropriate language must be given to the mother about the importance of the correct reconstitution of the formula and about the methods of cleaning and sterilising the feeding equipment. The mother should be observed to ensure that she understands the instructions. The method, frequency and volume of feeding should be understood. The mother should be advised to attend a child health centre regularly to check that progress is satisfactory and to provide guidance if necessary.

•

• •

NON-ENTERAL FEEDING Intravenous fluids or nutrition will be required in any newborn where there is the following: an abnormality of the gastrointestinal tract that limits bowel function and milk absorption (e.g. bowel atresia, imperforate anus, meconium ileus, gastroschisis, diaphragmatic hernia), or severe systemic illness which is likely to limit gut function (e.g. septicaemia, respiratory distress syndrome).

• •

A limited ability to tolerate enteral feeds during the acute phase of respiratory distress places the newborn at risk of aspiration.

HAEMORRHAGIC DISEASE OF THE NEWBORN Adequate supplies of nutrients and vitamins are available in breastmilk or formula, with the exception of vitamin K. Supplementation of all newborns with vitamin K virtually eliminates haemorrhagic disease of the newborn. In Australian, a single intramuscular dose of 1 mg of vitamin K is given at the time of birth. Parental apprehensions and fears may result in refusal; however, large-scale international studies have clearly showed no adverse effect of intramuscular administration of vitamin K. Oral administration is offered rarely (regime consisting of three oral doses of 2 mg at the time of birth, at hospital discharge and at 4 to 6 weeks of age).6 However, variable absorption and loss to follow-up (thus missing the second or third dose) often results in subtherapeutic administration and hence oral administration is discouraged. Haemorrhagic disease of the newborn is discussed in further Chapter 74.

PROBLEMS Vomiting Vomiting small amounts of feed (termed ‘positing’) is almost universal in the newborn because of physiological immaturity of the gastro-oesophageal sphincter. Maturation of the sphincter mechanism makes positing uncommon after 4 to 6 months of age. The vast majority of babies will have no pathological cause for their vomiting; a search for overfeeding or incorrect preparation of artificial formula should be made. The following features make an organic cause more likely. Green, bile-stained vomiting suggests a bowel obstruction. Vomiting without having passed a stool suggests a low level of bowel obstruction. Abdominal distension raises the possibility of either bowel obstruction or ileus due to conditions such as necrotising enterocolitis. Temperature instability or lethargy necessitates sepsis being excluded; vomiting and fever in newborns and infants is a common presentation for urinary tract infection. Projectile vomiting beyond the neonatal period may suggest pyloric stenosis. This condition usually presents between 1 and 2 months of age with projectile vomiting, a palpable pyloric mass and visible gastric peristaltic waves seen post-feed. Treatment is surgical. Blood mixed in the vomitus suggests blood has been ingested, either at the time of delivery or from a

• • • • •

•

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breastfeed. The blood is hence often maternal in origin and the mother has been unaware of it. If the blood is thought to be from the infant, evaluation is necessary. Rarely, oesophagitis complicating gastro-oesophageal reflux may cause blood-stained vomiting (Box 67.1). Vomiting and diarrhoea suggests a gastrointestinal infection. Adequate oral rehydration must be maintained if complications are to be avoided.

•

Colic Colic is characterised by inconsolable crying periods, especially in the evening. The infant is often distressed and red in the face, with legs drawn up as if in pain. Importantly, the infant is otherwise thriving and has settled periods during the day when well. Definitions of colic often quote the ‘rule of 3s’; that is, inconsolable crying for up to 3 hours per day, for 3 or more days per week, for up to 3 weeks’ duration. Colic and unsettled behaviours usually peak at around 6 weeks of age and resolve spontaneously at about 3 months of age. Importantly, many newborns present with less crying than a colicky baby that is nonetheless distressing to both baby and family. Comorbid vomiting, diarrhoea, perianal excoriation or weight loss are important clinical findings that can direct the clinician to ‘non-colic’ differentials. A physical examination to exclude inguinal hernias, otitis media, hair-tourniquet, anal fissure and so on is also necessary before the diagnosis of colic is made. Attention to feeding, handling and settling techniques may reduce the frequency of crying, but the ultimate cause remains unknown. Over-the-counter colic medication is often used, though with little evidence of efficacy. A maternal elimination diet or formula change are rarely indicated. Reassurance, support and close follow-up are key therapeutic aims.

Constipation Constipation refers to a hard consistency of the stool rather than the frequency with which the bowels are opened. Breastfed infants may not open their bowels for

BOX 67.1  The Apt test. The Apt test can determine whether the vomited blood is of maternal (i.e. ingested) or infant in origin. The Apt test is performed by diluting the bloody vomitus in normal saline and then adding an equal volume of 10% NaOH (caustic soda). Adult haemoglobin is denatured and turns brown; fetal haemoglobin stays pink. Note that due to safety concerns (i.e. exposure to 10% caustic soda), this test is not often utilised in postnatal healthcare settings. 626

up to 7 days, but only rarely are constipated. Artificially fed infants usually open their bowels each day and are likely to have hard stools if they do not. A newborn’s immature gastrointestinal system and reduced renal ability to balance solutes are important considerations when directing families to give neonates anything other than breastmilk or formula (such as water with brown sugar or prune juice). A poloxamer stool softener (10% Coloxyl drops) may be used; rarely, glycerine suppositories may be necessary for more severe cases. Assessment for causes (e.g. Hirschsprung’s disease) may be required if the constipation course, duration and severity is unusually protracted.

Slow weight gain In the first 3 months, the average weight gain is around 150 to 200 g per week. A weight gain consistently < 150 g per week is termed ‘failure to thrive’, and a cause should be sought. This should be done systematically with the possible causes being the environment, the mother, the breast, the feeding process or the newborn. A history is taken to examine the social circumstances, maternal physical and mental health (including mother’s nutrition), postnatal medical issues, adequacy of sleep and level of fatigue. A physical examination should be made of the breast and then of the newborn: congenital heart disease, structural abnormalities of the mouth, neuromuscular disease, hypothyroidism and infection should be excluded. Hypothyroidism is usually excluded if a newborn screening test result is normal. The possibility of a urinary tract infection should be checked by microscopic examination and culture of a urine sample collected via a sterile technique. The mother and newborn should be observed during a feed to determine the adequacy of attachment and suckling. Lastly, genetic factors and constitutional predisposition may be simple explanations. Thorough history and examination, as well as tracking growth on appropriate growth charts, can assist in formalising a diagnosis and hence treatment plans. Sometimes no cause for poor weight gain can be identified. In this case, it is necessary to maintain a positive attitude and develop an achievable plan for the number and duration of feeds, maternal diet, supports and rest. REFERENCES 1) Horta B, Victora CG. Short-term effects of breastfeeding: a systematic review on the benefits of breastfeeding on diarrhoea and pneumonia mortality. Geneva: WHO; 2013:16. 2) Horta B, Victora CG. Long-term effects of breastfeeding: a systematic review. Geneva: WHO; 2013. 3) Imdad A, Yakoob MY, Bhutta ZA. Effect of breastfeeding promotion interventions on breastfeeding rates, with special focus on developing countries. BMC Public Health 2011;11(Suppl. 3):S24.

Chapter 67  Neonatal Feeding and Nutrition

4) World Health Organisation. Evidence for the ten steps to succesful breastfeeding. 1998. Online. Available: . 5) Royal Women’s Hospital. Domperidone for increasing breast milk supply. June 2013. Online. Available: . [19 Apr 2015].

6) National Health and Medical Research Council, Paediatric Division of the Royal Australasian College of Physicians, Royal Australian and New Zealand College of Obstetrics and Gynaecology, Royal Australian College of General Practitioners, Australian College of Midwives. Joint statement and recommendations on vitamin K administration to newborn infants to prevent vitamin K deficiency bleeding in infancy. Canberra: NHMRC; 2010.

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Chapter 68  NEONATAL JAUNDICE Kypros Kyprianou

KEY POINTS Jaundice is present in about 50% of newborns in the first week after birth and can be visually detected in the newborn when the plasma bilirubin is approximately 80 µmol/L or more. The physiological processes of bilirubin production in newborns parallels that of children and adults: natural red cell destruction and decay, bilirubin binding to plasma proteins, conjugation by glucuronyl transferase in the liver, excretion into the biliary tract and finally resorption from the bowel lumen back into the bloodstream. There are various reasons why a newborn is at risk of developing jaundice. One reason is the transient immaturity of the glucuronyl transferase system. In this case, it is termed physiological jaundice which does not present as jaundice in the first 24 hours after birth and usually requires no treatment. Haemolysis is usually caused by maternal antibodies destroying fetal red blood cells, such as in rhesus isoimmunisation or ABO incompatibility. This may result in severe unconjugated hyperbilirubinaemia, which usually presents in the first 24 hours after birth. Unconjugated bilirubin, when present in high concentrations, may cross the blood–brain barrier and cause bilirubin encephalopathy and a characteristic type of brain damage termed ‘kernicterus’. Treatment of hyperbilirubinaemia to prevent kernicterus is by the use of phototherapy or exchange transfusion. Very high concentrations of unconjugated ‘free’ bilirubin, and/or an impaired blood–brain barrier (such as in extreme prematurity, sepsis or acidosis), increases the risk of kernicterus. Elevated levels of conjugated bilirubin are found in obstructive jaundice; this is likely to have a pathological cause. As such, prompt assessment, diagnosis and treatment are required, even though conjugated bilirubin does not cross the blood–brain barrier and hence does not cause kernicterus.

NORMAL BILIRUBIN METABOLISM The elimination of bilirubin in the fetus is aided by placental transference and is cleared by the maternal liver. Figure 68.1 shows the pathways of normal bilirubin metabolism in the newborn. An understanding of the primary bilirubin metabolites—and how they are reported in laboratory

measurements—is required when exploring and evaluating jaundice in the newborn. The total serum bilirubin equates to the sum of unconjugated bilirubin (sometimes referred to as indirect bilirubin) concentration and the conjugated bilirubin (or direct bilirubin) concentration. An understanding of both metabolites is important as they herald different but equally clinically important haematological diagnostic pathways. Haem is the precursor to bilirubin. Most of the haem is liberated from haemoglobin that is produced by

Chapter 68  Neonatal Jaundice

SITE

•

PROCESS

Tissues Spleen Liver Blood

Breakdown of haemoglobin

Circulation

Bilirubin bound to albumin

Liver

Bilirubin conjugated

Gut

Bilirubin

Stool

Excreted

Enterohepatic recirculation

FIGURE 68.1 

Pathways in the normal metabolism of bilirubin. Source: Courtesy of Prof. Norman Beischer.

physiological red blood cell decay and destruction. However, about 25% comes from red cell precursors and other haem-containing proteins such as cytochrome P-450 and myoglobin. Bilirubin is transported in the plasma bound to albumin as unconjugated bilirubin until processed by the liver. A small but variable amount (approximately 0.1%) of bilirubin in the plasma is unbound or free. It is only this fraction of bilirubin that is available to cross the blood–brain barrier and thought to cause kernicterus. The bilirubin is then transported into the hepatocyte where an intracellular enzyme, glucuronyl transferase, conjugates the bilirubin. Unlike unconjugated bilirubin, conjugated bilirubin is water soluble. The conjugated bilirubin is then secreted from the hepatocyte into the biliary system and thence into the bowel. Once in the bowel, bilirubin may be converted to urobilinogen by the action of gut bacteria. The gut (meconium and faeces) acts as a reservoir of bilirubin. The gut wall contains a glucuronidase enzyme which cleaves conjugated bilirubin back to unconjugated bilirubin. There is constant reabsorption of bilirubin from the gut: the enterohepatic recirculation of bilirubin. Urobilinogen is not reabsorbed or reconverted back to bilirubin. The serum bilirubin reaches a peak on the third day in the healthy term newborn and on the fifth day in the preterm newborn. Newborns are at risk of developing jaundice due to a number of reasons. Transient immaturity of the conjugation system in the liver. The uptake mechanism of unconjugated bilirubin from the blood, the intracellular transport of bilirubin, its conjugation by glucuronyl transferase and its transport out of the cell into the bile duct are all delayed in the newborn in comparison with the older infant. This results in unconjugated bilirubin circulating in the blood.

•

Excessive breakdown of red blood cells. The haemoglobin level falls gradually after birth from a mean of 19 g/dL at birth (but can be as high as 21 g/dL) to 11 g/dL at 3 months of age. The fetal red cell has a mean lifespan of only 80 days compared with that of the infant, which is 120 days. Birth trauma, particularly if there is haematoma formation, results in a large load of haemoglobin to be broken down. Gastrointestinal factors. The gut is sterile at birth and becomes colonised with bacteria over the first days of life. Bacteria are thought to play a role in the enterohepatic recirculation of bilirubin and its byproducts. Furthermore, bilirubin present in the meconium in the gut is available to be reabsorbed. Delay in the passage of meconium may be associated with an increased risk of jaundice.

•

CAUSES OF JAUNDICE There are three general possibilities for the origin of jaundice. 1. Prehepatic: increased production of bilirubin. 2. Intrahepatic: delayed or abnormal metabolism and clearance by the liver. 3. Posthepatic: inability to excrete conjugated bilirubin. The causes of jaundice considered in these three major groupings are shown in Box 68.1. The history and physical examination may provide important clues as to the likely diagnosis. Increased production of bilirubin occurs if there is haemolysis (see ABO and Rh-haemolytic disease later in this chapter). Inquiries need to be made as to whether the mother’s blood group is Rh-negative and whether she has had previous newborns affected either by ABO or Rh-haemolytic disease of the newborn. The presence of haematomas, especially cephalhaematoma, increases the load of destroyed red cells and hence bilirubin. Delayed physiological clearance of bilirubin by the liver is not usually associated with any special clinical features. Rarely, congenital infection will be the cause of a neonatal hepatitis leading to jaundice. Hepatitis usually results in not only a reduced ability to conjugate bilirubin in the hepatocyte, but also a reduced ability to excrete conjugated bilirubin. Inability to secrete conjugated bilirubin is usually due to anatomical abnormalities of the biliary system such as biliary atresia or choledochal cyst. Because bile does not pass into the bowel in normal quantities, the stool is very pale. Conjugated hyperbilirubinaemia results in a characteristic green tinge to the jaundice.

INVESTIGATIONS Jaundice occurs in 50% of newborns, but in the vast majority of cases this is not pathological and does not require investigation. There is great individual variation 629

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BOX 68.1  Causes of jaundice. Pre-hepatic: increased production of bilirubin Haemolysis ✚ Fetal–maternal blood group incompatibility: Rh or ABO haemolytic disease of the newborn ✚ Genetic causes: red blood cell enzyme defects such as G6PD deficiency (common) or pyruvate kinase deficiency (rare) Extravascular blood ✚ Cephalohaematoma; significant bruising in context of difficult delivery Polycythaemia ✚ Twin–twin transfusion ✚ Chronic fetal hypoxia Intra-hepatic: delayed or disordered metabolism of bilirubin by the liver Decreased bilirubin conjugation ✚ Congenital reduction in glucuronyl transferase (Gilbert syndrome; though doesn’t present in infancy; Crigler-Najar syndrome) Infection ✚ Hepatitis (TORCH infections) ✚ Sepsis Decreased transport of conjugated bilirubin out of the liver ✚ Congenital transport defect (very rare) ✚ Hepatocyte damage: tyrosinaemia, galactosaemia; α1 antitrypsin deficiency (Note: may present with obstructive jaundice) Hypothyroidism and, rarely, other endocrine disorders Post-hepatic: inability to secrete (conjugated) bilirubin: ‘obstructive’ jaundice Extrahepatic ✚ Extrahepatic biliary atresia ✚ Choledochal cyst Intrahepatic biliary atresia

in the bilirubin level, which results from a given load of bilirubin; hence, a precise definition of what constitutes physiological and pathological jaundice is precluded. In general, any term infant whose bilirubin is > 240 µmol/L by the third day after birth (> 48 hours of age) requires consideration as to the cause. A commonly accepted algorithm for the assessment of jaundice in the newborn is the maxim of too early (jaundice < 24 hours), too high (elevated unconjugated bilirubin from day 2 to day 10 of life) or too long (prolonged jaundice, > 10 days but especially more than 2 weeks). In addition, elevated conjugated bilirubin (> 25 µmol/L) or jaundice in any neonate that is lethargic 630

or one with temperature instability necessitates specific diagnostic and therapeutic interventions.

TOO EARLY If the jaundice presents in the first 24 hours, haemolysis is the most likely cause and should be sought on a blood film. The cause of haemolysis may be determined by performing a direct Coombs test (DCT, also known as direct antiglobulin test or DAT) and checking the mother’s and newborn’s blood group. The most common causes of haemolysis are ABO haemolytic disease of the newborn and Rh-haemolytic disease of the newborn (discussed later). Other causes are inherited disorders of the red cell membrane, which make the red cells more fragile. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency are differentials. Haemoglobinopathies (e.g. thalassaemia and sickle cell disease) do not usually present as a jaundiced neonate.

TOO HIGH If marked jaundice is present, investigation and treatment should be undertaken. Although most commonly no pathological cause is found, it is not otherwise possible to exclude pathological causes. Even if no cause is found, the combination of several factors such as prematurity, dehydration, delayed passage of meconium, bruising and physiological jaundice may result in bilirubin levels high enough to warrant treatment. Haemolysis due to red cell membrane disorders should be excluded as a cause by performing a blood film, particularly if the rise and peak in the bilirubin is different from the physiological peak at day 3. Crigler-Najar syndrome, which is an uncommon inherited disorder with a deficiency of glucuronyl transferase, presents in this way as a bilirubin level that continues to increase over weeks.

TOO LONG Prolonged jaundice is that which lasts more than 10 days, but especially greater than 14 days. The first test to be performed in this situation is an estimation of both unconjugated and conjugated bilirubin. If the conjugated bilirubin is not elevated, the possibilities that should be sought are urinary tract infection and breastmilk jaundice (see later in this chapter). Galactosaemia, fructosaemia and hypothyroidism may all cause prolonged jaundice but are usually included in newborn screening programmes. Lastly, congenital hepatitis may also present with prolonged jaundice.

OTHER CONSIDERATIONS Importantly, jaundice in a lethargic baby or one with temperature instability suggests the possibility of septicaemia. Prompt investigations should be undertaken to seek the cause of the lethargy, and intervention with appropriate antibiotic cover may be life-saving.

Chapter 68  Neonatal Jaundice

Elevated conjugated bilirubin (> 25 µmol/L) implies the presence of obstruction to the excretion of conjugated bilirubin. Obstructive jaundice can manifest with pale stools and dark urine. Causes of prolonged conjugated jaundice include extrahepatic biliary atresia, biliary cysts, congenital infections and inborn errors of metabolism. Urgent paediatric gastrointestinal assessment is required if obstructive jaundice is found in the newborn period. Conjugated jaundice (neonatal cholestasis) is discussed later in this chapter.

SERUM BILIRUBIN MEASUREMENT Jaundice tends to progress from the face to the feet. Previously, ‘rules of thumb’ have been used to assess jaundice in otherwise healthy, term newborns. (For example, if only the face is jaundiced, the total serum bilirubin is about 100 µmol/L; If jaundice is detectable on the abdomen, the bilirubin is about 200 µmol/L; If jaundice is present on the feet and soles, the bilirubin is about 300 µmol/L.) Differences in skin colour and genetic factors may alter these ‘rules’. Increasingly, non-invasive transcutaneous devices are being used in healthcare settings to estimate total serum bilirubin concentrations. Importantly, these ‘bedside measures’ are unreliable, and if hyperbilirubinaemia is suspected, then a true serum bilirubin (including conjugated and unconjugated bilirubin) should be measured. In prematurity, serum bilirubin measures should always be used to assess jaundice. Remember, the clinical history and examination of the jaundiced neonate is paramount. Combining all these facts with the knowledge that physiological jaundice peaks on the third day, and with good clinical acumen, one can be guided in decision making in the assessment of the jaundiced newborn.

to the newborn in the event of accidental breakage of the light globe as well as absorbing potentially harmful ultraviolet radiation (Fig 68.2). There is no role for phototherapy in the treatment of conjugated hyperbilirubinaemia in the newborn. Nomograms are used to determine the bilirubin level at which phototherapy treatment should be started. Figure 68.3 shows an example of a nomogram that is widely used. Recently, there has been a trend to introduce phototherapy only at much higher bilirubin levels if no pathological cause for the jaundice is likely, because there appears to be minimal risk of kernicterus in the well term infant until higher levels are attained. The main features of these charts are that: treatment must be commenced early if jaundice appears early because the most likely cause is haemolysis, which will continue to cause the bilirubin to rise preterm infants may develop kernicterus at lower levels of bilirubin, hence treatment is instituted at these lower levels. Many healthcare centres use their own protocols and nomograms to guide staff in the therapeutic use of phototherapy. Phototherapy is usually administered continuously, but because the rate-limiting step is migration of bilirubin from the plasma into the skin, the intermittent use of phototherapy (e.g. allowing the infant to be removed for breastfeeding) may be just as effective. Once phototherapy has been commenced, monitoring must be by serum assays of bilirubin, rather than the clinical degree of jaundice. The newborn is nursed naked, except for eye shields and nappy, in an incubator. Phototherapy causes premature ageing of the retina in some animals and it is

• •

TREATMENT Treatment is directed at the specific cause as well as preventing the (unconjugated) bilirubin from reaching potentially toxic levels. Phototherapy is the near universal first-line treatment if the serum unconjugated bilirubin exceeds certain thresholds. Further elevation in serum bilirubin may require the need for an exchange transfusion.

PHOTOTHERAPY Light in the visible spectrum, especially blue light of wavelength 450 to 460 nm, causes photoisomerisation and photo-oxidation of unconjugated bilirubin in the skin. While unconjugated bilirubin is chemically unaltered, this structural rearrangement renders it water soluble. The liver and the kidney can then excrete it without requiring conjugation. Specially designed light sources which emit high intensities of light at this wavelength should be used. A perspex cover prevents damage

FIGURE 68.2 

A jaundiced infant receiving phototherapy; the eyes are covered, but otherwise the child is naked. Source: Wikimedia Commons.

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25

428 µmol/L Total serum bilirubin (mg/dL)

Exchange transfusion

428

20

342

20

342

15

257

15

257

171

10

10 Infants at lower risk (≥ 38 weeks' and well) Infants at medium risk (≥ 38 weeks' + risk factors or 35–37 6/7 weeks' and well) Infants at higher risk ( 35–37 6/7 weeks' + risk factors)

5 0

Birth

24h

48h

72h

Age

96h

5 days

6 days

85

0 7 days

• Use total bilirubin. Do not subtract direct reacting or conjugated bilirubin. • Risk factors = isommune hemolytic disease. G6PD deficiency, asphyxia, significant lethargy, temperature instability, sepsis, acidosis, or albumin < 3.0 g/dL (if measured). • For well infants 35–37 6/7 weeks' can adjust TSB levels for intervention around the medium risk line. It is an option to intervene at lower TSB levels for infants closer to 35 weeks' and at higher TSB levels for those closer to 37 6/7 weeks'.

171 Infants at lower risk (≥ 38 weeks' and well) Infants at medium risk (≥ 38 weeks' + risk factors or 35–37 6/7 weeks' and well) Infants at higher risk ( 35–37 6/7 weeks' + risk factors)

5 0

Birth

24h

48h

72h 96h Age

µmol/L

Total serum bilirubin (mg/dL)

Cut-offs for commencing therapy

Phototherapy

25

85

0 5 days 6 days 7 days

• The dashed lines for the first 24 hours indicate uncertainty due to a wide range of clinical circumstances and a range of responses to phototherapy. • Immediate exchange transfusion is recommended if infant shows signs of acute bilirubin encephalopathy (hypertonia, arching, opistholonos, fever, high pitched cry) or if TSB is 2.5 mg/dL (85 µmol/L) above those lines.

FIGURE 68.3 

The graphs above show cut-off ranges for instigating phototherapy and exchange transfusion for newborns with unconjugated hyperbilirubinaemia. Note that the cut-off differs depending on age post-birth, gestational age and/or the presence/absence of accompanying illness. Abbreviations: G6PD = Glucose-6-phosphate dehydrogenase, TSB = Total serum bilirubin. Source: Wyllie R, Hyams JS, Kay M. Pediatric Gastrointestinal and Liver Disease. 4th edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figures 17.7 and 17.8.

recommended that the eyes not be exposed to phototherapy. Cardiorespiratory monitoring is useful to alert staff if eye shields become dislodged and cover the baby’s airway. Newer devices for delivering phototherapy are increasingly being used. An alternative method of delivering phototherapy is by a waistcoat containing fibreoptic bundles that administer phototherapy to the trunk. This appears to be effective and has the advantage that the newborn is not removed from the mother and does not need to wear eye shields. Similarly, a ‘bili-blanket’ (Fig 68.4) or ‘bili-bed’ may facilitate breastfeeding while still delivering phototherapy. However, their ease of use—and potential misuse, thus reducing efficacy— need to be taken into account when choosing the type of phototherapy to treat neonatal unconjugated hyperbilirubinaemia. Lastly, the location of treatment can be either at the mother’s bedside or in special care nursery. Local protocols will dictate where the newborn receives phototherapy, guided by the clinical concerns or underlying diagnosis. Balancing the need to promptly and adequately treat unconjugated hyperbilirubinaemia with the need to feed and foster maternal bonding are important considerations. When the risks of kernicterus are high, phototherapy may need to be conducted in a tertiary neonatal intensive care. 632

FIGURE 68.4 

A newborn receiving phototherapy via a ‘blanket’ light source. Source: iStockphoto/KarenMower.

In summary, the following precautions require emphasis: 1. identify the cause of jaundice; 2. monitor temperature frequently; 3. use eye shields and check position frequently; 4. monitor fluid balance and increase intake if necessary; and 5. measure bilirubin levels at

Chapter 68  Neonatal Jaundice

least every 6 to 12 hours (depending on the underlying cause of jaundice).

EXCHANGE TRANSFUSION Phototherapy is instituted in order to prevent the need for exchange transfusion. The level of bilirubin at which an exchange transfusion should be undertaken is suggested in Figure 68.3. The interpretations and precautions listed earlier under Phototherapy need to be observed. Exchange transfusion aims to replace the newborn’s blood volume with cross-matched blood, thus removing the bilirubin from the bloodstream. Further benefits of exchange transfusion include that it removes antibodies if they are contributing to haemolysis and assists in the correction of underlying anaemia. The transfusion process aims to exchange 80 to 90% of the total blood volume of the newborn and is accompanied by an expected halving of the pre-exchange bilirubin level. The need for exchange transfusion has decreased markedly since the introduction of anti-D globulin, which has resulted in a marked decrease in the incidence of Rh-haemolytic disease of the newborn. Complications of exchange transfusion can be lifethreatening and include air embolism, haemorrhage, infection, and fluid and electrolyte disturbances.

OTHER TREATMENTS There are no other established treatments for newborn jaundice. More commonly, however, adjunct treatment (in addition to phototherapy and/or in the lead-up to exchange transfusion) may be used. This includes haemodilution (with appropriate neonatal intravenous fluid) and, in some tertiary neonatal institutions, the use of intravenous immunoglobulin or albumin infusions. Drug therapy plays little role in the management of neonatal jaundice. For example, phenobarbitone induces the hepatic glucuronyl transferase, which may increase the speed of bilirubin metabolism, or mesoporphyrins (e.g. tin mesoporphyrin) may be utilised as they block the formation of bilirubin.

SPECIFIC CONDITIONS HAEMOLYTIC DISEASE OF THE NEWBORN (UNCONJUGATED HYPERBILIRUBINAEMIA) The prenatal diagnosis and management of Rh-haemolytic disease has been discussed earlier (see Ch 22).

Rh-haemolytic disease Approximately 15% of Caucasians are Rh-negative, with only 1% of Asian and African women Rh-negative. If

the mother is Rh-negative and the fetus is Rh-positive, any fetal red cells which cross into the mother’s circulation will be recognised as foreign. The woman may produce antibodies which can cross the placenta back to the fetus. Antibodies are most likely to be produced when there has been a previous transfusion of Rh-positive cells into the mother’s circulation such as occurs during pregnancy, at the time of abortion or during delivery. Since the advent of prophylaxis with anti-D globulin, the incidence of Rh-haemolytic disease has fallen dramatically. If the maternal plasma antibody titre rises to ≥ 1:16 (which is equivalent to ≥ 5 IU/mL) during pregnancy, then the risk of fetal anaemia increases. (See Chapter 22, Management of the moderate- or high-risk immunised pregnancy). Rhesus isoimmunisation and fetal anaemia are lifethreatening to the fetus and management should be undertaken by an experienced obstetrician. Intrauterine blood transfusion may be necessary on one or more occasions to prevent hydrops fetalis. Delivery may be indicated before term if the risks of intrauterine transfusion are greater than the risks of preterm birth. When the baby is born, blood is collected from the umbilical cord for blood group, direct Coombs test, and haemoglobin and bilirubin estimation. The indications for exchange transfusion are: born hydropic or pre-hydropic (oedematous, pale with marked hepatosplenomegaly) cord blood haemoglobin level < 10.0 g/dL cord blood bilirubin level > 70 µmol/L rapid rate of rise in bilirubin levels, or bilirubin levels approaching the level which may place the baby at risk of kernicterus (as per nomograms).

• • • • •

ABO haemolytic disease Unlike Rh-haemolytic disease, ABO haemolytic disease tends not to cause severe in utero fetal anaemia. The problems are those of neonatal hyperbilirubinaemia in the postnatal period and subsequent risk of haemolytic anaemia and kernicterus. The mother is usually of blood group O and the baby of group A. Because the maternal antibodies which cause the haemolysis are pre-existent, the first baby may be affected. This is different from the situation with Rh-haemolytic disease, where the maternal antibodies are only produced in response to an Rh-positive fetal blood transfusion. Presentation is with jaundice in the first 24 to 48 hours after birth. The direct Coombs test, which tests for antibody-coated fetal cells, may be positive or negative. The indirect Coombs test, which tests for antibodies in serum, is positive. Phototherapy or occasionally exchange transfusion may be necessary to treat hyperbilirubinaemia. 633

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RED CELL ABNORMALITIES

KERNICTERUS

Glucose-6-phosphate dehydrogenase deficiency is much more common than pyruvate kinase deficiency. In G6PD deficiency, oxidising agents lead to destruction of the red cell wall. Such agents are naphthalene (commonly contained in moth balls in which the baby’s clothing may have been stored), nitrofurantoin, salicylates, sulphonamides, some anti-malarials and fava beans (also known as broad beans). The infant may be exposed to these agents in sufficient quantities to cause haemolysis either directly or via breastmilk.

The ultimate aim in evaluating and treating jaundice is to prevent significant treatable sequelae as well as prompt assessment of any significant other causes of newborn jaundice (as described earlier). Kernicterus is the most significant sequela of marked unconjugated neonatal hyperbilirubinaemia. Kernicterus is caused by high levels of unconjugated bilirubin. When the plasma capacity to bind unconjugated bilirubin (less in premature infants) is exceeded, the additional free unconjugated bilirubin readily crosses lipid membranes, such as the blood–brain barrier. Here it damages cellular metabolism by inhibiting essential enzymes, and so causes brain damage. Transient encephalopathy or permanent brain damage may result. At toxic bilirubin levels, the newborn becomes lethargic, then hypertonic with opisthotonos (Fig 68.5). A high-pitched cry and seizures may ensue. If kernicterus does not result in death, there may be a transient recovery; however, long term neurological disability occurs. This manifests as choreoathetoid cerebral palsy, intellectual disability, paralysis of upward gaze and

OBSTRUCTIVE JAUNDICE   (NEONATAL CHOLESTASIS) Extrahepatic biliary atresia Biliary atresia often presents as prolonged conjugated jaundice. There is evidence of damaged (sclerosed) bile ducts due to an unknown cause in the perinatal period. Alternatively, congenital absence of the extrahepatic biliary tree can occur. In these settings, death is usual by 2 years of age unless treatment is instituted. Delay in the diagnosis of biliary atresia results in a poor prognosis for surgical intervention. Since the intrahepatic ducts are relatively less affected, treatment is by anastomosis of small bowel to the porta hepatis (a hepatoportoenterostomy or Kasai procedure). Ultimately, a liver transplantation is required.

Neonatal hepatitis Neonatal hepatitis is due to intrauterine infection with the TORCH agents (toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex) or metabolic causes, or it is idiopathic. Hepatosplenomegaly may be present.

Other causes Other causes of obstructive jaundice include intrahepatic biliary atresia or biliary cysts. Inborn errors of metabolism that cause conjugated hyperbilirubinaemia include galactosaemia, fructosaemia and tyrosinaemia. Cystic fibrosis and α1-antitrypsin deficiency are also important considerations.

BREASTMILK JAUNDICE Prolonged jaundice due to unconjugated bilirubin in the breastfed infant may occur without any identifiable cause. Once it has been established that there is no elevation of the conjugated bilirubin and that the baby is well, no other investigations may be necessary. The cause is uncertain but the presence of fatty acids liberated by high breastmilk lipase activity may facilitate the intestinal reabsorption of bilirubin. There is no specific test available to make the diagnosis. The infant is not at risk of kernicterus in the uncomplicated case because the bilirubin concentrations are not high enough and hence phototherapy is not required. 634

FIGURE 68.5 

This newborn has opisthotonic posturing. It can be caused by various neurological insults including kernicterus. In this case, however, it was caused by neonatal tetanus. Source: Magill AJ, Ryan ET, Solomon T, Hill DR. Hunter’s Tropical Medicine and Emerging Infectious Disease. 9th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 55.1.

Chapter 68  Neonatal Jaundice

high-frequency sensorineural hearing loss. If the baby dies, autopsy findings reveal the effect of unconjugated hyperbilirubinaemia on brain anatomy: the subcortical nuclei in the brain are stained bright yellow and there is widespread neuronal necrosis. Although rare in the developed world, kernicterus still occurs. The incidence of kernicterus due to Rhhaemolytic disease has fallen but despite this, vigilance should remain. Seventy-five per cent of newer cases of kernicterus can be attributed to hyperbilirubinaemia in the context of G6PD deficiency or haemolysis (ABO incompatibility), or can be idiopathic.1 Unfortunately, in the developing world, where healthcare systems

are affected by poverty and conflict, death and neurological disability from neonatal hyperbilirubinaemia still exists.2 REFERENCES 1) Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr 2002;140(4):396–403. 2) Kaplan M, Bromiker R, Hammerman C. Severe neonatal hyperbilirubinemia and kernicterus: are these still problems in the third millennium? Neonatology 2011;100(4):354–62.

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Chapter 69  NEONATAL NEUROLOGICAL PRESENTATIONS Kypros Kyprianou

KEY POINTS Throughout gestation—and even in the postnatal period—damage to the nervous system and developing brain can occur. The extent and permanence of this damage will depend on the source of the insult and the period of the particular developmental stage at which it occurs. There are a number of sources that are potentially damaging to the developing brain. These include, but are not limited to, genetic abnormalities, toxins such as alcohol, congenital infections, maternal undernutrition, prolonged fetal hypoxia, inborn errors of metabolism, bacterial meningitis or sepsis, hypoglycaemia and kernicterus. The floppy (hypotonic) newborn presents a diagnostic challenge, with abnormalities potentially anywhere along the central and peripheral nervous system: from problems in the brain, spinal cord, peripheral nerves or muscles. Disorders outside the nervous system may also cause hypotonia. Immaturity of anatomical brain structure as well as immaturity of the physiological control of blood supply are risks factors for intraventricular haemorrhage and periventricular leucomalacia, especially in the preterm newborn. Determining accurate long-term neurodevelopmental outcomes following a neurological insult, can be very difficult. This is in part due to neuronal plasticity, where the developing brain may take over the function of damaged areas.

DEVELOPMENTAL EVENTS There are five phases of brain growth. 1. Dorsal and ventral induction. The neural plate develops in the embryo at 16 days. The plate folds and fuses to form the neural tube on day 26. Neural crest cells migrate widely to innervate the gut and autonomic ganglia. By 6 weeks’ gestation, the basic structures of the brain have developed and the embryonic period is over. The cerebrum, optic vesicles, olfactory bulbs, cerebellum and brainstem are all present. Anencephaly, encephalocele, spina bifida and holoprosencephaly arise in this period of brain development.

2. Neuronal proliferation. The first neurones form at 6 weeks’ and neuronal proliferation is complete by 20 weeks’. Glial cell proliferation continues throughout life. Microcephaly has its origin in this period. 3. Neuronal migration. Cortical neurones are formed deep within the cerebrum from where they migrate to the cortex. Each successive wave of migrating cells passes beyond the previous one to form a more superficial layer of the cortex. This process is complete by 20 weeks’ in the cerebrum but continues until after birth in the cerebellum. Disorders during this period are those of abnormal migration such as lissencephaly, pachygyria and heterotopias. Bundles of axons form as the migration occurs. Disorders in this process

Chapter 69  Neonatal Neurological Presentations

may be associated with conditions such as absence of the corpus callosum. About 50% of all neurones formed subsequently die. The mechanisms and clinical importance of this process are uncertain. Autism may also have its origins in abnormal neuronal proliferation, migration and arrest.1,2 4. Neuronal differentiation. This occurs from 3 months to several years of age. The processes are poorly understood but are of clinical relevance: the neonatal brain has plasticity and may be able to recover from some injury; unilateral visual deprivation in the newborn period may result in permanent loss of visual acuity; and disorders of this process may hinder intellectual development. Neuronal differentiation may be involved in ‘learning’ that continues throughout most of life. 5. Myelination. While the first oligodendrocytes elaborate myelin at 20 weeks’, the majority of myelination begins around the time of birth and continues for several years. Oxidative metabolism in the brain is qualitatively similar to that in the adult. Glucose is the most efficiently metabolised, and indeed the sole source of, energy utilised in the stable state. Particular conditions exist in the neonate in which there is a compromise of oxygen supply (asphyxia) or in glucose supply (hypoglycaemia). Table 69.1 outlines anatomical anomalies that correspond to damage in one or more of the phases of brain development. This damage may be idiopathic, nutritional, genetic, infective or toxin mediated.

SPECIFIC NEONATAL CONDITIONS Neonatal conditions with a neurological presentation may occur prenatally, at birth or in the neonatal period.

NEONATAL ENCEPHALOPATHY An altered level of consciousness, with or without seizures, is the key manifestation of neonatal encephalopathy. In the term newborn, a specific cause of encephalopathy related to asphyxia is termed hypoxic ischaemic encephalopathy (HIE). However, other causes of encephalopathy must be considered. The severity of the hypoxic ischaemic encephalopathy categorised by a thorough bedside assessment of the neurological state of the newborn. Mild HIE presents with minimal evidence of neurological irritation, manifesting as hyper-alertness, tremulousness or irritability. There is normal muscle tone and no seizures. Prompt resolution of symptomatology over the first few days post-delivery ensues. Moderate HIE is demonstrated by an abnormal electroencephalogram (EEG), seizures, lethargy and hypotonia. Resolution occurs over a number of days, up to a few weeks. Severe HIE manifests in more severely depressed consciousness, often with abnormalities of brainstem function such as respiratory depression. Pronounced

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TABLE 69.1  NEURO-ANATOMICAL ABNORMALITIES AND THEIR DEFINITIONS. Abnormality

Definition

Anencephaly

The absence of the cranial vault above the bony orbits, associated with the absence of the cerebral hemispheres and midbrain.

Encephalocele

The protrusion of intracranial structures through a defect in the skull. The herniated sac may contain meninges and brain tissue (encephalocele) or only meninges (meningocele).

Spina bifida

A midline defect of the vertebrae, with consequent exposure of the neural canal contents. Synonyms include spinal dysraphism, rachischisis, myelomeningocele, myelocele and meningocele.

Holoprosencephaly

A heterogeneous central nervous system anomaly that results from a primary defect in induction and patterning of the rostral neural tube (basal forebrain). This defect leads to varying degrees of incomplete separation of the cerebral hemispheres.

Lissencephaly

A neuron migration abnormality characterised by disturbed migration of neurons from the ventricular germinal matrix to the cortex, manifesting as a ‘smooth brain’ or agyria.

Pachygyria

A neuron migration abnormality characterised by thick or coarse gyra.

Heterotopia

A neuron migration abnormality characterised by ectopic collections of neurons in abnormal locations.

Source: Definitions adapted from Copel JA, D’Alton ME, Gratacós E, et al. Obstetric Imaging. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Chapter 33, 174–180.

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neurological deficits include flaccidity, markedly abnormal EEG (with or without overt seizures) and depressed reflex responses. If death does not occur, symptoms may persist for several weeks.

Causes and investigation Often the cause is clear: a catastrophic event such as placental abruption or prolapsed umbilical cord causing prolonged hypoxia and asphyxia. In these cases, no specific investigations may be necessary. Other clues (e.g. pre-delivery abnormalities of fetal heart rate on CTG monitoring) may have been present indicating fetal distress of varying aetiologies (as discussed throughout the book). Acute bacterial meningitis may present as an encephalopathy, although it is often associated with other signs indicative of sepsis (e.g. temperature instability, respiratory distress, apnoea or hypotension). Depending on the neurological and cardiorespiratory stability of the newborn, a lumbar puncture should be performed to definitively diagnose meningitis if suspected. Other less common causes of neonatal encephalopathy are some inborn errors of metabolism. In these cases there will have been no history of asphyxia, and the presence of hypoglycaemia, unexplained acidosis and/or hyperammonaemia may be clues. A further clue may be deterioration towards the end of the first week of life: as metabolic demands in the newborn increase, the inborn error is unable to meet these demands. Consultation with a metabolic expert to determine the appropriate investigations and treatment is recommended. Irrespective of the cause, and depending on the severity, investigations of neonatal encephalopathy may include any or all of the following: cranial ultrasound, MRI and EEG.

Treatment Treatment is aimed at the specific cause. If there has been perinatal asphyxia, then supportive care is paramount. Supportive care includes the preservation of neurological, respiratory, cardiovascular and metabolic equilibrium. That is: 1. prevention of hypoglycaemia; 2. prevention of hypoxaemia and hypercapnia; 3. maintenance of adequate blood pressure; 4. control of seizures; 5. prevention of fluid overload; and 6. provision of adequate ventilation. The use of therapeutic hypothermia has been shown to improve survival and reduce long-term neurological sequelae of HIE.3 In severe HIE, therapeutic hypothermia is now the standard of care in most tertiary neonatal units (Box 69.1). No other specific therapies, such as induced coma, glucocorticoids or hyperventilation, have been shown to be beneficial in asphyxiated newborns. If the degree of asphyxia is severe, other non-CNS organ damage may ensue. Cardiovascular compromise may be evident; inotropes may be required to improve myocardial contractility and organ perfusion. Renal 638

BOX 69.1  Therapeutic hypothermia. Whole body hypothermia (33 to 34°C) for up to 72 hours is used in the neonatal intensive care setting as a key treatment of moderate or severe HIE. The time-critical period to commence treatment is in the first 6 hours, hence recognition (and if not already, transfer to a tertiary setting) is important. A Cochrane Review of term infants with moderate or severe HIE showed reduced mortality and major neurodevelopmental disability in those who underwent therapeutic hypothermia.3 As such, this has become a mainstay of treatment in Australian neonatal intensive care units. Adverse effects may include sinus bradycardia and thrombocytopenia, and potentially increase the need for inotropic support.

impairment or frank renal failure will manifest as oliguria or anuria. Liver impairment (deranged liver enzymes, coagulopathy) may also be evident. The degree of non-CNS organ impairment is highly variable.

Outcome The outcome relates to the cause. If encephalopathy follows from a severe hypoxic event around the time of delivery, the severity of the encephalopathy often peaks at 48–72 hours, before resolution. A slower rate of improvement correlates with poorer prognosis. Prognostication can be guided by various assessments conducted during the newborn period, including neurological examination, EEG and MRI brain studies. The classification of HIE severity (mild, moderate, severe) has been shown to be correlated with long-term outcomes. Mild HIE does not normally result in any long-term issues. Moderate HIE is associated with development of cerebral palsy and other neurological impairments, although earlier resolution of symptoms (normal neurological assessment within a week) reduces the likelihood of future neurological impairment. Severe HIE is associated with marked disability or death. Lastly, severe neonatal compromise demonstrated by prolonged resuscitation (chest compression for more than 60 seconds, delayed onset of spontaneous respirations for more than 30 minutes after delivery) and marked metabolic acidosis (base deficit > 16 mmol/L) in the first hours after birth are further predictors of death or severe disability.4 Hypoxic ischaemic encephalopathy is the likely cause of only about 10% of cases of cerebral palsy. Cerebral palsy occurs in 2 per 1000 births. Cerebral palsy:

Chapter 69  Neonatal Neurological Presentations

describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, cognition, communication, perception, and/or behaviour, and/or by a seizure disorder.5

SEIZURES Clinical manifestations The clinical manifestations of seizures are different in the newborn from those later in life because of the relative immaturity of the newborn’s brain. Seizures are often focal or multifocal rather than generalised. The pathways which result in focal seizures spreading to become a generalised seizure have not yet fully developed. Seizures may also be very subtle: sucking motions, unilateral hand or foot jerking, or cycling movements. Apnoea may occur in combination with other signs or be the only sign of seizures. Mild HIE may present with tremulousness. This may be difficult to differentiate from seizures. Features which allow this to be separated from seizures include the following: a tremor can be stopped by holding the limb whereas seizures are transmitted to the observer’s hand a tremor is often stimulus sensitive (i.e. it will follow arousal by a noise or touch).

• •

Causes and investigation The most common cause of seizures is hypoxic ischaemic encephalopathy. Other causes are listed in Box 69.2. HIE will most often be suggested by a history consistent with perinatal asphyxia. Hypoglycaemia and hypocalcaemia must be excluded in all newborns with seizures. Brain ultrasound or MRI will detect anatomical abnormalities and haemorrhage. Infection may be of congenital origin such as with cytomegalovirus or toxoplasma. Intracranial calcification is often seen on imaging; these newborns may have other stigmata of the disease. Supportive diagnostic evidence is provided by specific serology.

BOX 69.2  Causes of newborn seizures. Hypoxic-ischaemic encephalopathy Metabolic imbalance: hypoglycaemia, hypocalcaemia, hyponatraemia, hypomagnesaemia Infection: meningitis and encephalitis Anatomical brain abnormalities Intracranial haemorrhage Inherited metabolic disorders Neonatal drug withdrawal

Meningitis may present at any time after birth and is most commonly due to Group B streptococcus or gramnegative bacteria such as Escherichia coli. Inherited metabolic disorders should be sought if there is no history suggestive of asphyxia, if there is unexpected acidosis present or if there is a family history of metabolic disease or neonatal death of uncertain cause. An EEG should be performed as this may provide prognostic information or suggest a specific diagnosis.

Treatment Treatment is supportive and includes treating any underlying cause as well as administering anti-seizure medication. Drug treatment should be undertaken but may not be successful at controlling seizures. The drugs most commonly used are phenobarbitone and phenytoin (both at a loading dose of 20 mg/kg body weight and then 5 mg/kg/dose, twice a day).

General outcome The outcome is related to the cause. Brain malformations that present with seizures in the newborn period usually have a poor prognosis. The majority of neonates (approximately three-quarters) who have seizures do not go on to have epilepsy later in life.6 Seizures in the context of asphyxia and subsequent HIE can be difficult to prognosticate. The interplay between the severity of HIE, the presence or absence of neonatal seizures and the presence and degree of brain anomalies on MRI result in variable future neurodevelopmental outcomes and a risk of childhood epilepsy. Evidence does exist, however, that severe neonatal seizures (e.g. status epilepticus) can predict future epilepsy and poorer neurodevelopmental outcomes.6,7 Whether this is related to or independent of severity of HIE and brain injury remains controversial.8

SPINA BIFIDA Spina bifida and other congenital malformations of the central nervous system are discussed in later chapters.

THE FLOPPY NEWBORN The floppy (hypotonic) newborn may have a neurological or medical cause underlying this presentation (Fig 69.1). From a neurological perspective, issues anywhere within the system may cause hypotonia: from problems in the brain, spinal cord, peripheral nerves, neuromuscular junction or muscles. Alternatively, an underlying medical issue may present with hypotonia. Medical disorders causing hypotonia include HIE, hypothyroidism, chromosomal disorders such as Down syndrome, Prader-Willi syndrome, inborn errors of metabolism (e.g. organic acidurias) and hereditary connective tissue disorders. The history may occasionally be useful if there is a family history of muscle weakness. Hypotonia that is 639

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Infant exhibits weakness and flaccidity of all musculature.

Infant hangs like rag doll when lied under abdomen.

Infant is unable to sit up or hold up head. Head drops back when infant is lied by its hands.

FIGURE 69.1 

This illustration shows significant neonatal hypotonia. The examination reveals a degree of ‘floppiness’ and head lag far beyond that seen in neurologically normal newborns. Source: Jones HR, Burns T, Netter FH. Netter Collection of Medical Illustrations: Spinal Cord and Peripheral Motor and Sensory Systems. 2nd edn. Philadelphia: Saunders, 2013. Copyright © 2013 Saunders, An Imprint of Elsevier. Plate 9.1.

associated with relatively preserved muscle strength and tendon reflexes may indicate that the cause is cerebral in origin. If there is a relatively normal level of alertness, but overt weakness, this may indicate neuromuscular disease. Investigations may include brain imaging, serum creatine kinase, nerve conduction studies, electromyography and muscle biopsy. There are numerous causes of neuromuscular hypotonia. Spinal muscular atrophy (Werdnig-Hoffmann disease) is a rare condition, although one of the most common causes of newborns presenting with neuromuscular hypotonia. Onset of this disease in the newborn period carries a poor prognosis and most children die in infancy. Transient neonatal myasthenia gravis occurs in a small proportion of affected mothers. The major problems are difficulties in sucking and swallowing.

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There are various causes of congenital myopathies which are usually relatively mild and progress slowly. Congenital muscular dystrophy is usually more severe and creatine kinase is markedly elevated. Myotonic dystrophy is usually severe if it presents in the neonatal period with hypotonia and respiratory depression. Myotonia (failure of muscle to relax after contraction) may be difficult to demonstrate in the newborn, but the condition is inherited from the mother in an autosomal dominant fashion and the mother usually has myotonia and muscle weakness.

NERVE PALSIES Nerve palsies are acquired during the birth process as the result of stretching or pressure on nerves. There are two common types: brachial plexus palsy and facial palsy.

Chapter 69  Neonatal Neurological Presentations

Brachial plexus injury Brachial plexus may occur as the head is flexed laterally away from the shoulder during delivery, thus causing a degree of cervical nerve damage (Fig 34.5). There are three types, depending on which of the cervical roots are damaged. Features of these three types are summarised in Table 69.2. Differential diagnosis includes a fractured clavicle (Fig 34.7) or a fractured proximal humerus. These conditions should be associated with crepitation a limitation of passive movement due to pain. A functional recovery may occur, often by 6 months of age. Full recovery is to be expected; however, in a small number of cases (especially after a severe brachial plexus injury) full recovery never occurs. Treatment with physiotherapy is aimed at the prevention of contractures by maintaining a full range of passive movement. Rarely, nerve repair is attempted, though later in childhood.

Facial nerve palsy The 7th cranial nerve may suffer compression injury during the birth process and is also vulnerable to injury by forceps. Facial nerve palsy manifests as weakness of one side of the face, which is most readily discernible as an inability to wrinkle the forehead and turn up the angle of the mouth when crying (Fig 69.2). Generally, no specific treatment is required and a full recovery is expected. In severe cases, if the eyelid cannot be fully closed, there may be a need for frequent instillation of ‘artificial tears’ (methylcellulose drops) and/or patching to prevent corneal damage.

DRUG WITHDRAWAL (NEONATAL ABSTINENCE SYNDROME) The use and abuse by mothers of psychotropic drugs (both prescription and elicit) during pregnancy may predispose to neonatal withdrawal. As such, it is important to consider the possibility of withdrawal from these drugs in any infant who presents with a neurological abnormality. Recalling the features of neonatal withdrawal syndrome or neonatal abstinence syndrome may be aided by the following ‘withdrawal’ acronym. Wakefulness Irritability Tremulousness Hyperactivity Diarrhoea Rub marks Apnoea Weight loss or failure to gain weight Alkalosis: respiratory Lacrimation

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INTRACRANIAL HAEMORRHAGE Subarachnoid haemorrhage is relatively common and can occur idiopathically during the birth process or in the context of asphyxia or trauma at delivery. It is most often asymptomatic and benign. Subdural haemorrhage rarely results from birth trauma. Intraventricular haemorrhage, intracerebral haemorrhage and periventricular leucomalacia are almost exclusively confined to the preterm newborn and are discussed in Chapter 75.

FIGURE 69.2 

Left facial nerve palsy.

Source: Roy FH, Fraunfelder FW, Fraunfelder FT. Roy and Fraunfelder’s Current Ocular Therapy. 6th edn. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 107.1.

TABLE 69.2  BRACHIAL PLEXUS INJURIES. Name

Nerve roots involved

Muscles affected

Posture

Erb palsy

C5–6

Deltoid, biceps, brachioradialis

Arm internally rotated, elbow extended, forearm pronated, wrist flexed

Klumpke

C8–TI

Wrist flexors, hand intrinsics, sympathetic involvement (Horner syndrome)

As above plus claw hand

Combined

C5–TI

Entire arm, paralysis of diaphragm if C3–4 also involved

Flaccid arm

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Vomiting, poor feeding, excessive or repetitive sneezing and/or yawning may also occur. Generally, presentation may occur at any time from birth to the end of the first week. Neonatal abstinence syndrome rarely presents beyond the first week of life. Treatment will depend on the particular drug used during pregnancy. Opiate withdrawal is managed with oral morphine. Other agents such as diazepam or, rarely, phenobarbitone may be effective, particularly where there has also been maternal non-opioid drug abuse. The dosage is gradually reduced and finally withdrawn over a period of several weeks, depending on the baby’s clinical condition. The contraindications to breastfeeding are minimal, and need to be balanced with other important considerations (see Chapter 67). For example, if the mother is stable on a methadone program and/or not on a very high dose of an opiate, breastfeeding often continues. Importantly other soothing techniques such as swaddling, gentle rocking and holding are also an important aid in the management of neonatal withdrawal. The differential diagnosis includes hyperthyroidism, HIE, intracranial haemorrhage, hypoglycaemia, hypocalcaemia, polycythaemia and fetal alcohol syndrome. Lastly, withdrawal from prescription medication (e.g. SSRI/SNRI) and even in utero cigarette exposure should also be considered. This may present as poor feeding, hypertonicity and/or irritability. A thorough antenatal history should guide the assessment. Post-delivery family supports and being mindful of maternal–infant bonding are important considerations when assessing a newborn that is potentially withdrawing.

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REFERENCES 1) Courchesne E, Pierce K, Schumann CM, et al. Mapping early brain development in autism. Neuron 2007;56(2):399–413. 2) Wegiel J, Kuchna I, Nowicki K, et al. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 2010;119(6):755–70. 3) Jacobs SE, Berg M, Hunt R, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013;(1):CD003311. 4) Shah PS, Beyene J, To T, et al. Postasphyxial hypoxic-ischemic encephalopathy in neonates: outcome prediction rule within 4 hours of birth. Arch Pediatr Adolesc Med 2006;160(7):729–36. 5) Bax M, Goldstein M, Rosenbaum P, et al. Proposed definition and classification of cerebral palsy. Dev Med Child Neurol 2005;47(8):571–6. 6) Glass HC, Hong KJ, Rogers EE, et al. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res 2011;70(5):535–40. 7) Glass HC, Glidden D, Jeremy RJ, et al. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediatr 2009;155(3):318–23. 8) Kwon JM, Guillet R, Shankaran S, et al. Clinical seizures in neonatal hypoxic-ischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. J Child Neurol 2011;26(3):322–8.

Chapter 70  NEONATAL RESPIRATORY DISTRESS Kypros Kyprianou

KEY POINTS Respiratory distress occurs in about 3% of newborns. It is defined as a respiratory rate > 60 per minute, usually in association with chest wall recessions and an expiratory grunt. It may be associated with hypoxia and apnoea. A knowledge of pulmonary development and physiology is important for understanding disease processes and their treatments. There are numerous causes that must be established because they range from benign to lethal. The causes can be subcategorised into broad areas: 1. airway obstruction; 2. airway disease, including alveoli disease; 3. extrinsic disease (e.g. space occupying lesions in the thorax); or 4. non-respiratory causes such as sepsis or congenital cardiac disease. Airway obstruction may be due to anatomical malformation and present with stridor. Respiratory distress may accompany a diaphragmatic hernia, causing extrinsic compromise to the neonatal lung. Treatment consists of general measures such as the provision of supplemental oxygen and assisted ventilation if there is evidence of respiratory failure. Specific measures will depend on the diagnosis. Hyperoxygenation in term newborns may delay establishment of normal respiratory parameters, and in preterm newborns is associated with retinopathy of prematurity. Airway disease includes congenital pneumonia or respiratory distress syndrome (RDS), which is due to pulmonary surfactant deficiency and occurs almost exclusively in preterm newborns. ■ The management of RDS includes the use of antenatal steroids and administration of postnatal exogenous surfactant. These interventions have markedly reduced preterm mortality and morbidity. ■ Air leak syndromes (e.g. pneumothorax, pulmonary interstitial emphysema) have also diminished due to administration of exogenous surfactant to premature newborns with RDS.

PULMONARY PHYSIOLOGY MORPHOLOGY The lung bud develops at 4 weeks’ gestation but complete structural development of the lung (with the adult number of airway branchings) is not completed until well after birth. The terminal airway saccules and associated pulmonary vasculature may be adequate for gas exchange from about 23 to 24 weeks’ gestation in the event of

preterm birth. It is not until term that alveoli have a morphology similar to that of the mature lung (Fig 70.1).

Lung fluid Fluid is continually secreted by type 1 cells of the lung in large volumes: 100 to 150 mL/kg body weight per day in the term fetus. The lung is filled with lung fluid to a volume which is similar to the resting gas volume after birth. From about 25 weeks’, pulmonary surfactant begins to be

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Alveolus with lung fluid

Surfactant

Type 1 cell

The larger alveoli is more easily expanded by a given pressure because the radius is larger. Differential expansion of alveoli is therefore self-perpetuating and occurs particularly if there is surfactant deficiency; it may result in the complication of pulmonary interstitial emphysema and pneumothorax.

Type 2 cell Lymphatic vessel

Capillary

compliance =

∆ volume ∆ pressure

Compliance describes the distensibility of the lung, and in respiratory distress syndrome its value is about 20% of normal.

Gas exchange

FIGURE 70.1 

Structure of the fetal lung at term.

Source: Courtesy of Prof. Norman Beischer.

The primary purpose of the lungs is to take in oxygen necessary for metabolism and to maintain the body’s pH by the elimination of carbon dioxide. Hydrogen ions formed during metabolism may be buffered by bicarbonate: H+ + HCO3− ⇔ H2CO3 ⇔ H2O + CO2

produced by type 2 alveolar cells. This is comprised mainly of phospholipids with associated proteins important to its function, which is to reduce surface tension: its surfacetension-lowering characteristics are equal in magnitude to those of the best synthetic detergents.

As long as carbon dioxide is removed by the lung, the reaction continues and hydrogen ions continue to be buffered. Normal blood gas values, along with those of the fetus for comparison, are shown in Table 70.1.

Pulmonary blood flow

RESPIRATORY DISTRESS

Pulmonary blood flow is low in the fetus: only the nutritional requirements of the lung need be met. This is achieved by the pulmonary arteries being relatively constricted. The pulmonary pressure is high and the majority of the blood from the right side of the heart is directed to the systemic circulation via a patent foramen ovale and ductus arteriosus (Fig 64.1).

Lung aeration The production of lung fluid is turned off by catecholamines and prostaglandins, which rise during labour and parturition. The mechanical effect of compression of the thorax that occurs during birth is also important. As the chest recoils after delivery, air is drawn into the lungs. This is assisted by the large negative intrathoracic pressures (up to 80 cm H2O) generated in the first breaths. Lymphatic drainage is responsible for the remainder of the lung fluid being removed. Delayed drainage results in the clinical condition termed ‘transient tachypnoea of the newborn’ (see later this chapter). Surfactant is vital in lung function. The relationship between pressure and surface tension (the Laplace law) describes why it is much easier to breathe when the surface tension in the alveolus is low. It also describes the situation if there are two alveoli in communication which are differentially expanded. The Laplace law is: pressure = 644

2 × surface tension radius

DEFINITION Respiratory distress is defined as a respiratory rate that is > 60 per minute and is usually associated with accessory muscle use, intercostal and subcostal recessions, nasal flaring, head bobbing and expiratory grunt. There may or may not be accompanying hypoxia. Apnoeas may also occur, particularly in the context of sepsis or in the premature neonate. It has many causes (Box 70.1) and is not synonymous with respiratory distress syndrome (RDS), which is the most common cause of respiratory distress in the preterm newborn. The normal newborn has a respiratory rate in the range of 20 to 60 breaths per minute, commonly being 25 to 35 breaths per minute. Respirations are often irregular, with short 5- to 15-second periods of apnoea: this is termed ‘periodic respiration’ or ‘periodic breathing’ and is entirely normal. Reassurance for the inexperienced family member is often required.

CAUSES The causes of respiratory distress are shown in Box 70.1. Importantly, the most common presentation of neonatal sepsis is with respiratory distress. Hence, prompt evaluation of potential newborn sepsis is required in any newborn presenting with respiratory distress. Maternal diabetes and elective caesarean section without labour increase the risk of respiratory distress.

Chapter 70  Neonatal Respiratory Distress

TABLE 70.1  NORMAL BLOOD GAS VALUES IN THE NEWBORN. Sample site

pH

Base excess (mmol/L)

PaO2 (mmHg)

PaCO2 (mmHg)

Lacate (mmol/L)

Fetal and immediate post-labour values* Umbilical artery

7.10 to 7.38

–9.0 to 1.8

4.1 to 31.7

39.1 to 73.5

< 6.1

Umbilical vein

7.20 to 7.44

–7.7 to 1.9

30.4 to 57.2

14.1 to 43.3

—

7.31 to 7.47

—

32.8 to 61.2

28.5 to 48.7

1.4 to 4.1

48 hours of life† Capillary (via heel-prick sampling)

*Reference for these values: Women and Newborn Health Service, King Edward Memorial Hospital. Clinical Guidelines: Section B: Obstetrics and Midwifery Guidelines. Perth: OGCCU Apr 2004, revised Nov 2013. 5.14.1, Umbilical Cord Blood Collection/Analysis. Online. Available: http://kemh.health.wa.gov.au/development/manuals/O&G_guidelines/sectionb/5/b5.14.1.pdf, 3 Mar 2015. †Reference for these values: Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin’s Neonatal-Perinatal Medicine. 10th edn. Philadelphia: Saunders, 2015. Copyright © 2015 Saunders, An Imprint of Elsevier. Appendix B, 1817–36, Table B-7 Capillary blood gas reference values in healthy term neonates. Modified from Cousineau J, et al. Neonate capillary blood gas reference values. Clin Biochem 2005;38:906.

BOX 70.1  Causes of respiratory distress. Airway disease ✚ Respiratory distress syndrome ✚ Pneumonia ✚ Meconium aspiration syndrome ✚ Transient tachypnoea of the newborn ✚ Lung hypoplasia ✚ Tracheo-oesophageal fistula with aspiration Airway obstruction ✚ Choanal atresia ✚ Pierre Robin syndrome ✚ Laryngeal abnormality (e.g. congenital laryngeal cleft) Extrinsic causes ✚ Congenital diaphragmatic hernia ✚ Congenital lobar emphysema ✚ Pneumothorax Others ✚ Sepsis ✚ Congestive cardiac failure ✚ Metabolic acidosis with attempted respiratory compensation

MANAGEMENT Initial supportive care may be necessary before a specific diagnosis is made if the respiratory distress is severe. This consists of: nursing the newborn in an incubator/isolette for ease of observation and for optimal management of the thermal environment

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oxygen in amounts adequate to correct cyanosis non-invasive oxygen monitoring (the inspired oxygen concentration should be adjusted to maintain saturation at 91 to 95%) offering early non-invasive ventilatory support (e.g. nasal continuous positive airway pressure [nCPAP]) (Fig 70.2). Importantly, early use of nCPAP may better support neonates with respiratory distress and is increasingly

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FIGURE 70.2 

This newborn is receiving nasal continuous positive airway pressure (nCPAP). Its careful and judicious clinical use has allowed newborns with respiratory disease to be treated in non-NICU nurseries, reducing the need to transfer for intensive care. Source: iStockphoto/tioloco.

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being utilised in place of non-pressure oxygen supplementation (e.g. via a ‘head-box’ or increasing the inspired oxygen concentration in newborns cared for in an isolette). Treating any underlying cause of respiratory distress is also important. It can be difficult to differentiate the cause by history and examination alone. As such, prompt, early treatment (e.g. with antibiotics to cover presumed sepsis) is often utilised while ongoing assessment and definitive support of the respiratory system takes place. If the inspired oxygen requirement (FiO2) is > 40%, transfer to tertiary neonatal intensive care units is often required. Here invasive monitoring, by placing an indwelling arterial catheter into either the umbilical artery or a peripheral artery (radial, ulnar or posterior-tibial), is used to monitor and guide therapy. The arterial catheter allows for continuous arterial pressure reading as well as arterial blood gas sampling. Other interventions include supportive care via administration of intravenous fluids, as oral feeding should be ceased in tachypnoeaic newborns because of the risk of aspiration. If the respiratory distress is prolonged, then parenteral nutrition may be required. If the PaCO2 is elevated above 6.5 kPa (50 mmHg), assisted ventilation may be required. Assisted ventilation may be provided in the following forms.

•

Continuous positive airway pressure (CPAP) is most commonly administered either via tight-fitting nasal prongs. The newborn respires spontaneously against an applied positive pressure of 4 to 9 cm H2O (0.4 to 0.9 kPa), which prevents atelectasis at end expiration (Fig 70.2). Intermittent positive pressure ventilation (IPPV) requires endotracheal intubation and may be required when the PaCO2 is > 70 mmHg (Fig 70.3). Pulses of positive pressure are applied to the inspired gas, usually at a rate of 30 to 60/min. At end expiration, a positive pressure is maintained (positive end expiratory pressure [PEEP]) in order to prevent alveolar collapse. Much higher frequencies (300 to 1000/min) are used in specially designed oscillatory ventilators or jet ventilators. This method can improve gas exchange at lower peak airway pressures than conventional ventilation and may result in a lower incidence of complications.

FIGURE 70.3 

This newborn is intubated and ventilated. The use of nCPAP (as in Figure 70.2) is increasingly widespread in both the neonatal and special care settings. It is one of the factors that have reduced chronic lung disease (by reducing the need for intubation and ventilation).

Source: Rimoin DL, Pyeritz RE, Korf BR. Emery and Rimoin’s Principles and Practice of Medical Genetics. 6th edn. Oxford: Academic Press, 2013. Copyright © 2013 Academic Press, An Imprint of Elsevier. Figure 128.11.

•

Other indications for intubation and ventilation include cyanosis that persists in spite of maximal oxygen therapy (e.g. as occurs in persistent pulmonary hypertension) or severe and/or recurrent apnoea (e.g. as occurs in sepsis, severe HIE or extreme prematurity). The complications of assisted ventilation include:

• •

mechanical such as endotracheal tube blockage or dislodgement pulmonary air leaks such as pneumothorax (Fig 70.4) and pulmonary interstitial emphysema

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•

bronchopulmonary dysplasia or chronic lung disease which is due to a combination of high inspired oxygen concentrations along with the unphysiological positive pressures

INVESTIGATION Investigation consists initially of a history and physical examination. The history will provide information on 1. the gestational age; 2. whether there were any risk factors for intrapartum sepsis; 3. whether meconium was present in the liquor at delivery; and 4. whether positive pressure was administered at resuscitation, which makes pneumothorax more likely. The physical examination will provide information on the following possible causes. Respiratory distress syndrome occurs almost exclusively in preterm newborns. Pneumonia is usually associated with systemic signs of infection such as lethargy, apnoea, cardiovascular compromise or temperature instability.

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Chapter 70  Neonatal Respiratory Distress

•

Meconium aspiration syndrome may occur if there was meconium in the amniotic fluid; the thorax is often hyperinflated. Tracheo-oesophageal fistula is usually identified at delivery by the presence of copious secretion of fluid from the mouth and inability to pass a suction or feeding catheter into the stomach. Airway obstruction is identified if a stridor is heard. Choanal atresia is diagnosed by an inability to pass a catheter further than several centimetres through the nostril. Pierre Robin syndrome causes respiratory obstruction due to a hypoplastic mandible with retracted jaw; a jaw thrust may transiently assist this upper airway obstruction. Diaphragmatic hernia results in the abdominal contents occupying the thoracic cavity; there is a scaphoid abdomen and reduced air entry on the side of the hernia. Pneumothorax results in reduced air entry on the side of the lesion. Congestive heart failure may occur if congenital heart disease is present; there will be associated findings of a cardiac murmur and hepatomegaly. Investigations should commence with a chest X-ray. This will often lead to a diagnosis being made. Specific diseases will now be considered.

• •

• • •

RESPIRATORY DISTRESS SYNDROME Respiratory distress syndrome (RDS) is a disease of prematurity (previously called hyaline membrane disease). Hyaline membranes may be found in the alveoli postmortem but these are not specific to RDS and may occur in severe lung disease from other causes; hence, the term RDS is preferred. Respiratory distress is the term used to describe a clinical diagnosis in which signs of tachypnoea, grunt and accessory muscle use are evident. Respiratory distress syndrome is the term used for a condition which is predominantly due to surfactant deficiency in the setting of prematurity. The main cause of RDS is pulmonary surfactant deficiency. In babies born at less than 32 weeks’ gestation, the incidence increases with increasing degree of prematurity. It is uncommon after 35 weeks’ gestation. In RDS, the onset of respiratory distress may not be immediate but usually occurs within the first few hours after birth. The natural history without exogenous surfactant treatment is for the degree of respiratory distress to reach a plateau at about 12 hours and remain static until 48 to 72 hours, after which there is a gradual improvement. In the uncomplicated case, supplemental oxygen is not needed after about 1 week. Complications consist of air leak, either pulmonary interstitial emphysema or pneumothorax, and chronic lung disease (see overleaf). Often associated with RDS is a patent ductus arteriosus. The chest X-ray in RDS is characterised by a groundglass appearance and air bronchograms (Fig 70.5). However, the X-ray appearance is not pathognomonic and pneumonia may have a similar appearance.

FIGURE 70.5  FIGURE 70.4 

Bilateral pneumothoraces in a newborn infant; the lungs are collapsed and surrounded by gas in the pleural space. Source: Courtesy of Prof. Norman Beischer.

Respiratory distress syndrome characterised by fine uniform reticulogranular opacities (‘ground glass’ appearance) throughout the lung fields as well as air bronchograms. Source: Courtesy of Prof. Norman Beischer.

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PREVENTION The incidence of RDS can be reduced by the administration of corticosteroids (e.g. betamethasone) to the mother if premature delivery is thought to be likely. To be fully effective this must be given > 24 hours prior to delivery. Corticosteroids are protective for only 7 to 10 days, after which time administration should be repeated, particularly if the infant is likely to deliver at < 34 weeks’ gestation.

TREATMENT Supportive treatment with intravenous fluids, avoidance of thermal stress and maintenance of adequate cardiovascular output is important. However, it has been the following specific treatments which have significantly altered the outcome of newborns with RDS: 1. the use of positive pressure ventilation and nasal CPAP 2. the administration of corticosteroids to the mother in threatened preterm labour 3. exogenous surfactant to replace endogenous deficiency. Furthermore, a transition away from positive pressure ventilation (i.e. the intubated/ventilated premature newborn) to the use of nasal CPAP—even in the very preterm—is further contributing to improving the outcomes of RDS. Surfactant use has significantly contributed to the reduction in mortality and morbidity of RDS. Synthetic surfactant or exogenous mammalian surfactant can be used to replace the ‘surfactant deficiency’ that is the hallmark of RDS. Surfactant needs to be administered via the endotracheal tube directly to the lungs’ alveoli. It may be necessary to treat complications such as pneumothorax (Fig 70.4) or associated conditions such as patent ductus arteriosus which may complicate and delay the resolution of RDS.

CHRONIC LUNG DISEASE (BRONCHOPULMONARY DYSPLASIA) Chronic lung disease is a significant complication of RDS. It is a key determining factor in the length of hospital stay of preterm babies born less than 29 weeks’ gestation. It is defined as the ongoing need for supplemental oxygen beyond 28 days of life. It results from the combined effects of high inspired oxygen concentrations and the use of positive pressure ventilation in the immature (premature) lung. Chronic lung disease is an important complication because it can lead to the need for long-term oxygen therapy and/or to repeated hospitalisations with respiratory infections in the first years of life (Figs 70.6 and 75.2).

PNEUMONIA This is discussed in Chapter 72. 648

FIGURE 70.6 

Life on continuous oxygen therapy after discharge from hospital. This infant was delivered at 26 weeks’ gestation because his mother suffered an antepartum haemorrhage. He developed chronic lung disease following assisted ventilation for respiratory distress syndrome. He is shown aged 15 months, developmentally normal, with his mother and 6-week-old brother. Source: Courtesy of Prof. Norman Beischer.

PNEUMOTHORAX This is one form of pulmonary air leak, which includes pulmonary interstitial emphysema, pneumoperitoneum and pneumomediastinum. Pneumothorax may occur spontaneously and should be considered in any newborn with respiratory distress. It is commonly a complication of positive pressure ventilation and should be considered as a cause of any deterioration in the ventilated newborn. Diagnosis is by differential transilluminance of the hemithoraces using a bright light source or definitively by chest X-ray (Fig 70.4). If symptoms are mild, no specific treatment may be required. However, if symptoms are severe or there is underlying pulmonary disease, treatment is by drainage of gas from the pleural space. Needle thoracocentesis may provide short-term relief; however,

Chapter 70  Neonatal Respiratory Distress

definitive treatment will be the insertion of a chest drain or intercostal catheter.

MECONIUM ASPIRATION SYNDROME Meconium is present in the amniotic fluid in a small proportion of deliveries, and may be associated with fetal acidosis. Meconium aspiration syndrome is defined as the combination of respiratory distress and delivery in the context of meconium-stained liquor that cannot otherwise be explained. Sterile meconium, when aspirated, can begin a process of inflammatory pneumonitis. Additionally, meconium can cause mechanical obstruction and secondary surfactant deficiency. Lastly, the occurrence of meconium in the liquor in the first place points to an intrauterine pathological process (e.g. asphyxia, infection) that also contributes to respiratory morbidity.

RESUSCITATION OF A NEWBORN IN THE CONTEXT OF MECONIUMSTAINED LIQUOR Emerging guidelines from the International Liaison Committee on Resuscitation (ILCOR) no longer recommend suctioning in the vigorous newborn in the context of meconium-stained liquor. If an infant, however, is delivered depressed (i.e. floppy, apnoeic, weak respiratory efforts), meconium aspiration from the oropharynx and trachea is recommended. In this situation, the newborn should not be stimulated if a paediatric attendant is present to perform tracheal suctioning. Using direct laryngoscopy, the larynx is inspected: if meconium is present, the trachea is intubated with an endotracheal tube and suction applied as the tube is withdrawn. Alternatively, the trachea can be intubated with a large-bore suction catheter and this is used directly to apply the suction. Importantly, prolonged attempts (at intubation and tracheal suctioning) and delayed resuscitation may adversely affect the outcome; hence, proceeding promptly to appropriate neonatal resuscitation should occur.

INVESTIGATION AND TREATMENT The chest X-ray shows non-specific changes of hyperinflation and atelectasis, and needs to be matched with the clinical history. Subsequent management consists of admission of the newborn to a special care or intensive care nursery for close observation and treatment of respiratory distress as required. Antibiotics are often administered as concomitant infection cannot immediately be excluded.

OUTCOME Pneumothorax is a potential complication and may be seen on chest X-ray. Pulmonary hypertension of the

newborn may also develop, particularly if hypoxaemia is allowed to occur. This vasoconstrictive response of the pulmonary arterial vasculature results in a marked rightto-left shunt and hence further hypoxaemia. The mortality rate can be high, and treatment should be in a specialist centre. The use of new treatment modalities such as high-frequency ventilation, nitric oxide (as a pulmonary vasodilator) and extracorporeal membrane oxygenation may improve the outcome. Importantly, prevention is also a key consideration. Post-mature deliveries increase the risk of meconium-stained liquor. Good coordination of antenatal and immediate predelivery care between the obstetric and paediatric teams will allow prompt therapeutic responses to conditions that may cause fetal distress, hypoxia or birth depression.

TRANSIENT TACHYPNOEA OF THE NEWBORN Transient tachypnoea of the newborn (TTN) is a form of respiratory distress that is due to a delay in fluid resorption from the lung. Chest X-ray shows central perihilar streaking and sometimes effusions. Treatment is with oxygen, which is usually required at an inspired concentration of up to 40%. The respiratory distress settles over several hours to days. Complications are very uncommon, but it is important to provide adequate oxygen to prevent persistent pulmonary hypertension of the newborn. Depending on the clinical assessment, treatment for presumed sepsis may also take place as the clinical picture of TTN and sepsis can be similar. Nitrous oxide is utilised as a patent pulmonary vasodilator in infants with persistent pulmonary hypertension. These infants are tachypnoeaic and hypoxic despite ventilatory support and high inspired oxygen.

DIAPHRAGMATIC HERNIA This condition is due to herniation of abdominal contents through a diaphragmatic defect (Fig 70.7). The bowel in the thorax prevents normal development of the lung. The condition may be diagnosed prenatally on routine ultrasound imaging. Fetal surgery has been performed in which the bowel is replaced and the defect obliterated, but this may not increase postnatal survival and remains experimental. Presentation may be non-specific. There could be immediate evidence of significant respiratory distress at delivery. Alternatively, respiratory distress may occur over the first few hours. Definitive diagnosis is made radiologically. Initial treatment is to place an oral or nasogastric tube on free drainage in an attempt to prevent distension of the bowel with swallowed gas. Management of the respiratory distress using the general principles outlined in this chapter is required. Persistent pulmonary hypertension is very common and delivery in, or immediate transport to, a specialist centre is essential. The 649

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definitive treatment is surgery: the bowel is returned to the abdomen and the defect repaired. This occurs after the clinical condition of the newborn is stable. Diaphragmatic hernia is associated with significant mortality, related largely to the severity of pulmonary hypoplasia and pulmonary hypertension. Antenatal diagnosis to allow for appropriate expertise at and immediately after delivery may increase survival. Improved preoperative treatment of lung disease, followed then by corrective surgery, is also resulting in increasing survival rates.

FIGURE 70.7 

Radiograph of a left diaphragmatic hernia: gas-containing loops of bowel have herniated through the defect into the left chest; the mediastinum is shifted to the right. Source: Courtesy of Prof. Norman Beischer.

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FURTHER READING Buckmaster AG, Arnolda G, Wright IMR, et al. Continuous positive airway pressure therapy for infants with respiratory distress in non-tertiary care centers: a randomized, controlled trial. Pediatrics 2007;12(3):509–18. Department of Health and Human Services. Neonatal ehandbook. State Government of Victoria. Online. Available: ; [17 Feb 2014].

Chapter 71  THE SMALL FOR GESTATIONAL AGE AND LARGE FOR GESTATIONAL AGE NEONATE Kypros Kyprianou

KEY POINTS Small for gestational age newborns are prone to hypoglycaemia, hypothermia and polycythaemia. Large for gestational age newborns are typically infants of diabetic mothers, although a proportion of infants with birth weights ≥ 4500 g are born to mothers who did not have hyperglycaemia when tested in pregnancy. Newborns that are large for gestational age are at risk of obstructed labour, birth trauma and hypoglycaemia.

DEFINITIONS The terms used below define neonates born at various gestational ages. Preterm is delivery prior to 37 completed weeks of gestation (World Health Organisation definition). In Australia, about 9% of births are preterm. (See Chapter 75.)1 Term is delivery from 37 to 42 weeks’ gestation. Post-term is delivery after 42 completed weeks’ (Also see Chapter 13.) In addition to the age of gestation, various terms are used to describe the growth characteristics of newborns. ‘Small for gestational age’ is a birth weight < 10th percentile at any gestation. Some authors use a definition of < 3rd percentile. ‘Large for gestational age’ is a birth-weight > 90th percentile at any gestation. Some authors use a definition of > 97th percentile. The terms ‘low birth weight’ (< 2500 g), ‘very low birth weight’ (< 1500 g) and ‘extremely low birth weight’ (< 1000 g) are in common use but do not take into account the more important issues of gestational age and weight for gestation.

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In Australia, low birth weight newborns (1500 to 2500 g) comprise approximately 5.2% of all births, very low birth weight (1000 to 1500 g) 0.6% and extremely low birth weight (< 1000 g) 0.5%.2 In the Australian Indigenous population, maternal malnutrition and low socioeconomic status is unfortunately associated with higher rates of low birth weight infants (Box 71.1). A newborn who weighs 2300 g may be term and small for gestational age, 35 weeks’ gestation and appropriate for gestational age, or 30 weeks’ gestation and large for gestational age. This clearly demonstrates that when assessing fetal and newborn wellbeing, the entire clinical picture needs to be considered, not just their weight. The classification and aetiology resulting in fetal growth restriction are outlined in Table 71.1 and are further explored in Chapter 11.

THE SMALL FOR GESTATIONAL AGE NEWBORN Small for gestational age is usually defined as a growth parameter (usually weight) that is less than the 10th percentile for the given gestation. This will encompass constitutionally small infants and infants who suffered intrauterine growth restriction (IUGR). (See Chapter 11.)

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BOX 71.1  Indigenous facts. Babies born to Indigenous mothers are twice as likely as those of non-Indigenous Australian mothers to be of low birth weight. The risk factors for the low birth weight of Indigenous infants include: younger maternal age (1 in 5 Indigenous newborns are born to teenage mothers, compared to 1 in 25 non-Indigenous teenage mothers), low maternal BMI (a sign of poor overall nutrition) and antenatal smoking (Indigenous mothers are three times more likely than non-Indigenous mothers to smoke cigarettes). The Indigenous infant mortality rate is up to twice that of non-Indigenous infants. See also Chapter 43.

TABLE 71.1  CAUSES OF FETAL GROWTH RESTRICTION. Classification

Aetiology

Maternal

• • • • •

Placental

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Neonatal

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Severe malnutrition during pregnancy Maternal hypoxemia TORCH infections Maternal substance abuse, in particular alcohol and cigarettes Cultural and demographic variables: Indigenous Australians, younger or older mothers, certain ethnic groups (e.g. South-East and subcontinental Asia) Ischaemic placental disease Thrombotic illness (e.g. haematological or immunological disorders affecting the placenta) Placental confined genetic abnormalities Karyotype abnormalities Genetic syndromes (e.g. RussellSilver syndrome) Major congenital abnormalities Multiple gestation

When intrauterine growth restriction occurs, the small for gestational age newborn is characterised by a thin appearance with little subcutaneous fat. If growth of the head has been preferentially maintained (asymmetric growth restriction), the head appears inappropriately large for the body (Fig 71.1). There is relative 652

FIGURE 71.1 

Extremely small for gestational age infant. Source: Courtesy of Prof. Norman Beischer.

sparing of the head circumference (and usually length) when plotted on growth charts. This pattern suggests that the growth has been limited in the latter parts of pregnancy, often due to placental insufficiency. Symmetrical growth restriction, on the other hand, is identified by a global reduction in growth parameters. A growth-restricted infant whose head, length and weight are all affected implies issues beginning early in fetal development. Once the fetus has been delivered, there is a particular set of common problems which the growth-restricted newborn faces. Additionally, there are opportunities to explore the cause of growth restriction once the baby has been born. There will be no specific signs if the cause of the growth restriction has been maternal disease, placental dysfunction or sociocultural issues. Nevertheless, a physical examination must be made to exclude the possibility of congenital infection, fetal alcohol syndrome or chromosomal abnormalities associated with a newborn being small for gestational age.

Chapter 71  The Small for Gestational Age and Large for Gestational Age Neonate

PROBLEMS OF GROWTH RESTRICTION Hypothermia and hypoglycaemia Subcutaneous fat deposits are deficient. Therefore, hypothermia is likely to develop if adequate measures are not taken to combat it. All energy substrate available to the fetus has been utilised to subserve growth. Hepatic glycogen stores are likely to be deficient and thus hypoglycaemia is common. All small for gestational age newborns should have capillary blood sugar levels monitored shortly after birth, then every 3 to 4 hours until the clinical risk of hypoglycaemia has diminished (i.e. temperature stability and establishment of feeding).

Polycythaemia and other   haematological issues Polycythaemia is a response to chronic hypoxia. The growth-restricted newborn should have a haematocrit estimation made; if the value is > 65% in association with symptoms such as cerebral irritability or respiratory distress, tertiary neonatal input may be required, to minimise risk of severe hyperbilirubinaemia or cerebral infarction related to hyperviscosity. Other haematological issues (e.g. thrombocytopenia, leukopenia) may be associated with newborns born small for gestational age, especially in the context of maternal preeclampsia.

Birth depression Growth-restricted newborns may have been faced with a marginal supply of glucose and oxygen because of poor placental transfer. They may be prone to developing a degree of asphyxia during the course of labour, when they are faced with additional interruptions to their oxygen supply. The stressed fetus may pass meconium, hence increasing the risk of meconium aspiration syndrome. During labour, careful monitoring of the fetal heart rate (preferably by continuous electronic monitoring) is necessary. The need for resuscitation should be anticipated and appropriate personnel should be present at the delivery.

PROGNOSIS If a specific cause for growth restriction, such as congenital infection or chromosomal abnormality, is found then the prognosis will relate to the cause. In the majority, however, no such cause is identified. An important predictor of outcome is whether the head circumference is also reduced below the 10th percentile. As described, this is called symmetric growth restriction and implies an early or severe insult to the brain, with a reduction in the potential for growth. The causes are usually intrinsic (e.g. congenital infection; exposure to alcohol, drugs or toxins; or chromosomal

abnormalities). This group, which comprises approximately 20% of growth-restricted newborns, has a correspondingly worse neurological prognosis. Asymmetric growth restriction describes the situation where the head growth has been spared. In growth restriction due to chronic malnutrition and hypoxia, body length and mass is first reduced; brain growth is reduced only when compensatory circulatory mechanisms which protect the brain are overcome by severe deprivation. Placental insufficiency, particularly late in the second or third trimester, may cause asymmetric growth restriction. Severely growth-restricted newborns (< 3rd percentile) often exhibit some degree of catch-up growth in the first several years, but often remain small. Neurodevelopmental outcome is generally good, but there is an increased incidence of cerebral palsy and cognitive issues among growth-restricted newborns, particularly those in whom there is symmetric growth restriction and evidence of microcephaly at birth. Adult-onset disease (e.g. ischaemic heart disease, hypertension and chronic kidney disease) has been shown to occur in a greater proportion of adults who were noted to be small for gestational age at birth. This developmental origin of adult disease is referred to as the Barker hypothesis.

THE LARGE FOR GESTATIONAL AGE NEWBORN Large for gestational age (also referred to as fetal macrosomia) is defined as a birth weight > 90th percentile for the particular gestational age. Newborns who are large for gestational age appear ‘obese’, although the extra tissue may not be fat (Fig 23.1). More recently, a classification system (grade 1 > 4000 g, grade 2 > 4500 g, grade 3 > 5000 g) has been devised.3 The rationale helps clinicians stratify risk (i.e. the higher the grade, the increased likelihood of poorer neonatal outcomes). This classification also acknowledges the small but present risk of perinatal complications of infants weighing 4000 to 4500 g. Shoulder dystocia can occur as a complication of large for gestational age infants. Shoulder dystocia is subsequently associated with brachial plexus injury, birth depression and/or clavicular injury. Other neonatal complications include respiratory distress, hypoglycaemia and polycythaemia. The maternal risk factors are: high body mass index maternal diabetes previous macrosomic infant post-term pregnancy maternal birth weight over 4000 g. Other risk factors include multiparity, advanced maternal age and excessive weight gain in pregnancy.

• • • • •

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Maternal diabetes and large for gestational age babies are independently associated with an increased risk of neonatal hypoglycaemia. As such, these newborns should have 3- to 4-hourly capillary blood sugar estimations for at least 24 hours and until the blood sugar level is satisfactory and stable. As a result of the exposure of the fetus to high levels of glucose, hyperinsulinism may result. After birth, the high levels of glucose are no longer delivered, but the hyperinsulinism may take 3 or 4 days to abate. During this period, hypoglycaemia may be both profound and prolonged and the infusion of large quantities of glucose—and at times transfer for tertiary neonatal care—may be necessary. Syndromic causes of largeness for gestational age need to be considered, especially in the presence of dysmorphisms. Beckwith-Wiedemann syndrome is associated with largeness for gestational age. Clinical features

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of this syndrome include organomegaly, protruding macroglossia, exomphalos, ear abnormalities and hyperinsulinaemic hypoglycaemia. REFERENCES 1) Hilder L, Zhichao Z, Parker M, et al. Australia’s mothers and babies 2012. Perinatal Statistics Series no. 30. Cat. no. PER 69. Canberra: AIHW; 2014. 2) Li Z, Zeki R, Hilder L, et al. Australia’s mothers and babies 2011. Perinatal Statistics Series No. 28. Cat. no. PER 59. Canberra: AIHW National Perinatal Epidemiology and Statistics Unit; 2013. 3) Boulet SL, Alexander GR, Salihu HM, et al. Macrosomic births in the United States: determinants, outcomes, and proposed grades of risk. Am J Obstet Gynecol 2003;188(5):1372–8.

Chapter 72  NEONATAL INFECTION Kypros Kyprianou

KEY POINTS Fetal infections can occur from organisms that either cross the placenta or ascend via the vaginal tract. Infections, such as rubella and toxoplasmosis, may result in only mild symptoms in the mother but cause serious disease in the fetus. Group B streptococcal (GBS) neonatal sepsis can stem from non-infective colonisation of the vaginal tract. Due to the relative immaturity of its immune system, the newborn is largely reliant on passive immunity acquired from the mother. Two per cent of fetuses are infected before birth. Ascending bacterial infections may cause preterm labour or life-threatening infection in the newborn. Infections are the third most common cause of neonatal death after prematurity and congenital malformation. One of the most important factors in the prevention of neonatal infection is attention to appropriate hand hygiene. A neonate presenting with bacterial sepsis may have respiratory distress or other non-specific symptoms. Hence, a high level of suspicion and empirical treatment with intravenous antibiotics is required. In neonatal bacterial sepsis, clinical deterioration can be both rapid and dramatic, and the mortality rate from serious bacterial infection can be as high as 25%. Any suspicion of potential sepsis in a newborn requires urgent assessment.

IMMUNE SYSTEM There are reduced numbers of B-cells and T-cells in the newborn compared with the older child. Lymphoid tissue is sparse. Polymorphonuclear leucocytes are deficient in their function of tracking, attachment, ingestion and destruction of bacteria. Levels of complement, important in causing damage to foreign cell membranes, are half those of the adult. Immunoglobulin G (IgG) is the only class of immunoglobulin which crosses the placenta and at term, levels are can be higher than those of the mother. However, certain classes of IgG (such as IgG2) do not cross the placenta to a significant degree and this may explain the particular neonatal susceptibility to serious infection with organisms such as Group B streptococcus, Klebsiella and Escherichia coli.

ANTENATALLY ACQUIRED CONGENITAL INFECTIONS: THE TORCH INFECTIONS This section covers neonatal infections that have been acquired in utero. More specifically, this section covers those infections that can affect organ development. The TORCH group of organisms are: toxoplasmosis (Fig 72.1), other, rubella, cytomegalovirus and herpes simplex. Their presentation is quite different from that of acquired bacterial infections. Often there will be no history of a maternal infection. The presentation is usually at the initial physical examination, with findings of petechiae and hepatosplenomegaly. Other features include retinitis, intracranial

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30%. Surviving symptomatic congenital CMV may result in ongoing morbidity: cognitive impairment, cerebral palsy, deafness and/or visual impairment. Approximately 10 to 15% of the asymptomatic affected newborns can suffer from sensorineural deafness due to CMV.

Toxoplasmosis

FIGURE 72.1 

Neonatal toxoplasmosis. Non-contrast CT scan shows hydrocephalus and scattered intracranial calcifications, with a few seen in the periventricular region.

Source: Haaga JR, Dogra VS, Forsting M, et al. CT and MRI of the Whole Body. 5th edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 3.45.

calcification and periostitis. The specific cause should then be sought by immunological tests or polymerase chain reaction (PCR). Specific diseases, and treatments where available, are discussed throughout the chapter. (See also Chapter 19.)

Cytomegalovirus Despite being one of the most common acquired congenital infections (1%), antenatally acquired fetal cytomegalovirus (CMV) infection may be asymptomatic in a significant proportion of affected newborns. With severe involvement, the common features are microcephaly, intracranial calcification, neurological impairment (e.g. sensorineural hearing loss), liver derangement, hepatosplenomegaly and/or haematological issues (e.g. thrombocytopenia). (See Fig 19.1.) Identification of CMV in a newborn’s urine (by viral culture or PCR) is diagnostic. The demonstration of specific IgM antibodies in the blood may also be useful. IgG antibodies are not diagnostic as they can represent maternal transfer. Congenital CMV has no specific treatment, although there is equivocal evidence about the role of antiviral therapy (e.g. ganciclovir) in symptomatic congenital CMV infection. In newborns who present with significant organ involvement, the mortality rate can be as high as 20 to 656

This is an uncommon infection of the fetus, occurring in about 1 in every 10 000 births. It is cause by the protozoal parasite Toxoplasma gondii. The organism is acquired in mothers by direct oral ingestion of the parasite or cysts. This can be via the ingestion of undercooked meat containing Toxoplasma cysts or faecal–oral contamination from cat faeces. Infection in the mother can be asymptomatic or present as a mild, flu-like illness. Maternal-fetal transmission rates are approximately 30%. If the fetus is infected this can result in: fetal death, hydrocephalus, microcephalus, intracranial calcification, chorioretinitis, jaundice, hepatosplenomegaly and petechiae. Of those who have significant disease as newborns, about 25% die and the remainder have a high incidence of neurological disability. Treatment of congenital toxoplasmosis involves the anti-protozoal/antibiotic agents pyrimethamine and sulfadiazine. Concomitant corticosteroid and folate replacement therapy also has a role in treatment.

Rubella An Australian ophthalmologist, Sir Normal McAlister Gregg, was one of the first to note the associations between intrauterine-acquired rubella infection and the development of cataracts and heart defects. Since the advent of population-wide immunisation programs, rubella is now an uncommon cause of congenital infection. Fetal infection is particularly uncommon when the maternal infection occurs after the 20th week of gestation. Presentation in the newborn can be similar to congenital toxoplasmosis or cytomegalovirus, although with particular propensity for growth restriction, cataracts, congenital heart disease, deafness and bone lesions. Diagnosis is by urinary culture of the organism or more commonly a serological diagnosis (Fig 66.7).

Herpes simplex Perinatally acquired neonatal HSV infection occurs as the newborn is exposed to cutaneous maternal infection during vaginal delivery. Newborn infection can still occur even when there is no history of active vaginal herpetic lesions at the time of delivery. If the maternal herpes infection is primary, there will be no passive immunity and neonatal infection is more likely. The infection can present in the first week either as a serious, non-specific, septic-like illness or with a cutaneous vesicular rash. Diagnosis is by culture of the herpes virus from cerebrospinal fluid, or from samples taken from the eye, nose, throat, urine or faeces. Treatment is with aciclovir. Despite an improvement in prognosis with aciclovir, there is still

Chapter 72  Neonatal Infection

an appreciable mortality rate and neurological morbidity in survivors. The management of delivery in the presence of known active vaginal infection is discussed in previous chapters.

Syphilis In Australia, congenital syphilis is extremely rare. For example, six cases were reported (via mandatory notification) in Western Australia from 1991 to 2009.1 The clinical presentation can be varied, ranging from stillbirth to mucocutaneous lesions or asymptomatic infection. Asymptomatic infection of the newborn may develop signs of the disease months or even years later. When mucocutaneous syphilitic lesions are found in the newborn, there may be associated anaemia, oedema, failure to thrive, pyrexia and osteochondritis. The variability in presentation means diagnosis may be difficult. Adding to this are difficulties in interpreting serological diagnostic tests: positive serology may indicate a previous maternal infection and the absence of seropositivity does not necessarily exclude the diagnosis. Hence, clinical or radiographic signs of syphilis, especially if the mother had a history of syphilis during the pregnancy, warrant initiation of treatment. Lumber puncture is required to establish if neurosyphilis is present. In neonates, treatment with a single dose of benzathine penicillin (50 000 units/kg) intramuscularly may suffice. Alternatively, 10-day treatment regimes also exist: benzylpenicillin 50 mg/kg intravenously every 12 hours.

PERINATALLY ACQUIRED INFECTIONS: SUPERFICIAL AND SYSTEMIC BACTERIAL INFECTIONS Bacterial transmission can occur in the perinatal period (i.e. prior to, during and after delivery). The incidence of transmission (and hence infection) during this period can be minimised by attention to the following procedures. Handwashing is the most important method to prevent the transmission of perinatally acquired infections. Adequate handwashing with an antibacterial solution, or the use of antibacterial gel, is necessary before examination of any newborn. Avoidance of overcrowding. The incidence of infection increases in periods when there is overcrowding of the nursery. Lapses in handwashing protocols, as well as the close contact of infants, mothers, visitors and staff, may play a role in the spread of infection in overcrowded environments. Individual equipment is required for each cot. Cots require their own supply of nappies and dedicated examination equipment (e.g. stethoscopes). Equipment such as an ophthalmoscope should be cleaned by wiping with antibacterial solution between each

• •

•

use. Increasingly, single-use disposable equipment (e.g. oxygen and suction tubing) is replacing the need to sterilise and re-use equipment. Communal areas should be kept clean. Infant scales, baths and other communal areas should be wiped with antibacterial solution and scales covered with a clean towel or paper for each weighing. Cleanliness in preparation and storage of formula should be according to the manufacturer’s instructions and hospital policies. Perinatally acquired neonatal infections can be acquired in utero, during the birthing process or in the immediate postnatal period. They fit into two broad categories. 1. Superficial infection: common, less-invasive infections. 2. Systemic infection: neonatal bacterial sepsis and nosocomial-acquired infections in neonatal intensive care units.

• •

SUPERFICIAL INFECTION Oral candidiasis, conjunctivitis and omphalitis account for the vast number of postnatally acquired superficial infections.

Thrush (candidiasis) Candida albicans is the fungus that causes oral and cutaneous thrush. It may be acquired from the genital tract during delivery, feeding utensils (e.g. teats and bottles) or from the nipple/breast. In the mouth, the lesions present as thick, white, raised plaques with surrounding erythema. Unlike milk residue on the tongue, thrush plaques are difficult to wipe away. Cutaneous candidal infection in the nappy area presents as an erythematous rash with a clearly demarcated border. This ‘nappy rash’ often involves the flexures such as the groin, which differs from contact or irritant dermatitis (Fig 72.2). Treatment is with miconazole or nystatin preparations, either orally or topically depending on the site of infection. Rarely, serious systemic disease by Candida albicans occurs. In this case it may be in the sick preterm, where invasive catheters and antibiotic use predispose them to fungal infection.

Conjunctivitis Transient blockage of the lacrimal ducts is common and may predispose to conjunctivitis. Simple treatments include wiping the eyelids clean and perhaps massaging the lacrimal duct. If the infection is protracted or severe, a swab should be taken to allow identification of the organism. In this case, administration of an appropriate topical antibiotic ointment should occur. When there is a copious, bilateral, purulent eye discharge, gonococcal infection should be considered. Gonococcal ophthalmia can cause corneal ulceration if not treated promptly. 657

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Treatment for gonococcal ophthalmia is with cefotaxime 100 mg/kg intramuscularly or intravenously, as a single dose because topical antibacterial agents are inadequate. Conjunctivitis caused by Chlamydia trachomatis usually presents after the first week and is often culture negative. It is diagnosed by the presence of specific antibodies and is treated with systemic erythromycin. Dacryocystitis is uncommon (Fig 72.3) and requires treatment with systemic antibiotics.

Omphalitis Infection of the necrotic umbilical stump, particularly by Staphylococcus aureus, Streptococcus or E. coli, is called omphalitis. It manifests as peri-umbilical erythema and/ or purulent umbilical discharge (Fig 72.4). Cellulitis (more extensive peri-umbilical erythema, inflammation and tenderness) is treated with systemic antibiotics after a skin swab and blood cultures are taken.

Skin infection Superficial Staphylococcus aureus infection may present as skin pustules or paronychia (infection of the bed of the nails). In an otherwise systemically well newborn, treatment with topical antibiotics (after a swab has been taken) is often all that is usually required.

SYSTEMIC INFECTION: NEONATAL SEPSIS

FIGURE 72.2 

This newborn has a candidal skin infection of the nappy area. Note the ‘satellite’ lesions and flexural involvement. Source: Courtesy of Prof. Norman Beischer.

Life-threatening systemic neonatal infections are almost always caused by bacterial organisms which are acquired from the maternal genital tract during the birth process. The organisms responsible for infections change over time and differ from place to place. The organisms which are currently prevalent as causes of infection are Group B streptococcus (GBS, a beta-haemolytic organism called Streptococcus agalactiae), E. coli, Klebsiella, Pseudomonas, Pneumococcus, Staphylococcus aureus and, in the very preterm infant, S. epidermidis (also referred to as coagulase-negative staphylococci or CONS). Some organisms such as Listeria monocytogenes and Chlamydia trachomatis cause infections specific to neonates. Others such as Treponema pallidum can infect the fetus but cause few signs in the newborn and so must always be borne in mind.

1

FIGURE 72.3 

Acute dacryocystitis in a 4-week-old child with redness and swelling of left upper and lower lids and a prominent nasolacrimal sac (1). Source: Krachmer JH, Mannis MJ, Holland EJ. Cornea. 3rd edn. Philadelphia: Saunders, 2011. Copyright © 2011 Saunders, An Imprint of Elsevier. Figure 37.2A.

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FIGURE 72.4 

Omphalitis.

Source: Baren JM, Rothrock SG, Brennan JA, Brown L. Pediatric Emergency Medicine. Philadelphia: Saunders, 2008. Copyright © 2008 Saunders, An Imprint of Elsevier. Figure 39.9

Chapter 72  Neonatal Infection

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The risk factors for systemic bacterial infection are: prolonged rupture of membranes (various definitions exist but risk increases with rupture of membranes > 18 hours) known vaginal colonisation with GBS prematurity maternal fever any breach of the skin such as skin trauma indwelling catheters such as intravenous cannulas and endotracheal tubes.

Incidence The incidence of serious systemic infection is dependent on the population with the above risk factors. It is approximately 1 in 1000 term newborns.

Presentation The presentations may be varied and therefore a high index of suspicion is required. There may be respiratory distress and/or pneumonia. General, less-specific findings include temperature instability (hypothermia or fever), lethargy, poor feeding, vomiting, apnoea or pallor. Signs suggesting a focal site of infection may be present: a high-pitched cry, seizures or stiffness and posturing may suggest meningitis; bone or deep tissue involvement may present with fever and pseudoparesis of a limb.

Assessment and diagnosis Diagnostic sampling of blood, urine and cerebrospinal fluid (CSF) should occur prior to commencement of empiric antibiotics, but only if there is no immediate concern for life-threatening sepsis or overwhelming cardiac compromise (due to septic shock). Because many of the signs are non-specific, attempts are made to establish whether infection is present by performing the following investigations. Full blood count and blood film. Infection can cause a higher proportion of the white cells in the blood (leucocytosis) and/or an increase in immature or precursor neutrophil forms (‘left shift’). Neutropenia (< 2 × 109/L) or neutrophilia (> 8 × 109/L) are also suggestive of infection. Tests of acute phase reactants such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are at times performed; however, they lack specificity. Blood culture. It is mandatory to take blood for culture before antibiotics are commenced. Bacteraemia is usual with any severe infection. An adequate volume (e.g. 1  mL) of blood should be collected after careful cleansing of the skin with an appropriate topical antiseptic agent. To prevent culture-bottle contamination, the blood-taking needle should be replaced before injecting the blood into the blood culture bottle.

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Urine culture. A sterile sample needs to be collected to minimise the risk of false-positive results. This is done by suprapubic bladder aspiration. Lumbar puncture. If there is any possibility of meningitis, a lumbar puncture should be performed. Meningitis can still occur even when a presumed focus is found. Microscopy and culture of CSF is the only way to definitively diagnose or exclude congenital meningitis. Chest X-ray is often considered, especially if there are signs of respiratory distress. Other investigations may be undertaken as indicated. If there is abdominal distension, then an abdominal X-ray should be obtained. If there is a suggestion of septic arthritis or osteomyelitis, an X-ray of the appropriate body part should be taken. Lastly, an assessment of the baby’s general condition is important. If respiratory distress, apnoea or shock are present, then prompt commencement of therapy—empiric antibiotics, treatment of shock and respiratory support—is warranted. Following this, transfer for specialised tertiary care will be needed.

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Treatment If bacterial sepsis is suspected, the newborn should be transferred to an incubator to allow close observation and provide a neutral thermal environment. If the newborn is very unwell with shock or respiratory failure, supportive treatment must be undertaken immediately. This may consist of the provision of oxygen, respiratory support or intravenous fluid resuscitation. In most cases, a judgment based on the likely organisms will guide the choice of empiric antibiotics. Further to this, specific treatment will be dictated by the results of tests. A Gram stain of CSF may allow a tentative identification of the organism. Most organisms (up to 95% of early onset sepsis pathogens) are sensitive to a combination of benzylpenicillin and gentamicin; hence, these agents are often used as first-line empiric therapy in suspected neonatal sepsis.2 If meningitis is suspected, a third-generation cephalosporin and/or an antiviral (e.g. aciclovir for treatment of potential herpes meningoencephalitis) may also be administered empirically. The duration of antibiotic treatment varies according to the ultimate diagnosis: 48 hours if infection is thought unlikely in retrospect, and cultures are sterile 7 to 10 days for septicaemia 14 to 21 days for meningitis 4 to 6 weeks for osteomyelitis.

• • • •

SPECIFIC INFECTIONS Because of the common presentation and treatment, bacterial infections can be considered together. However, there are several infections which have special features. 659

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GROUP B STREPTOCOCCUS Infection with the lethal organism Group B streptococcus can closely mimic features of the respiratory distress in all respects. In presumed respiratory distress syndrome or transient tachypnoea, a blood count and culture should be performed to exclude infection. Any unusual deterioration in respiratory condition should alert one to the possibility of GBS sepsis. Antibiotics should be commenced promptly if GBS infection is suspected. GBS can cause neonatal sepsis, pneumonia or meningitis and despite optimal treatment, the mortality rate can be as high as 25%. Prophylactic treatment to prevent infection when the mother’s vaginal tract is known to be colonised by GBS is discussed in previous chapters. These steps have markedly reduced the incidence of early-onset GBS neonatal sepsis. In contrast, in the developed world, the rates of late-onset GBS neonatal sepsis have not significantly reduced. Table 72.1 outlines the differences between early- and late-onset GBS infection.

PNEUMONIA Newborns with pneumonia will present with respiratory distress and the need for supplemental oxygen therapy. Non-specific signs such as lethargy, apnoea, refusal of feeds, vomiting and temperature instability may precede the respiratory findings. The newborn’s temperature may in fact be low, particularly if the infection is severe and there are signs of shock. Viral infections, acquired transplacentally, can present with congenital pneumonia, including rubella, cytomegalovirus (CMV) or Coxsackievirus. However,

TABLE 72.1  DIFFERENCES BETWEEN EARLY AND LATE ONSET GBS INFECTIONS. Early onset GBS infection

Late onset GBS infection

Perinatally acquired bacterial colonisation prior to or during the birthing process

‘Community’ acquired in the postnatal period

Presentation in the first 0 to 7 days of life

Presentation from day 7 to day 90 of life

Incidence reducing due to improved perinatal management (e.g. screening and use of intrapartum antibiotics)

Incidence stable (i.e. rates unaffected by use of intrapartum antibiotics)

Common presentations: respiratory distress, sepsis, pneumonia, meningitis

Common presentations: sepsis, meningitis, focal infections (e.g. bone, joint, cellulitis)

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ascending, vaginally acquired bacterial infections are more common. Pathogens include GBS, E. coli, Klebsiella or Pseudomonas. The risks of bacterial sepsis, including pneumonia, are increased if there has been prolonged rupture of the membranes. Postnatally acquired infections (nosocomial) may occur after birth and are caused by similar respiratory pathogens to those which infect infants and older children (e.g. Streptococcus pneumonia). Diagnosis is confirmed on chest X-ray and causative organisms may be cultured from the blood and/or, less commonly, tracheal aspirate. Treatment of respiratory distress is with appropriate ventilatory support (i.e. supplemental oxygen, continuous positive airway pressure, or intubation and ventilation). Appropriate intravenous antibiotics, initially empiric and then targeted, should be used.

MENINGITIS Meningitis can accompany any serious systemic bacterial infection in the newborn. Diagnosis can only be made, or excluded, by lumbar puncture and examination of CSF. Meningitis, especially that caused by gram-negative bacteria, is prone to recur shortly after the cessation of treatment. An adequate duration of treatment (21 days) with intravenous antibiotics is necessary for gram-negative meningitis. Cranial ultrasound examinations are conducted to exclude abscess formation and hydrocephalus. Convulsions are common and may interfere with normal respiration, necessitating respiratory support. Among survivors of confirmed neonatal bacterial meningitis, the incidence of permanent neurological sequelae, such as hearing impairment, can be as high as 25%.

OSTEOMYELITIS/SEPTIC ARTHRITIS Although rare in the neonatal population, bone or joint infections should be suspected in the context of bone or joint tenderness, ‘splinting’ or pseudo-paresis. Initial plain-film X-ray may not immediately reveal bone infection; a repeat X-ray 10 to 14 days later may confirm bony involvement. Septic arthritis is diagnosed by culture of infected synovial fluid, acquired via joint aspiration. Antibiotic treatment should be for an extended period of time (e.g. up to 6 weeks). The prognosis is usually good, but epiphyseal damage may result in limb shortening or deformity and thus long-term follow-up is required.

VIRAL HEPATITIS Perinatally acquired transmission of hepatitis B (vertical transmission from infected mother to newborn) has declined since the universal introduction of hepatitis B vaccination, with the first vaccine usually given immediately postdelivery. Infants born to mothers whose hepatitis serology demonstrates previous infection are also given hepatitis B-specific immunoglobulin in the first

Chapter 72  Neonatal Infection

72 hours of life, in addition to the vaccine. In contrast to acute viral hepatitis B acquired later in life, perinatally acquired infection has a very high likelihood of progressing to chronic hepatitis B infection. Vertical transmission of hepatitis C occurs, especially if the mother is co-infected with HIV. Unlike for hepatitis B, there is no vaccine or immunoglobulin available to mitigate the risk of vertical transmission of hepatitis C. As such, guidelines for breastfeeding and mode of delivery exist to reduce mother–infant transmission. (See also Chapter 19.)

HIV/ACQUIRED IMMUNODEFICIENCY SYNDROME The majority of paediatric HIV/AIDS is prenatally acquired from the HIV-positive mother, and this proportion is increasing both as the incidence of the disease increases in females and as blood product screening is reducing the chance of transfusion-acquired disease in children. The virus, as well as maternal IgG antibodies, cross the placenta. The virus is also excreted in breastmilk. Most newborns are well at birth and remain asymptomatic for at least several months. Without treatment, about 20% will become infected with the virus. The diagnosis of transmission of the virus can be made by viral identification in the newborn. Confirmation that there has been no transmission of the virus requires waiting for negative serology at 15 to 18 months of age. Signs and symptoms of the disease include lymphadenopathy, recurrent infections, failure to thrive and progressive neurological disease. These features usually occur in the first months after birth. The virus is excreted in breastmilk and breastfeeding is contraindicated unless the risks of artificial feeding outweigh the risk of HIV transmission, as they may in developing countries.

INFECTIONS IN NEONATAL INTENSIVE CARE UNITS Some newborns are affected by hospital-acquired infections related to their neonatal intensive care unit admission. In a 10-year study of over 6000 neonatal admissions, up to 70% of newborns admitted to neonatal intensive care units were reported to have had at least one single episode of infection.3 These often premature newborns are at risk of various infections. Serious, but often preventable, infections include peripheral and central venous

line catheter-associated infections, ventilator-associated pneumonia and catheter-associated urinary tract infections. Other infections include ‘outbreaks’ of infective organisms such as Serratia marcescen, methicillinresistant Staphylococcus aureus (MRSA) or extended spectrum beta-lactamase (ESBL) producing organisms. Various prevention strategies are utilised by neonatal intensive care units to minimise hospital-acquired infections. These include universal hygiene measures, venous catheter insertion and management protocols, judicious use of antibiotics, promotion of breastfeeding with fresh human milk and prophylactic measures (e.g. prophylactic antifungal use).

NEONATAL INFECTIONS IN THE DEVELOPING WORLD Neonatal sepsis remains a significant burden of disease in the developing world. Comparisons with the developed world are hard, mainly related to large numbers of home births, variable documentation and reduced access to medical and laboratory services. Poor hygiene, emerging antibiotic resistance and lack of access to parenteral antibiotics or supportive care settings (e.g. special and intensive care units) are important contributing factors. Postnatally acquired infections may include neonatal pneumonia, neonatal tetanus and omphalitis. Lastly, ophthalmia neonatorum (gonococcal or trachomatous conjunctivitis) is a major cause of blindness among children in the developing world.4 REFERENCES 1) Kwan KS, Giele CM, Greville HS, et al. Syphilis epidemiology and public health interventions in Western Australia from 1991 to 2009. Sex Health 2012;9(3):272–9. 2) Vergnano S, Menson E, Kennea N, et al. Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011;96(1):F9–14. 3) Couto RC, Carvalho EA, Pedrosa TM, et al. A 10-year prospective surveillance of nosocomial infections in neonatal intensive care units. Am J Infect Control 2007;35(3):183–9. 4) Ganatra HA, Zaidi AK. Neonatal infections in the developing world. Semin Perinatol 2010;34(6):416–25.

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Chapter 73  CONGENITAL MALFORMATIONS Kypros Kyprianou

KEY POINTS The incidence of major congenital malformations is 2 to 4% of live-born infants, with minor malformations significantly more common. Major congenital malformations account for more than 25% of perinatal deaths despite the fact that the survival rate for infants with malformations has increased.1 Hypospadias is the most commonly reported condition at birth.2 For over half of congenital malformations, the exact cause is unknown. Chromosomal or genetic causes are increasingly being recognised: they were previously reported as 0.5%, but may be as high as 10%. Genetic abnormalities are present in 50% of spontaneous abortions. Prenatal diagnosis has had an impact on the numbers of infants born with particular conditions such as spina bifida and chromosomal abnormalities such as Down syndrome. Prevention of some conditions is possible: toxins such as alcohol, which causes fetal alcohol syndrome, can be avoided; rubella embryopathy is now rare because of immunisation; and the incidence of neural tube defects can be reduced by periconceptional dietary supplementation with folic acid. Physical screening of the newborn is used to detect congenital dislocation of the hip and other occult congenital conditions. Increasingly, oxygen saturation screening may be used to detect congenital heart disease. Heel-prick blood sample screening of newborns occurs early in the postnatal period. It is used to detect conditions such as hypothyroidism, phenylketonuria, cystic fibrosis and other rare, but at times treatable, inborn errors of metabolism. Appropriate counselling and support must be provided if a congenital malformation is found. Even minor malformations may not be minor in the eyes of the parents. Genetic counselling may be necessary to inform the parents of recurrence risks and to indicate whether prenatal diagnosis is possible in future pregnancies.

PREVALENCE The types and incidence of birth defects can be difficult to measure. Prevalence rates (unlike case-based statistics) take into account total births and terminations. Some conditions are common in otherwise healthy newborns (e.g. hypospadias, isolated renal anomalies, ventricular septal defect [VSD]). In terminations of pregnancy due to

birth defects, chromosomal abnormalities (70%) and central nervous system anomalies (12%) account for the vast majority of defects. Tables 73.1 and 73.2 outline prevalence rates for a number of congenital abnormalities. A malformation results from an abnormality of a developmental process (e.g. spina bifida). A deformation results from mechanical interference with normal

Chapter 73  Congenital Malformations

TABLE 73.1  PREVALENCE* OF COMMON BIRTH DEFECTS IN A SINGLE AUSTRALIAN PERINATAL DATA COLLECTION UNIT. Diagnosis

Prevalence

Hypospadias†

1/135

Obstructive defects of renal pelvis

1/250

Ventricular septal defect

1/311

Trisomy 21

1/339

Developmental dysplasia of hip

1/364

*Not cases; reported as 1/x number of births + terminations. †This figure used male babies only as the denominator. Source: Consultative Council on Obstetric and Paediatric Mortality and Morbidity, Victorian Department of Health.

development (e.g. talipes). A disruption results from interference with normal growth after a period of normal development such that destruction of that part results (e.g. bowel atresia). If there are multiple malformations, they may be part of: a syndrome (e.g. Down syndrome), in which there may be a readily identifiable cause of the various malformations an association, in which a combination of malformations commonly occur together but with no clearly identifiable cause (e.g. VATER association, where VATER is an acronym for vertebral, anal, tracheooesophageal and renal malformations) a malformation sequence, in which one malformation (e.g. renal agenesis) has led to other malformations (e.g. oligohydramnios and pulmonary hypoplasia). Deformations and disruptions are rarely genetically determined. Malformations may have chromosomal or environmental causes. The environmental causes are often not identified, but metabolic disease (e.g. maternal diabetes mellitus), infection (e.g. rubella) and drugs (e.g. thalidomide) are known causes of malformations.

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AN OVERVIEW OF CHROMOSOMAL AND GENETIC ABNORMALITIES Common fetal aneuploidies include trisomies (one chromosome too many) and monosomies. Down syndrome (trisomy 21) and Turner syndrome (monosomy X) are the most common aneuploidies. In addition to abnormalities of number, various forms of internal rearrangements of the chromosome are possible (e.g. translocations, deletions and inversions).

Aneuploidies and larger chromosomal rearrangements (e.g. 22q deletion in DiGeorge/velocardiofacial syndrome) present with classic phenotypical features either in the newborn or childhood period. Genetic testing (karyotype and G-banding) often confirms the already formed clinical suspicion. Furthering the genetic ‘diagnostic yield’ has been achieved with the advent of single nucleotide polymorphism (SNP) microarray testing. This test finds microdeletions (or duplications) that were previously undetected using traditional methods. The test is ordered, after discussion with a family, where subtler dysmorphic features are present, and/or without the appearance of a ‘classic’ phenotype. Lastly, the incidence of chromosomal embryonal pathology is quite high; however, up to 90% of embryos with chromosomal abnormalities do not survive to term. Hence, at birth, chromosomal abnormalities are present in approximately 0.5% of newborn infants. A revision of inheritance patterns is outlined in Box 73.1. A practical approach to the assessment of the newborn with dysmorphisms or malformations must take all these aspects into account. It involves: assessing all abnormalities present making a diagnosis, hence establishing the prognosis, and treating problems as required. Communication, discussion, counselling and support for the parents are paramount, in conjunction with establishing a recurrence risk for any future pregnancies.

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SPECIFIC ABNORMALITIES CONGENITAL HEART DISEASE Congenital heart disease occurs in 1% of births and causes serious problems in infancy in 30% of cases. It is the most common single-system malformation requiring treatment. Most structural abnormalities have their origin in the 4th to 8th week of gestation. It is at this time that the heart tube undergoes: 1. septation to form the two atria and later the two ventricles; and 2. the complex spiralling which defines the relationships between the heart chambers and the great vessels. The risk of congenital heart disease is increased if a sibling is also affected. The presentation often occurs in one of four ways: respiratory distress, cyanosis, cardiovascular shock and/ or detection of a cardiac murmur. Respiratory distress manifests as tachypnoea (> 60 breaths/min), and dyspnoea may be prominent with intercostal, subcostal and sternal recession. Hepatomegaly and oedema may occur if cardiac failure is advanced. The differential diagnosis includes all the causes of respiratory distress.

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TABLE 73.2  PREVALENCE OF BIRTH DEFECTS (BY SYSTEM) IN A SINGLE AUSTRALIAN PERINATAL DATA COLLECTION UNIT. System/defect

1/x*

n/10 000

Trisomy 21

339

29.5

Trisomy 18

1190

8.4

Trisomy 13

2564

3.9

364

27.5

2083

4.8

Hydrocephalus

1235

8.1

Spina bifida

1667

6.0

Anencephaly

1818

5.5

Microcephalus

5556

1.8

Encephalocele

8333

1.2

Skeletal

Limb reduction defects

1/x*

n/10 000

Cardiac

Aneuploidy

Developmental dysplasia of hip

System/defect

Central nervous system

Genito-renal system

Ventricular septal defect

311

32.2

Transposition of great vessels

1587

6.3

Coarctation of aorta

2041

4.9

Hypoplastic left heart syndrome

2222

4.5

Tetralogy of Fallot

2703

3.7

Cleft palate

1250

8.0

Cleft lip and palate

1818

5.5

2564

3.9

Anorectal atresia and/or stenosis

2273

4.4

2632

3.8

Oral/facial

Cleft lip Gastrointestinal

Hypospadias

135

74.1

Oesophageal atresia and/or stenosis

Obstructive defects of renal pelvis

250

40.0

Exomphalos

3226

3.1 3.2

1471

6.8

Intestinal atresia and/or stenosis

3125

Cystic kidney Renal agenesis/dysgenesis

1515

6.6

Diaphragmatic hernia

3571

2.8

4348

2.3

Gastroschisis

*Not cases; reported as 1/x number of births + terminations. Source: Consultative Council on Obstetric and Paediatric Mortality and Morbidity, Victorian Department of Health.

BOX 73.1  Inheritance patterns: a review. Autosomal dominant. A parent is affected and, on average, 1 in 2 of their children will be affected; males and females are equally affected. If incomplete penetrance occurs, the individual may not be affected even when the gene for the disease is present. Examples of diseases inherited in this manner are some forms of osteogenesis imperfecta, skin tags and preauricular pits. Autosomal recessive. If both parents are carriers, siblings have a 1 in 4 risk of being affected. Examples of diseases inherited in this manner are β-thalassaemia, cystic fibrosis, phenylketonuria and galactosaemia. 664

X-linked recessive inheritance. The risk to male offspring of carrier females is 1 in 2. If affected males reproduce, all their daughters will be carriers but none of their sons will be affected. Examples of diseases inherited in this manner are haemophilia and Duchenne’s muscular dystrophy. Multifactorial or polygenic inheritance. Many common single malformations are inherited in this fashion. Examples are cleft lip and palate, congenital dislocation of the hip and spina bifida.

Chapter 73  Congenital Malformations

•

Cyanosis can occur with or without respiratory distress. Marked central cyanosis may be the presenting feature or may be milder and associated with another dominant form of presentation. Cardiovascular shock presents as pallor and skin mottling with cold extremities. It may occur after a presentation with other symptoms or occur very suddenly, in which case there may be no signs of cardiac failure. Often the newborn is extremely ill, and unresponsive, and may have a severe metabolic acidosis. Cardiovascular shock may be the presentation of duct-dependent cardiac anomalies (e.g. coarctation of the aorta, hypoplastic left heart) where the systemic circulation relies on a patent ductus arteriosus (PDA). Once the PDA closes, there is rapid and profound shock due to markedly reduced cardiac output to the systemic circulation. Prostaglandin analogues provide a life-saving treatment to prevent PDA closure, before transfer and/ or prior to definitive surgical intervention. The differential diagnosis includes severe infection, asphyxia, intracranial haemorrhage, haemorrhagic disease of the newborn and inborn errors of metabolism. A cardiac murmur is often found when the presentation of congenital heart disease is with respiratory distress, cyanosis or shock. However, it may be the presenting sign in an asymptomatic newborn. Septal defects and valve stenoses often present in this way. Murmurs may be innocent. Transient murmurs, with no other significant findings, over the first 24 hours may also be heard; these are often innocent, though further investigation may be warranted depending on clinical concern. The investigations necessary for each of these types of presentation are similar. The history may raise the possibility of alternative diagnoses or increase the suspicion of congenital heart disease. A physical examination may result in finding evidence of other malformations or other diagnoses. A chest X-ray may indicate the presence of cardiomegaly and/or pulmonary plethora. An electrocardiogram (ECG) will establish whether there is a major change in the electrical axis of the heart, thus making particular diagnoses likely. If there is an oxygen saturation or blood pressure differential in the right arm compared to the leg, coarctation of the aorta may be present. Echocardiography almost always provides a definitive diagnosis and the need for angiography is uncommon. If there is the possibility of other diagnoses, appropriate evaluation and treatment should ensue. The common lesions which present in the newborn period are coarctation of the aorta, ventricular septal defect, transposition of the great arteries, hypoplastic left heart, tetralogy of Fallot and hypoplasia of the right heart, which includes pulmonary atresia and tricuspid atresia.

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Coarctation of the aorta This is the most common type of congenital heart disease to present with cardiac failure in the newborn

period. A constriction of the aorta is present proximal to the insertion of the ductus arteriosus. The left ventricle fails because of either: 1. the increased afterload; or 2. increased volume load if there is an associated ventricular septal defect, which is common. Femoral pulses are often weak or absent. The presentation is with feeding difficulty and tachypnoea in the first days, weeks or even months after birth. Coarctation of the aorta may present with an abrupt collapse (upon closure of the ductus arteriosus) in the first few days of life. Early surgical repair is required.

Ventricular septal defect This is the most common form of congenital heart disease. It is most commonly diagnosed because of a loud, harsh, systolic murmur. If the defect is large, cardiac failure may occur after the first month, with a presentation of tachypnoea and poor feeding. Peri-membranous defects nearly always require open surgical repair; small muscular defects often close with time.

Transposition of the great arteries This is the most common congenital heart malformation to present with cyanosis. In the usual form, the atria and ventricles are normally related on the appropriate side, but the pulmonary artery arises from the left ventricle and the aorta from the right ventricle. Oxygenation of systemic blood is dependent on mixing of blood between the two circulations via the ductus arteriosus and/or foramen ovale. Presentation is in the newborn period with cyanosis, which may initially be difficult to appreciate. Treatment is by immediate rupture of the interatrial septum (balloon atrial septostomy) using an intravenous catheter inserted percutaneously and guided by radiological imaging. Definitive treatment is by switching of the two arteries, which is performed at several weeks of age. Pulmonary atresia and tetralogy of Fallot (ventricular septal defect with overriding aorta, pulmonary valve stenosis and right ventricular hypertrophy) are other causes of cyanosis. These must be distinguished from persistent pulmonary hypertension of the newborn.

Hypoplastic left heart This is the most common cardiac lesion to present with shock. The left ventricle, mitral valve, aortic valve and ascending aorta are all hypoplastic to a variable degree. The systemic supply of blood is via a patent ductus arteriosus. The only flow in the aortic arch is retrograde, via the ductus arteriosus. Shortly after delivery, the newborn may appear surprisingly healthy but tachypnoea is common. When the ductus arteriosus closes within the first week after birth, there is a dramatic clinical deterioration. Peripheral pulses are difficult or impossible to palpate. Hepatomegaly is marked. While a definitive diagnosis by echocardiography is awaited, ventilatory support, prostaglandin 665

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analogues and antibiotics (given the presentation resembles septic shock) should be commenced. There is no definitive cure, with palliative surgery (in three ‘stages’ during the neonatal, infant and early childhood period) required. The aim of this surgery is to convert the right ventricle into a ‘systemic ventricle’. Cardiac transplantation offers another treatment option either following palliative surgery or even within the neonatal period.

CENTRAL NERVOUS SYSTEM Neural tube defects Spina bifida (Box 73.2) is due to failure of closure of the neural tube in the fourth week of gestation. It is the most common form of neural tube defect; other lesions include encephalocele and anencephaly. Fewer babies are born with neural tube defects than in the past. This is due to prenatal screening with subsequent termination, as well as periconceptional dietary supplementation with folic acid. Screening for the lesion is by the measurement of serum alpha-fetoprotein in maternal serum at 16 to 18 weeks’ gestation or by ultrasonography. Alphafetoprotein may also be elevated in multiple pregnancy and exomphalos and so careful examination of the fetus using ultrasound imaging is warranted. Meningomyelocele is the most common form of spina bifida. This is a cystic lesion containing maldeveloped spinal cord (Fig 73.1). The site is most often lumbar, but may be anywhere along the spine.

Prevention of many cases is feasible by the periconceptional administration of folic acid. All women planning a pregnancy should be encouraged to increase their dietary intake of foods rich in folic acid (fruits, leafy green vegetables, legumes and cereals), particularly in the month before and several months after conception. Lowrisk women should be offered folic acid 0.5 mg per day. Women with a higher risk of spina bifida (previous child or relative with a neural tube defect) should take folic acid 5 mg/day periconceptionally, and be offered genetic counselling, alpha-fetoprotein assay and tertiary level ultrasound examination.

Other CNS malformations Other CNS malformations are less common. These include: anencephaly, in which there is a rudimentary brain with absent cerebral hemispheres and an absence of the posterior skull bones

•

BOX 73.2  Spina bifida. If spina bifida is found, an assessment and treatment plan should be made and discussed with the family sensitively. The assessment should pay particular attention to: ✚ muscle paralysis and its level ✚ orthopaedic deformity of the lower limbs ✚ urinary incontinence and/or anal sphincter paralysis ✚ the presence or absence of hydrocephaly ✚ the presence or absence of Arnold-Chiari malformation of the brainstem ✚ scoliosis ✚ associated malformations such as congenital heart disease and chromosomal defects. The likely disabilities are discussed with the parents and a decision made as to whether treatment is to be undertaken. Treatment consists of closing the spinal defect within the first days and dealing with the ongoing problems as required. 666

FIGURE 73.1 

A small meningomyelocele with lower sacral nerve involvement in a 7-day-old infant, birthweight 3.835 g. The area of telangiectatic skin was noted at birth. Such a lesion could be mistaken for a naevus, but its position suggested the possibility of spina bifida. Careful examination revealed reduced perineal sensation. Source: Courtesy of Prof. Norman Beischer.

Chapter 73  Congenital Malformations

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microcephaly (head circumference < 10th percentile), which has numerous causes including congenital infection and chromosomal disorders hydrocephaly, which presents in the second half of gestation or at birth with dilated lateral ventricles and often a head circumference > 90th percentile. If detected, chromosomal abnormalities and associated defects need to be excluded.

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Fetal alcohol syndrome While it is difficult to separate the effects of alcohol from those of associated variables such as maternal nutrition and smoking, an intake of alcohol in excess of 40 to 60  g (about 4 to 6 standard drinks) daily during the first trimester, and possibly later in pregnancy, may lead to fetal alcohol syndrome. Lesser intakes of alcohol may also increase the risk of a number of malformations. Continuing uncertainty as to the extent of alcohol exposure necessary to affect the fetus has led a number of bodies to advise total abstinence throughout pregnancy. Features of fetal alcohol syndrome are: a reduction in birth weight with subsequent failure to thrive microcephaly with subsequent developmental delay, irritability and intellectual disability physical features of maxillary hypoplasia, a thin upper lip, short nose and shallow philtrum (Fig 73.2).

• • •

GASTROINTESTINAL TRACT Several disorders of the gastrointestinal tract may present with bowel obstruction. The presentation is often (but not always) with the clinical triad of: 1. bile-stained vomiting 2. abdominal distension, and 3. delayed passage of meconium. Radiographic features are dilated bowel loops and fluid levels as seen in Figure 73.3. If the obstruction is low, the presentation is initially with bile-stained vomiting. If the obstruction is above the second part of the duodenum, the presentation is with vomiting which is not bile-stained. Meconium may be passed initially and abdominal distension may not occur. If the obstruction is very low, the presentation is with delayed passage of meconium and it may be some time before abdominal distension and bile-stained vomiting occur.

Atresia Bowel atresia may occur anywhere in the gut and is thought to be due to a vascular accident during gut development. Presentation may be prenatal where dilated bowel loops are seen on ultrasound examination. Postnatally, the presentation is with the signs of bowel obstruction. Investigation includes the search for associated

FIGURE 73.2 

Characteristic facies of fetal alcohol syndrome with a saddle-shaped nose; maxillary hypoplasia; absent philtrum between the nose and upper lip; and short, thin upper lip. This child also has an incidental haemangioma (strawberry naevus) below the right nostril. Source: Lissauer T, Clayden G, Craft A. Illustrated Textbook of Paediatrics. 4th edn. Edinburgh: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figure 9.5.

anomalies (e.g. 30% of infants with duodenal atresia have Down syndrome) and radiographic contrast studies. General support, intravenous fluids and early surgical treatment are necessary.

Meconium ileus Hyperviscous meconium (as occurs in cystic fibrosis) may cause an ileus. In this case, the presentation is with signs of bowel obstruction in the distal small bowel. Bowel perforation may occur in utero. Treatment is by enemas, with surgery reserved for those where enemas do not relieve the obstruction.

Hirschsprung’s disease Hirschsprung’s disease occurs when there is failure of normal migration of neurenteric ganglion cells to the distal rectum and a variable length of bowel above. The presentation is with partial bowel obstruction, manifest most commonly as a delay in the passage of meconium. Definitive diagnosis is made by demonstrating aganglionosis of rectal mucosa obtained by biopsy. Treatment is surgical. 667

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Imperforate anus

Tracheo-oesophageal fistula

A careful initial examination will detect imperforate anus (Fig 73.4). There is a wide range of possible malformations of the anus, rectum and genitalia. Associated malformations of other organs may also occur. Treatment is by surgical correction.

In 90% of cases of tracheo-oesophageal fistula, there is oesophageal atresia with a blind proximal pouch and a fistula from the distal oesophagus to the trachea. Because of the inability to swallow, polyhydramnios is very common. Prenatal ultrasound may define the dilated proximal oesophageal pouch. Postnatally, the presentation may be with copious frothy secretions first noticed shortly after birth with choking or cyanosis due to overflow of secretions or milk from the proximal oesophageal pouch. Diagnosis is by the demonstration of an inability to pass a large feeding catheter beyond the obstruction (usually about 10  cm from the lips; see Fig 73.5). The initial management is to prevent aspiration by keeping the proximal oesophageal pouch free of secretions. Associated anomalies are common. Surgical treatment is aimed at anastomosis between the ends of the oesophagus and closing the tracheooesophageal fistula. This may need to be done in several stages.

FIGURE 73.3 

Left lateral decubitus radiograph shows a paucity of bowel gas with a few air fluid levels (arrows), consistent with intestinal obstruction. Source: Reid JR. Practical imaging approach to bowel obstruction in neonates: a review and update. Semin Roentgenol 2012;47(1):22. Figure 3.

H

D

FIGURE 73.5 

FIGURE 73.4 

Low imperforate anus in a male infant. White mucus or black meconium may pass through a perineal fistula from a low imperforate anus into the scrotal raphe. Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 17.100.

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S

Tracheo-oesophageal fistula and associated abnormalities. A radio-opaque catheter cannot be passed beyond the oesophageal atresia and is shown in the proximal pouch. The gas in the stomach (S) indicates that there is a fistula between the trachea and lower oesophagus. The stomach and proximal duodenum (D) are distended and no gas has passed more distally, signifying a duodenal atresia. Note also the associated skeletal malformation of hemivertebrae (H). Source: Courtesy of Prof. Norman Beischer.

Chapter 73  Congenital Malformations

Exomphalos (omphalocele)   and gastroschisis

DEVELOPMENTAL DYSPLASIA   OF THE HIP

These are the two common forms of anterior abdominal wall defect. They must be distinguished from each other because gastroschisis requires urgent surgical treatment. In utero diagnosis is often by ultrasound imaging. Omphalocele is often associated with chromosomal anomalies and, if found on prenatal ultrasound scan, amniocentesis may be offered. Exomphalos is a midline abdominal wall defect with herniation of bowel contents and sometimes liver into the umbilical stump and membranous covering. Treatment is surgical, although this may be delayed. Treatment of associated malformations may also be necessary. Gastroschisis is the prolapse of intestine through a paramedian abdominal wall defect. There is no membranous covering. The bowel should be carefully positioned without causing a volvulus and wrapped in clear plastic wrap (Fig 73.6). Fluid loss from the bowel may be large. Intravenous fluids and early surgical treatment are necessary.

Previously, this disorder was known as congenital dislocation of the hip. This term has now been replaced by developmental dysplasia of the hip (DDH). This is an important acknowledgement of the developmental nature of this anomaly, where the hip may be either clearly dislocated at birth or at risk of displacement due to significant acetabular dysplasia. In DDH, the acetabulum fails to develop normally because the head of the femur is not in the acetabulum due to deflexion of the fetal leg. This explains why the condition is more common when the fetus is in the breech position and in the primipara in whom the fetal mobility is constrained by the tight, unstretched uterine and abdominal wall musculature. The Ortolani and Barlow manoeuvres described in Chapter 66 are used to detected any immediate hip dislocation and hence prompt further assessment and treatment. A dynamic hip ultrasound will confirm the bedside examination of a dislocated hip. In cases where hip dysplasia is suspected due to risk factors, even if a bedside examination is normal, a postnatal hip ultrasound should be requested to assess for dysplasia. Risk factors for hip dysplasia include a positive family history of DDH or breech position. To allow for a degree of hip (acetabular) maturation, the ultrasound is best performed at 6 to 8 weeks of age. If hip dysplasia is found on ultrasound scanning, then close follow-up and repeat scanning is required to monitor for the natural deepening of the hip joint and acetabular maturation. If hip dysplasia persists (due to slow or absent acetabular maturation), if there is evidence of an overt dislocation or if there is significant dysplasia that is unlikely to improve, then non-surgical treatment is promptly initiated with a pelvic–hip–thigh harness (e.g. Pavlik harness). This treatment holds the affected leg in abduction and flexion, thus promoting acetabular growth and maturation. Rarely is more intense plastering or surgery required. Due to improved awareness and screening of DDH, this condition can often be conservatively or nonsurgically managed as described here. A missed or late diagnosis may result in long-term morbidity, even after surgical reduction of the hip. Poor outcomes include persistent limp and early osteoarthritis.

Diaphragmatic hernia Prenatal diagnosis by ultrasound imaging is now frequent, in which case delivery can be planned to take place in a tertiary referral hospital with the facilities for early initial treatment and surgical correction.

FIGURE 73.6 

Gastroschisis. Loops of bowel and a portion of liver extravasate through a defect in the abdominal wall, which lies slightly to the right of the insertion of the umbilical cord. Eviscerated contents are not covered by a membranous sac in gastroschisis. Source: Odze RD, Goldblum JR, Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas. 2nd edn. Philadelphia: Saunders, 2009. Copyright © 2009 Saunders, An Imprint of Elsevier. Figure 8.16.

GENITALIA Undescended testes By term, both testes should have descended into the scrotum and hence be easily palpable. If there is maldescent (testes palpable higher within the inguinal region or high in the scrotum), descent may still occur in the ensuing several months. If they do not descend, surgical treatment is required to fix them in the scrotum as a maldescended testes has a higher risk of spermatogenesis 669

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failure or development of cancer. Importantly, if testes are impalpable, they need to be ‘found’ by ultrasonographic assessment of the newborn pelvis and abdomen; rarely, disorders or sex differentiation are discovered in this way.

Hypospadias Hypospadias is the most common congenital anomaly. It occurs where there is incomplete fusion of the urethral groove, thus causing the urethral meatus to lie on the undersurface (ventral) aspect of the penis, anywhere from the glans to the perineum (Fig 66.35). There is often

an associated penile curvature termed ‘chordee’. Surgical correction is required but is of varying complexity, depending on the position of the urethral meatus and the presence or absence of chordee. Circumcision should be postponed until after definitive surgery has been completed, as the foreskin may be required in the corrective procedure.

Ambiguous genitalia Ambiguous genitalia are diagnosed when, on physical examination, there are anomalies of the apparent size of the phallus and/or scrotum/labia (Fig 73.7). The most

A

B

C

D

FIGURE 73.7 

Various causes of genital ambiguity. A Congenital adrenal hyperplasia. B Mixed gonadal dysgenesis. C True hermaphrodism. D Posteriorly displaced urogenital sinus. Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 14.58A to D.

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Chapter 73  Congenital Malformations

common form is caused by congenital adrenal hyperplasia in which an inherited enzyme deficiency leads to the excess production of virilising hormones. Urgent investigation is required to determine the cause of the condition, the chromosomal sex and the extent of the anatomical abnormalities. Only with this information should the sex of rearing be determined and a name given to the newborn. A holistic, multidisciplinary approach is required (e.g. surgical team, endocrine team, neonatal team, counsellors) to ensure the family are well supported.

FACE Cleft lip and cleft palate Cleft palate may occur with or without a cleft of the lip (Fig 73.8). The cause is multifactorial. The recurrence risk is related to the specific type and extent of the lesion. Treatment is by careful attention to feeding and then surgical correction of the lip in the first few months. The palate is repaired later.

CHROMOSOMAL Down syndrome Trisomy 21 is the most common chromosomal anomaly at birth. It occurs in about 1 in 700 births and is a common

cause of intellectual disability. The risk is related very much to maternal age, ranging from about 1 in 2000 at age 18 years to 1 in 40 at age 45 years. The cause in 95% of cases of trisomy 21 is non-disjunction during oogenesis in the mother. In 2.5% of cases there is a translocation involving chromosome 21, and the remainder have mosaicism with only some cells containing trisomy 21 (Fig 73.9). About 30% of all babies with Down syndrome are born to mothers over the age of 35 years. The exact percentage depends on the frequency of screening. About 70% of women of this age group choose to have screening by amniocentesis or chorionic villus sampling followed by termination of the affected fetus. This has resulted in a 20 to 50% reduction in the birth prevalence of trisomy 21. A number of features may be detected by ultrasound imaging (e.g. nuchal cystic hygroma), but identification of these features requires a high degree of expertise and the method is not suitable for routine screening. Non-invasive prenatal testing (NIPT) involves the detection and analysis of fetal DNA that has traversed the placenta and crossed into the maternal bloodstream. NIPT is an alternative and (as its name suggests) non-invasive screening method for Trisomy 21 and other aneuploidies. The clinical diagnosis is often suspected because of the presence of a number of characteristic features in the newborn. A formal diagnosis can be made promptly with definitive genetic testing. Modern fluorescence in situ hybridisation (FISH) techniques may deliver results within 24 hours. Common physical findings include the following. Head: upward slant of the eyes (> 80%), prominent epicanthic folds (55%), flat nasal bridge, protruding tongue, short neck, flat occiput, brachycephaly, Brushfield’s spots (best appreciated under magnification using an ophthalmoscope as pale speckling of the periphery of the iris). Limbs: short, broad hands and short, incurved little fingers with single phalangeal crease, bilateral single palmar creases, wide spacing between first and second toes. Neurodevelopmental: generalised hypotonia is very common (> 75%) and there may be associated difficulty with feeding; mild to moderate intellectual impairment is usual. Cardiovascular: congenital heart defects, most commonly atrial and ventricular septal defects, occur in 40%. Gastrointestinal: duodenal atresia and umbilical hernias.

•

• • • • FIGURE 73.8 

Trisomy 18 (Edwards’ syndrome)

Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 2.46.

This is the next most common autosomal chromosomal anomaly at birth, with an incidence of 1 in 7000 births. Newborns have a characteristic set of features: micrognathia, prominent occiput, malformed ears, flexion deformity

Bilateral cleft lip with associated cleft palate.

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C

D

A

B

E

FIGURE 73.9 

Clinical photographs of several minor anomalies associated with Down syndrome. A Characteristic facial features with upward-slanting palpebra fissures, epicanthal folds, and flat nasal bridge. B Brushfield’s spots. C Bridged palmar crease, seen in some infants with Down syndrome. There are two transverse palmar creases connected by a diagonal line. D Wide space between the first and second toes. E Short fifth finger. Source: Zitelli BJ, McIntire SC, Nowalk AJ. Zitelli & Davis’ Atlas of Pediatric Physical Diagnosis. 6th edn. Philadelphia: Saunders, 2012. Copyright © 2012 Saunders, An Imprint of Elsevier. Figure 17.100.

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of the hands/fingers and ‘rocker-bottom’ feet. Less than 10% of affected infants survive the first year.

Sex chromosome abnormalities Many sex chromosome abnormalities are not associated with phenotypic differences in the newborn period and are usually not diagnosed until later. Turner’s syndrome (45,XO), with an incidence of 1 in 5000 births, should be identified in the newborn period by the presence of a webbed neck, low posterior hair line, lymphoedema of the dorsum of the hands and feet (Fig 73.10), widely spaced nipples and congenital heart disease (e.g. coarctation of the aorta).

anger and searching for a cause, prior to resolution. During this period the parents’ usual problem-solving capabilities are diminished and they may not take on board what is being said. As such, the same questions may be asked repeatedly, and need to be answered repeatedly and calmly. There should be adequate opportunity for the parents to obtain further information and to be supported through this period. Information written in language that is appropriate for a lay person may be useful.

SKELETAL DYSPLASIAS   AND DWARFISM Skeletal dysplasias may present as shortness or a disproportionate body habitus. Often other anomalies coexist. Many distinct syndromes are recognised. The most common are achondroplastic dwarfism (Fig 66.17) and osteogenesis imperfecta (Fig 73.11).

COMMUNICATION WITH THE PARENTS AND GENETIC COUNSELLING The parents should have the abnormalities described and demonstrated to them. The parents’ mental image of the baby may be far worse than the reality. The normal features of the baby should also be given emphasis. A realistic appraisal of the prognosis should be discussed frankly with the parents. Even when malformations appear to be minor, the parents have to adjust to the ‘loss’ of the ‘perfect baby’ they have been waiting so long to meet. This adjustment process may involve many of the same processes involved in perinatal death: initial numbness and disbelief that gives way to tearfulness, guilt,

A

B

FIGURE 73.11 

Osteogenesis imperfecta type II. A radiograph of this newborn with osteogenesis imperfect type II shows marked shortening of the long bones of the lower extremities with bowing due to multiple fractures sustained in utero.

Source: Weissman BN. Imaging of Arthritis and Metabolic Bone Disease. Philadelphia: Mosby/Elsevier, 2009. Copyright © 2009 Mosby/Elsevier, An Imprint of Elsevier. Figure 32.9.

C

FIGURE 73.10 

Redundant nuchal skin (A) and puffiness of the hands (B) and feet (C) in Turner’s syndrome.

Source: Sybert VP, McCauley E: Turner’s syndrome, N Engl J Med 351:1227–1238, 2004. Copyright © 2004 Massachusetts Medical Society.

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Genetic counselling should be available to any couple with a past or family history of birth malformations or genetic diagnoses. This should ideally be done prior to conception. Here the issue of interest is the particular risk that a child may be affected by the condition and the implications for such a child. If conception has occurred, the issue of interest is whether a diagnosis can be made on the fetus. This may involve ultrasound imaging, or molecular genetic or histochemical tests on fetal tissue. This is a rapidly advancing area and gene sequences coding for particular diseases are being discovered regularly.

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REFERENCES 1) Li Z, Zeki R, Hilder L, et al. Australia’s mothers and babies 2011. Perinatal Statistics Series No. 28. Cat. no. PER 59. Canberra: AIHW National Perinatal Epidemiology and Statistics Unit, 2013. 2) Abeywardana S, Sullivan EA. Congenital Anomalies in Australia 2002–2003. Randwick: AIHW National Perinatal Epidemiology and Statistics Unit, 2008. Online. Available: ; [Feb 2015].

Chapter 74  NEONATAL HAEMATOLOGY Kypros Kyprianou

KEY POINTS The newborn has a higher haemoglobin concentration than infants and adults, which falls gradually to a nadir at approximately 3 months of age. A newborn’s haemoglobin is mainly of fetal type, which has a higher oxygen affinity than adult haemoglobin, allowing more efficient oxygen extraction from the placental circulation. Maternal antibodies can be protective or potentially destructive: they can cross the placenta and provide passive immunity or cause haemolysis or thrombocytopenia. Anaemia in a newborn may occur as the result of haemolysis, infection or blood loss. Polycythaemia (haematocrit > 65%) occurs in response to chronic fetal hypoxia and/or is seen in newborns who are small for gestational age. Haemorrhagic disease of the newborn can be almost completely eradicated by the routine administration of vitamin K to the newborn in the immediate postnatal period.

INTRODUCTION The blood is composed of two major components: 1. cells, which includes red cells, white cells and platelets; and 2. plasma, which includes many constituents such as electrolytes, coagulation factors and immunoglobulins.

RED BLOOD CELLS Prior to 20 weeks’ gestation, haemopoiesis occurs mainly in the liver and spleen. At 20 weeks’, haemopoiesis begins in the medullary cavities of bones, particularly the long bones. By term, unless there is a reason for increased haemopoiesis, all red cell production is in the bones. In the second and third trimesters, over 90% of haemoglobin is haemoglobin F (Hb F or α2γ2), which is structurally different from adult haemoglobin, haemoglobin A (Hb A α2β2). By term, the proportion of Hb F is 50 to 80%.

There are two compensatory mechanisms which allow adequate oxygen transport in the fetus despite normal fetal PaO2 being 25  mmHg. First, Hb F binds oxygen more avidly than Hb A and can therefore bind more oxygen at a given partial pressure of oxygen. Second, the relatively hypoxic environment of the fetus causes an increase in red cell production and hence the fetus has a higher haemoglobin concentration than later in life. The normal term fetus has a haemoglobin value of 18  g/dL (range 14–22  g/dL). At delivery, with the marked increase in PaO2 which occurs with lung respiration, erythropoietin production in the kidney is suppressed and red cell production is reduced. Haemoglobin decreases to a mean of 14  g/dL at 1 month of age and reaches a nadir at 3 months of age when the mean value is 11  g/dL. This stimulates erythropoietin production and the haemoglobin subsequently increases to adult levels.

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The volume of blood shared by the placenta and the fetus may be preferentially transfused to one or the other at the time of delivery, depending on the position of the newborn in relation to the placenta and the time at which the cord is clamped. Elevation of the newborn above the level of the placenta and early clamping of the umbilical cord decrease the amount of blood that the newborn receives. Delayed cord clamping in preterm infants (thus allowing for placental-to-fetal transfusion) may reduce the risk of intraventricular haemorrhage. Controversy exists whether delayed cord clamping is beneficial for the term newborn.

WHITE BLOOD CELLS There are three major types of white blood cells: 1. myeloid cells produced in the bone marrow, including neutrophils, which are important in resistance to bacterial infection 2. lymphocytes produced in the reticuloendothelial system (lymph nodes, liver, spleen and thymus), which are important in resistance to viral, fungal and parasitic infection 3. monocytes produced in the marrow, which also have a role in resistance to infection. The newborn has a higher white cell count than the adult. Leucocytosis is defined as a white cell count > 30 × 109/L and leucopenia as a white cell count < 5 × 109/L. Leucocytosis, leucopenia or an increased proportion of immature white cells is suggestive of infection. Neutropenia is most commonly caused by infection but also occurs in the severely growth-restricted newborn, particularly if the mother has severe preeclampsia. In the term newborn, the lymphocyte function is immature. There are rare, life-threatening, inherited disorders of lymphocyte function that may present in the newborn period.

PLATELETS Platelets are produced as megakaryocytes in the marrow which break down to form platelets in the blood. In the newborn, the levels are similar to those in the adult (300 × 109/L, range 150–450 × 109/L). Thrombocytopenia, which predisposes to haemorrhage, is discussed later in this chapter.

COAGULATION FACTORS Coagulation is a complex system that can be viewed in terms of a cascade. This can be activated either via an intrinsic pathway (in which clotting factors I, II, V, VIII, IX, XI, XII are involved) or an extrinsic pathway (in which factors I, II, V, VII and X are involved). The intrinsic pathway is tested in the laboratory by measurement of the partial thromboplastin time (variously abbreviated 676

to PTT, PTTK or APTT). The extrinsic system can be assessed by measurement of the prothrombin time (PT). Normal values differ between laboratories. Vitamin K is essential for the formation of factors II, VII, IX and X. Fetal vitamin K is derived from the mother. After birth, vitamin K is obtained from the diet and from putrefactive bacteria in the gut. Breastmilk contains low concentrations of vitamin K and the gut takes some time to become colonised by bacteria after birth. Deficiency of these clotting factors is the primary cause of haemorrhagic disease of the newborn. Normal coagulation depends on adequate vitamin K and an adequate ability of the liver to produce the clotting factors. Vitamin K is a fat-soluble vitamin and diseases in which there is steatorrhoea such as cystic fibrosis impair its absorption. Any cause of liver disease may also interfere with coagulation.

ANAEMIA PHYSIOLOGICAL There is a physiological decrease in haemoglobin concentration after birth. This does not require treatment. In the preterm newborn, this may be more exaggerated (Box 74.1).

PATHOLOGICAL Pathological anaemia can be the result of blood loss, blood destruction or failure of red cell production.

BOX 74.1  Anaemia in the premature newborn. During the final months of pregnancy, growth and nutrition of the fetus are the final steps prior to delivery. By this time, organ development is near complete, and the newborn spends the final months in utero laying down subcutaneous fat as well as building micronutrient stores from the mother, via the placenta. Premature newborns hence fail to benefit from this important nutritional gain. Anaemia of prematurity often ensues as iron stores in the newborn are rapidly depleted ex utero. As such, iron replacement is required. This is especially the case in infants born < 32 weeks’ gestation. Preterm newborns with a birth weight < 1500 g should receive supplemental iron (1 mg/kg/day elemental iron) for at least 6 months. Unless they receive this supplement, they are at risk of iron deficiency, which has been shown to reduce neurodevelopmental outcomes.

Chapter 74  Neonatal Haematology

Blood loss: before and during birth Blood loss can occur before birth, such as in twin-to-twin transfusion or during birth as in blood loss from vasa praevia. Twin-to-twin transfusion. In monochorionic twin gestations, placental vascular anastomoses may result in one twin being born anaemic and the other plethoric (Fig 74.1). This occurs to some extent in about 40% of monochorionic twin pregnancies. Feto-maternal transfusion. This may occasionally be severe enough to cause fetal anaemia. It can be tested for by detection of fetal red cells in the maternal blood using the Kleihauer test. Vasa praevia. This occurs when vessels, which are coursing to the main placental bulk from a velamentous insertion of the umbilical cord, rupture spontaneously during labour or be torn during artificial rupture of the membranes (Figs 2.11 and 2.12). Caesarean section. If there is an anterior placenta, damage may occur during the delivery and loss of fetal blood may occur.

• • • •

Blood loss: after birth Blood loss following birth can occur due to a number of reasons: haemorrhagic conditions such as haemorrhagic disease of the newborn or thrombocytopenia birth trauma including large cephalohaematomas, rupture of the liver or spleen or adrenal haemorrhage haemorrhage from an inadequately clamped umbilical cord.

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Blood destruction Haemolysis occurs in: haemolytic disease of the newborn due to maternal antibodies

•

FIGURE 74.1 

These 28-week twins clearly demonstrate a plethoric twin and paler ‘donor’ twin. Source: Courtesy of Prof. Norman Beischer.

•

red cell membrane defects (e.g. hereditary spherocytosis) or enzymatic defects (e.g. glucose-6-phosphate dehydrogenase or pyruvate kinase deficiency) infection.

•

Red cell destruction by   maternal antibodies Several types of maternal antibodies can cross the placenta and destroy the fetal red cells. Anti-A and anti-B antibodies are the most common; however, while severe jaundice after birth may occur, anaemia before birth does not occur. Rhesus disease is still the cause of the most serious haemolytic disease. Other antibodies such as anti-c, anti-C and anti-E in the Rh system may also cause haemolysis. Antibodies to the Kell or Duffy antigens may also cause similar disease. If haemolysis has occurred due to red-cell destruction by maternal antibodies, the Coombs test is positive and the reticulocyte count is elevated. Anaemia ranges from mild to severe. Antenatal assessment of the severity of fetal anaemia and the possible need for intrauterine transfusion or early delivery is the key to management. Severely affected infants require correction of anaemia at birth by exchange transfusion. Immediate exchange transfusion is indicated if the haemoglobin value is < 10 g/dL or if there is evidence of hydrops fetalis (oedema, ascites, pleural effusion). Exchange transfusion may be necessary to treat severe hyperbil­ irubinaemia. Complications include hypoglycaemia (due to pancreatic islet cell hyperplasia caused by anti-Rh antibodies growth-promoting effects on the neonatal pancreas) and significant anaemia requiring top-up transfusion may develop at 1 to 2 months of age. Rarely, intrauterine fetal transfusion is also used successfully to treat fetal anaemia in the context of red cell destruction by maternal antibodies.

Hydrops fetalis Conceptually, hydrops fetalis is the fetal equivalent of ‘congestive heart failure’: the fetal heart being strained and unable to meet the output demands. Subsequent failure ensues, manifesting as oedema, ascites and effusions (Fig 74.2). The two common pathways to this fetal cardiac strain are severe anaemia and/or significant fetal tachycardia. Hydrops fetalis may be diagnosed in utero by ultrasound or at birth by the presence of marked subcutaneous oedema, distended abdomen (ascites) and respiratory distress (due to pleural effusions). The most common causes are severe haemolytic disease, cardiac failure due to fetal arrhythmia, chronic anaemia due to blood loss (such as in twin-to-twin transfusion or congenital infections). Severe anaemia from a haemoglobinopathy (complete α-globulin gene deletion) can also cause hydrops fetalis. Conversely, β-thalassaemia does not present with hydrops. Prenatal investigation includes cord blood sampling for blood 677

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rhage, birth trauma can cause liver rupture or haemorrhagic disease of the newborn. The causes of haemorrhage in the newborn include deficiencies of vitamin K-dependent clotting factors (e.g. haemorrhagic disease of the newborn), transient deficiencies due to hypoxia or infection (e.g. disseminated intravascular coagulation) and inherited disorders (e.g. haemophilia).

HAEMORRHAGIC DISEASE   OF THE NEWBORN FIGURE 74.2 

This newborn is hydropic, intubated and ventilated. The widespread oedema is visible; the distended abdomen is due to ascites. Bilateral pleural effusions and marked neonatal anaemia are also present. Source: Courtesy of Prof. Norman Beischer.

count, chromosome analysis and a search for infections such as the TORCH agents and parvovirus B19.

Failure of red cell production Failure to produce red cells is rare but occurs in the congenital hypoplastic anaemia (Diamond-Blackfan syndrome). Congenitally acquired parvovirus B19 can cause bone marrow failure or aplastic anaemia.

POLYCYTHAEMIA In polycythaemia, the haemoglobin concentration is elevated. The usual definition is a central haematocrit > 65%. As the haematocrit rises above 65%, viscosity increases to levels where the microcirculation is impaired and clinical signs such as cerebral irritability, respiratory distress, hypoglycaemia and haematuria may occur. The cause of fetal polycythaemia is chronic hypoxia, most commonly due to placental insufficiency, which may also result in growth restriction. Treatment, if required, may involve haemodilution (with intravenous fluids) or a partial exchange transfusion (in which newborn blood is withdrawn and replaced with plasma or a plasma substitute). Increasingly, observation and maintenance of adequate hydration is sufficient management of polycythaemia.

HAEMORRHAGIC CONDITIONS IN THE NEWBORN Haemorrhagic conditions can occur in a number of ways: sudden cardiovascular shock can cause adrenal haemor678

Vitamin K is present in low concentrations in the newborn and in breast milk. Adequate levels are required by the liver for the production of the clotting factors II, VII, IX and X. Where additional vitamin K is absent, 1 per 500 fully breastfed newborns will develop haemorrhagic disease. The major clinical features are oozing from the umbilicus, mucosal surfaces or circumcision site. Internal bleeding most commonly occurs in the abdomen or head; haematemesis is another common presentation. Haemorrhage may, however, also occur in the skin, renal tract or any other organ. The bleeding most commonly occurs in the first 10 days (early form) or at 4 to 6 weeks of age (late form). There is a high mortality and morbidity rate with both types. The diagnosis is established by performing clotting studies and establishing that the platelet count is normal. The prothrombin time and partial thromboplastin time are prolonged. Supplementation of all newborns with vitamin K virtually eliminates haemorrhagic disease. Vitamin K is given as a single intramuscular dose of 1 mg at the time of birth. Due to reduced adherence (and need for multiple doses), oral vitamin K is discouraged. However, if a family chooses the oral over the intramuscular preparation, three oral doses of 2 mg each is advised. They are given at the time of birth, at hospital discharge (day 2 to 7) and at 4 to 6 weeks of age. Missing the second and/or third dose reduces the efficacy of this method, hence increasing the likelihood of haemorrhagic disease of the newborn. Treatment of the established condition is by administration of vitamin K, 2 mg intramuscularly. If the bleeding is life-threatening, intravenous administration of fresh frozen plasma is indicated. Blood transfusion may also be necessary if there are signs of cardiovascular shock or severe anaemia.

DISSEMINATED INTRAVASCULAR COAGULATION This is a group of disorders in which the haemorrhagic tendency is a consequence of the acute and inappropriate activation of the clotting mechanism. The bleeding occurs because of the resultant depletion of plasma clotting factors and platelets. Activating factors include infection

Chapter 74  Neonatal Haematology

and hypoxia. The partial thromboplastin time and prothrombin time are prolonged. The plasma fibrinogen and platelet count are depressed and fibrin degradation products are elevated. The treatment is to ‘turn off’ the activating process by treating the underlying cause and replacing the deficiency with fresh frozen plasma or plasma concentrates.

PLATELET ABNORMALITIES A deficiency of the number of platelets or of their function may result in petechiae (pinhead-sized haemorrhages in the skin) or ecchymoses (larger skin haemorrhages or bruises). See also the sections on petechiae in Chapter 66.

THROMBOCYTOPENIA Thrombocytopenia historically was defined as a platelet count < 150 × 109/L (based on the 5th percentile of normal adult values). However, some newborns have normally lower platelet counts. Hence, a platelet count < 100 × 109/L in the newborn is often used to define neonatal thrombocytopenia. Thrombocytopenia usually results from an increased destruction of platelets, which may be due to factors in the mother, fetus or newborn. Qualitative defects of the platelets are rare. Intracranial haemorrhage is rare and haemorrhage is unlikely to develop if the platelet count is > 30 × 109/L.

Mother Maternal conditions predisposing to neonatal thrombocytopenia include SLE, ITP and a condition known as NAIT. Maternal idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) are conditions in which antiplatelet antibodies are formed, cross the placenta and cause destruction of the fetal platelets. Neonatal alloimmune thrombocytopenia (NAIT) is caused by fetal platelets crossing the placenta (from fetus to mother). If the fetal platelets are recognised as foreign by the mother, an antibody response is mounted. The resultant maternal antibodies cross the placenta (from mother to fetus) and destroy fetal

• •

platelets. This is analogous to the maternal development of rhesus antibodies against the fetal red cell in rhesus-haemolytic disease. The condition is transient (though multiple platelet transfusions may be required) and by 3 months of age the maternal antibody titre in the baby’s circulation is low enough for spontaneous recovery to have occurred. Intravenous immunoglobulin (IVIG) is also a treatment option in NAIT. In the context of fetal thrombocytopenia, it is not known whether delivery by caesarean section reduces the risk of haemorrhage during delivery. Exposure to maternal drugs such as thiazide diuretics and sulphonamides can lead to neonatal thrombocytopenia.

•

Fetus and newborn Various diseases of the fetus and newborn can cause thrombocytopenia: infection with bacteria or viruses severe erythroblastosis (haemolytic disease) exchange transfusion platelet destruction in giant haemangiomas (Kasabach-Merritt syndrome).

• • • •

BLOOD IN THE STOOL Blood in the stool is not an uncommon clinical presentation. A logical approach will aid in establishing the cause. Causes of blood in the stool include swallowed maternal blood, disturbances of coagulation, malrotation with volvulus, necrotising enterocolitis and infection. Bloodstreaked stools could also be due to an anal fissure, but other causes (such as milk protein intolerance and necrotising enterocolitis) must be considered. Ingested blood may be from the maternal perineum at birth or from the breast (usually there is an associated cracked nipple, but spontaneous bleeding during a breastfeed may occur without the mother being aware of the occurrence). Further to the bedside clinical history and examination, laboratory tests may be required guided by the degree of clinical suspicion of the cause. These include a blood count (looking for signs of infection or thrombocytopenia), clotting studies, and/or X-ray of the abdomen.

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Chapter 75  THE PRETERM NEONATE AND PERINATAL TRANSPORT Kypros Kyprianou

KEY POINTS Survival rates for premature newborns have increased dramatically, especially in developed countries. Low birth weight is associated with a higher mortality than that for babies who are born heavier than 2.5 kg. Low birth weight newborns comprise approximately 6% of all births but can account for up to 80% of neonatal deaths. There are two quite separate issues involved in the causation of low birth weight: prematurity and small for gestational age. Preterm newborns are prone to a particular set of problems which include hypothermia, hypoglycaemia, jaundice, respiratory distress syndrome, patent ductus arteriosus, intraventricular haemorrhage, periventricular leucomalacia, apnoea, necrotising enterocolitis and retinopathy of prematurity. A neonatal intensive care unit allows for specialised care of the premature newborn. Where the likelihood of preterm labour and delivery is suspected, specialised obstetric and neonatal care should be made available. This will necessitate moving the mother and unborn child to a specialised hospital: morbidity and mortality outcomes are improved in this way. Not all high-risk deliveries can be anticipated and the sick or preterm newborn may need to be transferred for definitive care to a neonatal intensive care unit after delivery. The care of the preterm newborn involves added considerations, above and beyond those of term newborns. These include consideration of survival prospects, the likelihood of long-term disability, the emotional needs of the baby and the parents, ethical considerations, resource implications, the appropriate use of cutting-edge technology and the need for critical evaluation of neonatal care practices.

PREMATURITY: DEFINITIONS A number of definitions—based on weight and gestation—have been formulated. This facilitates data collection and allows for comparison between research studies. From this, generalisations can be made and information can be provided to families. • Low birth weight < 2500 g • Very low birth weight < 1500 g • Extremely low birth < 1000 g weight • Prematurity < 37 weeks’ gestational age (GA) at birth

• Late preterm 34 to 34 + 6 weeks’ GA GA at or below 32 weeks • Very premature GA at or below 25 weeks • Extremely premature The general issues faced by newborns when transitioning to extrauterine life prematurely are the same now as they were over 100 years ago: The premature infant is born with the skin and the skeleton, and the organs of a seven-months fetus. He is called upon to play the part of a newborn infant with the personalia of a fetus. He is admirably fitted to continue living in the uterus, but is ill provided to meet the exigencies of an extra-uterine existence. He is suddenly forced

Chapter 75  The Preterm Neonate and Perinatal Transport

into surroundings of a kind which impose upon him urgent calls to which he is little able to respond. His tissues have not had time to mature, and he is not ready for so complete a change in environment … Ballantyne JW. The problem of the premature infant. BMJ 1902, May 17.

• •

RECOGNITION Accurate maternal menstrual history or the measurement of fetal size using ultrasound imaging prior to 20 weeks’ gestation are the preferred methods of assessing gestational age. However, where these data are not available, or may be inaccurate, assessment of gestational age of the newborn can be made by physical examination. It relies on two sets of characteristics: physical and neurological.

PHYSICAL FEATURES A number of unique physical features are found in premature newborns. These are not necessarily pathological, but reflect particular stages of fetal development at given gestations. Skin. The skin is very thin in the immature infant. At < 27 weeks’ it is dark red and gradually thickens during gestation and may be desquamating by term. Lanugo. Fine hair over the body is present in the immature newborn and has largely cleared by term (Fig 2.4). Plantar creases. The area covered by deep creases on the sole of the foot extends during gestation, from toes to heel. By 34 weeks’ gestation there are creases present over the anterior third of the sole, with the rest of the sole relatively smooth. By 38 weeks’ they

• • •

A

are visible over the anterior two-thirds and by 40 weeks’ creases extend over the whole sole. Breast. In the very preterm newborn, the nipple is barely visible and the areola non-existent. These develop during gestation and by 34 weeks’ gestation a breast nodule becomes palpable. Eyes and ears. Ear cartilage develops progressively in the ear from the centre to the periphery. Until 32 weeks’ gestation there is so little cartilage present that the ear retains the shape that has been applied to it. By term, the ear is fully shaped and recoils immediately after deformation. The eyelids are often fused until 25 weeks’ gestation. Genitalia. In the female, the labia minora and clitoris are prominent early in gestation. Only by term have the labia majora developed to cover the labia minora and clitoris. In the male, the testes descend into the scrotum at about 29 weeks’ gestation but may not be deep within the scrotum until term. Coincident with testicular descent is the development of increased rugosity of the scrotum.

B

•

NEUROLOGICAL FEATURES As gestation progresses, there is an increase in muscle tone, particularly flexor tone. The very preterm newborn adopts a deflexed posture of the limbs (Fig 75.1); by term there is marked limb flexion at rest. There is a concomitant increase in muscle strength. Several reflexes develop during the third trimester: the pupil responds to light from 29 weeks’ gestation, there is a blink response to a tap on the glabella from 32 weeks’ and flexion of the arms or neck when pulled by the wrists from supine from 34 weeks’.

C

FIGURE 75.1 

Fetal position according to maturity. A At 28 weeks’ maturity the infant is hypotonic with extended limbs. B At 32 weeks’ the lower limbs are flexed. C At 36 weeks’ all limbs are flexed. Source: Courtesy of Prof. Norman Beischer.

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These features may be scored, as in the Dubowitz assessment, to allow a calculated gestational age to be arrived at. The newer Ballard assessment similarly uses physical and neurological assessments to assist in assessing the degree of prematurity. Importantly, due to variation in genetic and physical characteristics of newborns, most methods have an accuracy of ± 2 weeks either side of estimated gestation.

Per cent 80 70 60 50 40 30

VIABILITY In Australia, the resuscitation and definitive tertiary care should be offered to nearly all premature infants from a gestational age of 25 weeks. Newborns born between 24 and 24 + 6 weeks’ gestation are increasingly offered tertiary neonatal care, depending on individual circumstances. A difficult ‘grey zone’ exists between the ages of 23 and 23 + 6 weeks’ gestation. Different jurisdictions and state-based protocols exist around Australia to guide clinicians. Appropriate counselling of parents and close communication between paediatric and obstetric staff is required when there is the prospect of a newborn being delivered on the cusp of viability.

PROBLEMS OF PREMATURITY The preterm newborn faces a particular set of problems that relate either to immaturity of organ or enzyme systems or to a deficiency of energy substrates which have not yet been accreted.

RESPIRATORY DISTRESS SYNDROME AND CHRONIC LUNG DISEASE Respiratory distress syndrome (RDS) is due to pulmonary immaturity and in particular a deficiency of pulmonary surfactant. It is one of the leading causes of mortality in the very preterm infant. It is discussed further in previous chapters (see Chapter 70). Premature newborns who have ongoing oxygen requirements (for more than 28 days or beyond 36 weeks’ gestation) have developed chronic lung disease. In an Australian and New Zealand cohort of newborns treated in tertiary centres, the incidence of chronic lung disease (CLD) is approximately 50 to 60% in newborns born between 24 and 25 weeks’, reducing markedly thereafter to < 5% of infants born at 31 weeks’ (Fig 75.2).

HYPOGLYCAEMIA Hypoglycaemia is prevented in the adequately nourished term newborn by the utilisation of glycogen, which is stored mainly in the liver. This store is largely accumulated during the last 2 months of gestation and may be deficient in the preterm infant. Hypoglycaemia may cause signs such as jitteriness, cyanosis, convulsions or apnoea, but it can be 682

20 10 0

24

25 26 27 28 29 30 Gestational age at birth (completed weeks)

31

FIGURE 75.2 

The incidence (and confidence intervals) of chronic lung disease in premature infants from Australia and New Zealand Level 3 NICU registry data. The incidence of chronic lung disease in premature infants born after 31 weeks’ gestation age is rare.

Source: Chow SSW. Report of the Australian and New Zealand Neonatal Network 2011. Sydney: ANZNN, 2013. Figure 21.

asymptomatic. Hypoglycaemia should be routinely checked for on a regular basis until adequate caloric intake has been established and normoglycaemia has been documented. Blood sugar level may be measured in the nursery using commercial blood glucose test strips, but laboratory estimation is much more accurate. Definitions of hypoglycaemia vary, but since there is evidence that blood sugar levels at or below 2.5 mmol/L are associated with abnormal central nervous system function, this is a useful ‘cut-off’ point. Hypoglycaemia should be treated promptly. In the mild case, an increase in feed volume may be sufficient if feeding has already been established. If the hypoglycaemia is more profound or persistent, an intravenous infusion of 10% dextrose should be commenced. The feed volumes that are shown in Table 75.1 may need to be exceeded.

JAUNDICE The preterm infant is predisposed to jaundice because of a relatively less mature bilirubin conjugation mechanism. The risk of kernicterus is also greater at a given bilirubin level because: 1. hypoalbuminaemia results in a reduced ability to bind circulating bilirubin; 2. functional immaturity of the blood–brain barrier results in an increased likelihood of free bilirubin crossing from the blood into the brain; and 3. the often present concurrent respiratory failure results in acidosis, which increases the risk of kernicterus. Jaundice and its treatment are covered in Chapter 68. Phototherapy is commenced in the very preterm infant at lower levels than those shown for mature newborns.

Chapter 75  The Preterm Neonate and Perinatal Transport

TABLE 75.1  APPROXIMATE FLUID REQUIREMENTS OF PREMATURE NEWBORNS. Postnatal day

Fluid (mL/kg body weight/day)

1

60

2

90

3

120

4–6

150

7 onwards

150–180

Note: The volumes above may need to increase or decrease depending on the presence of hypoglycaemia, hypo-/ hypernatraemia, birth asphyxia and whether intravenous or oral fluids are required. Source: Courtesy of Prof. Norman Beischer.

THERMOREGULATION The preterm newborn has a greater heat loss than the older child or adult because of high insensible water loss due to thin permeable skin, a large surface-area to bodymass ratio and little subcutaneous fat (most of which is laid down during the last 4 to 6 weeks of gestation). Thermal stress, particularly cold stress, reduces the chance of survival. Newborns weighing < 2000 g at birth are often nursed in an incubator set at the appropriate temperature (thus providing a neutral thermal zone and minimising energy expended on thermoregulation). An alternative is to nurse the newborn on a servocontrolled radiant overhead heater cot, often used in the first few hours of life when procedures and intervention necessitate ease of access to the tiny newborn (Fig 75.3). Heat loss by evaporation is high due to the large insensible water loss, especially in extreme prematurity. This can be reduced by nursing the baby in a highhumidity environment. Technology need not get in the way of human emotion and bonding: once the small baby is clinically stable and tolerates handling without instability, warmth can be adequately provided for periods by cradling the naked baby directly against the parent’s skin beneath clothing: the ‘kangaroo’ method (Fig 75.4).

RETINOPATHY OF PREMATURITY Retinopathy of prematurity (ROP), previously termed retrolental fibroplasia, occurs when the immature retinal vasculature, which normally develops in a centrifugal pattern from the optic disk outwards, is exposed to high partial pressures of oxygen in the blood. Hyperoxia leads to retinal vasoconstriction and if this is prolonged,

ischaemic damage occurs. This is followed by a proliferative phase of growth of abnormal new vessels from the retina into the vitreous humour. In severe cases, haemorrhage and oedema ensue and in the resulting organisation, fibrous scarring and retinal detachment may occur. Ophthalmological assessment must be routine in high-risk preterm newborns. The incidence of the disease is minimised by careful monitoring of blood oxygen levels and avoidance of periods of hyperoxaemia. All preterm newborns that require oxygen therapy must have non-invasive oxygen monitoring. As described in Chapter 70, if FiO2 is > 40%, then specialist tertiary care is often required to ensure adequate balance of oxygenation and ventilation is achieved. In established disease, retinal detachment may be prevented by the use of cryoor laser therapy to the retina. ROP is most common in the least mature newborns and is uncommon in babies born after 34 weeks’ gestation (and in developed countries, this condition is rarely seen in infants born after 32 weeks’ gestation). Furthermore, modern tertiary neonatal care has resulted in milder ROP, often not requiring specific treatment. For example, severe ROP requiring treatment is documented in only 3.5 to 5% of surviving infants born before 31 weeks’.1

INTRAVENTRICULAR HAEMORRHAGE AND PERIVENTRICULAR LEUCOMALACIA Major developmental changes are occurring in the brain of the very preterm baby. The germinal matrix, situated inferolaterally to the lateral ventricles, is the site of formation of the cortical neuronal cells. Although the cortical neurones have already migrated to the cortex by 25 weeks’ gestation, the area remains metabolically active with a high blood flow. Haemorrhage in this area may result if there are major perturbations in blood pressure and cerebral blood flow. This occurs in about 20% of newborns of < 30 weeks’ gestation. In the majority, the haemorrhage is localised and no long-term neurological sequelae result. If the haemorrhage is more extensive (Fig 75.5) and involves the cerebral parenchyma, there is a risk of permanent damage resulting in cerebral palsy. Haemorrhage into the lateral ventricles may result in impaired drainage and resorption of cerebrospinal fluid, leading to obstructive hydrocephalus, which may require surgical treatment. The cerebral vasculature undergoes a gradual change in mid-gestation from supplying the brain parenchyma via penetrating cortical arteries to supply being via the basal cerebral arteries as in the mature brain. At 24 to 30 weeks’ gestation, the areas adjacent to the lateral ventricles are relatively less well-perfused than other regions. If there is a critical reduction in cerebral blood flow, 683

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FIGURE 75.3 

A small preterm infant being cared for in an intensive care nursery. His temperature is being maintained by a servocontrolled overhead radiant heater. Vital signs are being electronically monitored. A catheter has been placed via an umbilical artery into his aorta to enable systemic blood pressure to be recorded and blood samples to be obtained painlessly for monitoring his biochemical and blood gas status. He is receiving a blood transfusion and his other intravenous infusion is to supply fluids, calories and electrolytes. Because of severe respiratory distress syndrome, his breathing is being assisted by a mechanical ventilator. To maintain his blood oxygen level at appropriate levels, oxygen saturation is being continuously measured. Source: Courtesy of Prof. Norman Beischer.

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Chapter 75  The Preterm Neonate and Perinatal Transport

infarction in this area may occur, resulting in focal neuronal necrosis and subsequent cystic formation. This condition is termed ‘periventricular leucomalacia’. This occurs in only about 1% of newborns < 30 weeks’ gestation (and higher in infants of extremely low birth weight) but carries with it a very high risk of cerebral palsy.

APNOEA OF PREMATURITY

A

While it is normal for newborns to have periodic breathing, the preterm newborn is prone to apnoea, which is defined as a cessation of breathing for > 20 seconds. Apnoea is often associated with bradycardia and the lower the gestational age, the more common the condition. If the newborn is otherwise well, and apnoea is not the presenting sign of sepsis or intraventricular haemorrhage, it is likely to be due to the immaturity of the brainstem centres responsible for the automatic regulation of breathing. It can be treated with some success by using a stimulant such as caffeine. The ultimate treatment of extreme apnoea of prematurity (recurrent, prolonged or associated with marked bradycardia) is ventilatory (invasive or non-invasive) support of the immature respiratory system.

NECROTISING ENTEROCOLITIS

B FIGURE 75.4 

Parental involvement in neonatal care. A Skin-to-skin contact between infant and parent (kangaroo care) promotes bonding. B Mother giving her baby expressed breastmilk (in syringe) via nasogastric tube, allowing close eye and skin contact between mother and baby.

Source: Lissauer T, Clayden G, Craft A. Illustrated Textbook of Paediatrics. 4th edn. Edinburgh: Mosby, 2012. Copyright © 2012 Mosby, An Imprint of Elsevier. Figures 9.5, 10.10a and 10.10b.

Necrotising enterocolitis (NEC) is an acute inflammatory disease of the bowel, predominantly of the extremely low birth weight (< 1500 g) premature infant. It has an incidence of up to 6.5% in premature newborns born after less than 28 weeks’ gestation, sharply decreasing to < 1% in infants born after 28 weeks’ gestation.1 The aetiology appears to be multifactorial, with a number of associations having been established: hypotension and gut hypoxia, emboli from indwelling catheters, artificial enteral feeding (the disease is uncommon prior to the commencement of milk feeds and breastmilk appears to be protective) and/or sepsis. The presentation may be either: 1. non-specific with lethargy and/or increased apnoea; or 2. localised with acute abdominal distension and the passage of a bloody stool. Radiographic features are characteristic: gas is present in the bowel wall and may be visible in the portal venous system. Ileus with gaseous bowel distension (Fig 75.6) or perforation of the bowel with free gas in the abdomen may be present. Treatment comprises active resuscitation with the provision of ventilatory support, as well as cardiovascular support (inotropes, intravenous fluid resuscitation). Antibiotics and bowel rest are necessary. Surgery is indicated if these measures do not result in an improvement in the baby’s condition. Sequelae include bowel perforation in the acute stage, stricture and, later, short-bowel syndrome. The mortality rate depends on the severity of the disease, but can be as high as 20% in severe cases, especially in extreme prematurity. 685

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A

B

C

D

FIGURE 75.5 

Intraventricular haemorrhage (H) demonstrated by ultrasonography. The blood shows up as hyperechoic or ‘whiter’ on ultrasound, in contrast to the hypoechoic (dark) ventricular fluid. A Grade 1: Sagittal view showing a haemorrhage, subependymal in site which does not extend into the lateral ventricle (V). B Grade 2: The haemorrhage is more extensive: there is blood in the ventricle which, however, is not distended with blood. C Grade 3: A larger haemorrhage has filled and distended the ventricle. D Grade 4: Coronal view showing a haemorrhage which has involved a large area of the periventricular matter as well as filing the ventricle. Source: Courtesy of Prof. Norman Beischer.

PATENT DUCTUS ARTERIOSUS Patency of the ductus arteriosus (PDA) is essential during fetal life: the right ventricular output bypasses the pulmonary circulation and is shunted directly to the aorta via the ductus arteriosus. After birth, the ductus must close or cardiovascular problems of left ventricular volume overload will develop. Under normal circumstances, the smooth muscle in the ductal wall constricts under the influence of the marked increase in the partial pressure of oxygen that occurs with the establishment 686

of respiration and the local production of prostaglandin F2 alpha. Immaturity of the ductal smooth muscle and a reduced ability to produce local prostaglandins are the reasons why patency of the ductus arteriosus is common in preterm newborns. After delivery, the pulmonary vascular resistance falls mainly as the result of the increase in PaO2. The pressure in the pulmonary artery rapidly becomes lower than the arterial pressure in the systemic circulation. If the ductus arteriosus is patent, blood will flow in a left-to-right direction. If the ductus arteriosus remains patent, the left

Chapter 75  The Preterm Neonate and Perinatal Transport

ventricle pumps to both the systemic circulation and, via the ductus arteriosus, to the pulmonary circulation. In this case, the increased volume load on the left ventricle leads to left ventricular failure. The clinical presentation of patent ductus arteriosus is with respiratory distress, often on days 4 to 7, just as the newborn is recovering from respiratory distress syndrome. There is a widened pulse pressure causing a bounding pulse and often a continuous murmur. Cardiomegaly and pulmonary plethora are seen on chest X-ray. Echocardiography provides a definitive diagnosis. Not all premature newborns with a PDA have clinically significant cardiorespiratory compromise. This, coupled to the lack of efficacy of particular treatments, as well as potential treatment side effects, has meant that PDA treatment is increasingly conservative. Treatment options include fluid restriction and/or the use of an NSAID (e.g. indomethacin), the latter acting by inhibiting the formation of prostaglandin E, which dynamically opposes the constrictive effects of prostaglandin F2 alpha on the ductus. Drug treatment is often reserved for premature infants that have been unable to be weaned off mechanical ventilation. Very rarely, surgery for PDA ligation is necessary.

PROGNOSIS SURVIVAL Survival for preterm newborns cared for in a modern intensive care unit has been increasing over the past two decades. Key factors that have significantly contributed to the improved survival are the use of antenatal corticosteroids to enhance lung maturity when preterm birth is thought to be imminent, as well as the use of exogenous lung surfactant. Australia-wide data shows that over 60% of 24-week premature infants survive to discharge. This percentage steadily increases with each week of gestation. By 31 to 32 weeks’ gestation, survival rates parallel that of term newborns (Table 75.2). In a NSW/ACT study, survival to discharge was 30% in 23 weeks’ gestation infants after the initiation of intensive care therapy (Fig 75.7).2

NEURODEVELOPMENTAL OUTCOME The risk of disability in prematurity is generally higher than in term newborns. This may be neurological, visual, auditory or behavioural. In extreme prematurity (22 to 25 weeks’), 1/4 to 1/3 of surviving neonates are left with severe disability when assessed in infancy.3,4 As gestational age increases, the risk of severe disability falls.5 For example, premature neonates weighing 1500 to 2500 g at

TABLE 75.2  SURVIVAL RATES OF PREMATURE INFANTS.

FIGURE 75.6 

Radiographic features of necrotising enterocolitis. There is intramural gas in the extended loops of bowel. Gas has penetrated through the intestinal wall into the portal venous system and can be seen throughout the liver. Source: Courtesy of Prof. Norman Beischer.

Gestation at birth (weeks)

Survival at time of discharge home (%)

< 24

52.7

24

63.7

25

78.7

26

83.9

27

92.6

28

93.7

29

97.5

30

98.1

31

98.6

32

98.7

Source: Adapted from Chow SSW. Report of the Australian and New Zealand Neonatal Network 2011. Sydney: ANZNN, 2013. Table 28.

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birth have an incidence of 6 to 8% of severe disability. By comparison, severe disability can still occur in up to 5% of full-term neonates.6 Despite this, however, survival with minimal to no disability is not an unrealistic expectation for the families of premature infants. For example, up to 50% of extremely premature neonates who survived until discharge, when assessed at 30 months of age, may have minimal to no disability.4 Intellectual disability (defined as > 2 standard deviations below the mean on standardised cognitive testing) is documented in prematurity, particularly in infants born < 26 weeks’ gestation (see Table 75.3). Twenty to 50% of premature infants born between 24 and 29 weeks’ can have normal intelligence.7 Cerebral palsy (a motor disorder of movement and posture) can occur in 10 to 27% of premature infants born between the ages of 24 to 27 weeks’ gestation. Additionally, the functional ability of premature infants (when

TABLE 75.3  RISK OF INTELLECTUAL DISABILITY REDUCES WITH INCREASING GESTATIONAL AGE. Gestational age at birth (weeks)

Rate of intellectual disability (%)

24 to 25

30–50

26 to 29

10–30

assessed at infant and/or school age) is an important neurodevelopmental outcome. While 83% of extremely low birth weight infants can walk independently by 22 months of age, more subtle deficits (such as poorer participation in sports in teenage years) can appear later in life.4

GROWTH For the purposes of the assessment of growth of the preterm newborn, the chronological age should be corrected for the number of weeks of prematurity, until the second or third birthday. Even when this allowance is made, preterm infants are slightly lighter and shorter than term infants. By this time, the scaphocephaly—a feature of many very preterm infants—has largely resolved.

Follow-up and post-discharge care Preterm newborns may go home with continuing problems of feeding difficulties, oxygen dependence, ongoing surgical problems (such as inguinal hernias) or neurodevelopmental issues. Because of this, many units organise a home visiting service staffed by experienced neonatal intensive care unit and/or midwifery staff. Close multidisciplinary follow-up of newborns < 1500 g is desirable because of the increased risk of disability. Some disability is subtle and may first present in the school years with difficulty in accomplishing the tasks demanded in such an environment. A follow-up multidisciplinary team often is comprised of: 1. a physiotherapist to assess motor function and development;

Panel A: Male infants 1.0

31 weeks 30 weeks 29 weeks 28 weeks 27 weeks

0.9 0.8

1.0 0.8

26 weeks

0.7

25 weeks

0.6

24 weeks

0.5 0.4 0.3

23 weeks

0.2

31 weeks 30 weeks 29 weeks 28 weeks 27 weeks

0.9

Cum Survival

Cum Survival

Panel B: Female infants

26 weeks

0.7

25 weeks

0.6

24 weeks

0.5 0.4 0.3

23 weeks

0.2

0.1

22 weeks

0.0

0

5

10

15 20 25 30 35 40 45 50 55 60 Time to death (days)

0.1

22 weeks

0.0

0

5 10

15 20 25 30 35 40 45 50 55 60 Time to death (days)

FIGURE 75.7 

Day-by-day actuarial survival rate to discharge (Kaplan-Meier method) recalculated at daily intervals on the surviving cohort and stratified by gestation among (A) male and (B) female infants of 22 to 31 weeks’ gestation born between 1997 and 2006 and admitted to a neonatal intensive care unit. Graphs are truncated at day 60 of life. Source: Reproduced from Actuarial day-by-day survival rates of preterm infants admitted to neonatal intensive care in New South Wales and the Australian Capital Territory. Abdel-Latif ME, Kecskés Z, Bajuk B, Arch. Dis. Child. Fetal Neonatal Ed. May 2013; 98(3); F212-7 Copyright © 2013, BMJ Publishing Group Ltd and the Royal College of Paediatrics and Child Health, withpermission from BMJ Publishing Group

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2. a psychologist to assess neurodevelopment and function; 3. an audiologist; 4. an ophthalmologist; and/or 5. a developmental paediatrician to provide a global assessment including any medical problems. Early identification of abnormality or deviations from the usual course of development should be identified. Emerging research is showing the importance and value of early intervention programs to improve neurodevelopmental outcomes of premature infants. Lastly, a somewhat unexpected emerging long-term risk for premature infants is supported by evidence showing their increased risk of adult-onset illnesses such as insulin resistance, hypertension and effects on reproduction: the so-called Barker hypothesis (see Chapter 71).

Cost and ethics Care for the sick newborn in a neonatal intensive care unit can cost hundreds or even thousands of dollars per day. The more preterm the baby, the longer such care is likely to be required, and hence the higher the costs of care. For example, the total hospital cost for a neonate surviving until discharge that is born at 24 weeks’ may run into the tens or even hundreds of thousands of dollars. However, even in extreme prematurity, the treatment is cost-effective if judged in terms of ‘qualityadjusted life years’ in which the cost is weighed against the future return of that individual to society. The majority of babies with a birth weight > 750 g do survive if treated in a neonatal intensive care facility. How small is too small to make the use of neonatal intensive care worthwhile? If complications occur, what should the indications be for the withdrawal of treatment? These are ethical questions which society, as well as parents and caregivers, must be involved in debating, for there are no ready answers. In countries where health resources are scarce, the costs of care of the very preterm newborn must be weighed against the cost of other treatments such as immunisation, which may confer benefits to a greater number of individuals.

with a poorer outcome than in utero transport and delivery in a tertiary hospital. Prediction of which pregnancies are at risk is paramount in the organisation of in utero transfer. Table 75.4 lists conditions or situations which suggest a high risk and in which in utero transfer should be considered. Note that some are of maternal origin where the primary concern is the mother’s wellbeing (e.g. preeclampsia). Others require close fetal surveillance and possible preterm delivery. Transfer of the mother undelivered is safest for the high-risk fetus that is likely to need neonatal intensive care. Newborn intensive care has been regionalised and classified as follows. Level 1 provides routine care for well term or closeto-term newborns. An ability to stabilise the unexpectedly sick newborn prior to retrieval is required. Level 2 provides more sophisticated care, including intravenous fluids and basic respiratory support. Increasingly, simple ‘bubble CPAP’ circuits (Fig 75.8) have allowed level 2 nurseries to also offer intermediary level respiratory support, and at times minimising the need to transport to level 3 centres. Generally, preterm infants of ≥ 32 weeks’ gestation may usually be safely delivered in such a unit.

• •

TABLE 75.4  CONDITIONS WHICH MAY NECESSITATE IN UTERO TRANSFER OF THE FETUS TO A TERTIARY REFERRAL HOSPITAL WITH NEONATAL INTENSIVE CARE FACILITIES. Maternal disease

Poorly controlled diabetes with fetal compromise Significant renal impairment

TRANSPORT AND RETRIEVAL Prenatal transport refers to the process whereby the mother and her unborn fetus are transferred to a hospital where a higher level of obstetric and/or neonatal care is available because of an identified high-risk situation for either the mother or her fetus. The uterus is a far better incubator than technology can ever produce. Postnatal retrieval refers to the transfer of a newborn who is in need of a higher level of newborn care. As such, the newborn is ideally retrieved from the hospital of birth by a fully equipped retrieval service. Every effort must be made to deliver the high-risk newborn at the site where the necessary level of newborn care is available. Transfer of the fetus in utero is preferable, because delivery in a peripheral hospital and subsequent retrieval is associated

Severe hypertension/preeclampsia

Systemic autoimmune disease Pregnancy related

Threatened preterm labour Multiple pregnancy Preterm rupture of membranes Antepartum haemorrhage Rhesus isoimmunisation

Fetal disorders

Severe growth restriction Malformations likely to require surgery or intensive care

Source: Courtesy of Prof. Norman Beischer.

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10 9 8 7 6 5

FIGURE 75.8 

Bubble CPAP circuit.

Source: Fisher and Paykel Healthcare Limited.

•

Level 3 provides full newborn intensive care, including assisted ventilation and parenteral nutrition. Newborns of ≤ 32 weeks’ gestation require delivery and care in a level 3 facility.

In some cases, the need for newborn intensive care has not been anticipated: preterm delivery may have occurred in an apparently low-risk mother or a complication such as antepartum haemorrhage necessitated preterm delivery. If this occurs in a level 1 or level 2 setting, these newborns will require transport by a retrieval team to a more appropriate tertiary unit. 690

Coordinated regional retrieval systems now exist in most places where perinatal regionalisation has occurred. Ideally, the nearest regional level 3 newborn unit provides a retrieval facility, which comprises a constantly manned telephone advice line and a mobile intensive care cot. The mobile cot is manned by staff with current skills in newborn intensive care who are also conversant with the particular issues involved in retrieval, such as pressure differences that occur with altitude in aircraft retrievals. Retrieval of a newborn falls into two broad categories: 1. the premature newborn whose care demands are

Chapter 75  The Preterm Neonate and Perinatal Transport

higher than the service and ability that the nursery can adequately provide; and 2. the term newborn whose clinical state is such that higher level care is required. Common conditions requiring neonatal transport are shown in Box 75.1. These guidelines may vary depending on the availability of local facilities and expertise. Just under one-quarter of neonates in level 3 nurseries around Australia and New Zealand have been retrieved from a lower level nursery setting. Transport equipment must be designed to travel in different transport modalities. The transport modality will vary depending on local facilities but in general, transports over a short distance (< 50 km) are undertaken by road ambulance (Fig 75.9), intermediate distance (50 to 200 km) by helicopter and long distance (> 200 km) by fixed-wing aircraft. The principles involved in a transport are as follows. 1. Resuscitate and stabilise the newborn prior to moving. Ideally, this will have been already done by the referring hospital. 2. Keep the newborn warm in a neutral thermal zone. 3. Maintain the blood sugar > 2.5 mmol/L by the infusion of intravenous 10% dextrose (especially important in infants < 34 weeks’ gestation). 4. Provide adequate oxygen to ensure optimal saturation. Oxygen saturation should be measured continuously during transport. Hyperoxia should be avoided in premature infants. 5. Obtain adequate documentation of the history from the referring hospital and maintain adequate documentation of the baby’s condition during the transport. 6. Consider any special requirements. These may include a pharyngeal airway in the baby with airway obstruction due to micrognathia, or an intragastric tube to empty the newborn’s stomach and maintain free drainage if gastrointestinal obstruction is suspected.

7. Consider the mode of transport. Noise and vibration may be deleterious to the sick baby. Altitude (heli­ copter or fixed-wing plane transport) reduces the ambient oxygen pressure and needs to be taken into consideration. 8. Keep the parents informed. They should have an opportunity to meet the retrieval team and farewell their baby. If the mother is not to be transferred immediately, every effort should be made to allow mother–baby interaction (albeit briefly) prior to transport. Encouraging the mother to take a digital photograph of her baby is a good idea. 9. Consent for transport should be obtained. Information about the retrieval team and the hospital where the newborn will be cared for should be left with the immediate family. Clinical decisions will be made on the need for cannulas, chest drains or endotracheal intubation for assisted ventilation. These should be made if necessary prior to moving the newborn; procedures may be difficult and hazardous during transport. Monitoring of vital signs (heart rate, oxygen saturation, temperature), blood sugar and blood gases should be undertaken. The mother should be transferred either with the newborn or as soon as possible afterwards. It is desirable that she be with her baby, so that expressed breastmilk is available for her baby when required and that maternal– infant bonding is promoted. Even in the case of maternal separation, expressing of colostrum/breastmilk can continue with midwifery support. This may instil a feeling that the mother can ‘do something for her baby’, and should not be underestimated.

BOX 75.1  Conditions requiring neonatal transport to a tertiary referral centre. Prematurity ≤ 32 weeks Respiratory distress requiring > 40% oxygen Severe birth asphyxia Convulsions Recurrent apnoea Jaundice requiring exchange transfusion Severe or multiple abnormalities requiring diagnosis or management Need for surgery Suspicion of severe cardiac disease

Source: Courtesy of Prof. Norman Beischer.

FIGURE 75.9 

Transportation of a sick newborn by a road ambulance. The transport system must be equipped and staffed so that it becomes an extension of an intensive care nursery. Source: Image courtesy of Ms Christine Fry, Paediatric, Infant, Perinatal Emergency Retrieval (PIPER), Royal Children’s Hospital, Melbourne.

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A FINAL NOTE: CARING FOR THE PARENTS The expected or unexpected birth of a preterm newborn is a great stress on the parents and family. Before the delivery of a preterm newborn, many issues will be of concern to the parents. Hence, they will receive some reassurance in having expectations regarding the following issues discussed: birth weight and physical appearance risk of death and serious morbidity duration of hospitalisation procedures (resuscitation, intubation, ventilation, surfactant) diseases (respiratory distress syndrome, sepsis, jaundice) need for transport to a tertiary centre (if the baby is not born there) the role of parents in intensive care. Parents often experience a grief reaction after the birth of a preterm newborn. This and the many vicissitudes associated with prolonged hospitalisation may be minimised by measures such as the following: transporting the mother to be near her newborn encouraging frequent close contact with the preterm newborn allowing rooming-in prior to discharge parent support groups cuddling/holding the newborn even while still ventilated encouraging the parents to nurse the newborn skin-to-skin for appropriate periods (the ‘kangaroo’ method) discharging the newborn from hospital as early as possible

• • • • • • • • • • • • • •

692

•

providing home visiting for a period after hospital discharge. Thankfully, as discussed in this chapter, there are generally good long-term survival outcomes and an overall low risk of significant disability. These facts should be clearly stated to the families of premature newborns. REFERENCES 1) Chow SSW. Report of the Australian and New Zealand Neonatal Network 2011. Sydney: ANZNN; 2013. 2) Abdel-Latif ME, Kecskés Z, Bajuk B, NSW and the ACT Neonatal Intensive Care Audit Group. Actuarial day-by-day survival rates of preterm infants admitted to neonatal intensive care in New South Wales and the Australian Capital Territory. Arch Dis Child Fetal Neonatal Ed 2013;98(3):F212–17. 3) Stephens BE, Vohr BR. Neurodevelopmental outcome of the premature infant. Pediatr Clin North Am 2009;56(3):631–46. 4) Wood NS, Marlow N, Costeloe K, et al. Neurologic and developmental disability after extremely preterm birth. N Engl J Med 2000;343(6):378–84. 5) Moore T, Hennessy EM, Myles J, et al. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ 2012;345e7961. 6) Aylward GP. Neurodevelopmental outcomes of infants born prematurely. J Dev Behav Pediatr 2005;26(6):427–40. 7) Behrman R, Butler A. Chapter 11: Neurodevelopmental, health, and family outcomes for infants born preterm. In: Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes. Preterm birth: causes, consequences, and prevention. Washington: National Academies Press; 2007.

INDEX Page numbers followed by ‘f ’ indicate figures, ‘t’ indicate tables, and ‘b’ indicate boxes.

A abdomen  514f, 573f, 612 abdominal examination in antenatal visits  41–42 in clinical labour assessment  227–229, 228f deflexed vertex presentation diagnosis and  296 in gynaecological examination  355–357 involution and  323 neonatal assessment  612 pelvic pain and  510 abdominal hysterectomy  559–560 abdominal leak point pressure  498–499 abdominal pain midcycle  405–406 in pregnancy  204 in prepubertal girls  373 abdominal pregnancy  62 abdominal pruritus  209 abdominal sacrocolpopexy  490 abdominal station  231 ablation endometrial  395–396, 396f laser  557 radiofrequency electrothermal  395–396, 396f ABO haemolytic disease  633 ABO incompatibility  181 abortion PID after  480 safety of  342–343 tubal  61 tubal, missed  62 see also post-abortal endometritis; termination of pregnancy abscess Bartholin’s duct  538 breast  148f, 338, 621–622, 621f vulvar  539 accessory breast  522–523, 523f accessory nipple  522–523 accoucheur  236–237, 237f achondroplasia  606, 606f acne vulgaris  425b, 427, 427f acquired immunodeficiency syndrome (AIDS)  661 acupuncture  316 acute fatty liver of pregnancy  169 acute vasodilation  312 adenocarcinoma in situ  557, 558f adenomyosis  393f clinical features of  565 diagnosis of  565 epidemiology of  565 pathology of  565 treatment of  565

admission with breech presentation  123–124 first-stage labour management and  230 preterm labour and  100 adolescence amenorrhoea in  375 dysmenorrhoea in  375 gynaecology of  372b menorrhagia in  375 menstrual problems in  375 pelvic pain in  376 sexual activity in  375–376 adoption  82 adrenal glands  429, 434–435 adrenaline  590 AEDs see antiepileptic drugs aftercoming head  125–126, 258–259 age as breast cancer risk factor  529 cervical cancer and  550f genital tract infection and  467 maternal  29–30, 267–268 of menopause  434b vaginal discharge and  467 see also gestational age AIDS see acquired immunodeficiency syndrome alcohol Indigenous women and  348 pregnancy and  37 prepregnancy consultation and  31 see also fetal alcohol syndrome alertness, of newborn  586 alopecia  426 alpha-fetoprotein Down syndrome and  71–73 FGR risk factors and  93b neural tube defects and  666 alpha-thalassaemia  164–165 alternative birthing centre  230 amastia  522–523, 523f ambiguous genitalia  373, 670–671, 670f ambulatory hysteroscopy see hysteroscopy amenorrhoea  323, 379f, 414–419, 414b in adolescence  375 aetiology of  415–416, 417t assessment of  418 causes of  416–418, 417t hypothalamic  416, 417t, 418–419 lower genital tract  418 ovarian failure  416–419, 417t pituitary  416, 417t uterine disorders in  417t, 418

693

Index

amenorrhoea (cont.) classification of  417t investigations for  359t lactational  462 management of  418–419 pathogenesis of  415 primary  415 secondary  415–416 American Fertility Society  516, 517f AmniHook  247 amniocentesis  74–75, 153t–154t aneuploidy screening with  71–75 chorioamnionitis and  146 cytomegalovirus and  155 Down syndrome screening with  74–75, 671 facial abnormalities and  78 listeriosis and  148 miscarriage rate of  70b toxoplasmosis and  160 varicella fetal infection and  157 amnionicity, of twins  112–113 amniotic and chorionic membranes see membranes, amniotic and chorionic amniotic band  16 amniotic band syndrome  18f amniotic fluid  96–97, 97f, 281–282 amniotic fluid embolism aetiology of  313 clinical features of  313 treatment of  313 amniotic sheets  16 amniotomy cervical dilation and  232–233 inadequate progress of labour and  290 preeclampsia and  137 vasa praevia and  88 amoxycillin  146, 479 ampicillin  146 anaemia  163 aetiology of  165 blood destruction and  677 blood loss and  677 causes of  164–165 folic acid deficiency and  164 haemoglobinopathies and  164–165 iron deficiency and  164 clinical sequelae of  163 hydrops fetalis and  677–678 management of  165–166 pathological  676–678 physiological  676 physiology of  163 preterm birth and  676b prevention of  165 red blood cell destruction and  677–678 red blood cell production failure and  678 screening for  165 anaesthesia for caesarean section  319–321 general  320–321 spinal  312, 320 see also epidural anaesthesia anal sphincter  254, 486f

694

analgesia methods of  316–317, 316b regional  271 analgesic agents  316 anaphylactic shock  312 anatomy of bladder  492–493, 493f epidural  318f of fetal circulation  585f gynaecological  356f of lower urinary tract  492–493 of nipple  521 see also breast; pelvic organ prolapse; reproductive system (female) androgen delayed menarche and  375 serum levels of  428 sources of  426 androgen excess see hyperandrogenism androgenic alopecia  426 android pelvic shape  9t anencephaly  77, 637t, 666–667 postdates pregnancy and  107 prevalence of  664t aneuploidy  71–75, 76f, 664t anorectal incontinence  254 anovulation hypothalamic dysfunction and  405–406 infertility from  405–406 luteinised unruptured follicle syndrome and  406 management of  406 ovarian dysfunction and  406 pathophysiological classification of  405–406 PCOS and  405–406 pituitary dysfunction and  406 antacid preparations  203–204 antenatal care birth preparation and  40 diabetes mellitus and  189 health promotion in  39 maternal support and  40 objectives of  39–40 pregnancy complications and  40 preventative medicine in  39 antenatal depression  198 antenatal visits at 28 weeks gestation  43–44 at 36 weeks gestation  44 first  32, 42–43, 188 after first  40–44 frequency of  40 investigations in blood group antibody screening in  43–44 glucose tolerance testing in  43 Group B streptococcus screening in  44 haemoglobin in  43 routine in  40–44 abdominal examination in  41–42 auscultation and  42 blood pressure and  41 examination in  40–42 fetal movements and  41 maternal weight and  40–41 palpation in  41–42

Index

patient history in  40 urinalysis in  42 antepartum haemorrhage (APH) aetiology of  85–86, 86t caesarean section indications and  270 fetal wellbeing and  85 induction of labour and  244b management of  85–86 resuscitation and  85 anterior compartment prolapse  488 anterior fontanelle presentation see deflexed vertex presentation anterior midline plication  488 anthracycline  531–532 anthropoid pelvic shape  9t anti-androgen medication  428–429 antibiotics breast infection and  527 in caesarean section preparation  271 in first-stage labour management  235 gonorrhoea resistance to  477 preterm labour treatment with  100 antibodies antiphospholipid  177 crossing placenta  176 isoantibody  176 maternal  677–678 red blood cell destruction by  677–678 see also anti-red blood cell antibodies antibody screen  34–35, 43–44 anticholinergic drugs  313, 501–502, 502t anti-D miscarriage and  58 passive administration of  181–182, 181f antiepileptic drugs (AEDs)  192, 200t anti-fibrinolytic agents  565 anti-La syndromes  180 anti-oestrogens  422 antiphospholipid antibodies  177 antiphospholipid syndrome  177t, 179–180 antipsychotics  200t anti-red blood cell antibodies ABO incompatibility and  181 blood transfusions and  180–181 consequences of  181 detection of  182 fetomaternal haemorrhage and  181 pregnancy management with  182–184 antigen status and  182–183 high-risk  183–184, 183t low-risk  183, 183t moderate-risk  183–184, 183t anti-Ro syndromes  180 antisepsis  236 anus  612–613, 613f, 668, 668f aorta  665 apex  483 Apgar score  590–591, 590t APH see antepartum haemorrhage apnoea  587b, 685 appendicitis  168 appendix  169f Apt test  626b Arabin pessary see pessary

areola  521 ARM see artificial rupture of the membranes arms  293, 606–607 aromatase inhibitors  518t, 531 aromatherapy  316 arthritis  660 arthrogryposis  606 artificial feeding first feed in  624 frequency and duration of  624 hospital discharge and  625 method of  624–625 reasons for  624–626 volume of feed in  624–625, 625t artificial infant formula  327, 624–626 artificial rupture of the membranes (ARM) adverse effects of  247 in augmentation of labour  289 contraindications to  245 cord prolapse with  247 induction of labour with  247 infection with  247 mechanism of action of  247 technique of  247 Asherman’s syndrome  409–410, 464 asphyxia birth  291–292, 586 prolonged  587b risk factors for  587b shoulder dystocia and  291–292 see also birth asphyxia assisted breech delivery see breech delivery assisted reproductive technology  401b assisted ventilation neonatal resuscitation with  588–589 oxygen concentration with  589–590 RDS treatment with  648 in respiratory distress management  645–646 asthma  144, 313 atresia  634, 667 atrophic vaginitis  541 augmentation of labour adverse effects of  289 contraindications for  289 rationale for  288 regimen for  289 auscultation of fetal heart  42, 232–233, 233f–234f Australian Indigenous women see Indigenous women autoimmune disease  177–180, 177t autoimmune hyperthyroidism  177t, 178–179, 178f autoimmune hypothyroidism  177t, 179 autonomic dysreflexia  194 autosomal dominant inheritance  664b autosomal recessive inheritance  664b azithromycin  472, 476, 478–479 azoospermia  404–405

B bacille Calmette-Guérin (BCG)  595 bacterial infections  145–149 bacterial vaginosis  359–360, 360f, 541 aetiology of  473–474

695

Index

bacterial vaginosis (cont.) diagnosis of  473 incidence of  473–474 pregnancy and  474 treatment of  473–474 bacteriuria  348–349 Bakri balloon tamponade  304f balanitis  474 balloon tamponade  304, 304f banded karyotype  75 Bandi’s physiological ring  220f bariatric surgery  50 Barnes forceps  260f barrier contraception  458–460 Bartholin’s duct  4 Bartholin’s duct abscess  538 Bartholin’s gland  4 Bartholin’s gland cancer  543–544 bathing  593 BCG see bacille Calmette-Guérin bearing down  224, 236, 258 bed-sharing  594 behaviour health  347, 375–376 newborn  586, 594 PMDD and PMS and  386–387 Behçet’s disease  539 Bell’s palsy  194 benign breast disease  525–527 beta-adrenergic agonists  101, 179 beta-thalassaemia  164 Bethesda System  551t bicornuate uterus  365f, 409, 409f biliary atresia  634 bilirubin levels of  630–631 metabolism  628–629, 629f unconjugated  629 bimanual examination  357f biofeedback  316 biological therapy  531 biopsy breast assessment with  525, 526f colposcopy with  556f of endometrium  394f heavy menstrual bleeding and  391–392 biparietal diameter  33, 94f bipolar disorder  198 birth blood loss and  677 cord around neck and  236 diabetes mellitus and  189–190 earlier-than-planned  243 expected date of  33 expediting  249 ‘hands-off’ management of  237 home  230 mechanisms of  221–224, 222f descent in  221–223 extension in  223 external rotation in  223, 223f internal rotation in  223 trunk delivery in  223–224

696

mode of  44t, 45, 189 place of  38, 275 post-term  651 precipitate  253 preparation for  40, 236 antisepsis in  236 instruments for  236 position of the woman in  236 universal precautions in  236 term  651 timing of  45, 189 unregulated attendants to  230 vacuum  257–258, 258t, 264 vulva, vagina and perineum inspection after  241 see also preterm birth; vaginal birth birth asphyxia  291–292, 586 birth canal  7–10, 9f birth mechanisms and  221–224 labour and  216b postpartum haemorrhage and  303 birth centre  230, 231f birth defects  70–71 birth depression see neonatal respiratory depression birth marks  604–605 birth position  226b, 236 birth suite  303 birth trauma  190, 485b, 678–679 birth weight long-term survival  99f neonatal death and  95f, 680b stillbirth and  95f bisexuality  443–444 Bishop’s score see cervical score bladder anatomy of  492–493, 493f development of  19 first-stage labour management and  235 gynaecological history and  355 innervation of  506t neurourology of  494f of newborn  493 bladder diary  498, 499f bleeding from cervix  90 early pregnancy  55, 56f, 56t, 60 from genital tract  90 miscarriage and  57 neonatal vaginal  373 uterine  379f see also dysfunctional uterine bleeding; heavy menstrual bleeding; menstruation; postmenopausal bleeding blighted ovum  57 blood composition of  675–676 coagulation factors in  676 platelets in  676 red blood cells in  675–676 white blood cells in  676 cord  238 destruction of  677 fetal sampling of  281, 281b full blood examination  34 pulmonary  644

Index

reproductive anatomy and  6f in stools  679 villi and  22f see also red blood cells; white blood cells blood flow, pulmonary  644 blood gas values  645t blood group  34–35, 43–44 blood loss birth and  677 caesarean section and  677 cervical lacerations and  255 heavy menstrual bleeding and  396 normal menstrual bleeding and  379 see also postpartum haemorrhage blood pressure  41, 136 blood sugar management  185b diabetes, effect on pregnancy and  187–188 diabetic management and  189 glycosuria and  42 hypoglycaemia and  653, 682 transport and retrieval and  691 blood tests in caesarean section preparation  271 in gynaecological investigations  358 heavy menstrual bleeding and  391 neonatal sepsis and  659 blood transfusion  180–181 blood volume  136–137, 676 B-Lynch compression sutures  304f body stalk  16 body temperature fertility awareness and  461 ovulation and  405f of preterm newborn  683 bonding  594–596 breastfeeding and  618 caesarean section recovery and  324 genetic conditions and  80–83 mental illness and  197 phototherapy and  632 suppression of lactation and  623 transport and retrieval and  691–692 bone loss  435–436 bony pelvis see pelvis bottle feeding see artificial feeding botulinum toxin  502 bowel atresia  667 bowels  235, 337, 355 brachial plexus injury  291, 291f, 641, 641t brachial plexus palsy  291f brachytherapy  561f bradycardia  588 brain  586 damage to  636b development of  16–18, 17t, 636–637 growth restriction prognosis and  653 head size and  607 imaging of  81 neurophysiology of lower urinary tract and  493 preeclampsia and  132–133 branchial cysts  610 Braxton Hicks contractions  204–205 BRCA genes  529, 529t, 532

breast accessory  522–523, 523f anatomy of  326f, 521–523, 618 external  618 internal  618 lobular architecture in  521–522, 522f nerve supply in  522 pregnancy and  618 vasculature in  522 anomalies of  521–523 assessment of  524–525 biopsy in  525, 526f clinical examination in  524, 524f cytology in  525 histology in  525 history in  524 mammography in  524–525, 525f, 532 MRI in  525 neonatal  612 ultrasonography in  525 disorders of  521b, 525–527 engorgement of  621, 621f pain in  521b, 527 physiology of  523–524 of preterm newborn  681 soreness of  207 stimulation of  325–326, 338 breast abscess  148f, 338, 621–622, 621f breast cancer  521b in antepartum  532 classification and staging of  528 DCIS and  528 follow-up  532 histopathology of  528 hormone replacement therapy and  437, 529 incidence of  528–533 inflammatory  533f locally advanced  532–533 lymph node status and  529–530 metastatic  533 Paget’s disease of the breast and  528 in peripartum  532 prevention of  532 risk factors for  529, 529t screening for  532 symptoms of  527 treatment of  530–532 chemotherapy in  531–532 endocrine and biological  531 radiation therapy  530–531 surgical  530 breast cyst  526 breast expression  623, 623f breast infection  527 breastfeeding and  621–622 diagnosis of  147 management of  147, 148f pathogenesis of  147 breast involution  523–524 breast lumps  521b breast milk  618 coming-in of  619 composition of  619

697

Index

breast milk (cont.) flow of  338 human donor  624 insufficient supply of  622 overabundance of  622 stasis  338 volume of  338 breast milk jaundice  634 breast reconstruction  523f, 530, 531f breast refusal  623 breastfeeding anatomy and  326f antenatal preparation for  619 benefits of  327b bonding and  618 breast infection and  621–622 contraception and  334 contraindications to  328 diabetes mellitus and  190 functions of  618 inability to suck and  622 international perspective on  617–618 management of  619–624 medications and  328 multiple sclerosis and  192 oestrogen and  323 oxytocin production during  325–326 physiology of  325–328, 523–524 problems with  333, 338, 620–623 caregiver-related  623 maternal  621–622 neonatal  622–623 psychological  622 prolactin production during  326 promotion of  327 sleep and  328 successful  327b technique of  620 breech delivery assisted  125–126 aftercoming head in  125–126 breech and legs in  125 head entrapment and  126 preparation for  125 shoulders in  125 trunk in  125 vaginal  249–250, 258–259 breech extraction  126–127, 250 breech presentation  120–127 admission with  123–124 aetiology of  121 antenatal management of  121–123 assisted breech delivery and  125–126 breech extraction and  126–127 caesarean section with  122–123, 123t diagnosis of  121 external cephalic version and  122 head entrapment and  126 incidence of  120–121 intrapartum management of  123–127 labour with  124–126 lower uterine segment and  123 predisposing factors  121 prognosis with  127

698

vaginal birth with  122–127, 123b, 123t varieties of  121f Brenner tumours  577 broad ligaments  7 bromocriptine  420–422 bronchial asthma  144 bronchopulmonary dysplasia  648 brow presentation  264, 294 aetiology of  297–299 brow prominence after  298f–299f clinical course of  299–300 diagnosis of  299 diameters and measurements of  295t illustration of  299f incidence of  297 management of  300 bubble CPAP circuit  689, 690f bulbocavernosus muscles  5f Burns-Marshall method  124f

C CA 125 tumour marker  573 cabergoline  420–421 caesarean hysterectomy  272 caesarean section  267 additional procedures with  272 adverse effects of  273–274 anaesthesia for  319–321 epidural top-up  320 general  320–321 spinal  320 blood loss and  677 with breech presentation  122–123, 123t complications with  273–274 consent to  270–271, 319–321 decision equation for  269, 269f future parity in  269 maternal preference in  269 risk tolerance in  269 difficulties with  272 elective  268 emergency  268 hospital discharge after  333–334 hysterectomy with  272 incidence of  267–268 indications for  268–270 antepartum haemorrhage and  270 cephalopelvic disproportion and  270 eclampsia and  270 fetal compromise and  269–270 inadequate progress in labour and  269–270 malpresentation and  270 maternal preference and  270 multiple pregnancy and  270 obstructed labour and  269 preeclampsia and  270 uterine scar and  269 induction of labour and  244 with oblique lie  128 placenta accreta and  269, 273–274, 274t placenta praevia and  88, 274, 274t postoperative care after  272–273 procedure of  270–274 preparation for  270–271

Index

surgical technique  271–272, 272f uterine incision  268, 268f recovery after  324 repeat elective  274 rise in  267b scar from  307, 307f shoulder dystocia and  293 sterilisation with  272, 273f with transverse lie  128 types of  268 uterine rupture and  273–274, 307, 307f vaginal birth compared to  269, 269f see also trial of labour after caesarean section CAH see congenital adrenal hyperplasia calcium  36, 48 calcium channel blockers  100 calendar method  461–462 cancer Bartholin’s gland  543–544 hormone replacement therapy and  437 vulvar  542–544 see also breast cancer; cervical cancer; endometrial cancer candidiasis  359–360, 540–541, 657 diagnosis of  474–475 incidence of  474–475 lichen sclerosus and  536–537 neonatal  657, 658f non-albicans  474 paediatric  542 recurrent  475, 540 treatment of  474–475 capillary malformations  604–605 caput  227, 608 carbamazepine  192 carbohydrates  619 carboplatin  579 carcinoma of cervix  90, 173 embryonal  582 see also adenocarcinoma in situ; choriocarcinoma; ductal carcinoma in situ cardiac arrest, in pregnancy  314 aetiology of  314 diagnosis of  314 management of  314 cardiac disorders  140b aetiology of  142 classification of  142 clinical features of  142 management of antenatal  142–143 delivery and  143 intrapartum  143 labour and  143 prepregnancy  142 puerperium and  143 physiological changes in pregnancy and  141 prognostic factors  142 cardiogenic shock  312–313 cardiomyopathy  143, 312–313 cardiopulmonary system  584–586 cardiotocography continuous  233, 234b fetal compromise and  281

fetal wellbeing assessment with  96, 233 in labour assessment  229–230 postdates pregnancy and  108 cardiovascular disease  348, 435–437 cardiovascular system development of  18–19 neonatal assessment of  606, 612 preeclampsia and  132 puerperium and  324 structural abnormalities of  77 care see antenatal care; intrapartum care; neonatal care; postnatal care caregivers  38, 230–231, 623 carpal tunnel syndrome  194 catheter  498 catheterisation  4f, 168b, 175 cefotaxime  479 central nervous system  77–78, 664t, 666–667 cephalhaematoma  266f, 608, 608f cephalic presentation  294, 295t cephalic version see external cephalic version cephalopelvic disproportion  270, 286–288 cerebral haemorrhage see intracranial haemorrhage cerebral palsy  194, 279, 688 cerebral venous thrombosis (CVT)  193 cerebrovascular disease  193–194 cervical cancer aetiology of  550 age-standardised rate of  550f HPV and  547–550, 551f, 561–562 incidence of  548, 549f invasive  558–561 clinically  559–560 diagnosis of  558 management of  558–560 microinvasive  558 post-treatment follow-up for  561 prognosis of  561 stages of  558–560 staging of  558, 559t mortality from  343–344, 549f pathogenesis of  550 during pregnancy  561 progression of  552f from transformation zone  550f vaccine for  561–562 cervical cap  453t, 460 cervical cerclage  103, 105f cervical condyloma  547f cervical dilation  220, 220f, 232–233 cervical ectopic pregnancy  62, 62f cervical ectropion  90, 546f cervical fibroid  548f cervical funnelling  104f cervical hypertrophy  171f cervical insufficiency  103 management of  103 cervical cerclage in  103, 105f pessary in  103, 105f progesterone in  103 cervical intraepithelial neoplasia (CIN) clinical features of  173 colposcopy images of  556f detection of  555–556

699

Index

cervical intraepithelial neoplasia (CIN) (cont.) management of  173 progression of  552f screening for  360–361 cervical sample in  360–361 HPV and  361 liquid-based cytology in  361 Pap smear in  361 treatment of  556–557 cervical lacerations clinical features of  254 management of  255 uterine rupture and  308 cervical mucus  410 cervical polyps  90 cervical ripening  245–246 cervical samplers  554f cervical score  245, 245t cervical screening  553–556 algorithm for  555f cervical samplers for  554f HPV testing and  555 methods of  553–556, 554f–555f in pregnancy screening  35 reporting and  553–555 cervical smear see Papanicolaou smear cervical tears  265 cervicitis  475–478, 546 cervix adenocarcinoma in situ  557, 558f amenorrhoea and  417t benign disorders of  545–547 benign tumours in  546–547 cervicitis in  546 congenital abnormalities and  545 endocervical polyps in  546–547, 547f eversion and nabothian cysts in  546, 546f leiomyomas in  547 papillomas in  547 bleeding from  90 carcinoma of  90, 173 examination of  227, 229f innervation of  506t labour initiation and  217–219, 218f loop excision of  557 malignant disorders of  547–550 normal  104f premalignant disorders of  547–550 structural changes in  217 submucous fibromyoma extrusion through  564 support for  484f see also pre-invasive disease of the cervix chancre  471–472, 472f chancroid  472 chemotherapy  531–532, 560 chest compressions  590 chest wall  612 chickenpox see varicella children growth charts for  599f–600f sexual assault of  447 see also newborn chlamydial infection  148–149 conjunctivitis caused by  657–658

700

consequences of  476 diagnosis of  476 among Indigenous women  348–349 LGV and  472 management of  476 microbiological investigations  358 pregnancy and  476 testing sites  476 treatment of  476 vaginal discharge from  467 cholecystitis  170 cholelithiasis  170 cholestasis, neonatal  634 cholestasis of pregnancy clinical features of  169, 209 diagnosis of  209 management of  169, 209 pathogenesis of  169 pathophysiology of  209 chorioamnionitis diagnosis of  146 management of  146 pathology of  145–146 predisposing factors  146 prolonged labour and  289 choriocarcinoma  65–66, 65f, 582 chorionic villi  22f chorionic villus sampling (CVS)  74–75, 75f chorionicity, of twins  112–113 chromosomal abnormalities  663, 671–673 in miscarriage aetiology  56 sex  673 chronic lung disease (CLD)  648, 682, 682f chronic renal insufficiency  174–175 cicatricial pemphigoid  538–539 CIN see cervical intraepithelial neoplasia circulation, of fetus  22–24, 584–585, 585f circumcision  613 circumvallate placenta  241f classical caesarean section  268 clavicle fracture  291, 293f CLD see chronic lung disease clear cell ovarian tumours  575 cleft lip  78, 79f, 622, 671, 671f cleft palate  78, 622, 671, 671f cleidotomy  293 climacteric  13, 434 clinical features of  435 bone loss in  435 cardiovascular risk and  435 menstruation and  435 urogenital atrophy in  435 vasomotor symptoms in  435 clindamycin  473, 479 clitoridectomy  344 clitorimegaly  613f clitoris  3 excision of  344 neonatal assessment of  612–613 clomiphene citrate  422 clubfoot  615f clue cells  360 CMV see cytomegalovirus coagulation disorders  166–167, 307

Index

coagulation factors  676 coarctation of aorta  665 coelomic metaplasia  513 COH see controlled ovarian hyperstimulation coitus see sexual intercourse cold stress  594, 683 colic  626 colostrum  325, 619 colour, of newborn  598 colpocleisis  490 colposcopy cervical screening with  555–556, 555f CIN images with  556f with punch biopsy  556f combined hormonal contraception  455–458 combined oral contraceptive pill see oral contraceptive pill combined spinal epidural (CSE)  317, 319f complete miscarriage  58–59, 58t compound presentation  287f compression neuropathies  207 compression sutures  304, 304f conception, rate of  401b conceptus  17t, 176 condom correct fit of  459f failure rate of  453t female  459 male  458–459 condylomas  547, 547f condylomata  541 congenital abnormalities benign cervical disorders and  545 epilepsy and  192 gender phenotype and genotype discordance and  373 genital ambiguity and  373, 670–671, 670f imperforate hymen and  372–373, 540 incidence of  662b of Müllerian system  170 parental communication and  673–674 prevalence of  662–663, 663t–664t screening for  114 congenital adrenal hyperplasia (CAH)  426–427, 670f congenital cysts, of vagina  540 congenital dermal melanocytosis  604–605 congenital heart disease  663–666 congenital hypothyroidism  595f congenital rubella syndrome  155–156, 156f congenital vulvovaginal disorders  540 conjunctivitis  609, 657–658 consent to caesarean section  270–271, 319–321 to gynaecological examination  355–357 to instrumental birth  261 to laparoscopy  369 sexual assault and  447–448 constipation  204, 626 continuous positive airway pressure (CPAP)  646 bubble  689, 690f nasal  645–646, 645f, 648 contraception  334, 451b barrier  458–460 benefits of  343 combined hormonal  455–458 evidence-based prescription of  452–453

failure rates of  453t gynaecological history and  355 initiation of  453 long-acting reversible  454–455 maternal mortality and  343 medical eligibility criteria for  452, 453t permanent  462 pregnancy risk and  452–453 public health and  452–453 unmet need for  340b see also condom; diaphragm; emergency contraception; intrauterine contraceptive device; oral combined hormonal contraception; oral contraceptive pill; progesterone only pill contraceptive implants  454 controlled cord traction  239 controlled ovarian hyperstimulation (COH)  411 convulsions  136, 138–139 copper IUD see intrauterine contraceptive device cord see umbilical cord cord blood  238 cord entanglement  283–284 cord presentation  282–283, 282f cord prolapse from artificial rupture of the membranes  247 diagnosis of  282–283 incidence of  282 management of  283 predisposing factors of  282 types of  282–283 cornual pregnancy  62 coronary occlusion  312–313 corpus luteum cysts  574 corticosteroids  178 lichen sclerosus management with  536–537 placenta praevia management with  87 preterm labour treatment with  100 preterm newborn survival rates and  687 PUPPP management with  209 corticotrophin-releasing factor  217 corticotrophin-releasing hormone (CRH)  219f co-sleeping  594 counselling  673–674 cow’s milk  624–626 CPAP see continuous positive airway pressure cramps see muscle cramps cretinism  595f CRH see corticotrophin-releasing hormone crusted scabies  473 cryotherapy  557 CSE see combined spinal epidural culdoplasty  490 culture  383 curettage  82, 307, 309, 409–410, 438, 566 Cushing’s syndrome  427 CVS see chorionic villus sampling CVT see cerebral venous thrombosis cyanosis  598, 665 cyproterone acetate  428–429 cystadenoma  576 cystectomy  575 cystic fibrosis  75 cystic hygroma  610, 611f cystic kidney  664t

701

Index

cystourethroscopy  499 cysts branchial  610 breast  526 corpus luteum  574 eversion  546 follicular  574 nabothian  546, 546f theca lutein  574 vaginal  540 see also ovarian cysts cytokines  218t, 219f cytology breast assessment with  525 cervical screening with  553, 554f pre-invasive disease of the cervix and  550–552, 552f see also liquid-based cytology cytomegalovirus (CMV)  152–155, 153t–154t, 468 management of  155 neonatal infection with  656 seroconversion and  155 seronegative mother  155, 155b cytoreductive surgery  575–576

D dacryocystitis  657–658, 658f danazol  389, 518t DCIS see ductal carcinoma in situ decidual cast  58f deep pelvic grip  42 deep vein thrombosis  141 deficient placentation  131 deflexed vertex presentation  294 aetiology of  295–296 diagnosis of  296 diameters and measurements of  295t management of  297 occipitoposterior position and  295–297 posterior position sequelae and  296 deflexion of fetal head  294–295 deformation  662–663 delay in labour see inadequate progress in labour; prolonged labour delayed ejaculation  446 delivery cardiac disorders and  143 with eclampsia  139 epilepsy and  192 expected date of  33 fetal compromise and  282 fetal growth restriction and  94 forceps  261–263 with genetic or structural abnormalities  81 of head  236 manipulative  250 mechanisms of  222f, 301f of membranes  239–240, 239f mid-cavity  261–263 multiple sclerosis and  192 normal  236 pelvic diaphragm muscles and  223f of placenta  239–240, 239f of posterior arm  293 with preeclampsia  137

702

of shoulders  237 of trunk  223–224, 237 of twins  117–118 see also breech delivery; instrumental delivery Depo-Provera  454 depot medroxyprogesterone acetate (DMA)  453t, 454 depression, antenatal and postnatal  197b, 198 depression, respiratory see neonatal respiratory depression dermoid cyst of ovary  581 DES syndrome see diethylstilboestrol syndrome descent  221–223, 238 desquamative inflammatory vaginitis  467, 541–542 detrusor leak point pressure  498–499 detrusor overactivity  498–499, 500f developing world  661 development see embryonic and fetal development developmental dysplasia of the hip (DHH)  613–615, 614f, 663t–664t, 669 dexamethasone  429 DHEA-S  428, 428t DHH see developmental dysplasia of the hip diabetes mellitus  185b aetiology of  186 antenatal care and  189 birth management and  189–190 breastfeeding and  190 classification of  186 diagnosis of  186–187 among Indigenous women  348 induction of labour and  244b large for gestational age and  654 management of  188–190 puerperium  190 surveillance in  188 in miscarriage aetiology  56 physiology and  186 pregnancy and  187–188 prepregnancy  186, 188 see also gestational diabetes mellitus diameters  33, 94f, 295t diaphragm  453t, 459–460, 460f diaphragmatic endometriosis  514f diaphragmatic hernia  649–650, 650f, 669 diathermy  395–396, 396f DIC see disseminated intravascular coagulation dicephalic fetus  287f dichorionic twins see twins diet diabetes management with  188–189 in pregnancy  36, 46–47, 47t for women  47t diethylstilboestrol syndrome (DES syndrome)  558 diphtheria  161 discharge, from hospital  333–334, 625 discharge, vaginal see vaginal discharge discrimination  346 dislocation of hip  613–615 disparate sexual desire  445 displaced urogenital sinus  670f disposable menstrual pad  382f disruption  662–663 disseminated intravascular coagulation (DIC)  678–679 aetiology of  167

Index

clinical features of  167 investigations for  167 pathogenesis of  166 treatment of  167 DMA see depot medroxyprogesterone acetate DNA testing  469 domicile  594 domperidone  326 donovanosis  473 dopamine receptor agonists  420–421 Doppler studies  96–97 dorsal induction  636 Down syndrome  71–75, 671 anomalies associated with  672f features of  601b karyotype of  71f–72f phenotype of  72f prevalence of  663t–664t screening for  71–75 combined testing, first trimester  73 diagnostic tests for  74–75, 671 dichorionic twins and  114 integrated testing, first and second trimester  73–74 maternal serum, second trimester  71–73 nuchal translucency, first trimester  73, 73f ultrasound, second trimester  74 doxycycline  476, 479 doxylamine  53 drug withdrawal  641–642 drugs, illicit  31, 37 Dubowitz assessment  682 duck-tail sign  486f ductal carcinoma in situ (DCIS)  528 duct ectasia  526–527 ducts Bartholin’s  4, 538 ejaculatory  404–405 paraurethral  3 ductus arteriosus  584–585 duration of labour  224 dwarfism  673 dysfunctional uterine bleeding  390, 392–396 dysgerminoma  581 dysmenorrhoea adenomyosis and  565 in adolescence  375 aetiology of  383 clinical features of  383–384 primary and secondary  383 treatment of  384–386 dysmorphic features  598 dyspareunia  446–447 dystocia aetiology of  285–286 bony pelvis and  286 fetal causes of  286 soft tissues and  286 uterine muscle dysfunction and  285–286 see also shoulder dystocia

E early pregnancy  11, 113–114 early pregnancy bleeding  55, 56f, 56t, 60

ears  18, 609, 681 eclampsia caesarean section indications and  270 characteristics of  138–139 clinical features of  138 convulsion first aid and  138–139 delivery with  139 diagnosis of  138 incidence of  138 management of  138–139 pathogenesis of  138 prognosis with  139 prophylaxis of  138 stabilisation of  139 ectocervix  546 ectodermal layer  16–18 ectoparasites  473 ectopic pregnancy  61–64 cervical  62, 62f diagnosis of  62 management of  62–64 outcomes of  61–62, 62f pathology and clinical features of  61–62 predisposing factors  61 sites of  61f, 62 symptoms triad of  61 tubal  61–62, 61f–63f EDB see expected date of birth EDC see expected date of confinement EDD see expected date of delivery Edinburgh Postnatal Depression Scale  197b education  346 Edwards syndrome  71, 72f, 664t, 671–673 ejaculation  446 ejaculatory ducts  404–405 electric pump, for breast expression  623f electrocardiography  282 electroconvulsive therapy  199–200 embolisation  304, 395f embolism see amniotic fluid embolism; pulmonary embolism; thromboembolism embryo  5, 17t 21-day old  18f development of  17t high-order multiple pregnancy and  118–119 IVF and ICSI and  411–412 length of  33 trophoblast and  14b embryonal carcinoma  582 embryonic and fetal development  16–20 ectodermal layer in  16–18 endodermal layer in  19–20 mesodermal layer in  18–19 pre-implantation  16 stages of  17t embryonic disc  16, 19 embryonic haemoglobin  19 embryonic remnant theory  513 emergency contraception  460–461 copper IUD  461 hormonal  461 levonorgestrel  461 Yuzpe method of  461

703

Index

emotional wellbeing of Indigenous women  347–348 during menstruation  381 in pregnancy  196–197 employment  37 encephalocele  77, 608–609, 637t, 664t encephalopathy  637–639 endocervical polyps  546–547, 547f endocervix  546 endocrine disorders  56 endocrine therapy  531 endodermal layer  19–20 endodermal sinus tumour  582 endometrial ablation  395–396, 396f endometrial atrophy  323 endometrial cancer  365f, 397f–398f clinical presentation of  567–568 epidemiology of  566 management of  568 pathology of  566–567 screening for  567 stages of  568b types 1 and 2 of  566–567 unopposed oestrogen and  568b endometrial echo  364f endometrial growth  380f endometrial hyperplasia  394f clinical features of  566 management of  566 pathology of  566 predisposing factors of  566 spectrum of  567f unopposed oestrogen and  568b endometrial polyps  565 endometrial sampling  366 endometrioid ovarian tumours  575 endometrioma  577 endometriosis  384f of abdominal wall  514f aetiology of  513–514 characteristics of  513, 513b clinical features of  515–516 diaphragmatic  514f examination and  516 infertility and  408, 516 investigations of  516 management of  516–517, 518t pathology of  514 prognosis of  517–519 staging of  515–516, 517f surgical findings of  514–515 vaginal discharge from  467 endometritis  336, 464 see also post-abortal endometritis; postpartum endometritis endometrium  386f, 394f, 432 endotracheal tube  588 engorgement of breasts  621, 621f epididymis  404–405 epidural anaesthesia CSE  317, 319f effectiveness of  317 epidural anatomy and  318f

704

establishing and maintaining  317 fetal compromise after  277 PCEA  317 performance of  318f PIEB  317 risks of  318t technique of  317 top-up  320 epilepsy antiepileptic drugs for  192, 200t breastfeeding and  328 congenital abnormalities and  192 intrapartum care and  193b labour and delivery and  192 postnatal care and  192–193 pregnancy outcomes with  192 prepregnancy planning with  192 seizures and  192 surveillance with  192 episiotomy complications of  253 indications for  249–250, 249b expediting birth and  249 manipulative delivery and  250 perineal tear avoidance and  249 traction force reduction and  250 infection from  253 puerperium care after  253 repair of  252–253, 252f perineal muscle approximation in  253 perineal skin closure in  253 surgical closure in  252–253 vaginal epithelium repair in  252–253 scarring from  254 surgical incision technique for  250, 250f–251f wound breakdown from  253 epistaxis  205 epithelial cells  466 epithelial hyperplasia  526, 529 epithelial ovarian cancer see ovarian cancer epithelial ovarian tumours  574–579 Epstein–Barr virus  468 Erb palsy  641t erectile dysfunction  446 ergometrine  238 erosive autoimmune dermatosis  467 erythema toxicum  601, 603f Escherichia coli  174 Essure  462f ethics  689 ethinyl oestradiol  456 eversion cysts  546 examination in antenatal visits  40–42 bimanual  357f of breast  524, 524f of cervix  227, 229f endometriosis and  516 fibromyoma of uterus and  564 full blood  34 for genetic conditions  81 heavy menstrual bleeding and  390–391 for infections  336

Index

in labour assessment  227–229, 228f–229f of lymph nodes  524, 524f neonatal physical  597–615 of ovaries  573 of perineum  510 pregnancy screening and investigations and  34 in prepregnancy consultation  30 preterm labour and  99–100 rectal  498 for sexual assault  448 with speculum  357f for structural abnormalities  81 of vulva  468, 510 see also abdominal examination; gynaecological examination; pelvic examination; vaginal examination excessive uterine bleeding see heavy menstrual bleeding exchange transfusion  633 exercise  36–37, 188–189 exomphalos  78, 669 expected date of birth (EDB)  33 expected date of confinement (EDC)  33 expected date of delivery (EDD)  33 external anal sphincter  254 external cephalic version adverse effects of  122 breech presentation and  122 contraindications for  122 efficacy of  122 with oblique lie  128 technique of  122, 122f with transverse lie  128 external genitalia (female)  2–4, 7 external rotation  223, 223f extraembryonic coelom  16 extrahepatic biliary atresia  634 extramammary Paget’s see vulvar Paget’s disease eyes  18, 609, 681

F face  78, 609–610, 671 face presentation  264, 294 aetiology of  300 clinical sequelae of  300–301 delivery mechanism with  301f diagnosis of  300 diameters and measurements of  295t incidence of  300 management of  301 facial nerve palsy  641, 641f failure to thrive  626 fainting  208 fallopian tubes  406–408, 408f, 506t family  230–231, 595–596 family history  354 family planning  452–453 fat, in breast milk  619 fat necrosis  605 fatigue  208 fatty liver of pregnancy see acute fatty liver of pregnancy feeding neonatal  617b, 625–626 non-enteral  625 see also artificial feeding; breastfeeding

female genital mutilation (FGM)  170, 344 female sexual arousal disorder  446 female sexual problems see sexual dysfunction female sterilisation  453t, 462 fentanyl  316 Ferguson’s reflex  217 Ferriman–Gallwey score  427 fertilisation  14–16, 15f fertility gynaecological history and  355 rate of  401b see also infertility; subfertility fertility awareness calendar method of  461–462 efficacy of  461–462 failure rate of  453t lactational amenorrhoea method of  462 mucus method of  461 temperature method of  461 fertility control  334, 451b fetal alcohol syndrome  667, 667f fetal biometry  94f fetal biophysical profile  97 fetal blood sampling  281, 281b fetal compromise aetiology of  277–279, 278f fetal conditions in  279, 279b maternal hypotension in  277 maternal oxygenation in  277 placental abruption in  278 placental insufficiency in  278 umbilical cord in  278–279 uterine hyperstimulation in  278 augmentation of labour and  289 caesarean section indications and  269–270 consequences of  279 cerebral palsy and  279 perinatal mortality  279 after epidural anaesthesia  277 instrumental delivery indications and  258 management of  279–282 amniotic fluid quantity and  281–282 assessment and treatment of underlying cause in  280–281 cardiotocography in  281 delivery and  282 electrocardiography in  282 fetal blood sampling in  281, 281b fetal wellbeing assessment in  281–282 intrauterine resuscitation in  280 meconium staining in  281–282 in second stage of labour  224 fetal death  286 see also stillbirth fetal development see embryonic and fetal development fetal distress see fetal compromise fetal growth restriction (FGR)  91–95 causes of  92–93, 93b, 652t diagnosis of  92 labour management and  94–95 management of  93–94 morbidity and mortality from  92f problems with  653 prognosis of  653

705

Index

fetal growth restriction (FGR) (cont.) risk factors for  93b tests for  94t timing of delivery and  94 see also intrauterine growth restriction (IUGR) fetal gynaecological problems  372 fetal heart monitoring see auscultation of fetal heart fetal hydrops see hydrops fetalis fetal infection prolonged labour and  289–290 with rubella  156–157 with toxoplasmosis  160 with varicella  157 fetal membranes  232 fetal trauma  289–290 fetal tumours  79–80 fetal wellbeing assessment  95–97, 232–233 amniotic fluid and  96–97, 97f antepartum haemorrhage and  85 auscultation of fetal heart and  232–233, 233f–234f cardiotocography in  96, 233 Doppler studies for  96–97 fetal compromise and  281–282 induction of labour and  245 postdates pregnancy and  108 ultrasound for  96–97 fetomaternal haemorrhage  24–25, 181 fetomaternal transfusion  677 fetus  17t at 8 weeks’ gestation  22f adaptation of  584b asphyxia risk factors  587b cardiopulmonary system of  584–585 circulation of  22–24, 584–585, 585f dicephalic  287f flying  296f growth of  93, 94t, 114–115 immune system of  176 kidneys of  586 movements of  41, 108 transition of  584b see also congenital abnormalities; genetic conditions; structural abnormalities FGM see female genital mutilation FGR see fetal growth restriction fibre  204 fibrinogen  167 fibroadenoma  525–526, 526f fibroids  390, 392–396, 394f, 548f fibroma  580 fibromyoma see uterine fibromyoma FIGO see International Federation of Gynecology and Obstetrics FISH see fluorescent in-situ hybridisation fissures  539 fistula genital tract  286 lateral  610 rectovaginal  254 tracheo-oesophageal  668, 668f urogenital  496 vesicovaginal  289, 342 flexor tone  297–299 floppy newborn  639–640, 640f

706

fluid intake and management in first-stage labour management  235 for newborns  683t urinary incontinence and  501 fluorescent in-situ hybridisation (FISH)  75, 76f flying fetus  296f folate  47 folic acid deficiency of anaemia and  164 clinical sequelae of  164 management of  165 predisposing factors  164 prevention of  164 vitamin B12 deficiency and  164 preconceptual  31 follicle-stimulating hormone (FSH)  414–419,  422–423 follicular cysts  574 follicular phase, of menstrual cycle  10, 380f fontanelles  607–608, 608f forceps history of  257 pros and cons of  257–258, 258t technique with  262f–263f types of  259f–260f, 260–261, 486f forceps delivery  261–263 foregut  19 foreign bodies, in vagina  541 forensic examination  448 formula see artificial infant formula friends  230–231 frozen pelvis  509f FSH see follicle-stimulating hormone full blood examination  34 functional ovarian cysts  573–574 fundal height  41, 93, 108 fundal palpation  41 fundus  41b, 324f

G gamete intra-fallopian transfer (GIFT)  411 gametogenesis  11–13, 12f Gardnerella vaginalis  360 gas exchange  644 gastric acidity reduction  271 gastric contents aspiration  313 gastrointestinal system development of  19–20 disorders of  667–669 problems with  168–170 puerperium and  325 structural abnormalities of  78 gastro-oesophageal reflux see oesophageal reflux gastroschisis  78, 78f, 669, 669f gays  443 GBS see Group B streptococcus GDM see gestational diabetes mellitus gender identity  443–444 phenotype and genotype discordance  373 transgender  443 gene BRCA  529, 529t, 532

Index

breast cancer risk factors and  529 deletions  164–165 Rh  182–183 single gene disorders  70 general anaesthesia  320–321 general practitioner  38 genetic abnormalities  663 see also chromosomal abnormalities; congenital abnormalities genetic conditions  71–76 pregnancy management with  80–83 adoption and  82 counselling in  81–82 history and examination in  81 imaging in  81 invasive testing in  81 labour and delivery in  81 lethal abnormalities and  82 neonatal care and  81 ongoing care and  82 post-termination care in  82–83 risk of recurrence and  82 termination of pregnancy and  82 screening for  76 genetic counselling  673–674 genetics  529, 529t genital atrophy  398, 435 genital tract amenorrhoea and  418 bleeding from  90 physiology of  466–467 puerperium and  323–324 genital tract fistula  286 genital tract infection age and  467 defences against  466–467 epithelial cells and  466 hormones and  466 lower  466b physiology and  466–467 upper  466b vaginal pH and  466–467 genital ulcer  468, 472 genital warts  471, 471f genitalia ambiguous  373, 670–671, 670f defects of  664t, 669–671 external (female)  2–4, 7 female genital mutilation and  170, 344 innervation of  506, 506t, 508f internal (female)  4–7, 6f neonatal assessment of  612–613 of preterm newborn  681 genitourinary system  78 gentamicin  146 germ cell ovarian tumours  580–582 gestational age assessment of  33 induction of labour and  244 postdates pregnancy and  108 ultrasound for  33 intellectual disability risk and  688t labour assessment and  227

perinatal mortality and  107t see also large for gestational age; small for gestational age gestational diabetes mellitus (GDM)  186 caesarean section incidence and  267–268 follow-up of  190 incidence of  186 screening for  186–187, 186t gestational hypertension  131 gestational sac  33, 55, 62f–63f gestational thrombocytopenia  166 gestational trophoblastic disease (GTD)  64–68 choriocarcinoma and  65–66 classification of  64–65, 65b clinical features and pathology of  65–66 diagnosis of  66 histopathology and cytogenetics of  65 hydatidiform mole and  65 invasive  65, 67–68 localised  64, 66–67 management of  66–68 predisposing factors  65 GIFT see gamete intra-fallopian transfer glucose tolerance testing  43 glyceryl trinitrate  101 glycosuria  42 GnRH see gonadotrophin-releasing hormone GnRH analogues  518t, 565 goitre  610 gonadal dysgenesis  670f gonadotrophin-releasing hormone (GnRH)  416 gonococcal ophthalmia  657–658 gonorrhoea  149, 360f antibiotic resistance of  477 diagnosis of  477 risk factors for  476–477 STIs and  476–477 treatment of  477 granuloma inguinale  473 granulosa cell tumours  580 grasp reflex  606–607, 607f Graves’ disease see autoimmune hyperthyroidism grief reaction  692 Group B streptococcus (GBS) antenatal investigations and  44 clinical features of  149 epidemiology of  149 neonatal infection with  660, 660t neonatal sequelae of  149 prevention of  149, 150f, 151b growth of boys  599f of dichorionic twins  114–115 of fetus  93, 94t, 114–115 of girls  600f of preterm newborns  688–689 growth discordance  115 growth restriction see fetal growth restriction; intrauterine growth restriction GTD see gestational trophoblastic disease Guthrie test  594–595 gynaecoid pelvic shape  9t gynaecological examination  355–357 consent to  355–357

707

Index

gynaecological examination (cont.) gynaecological anatomy and  356f screening in  357, 357t gynaecological history bowel and bladder and  355 contraception and  355 family history in  354 fertility and  355 introductions in  353–355 medical history in  354 medications and  354 menstrual history and  354–355 obstetric history and  354 pelvic pain and  355 presenting complaint and  354–355 previous  354 pruritus and  355 psychological history in  354 social history in  354 surgical history in  353–354 vaginal discharge and  355 gynaecological investigations  358b blood tests in  358 for common gynaecological presentations  359t endometrial sampling in  366 hysteroscopy in  366–368 imaging in  361–365 laparoscopy in  368–369 microbiological  358–360 ovarian cancer screening in  358 pelvic MRI in  364–365 pelvic ultrasound in  361–364 gynaecological pain  505–506 gynaecological presentations  354–355, 359t gynaecological problems, neonatal  372–373 gynaecology  372b

H haematogenous spread  514 haematological system development of  19 neonatal  675b preeclampsia and  132, 137 puerperium and  325 haematoma cephalhaematoma  266f, 608, 608f neonatal assessment and  608 paravaginal  308 periorbital  266f sub-aponeurotic  265 subgaleal  608, 608f vaginal  255–256 vulval  255–256, 255f, 308 haematometra  566 haemoglobin in antenatal investigations  43 embryonic  19 in newborn  675 sickle cell  165 haemoglobinopathies alpha-thalassaemia and  164–165 anaemia and  164–165 beta-thalassaemia and  164

708

classification of  164 management of  165–166 screening for  75–76 sickle cell haemoglobin and  165 haemolysis  677 haemolytic disease  180t, 181, 633 haemorrhage fetomaternal  24–25, 181 intracranial  193, 265, 641 intraventricular  683–685, 686f in newborn  678–679 scleral  610f see also antepartum haemorrhage; postpartum haemorrhage haemorrhagic disease of the newborn  625, 678 haemorrhoids  206–207, 333, 337 hair  374, 426, 604 hands  331f, 605–606, 657–659 Hashimoto’s disease see autoimmune hypothyroidism Hb electrophoresis  35 hCG see human chorionic gonadotrophin head aftercoming  125–126, 258–259 circumference of  598, 601f deflexion of  294–295 delivery of  236 diagnosis of position of  264f encephalocele and  608–609 entrapment of  126 extra-cranial swellings and haematomas and  608 fontanelles and sutures and  607–608 neonatal assessment of  607–609 shape and moulding of  607 size of  607 station of  229f headache clinical features of  207 management of  207 pathophysiology of  207 in pregnancy  193 secondary  193 tension  193 HEADS assessment  375–376 health behaviour  347, 375–376 health literacy  346 healthcare access  346–347 healthcare providers  349 hearing  609f heart auscultation of fetal  42, 232–233, 233f–234f beat  42 hypoplastic left  665–666 of newborn  585–586 see also auscultation of fetal heart heart disease  142, 663–666 heartburn see oesophageal reflux heavy menstrual bleeding  378 aetiology of  390 clinical features of  390–392 diagnosis of  390–392 history and examination and  390–391 investigations of  391–392 biopsy in  391–392 blood tests in  391

Index

hysteroscopy in  392 imaging in  391, 391f–392f treatment of  392–396 acute blood loss and  396 fibroids and  392–396 hormonal  392–395 non-hormonal  392 organic disorders and  392 surgical  395–396 see also menorrhagia HELLP syndrome  138 hepatitis  153t–154t management of  159 neonatal  634, 660–661 in pregnancy microbiological serology  35 hepatitis B  159, 595 hepatitis C  160, 328 hepatobiliary system  168–170 hepatomegaly  612 hermaphrodism  670f hernia  612, 649–650, 650f, 669 herpes genitalis  538 herpes gestationis  209, 211f herpes simplex virus (HSV)  153t–154t appearance of  470f diagnosis of  470 management of  158, 470 maternal infection with  158 neonatal  158, 601–604, 603f, 656–657 pregnancy and  158, 470 prevalence of  158 primary  470 recurrent  470 STIs and  469–470 suppression of  470 vulvar  469–470 heterosexuality  443 heterotopia  637t heterotopic pregnancy  62 hidradenitis suppurativa  539 high presenting part  85, 245, 247, 282 high station  259 high uterosacral vault suspension  490 hindgut  20 hips developmental dysplasia of  613–615, 614f, 663t–664t, 669 dislocation of  613–615 neonatal assessment of  613–615 Hirschsprung’s disease  667 hirsutism  425b acne vulgaris and  427, 427f androgen excess and  426–429 clinical assessment of  427 congenital adrenal hyperplasia in  426–427 diagnosis of  427–428 idiopathic  426, 428–429 investigations for  359t, 427–428, 428t management of  428–429 mild  428–429 pathogenesis of  426 PCOS and  426, 432 upper lip  426f virilisation and  427–428

histology  525, 552–553 HIV see human immunodeficiency virus holoprosencephaly  637t homebirth  230 homosexuality  443 hormone replacement therapy (HRT) adverse effects of  437 breast cancer in  437, 529 venous thromboembolism in  437 benefits of  436–437 bone loss prevention  436 cancer  437 cardiovascular disease  436–437 lipid profile  436–437 vasomotor symptom  436 contraindications to  435–436 decision equation for  436f menopause management with  436–438 non-hormonal alternatives to  438 postmenopausal bleeding and  396 regimen of  437–438 cyclic or continuous  437 oestrogen in  437 oral  437 progestogens in  437 raloxifene in  437 testosterone in  437–438 tibolone in  437 topical vaginal  437 transdermal  437 hormones  218t, 325, 443, 466 see also specific hormone hospital see admission; discharge, from hospital hot flush  435 HPV see human papilloma virus HRT see hormone replacement therapy HSV see herpes simplex virus human chorionic gonadotrophin (hCG)  11, 13, 19–21, 33, 66 human immunodeficiency virus (HIV)  153t–154t, 158–159 breastfeeding and  328 infants with  159 maternal infection with  158–159 maternal mortality from  343 neonatal infection with  661 in pregnancy microbiological serology  35 human papilloma virus (HPV) cervical cancer and  547–550, 551f, 561–562 cervical screening and  555 CIN screening and  361 genital warts and  471f prevention of  470–471 STIs and  470–471 testing for  361, 555 types of  551f vaccination for  361, 470–471, 547–550, 561–562 vulvar cancer and  542–544 vulvar intraepithelial neoplasia and  542–543 hydatidiform mole  65, 66t, 67f–68f hydrocephaly  664t, 666–667 hydrops fetalis  80, 80f, 677–678 hygiene  331f, 381–383, 657–659 hymen  3–4, 372–373, 540 hyperandrogenism  418, 425b

709

Index

hyperandrogenism (cont.) delayed menarche and  375 hirsutism and  426–429 in miscarriage aetiology  56 ovarian hyperthecosis and  427 pathogenesis of  426 PCOS and  429 hyperemesis gravidarum  52 aetiology of  52 assessment of  53 clinical features of  52 treatment of  53 hyperplacentosis  132 hyperplasia see congenital adrenal hyperplasia; endometrial hyperplasia; epithelial hyperplasia hyperprolactinaemia  414b aetiology of  419, 420t assessment of  419–420 clinical features of  419 management of  419–421 physiology and  419 hypertension chronic  131 classification of  130–131 gestational  131 induction of labour and  244b pregnancy-induced  115 hypoglycaemia  653, 682 hypogonadotrophic hypogonadism  415 hypomenorrhoea  379 hypoplastic left heart  665–666 hypospadias  614f, 663t–664t, 670 hypotension maternal  277, 278b with oxytocin infusion  248 supine  208 see also postural hypotension syndrome hypotensive maternal collapse  310–313 hypothalamus amenorrhoea and  416, 417t, 418–419 anovulation and  405–406 delayed puberty and  373–374 male factor infertility and  404 menstruation and  12f hypothermia  329–330, 638, 653 hypothyroidism  177t, 179, 595f hypotonia  639–640, 640f hypovolaemia  310–312 hypoxia  289–290, 586–587 see also respiratory hypoxia hypoxic ischaemic encephalopathy  637–639 hysterectomy caesarean section and  272 dysfunctional uterine bleeding treatment with  395–396 endometrial cancer treatment with  568 fibromyoma treatment with  565 invasive cervical cancer treatment with  559–560 ovarian tumour surgical management with  575–576 postpartum haemorrhage management with  304 hysteroscopy ambulatory  367–368 in gynaecological investigations  366–368 heavy menstrual bleeding and  392

710

indications for  366 instrumentation for  366–367 technique of  367

I ICSI see intracytoplasmic sperm injection idiopathic hirsutism  426, 428–429 iliac ligation  304 immature teratoma  582 immune system of fetus  176 of newborn  655 puerperium and  325 immune thrombocytopenic purpura (ITP)  166, 177–178, 177t, 679 immunisation see vaccinations impacted shoulders see shoulder dystocia imperforate anus  612–613, 613f, 668, 668f imperforate hymen  372–373, 540 Implanon  454 implantation  16 in vitro fertilisation (IVF)  411–412 inadequate progress in labour  289 amniotomy and  290 caesarean section and  269–270 first stage and  289 latent phase and  289 second stage and  289 see also prolonged labour incarceration of the uterus  171, 171f, 175, 564 incomplete miscarriage  58t, 59, 59f incontinence anorectal  254 from perineal tears  254 in puerperium  333, 337 stress  175 see also urinary incontinence incoordinate uterine action  285, 288f incubator  594, 631f, 645, 683 Indigenous newborns  652b Indigenous women alcohol consumption by  348 cardiovascular disease among  348 diabetes among  348 discrimination against  346 education, language and health literacy of  346 health of  345–346 barriers to healthcare access and  346–347 cultural concepts of  346 factors influencing  346–347 socioeconomic determinants of  347 healthcare providers and  349 infections among  348–349 nutrition for  347 obesity and underweight among  347 pregnancy of  345–349 reproductive health of  345b smoking by  348 social and emotional wellbeing of  347–348 indomethacin  101 induction of labour assessment prior to  245 caesarean section and  244 contraindications to  244–245

Index

fetal risk tolerance and  244 fetal wellbeing assessment and  245 gestational age assessment and  244 incidence of  243 indications for  243–244, 244b postdates pregnancy and  109 risk-benefit equation with  243–244, 243b suitability for  244 techniques for  245–248 artificial rupture of the membranes in  247 cervical ripening  245–246 oxytocin infusion in  247–248 prostaglandins in  246–248 transcervical balloon catheter in  247 inevitable miscarriage  58t, 59 infant see newborn infantile haemangioma  604–605 infections with artificial rupture of the membranes  247 bacterial  145–149 caesarean section complications and  273 with episiotomy  253 examination for  336 among Indigenous women  348–349 monitoring and treatment for  337b mycoplasmal  149–150 neonatal death from  655b prevention of  330 protozoal  152, 153t–154t, 160–161 in puerperium  333, 336, 337b reproductive tract  145–147 respiratory tract  205 Staphylococcus  658 with transcervical balloon catheter  247 transplacental  147–149 tubal  407 ureaplasmal  149–150 viral  152, 153t–154t vulvovaginal disorders and  540–542 wound  336 see also breast infection; chlamydial infection; fetal infection; genital tract infection; maternal infection; neonatal infection; sexually transmitted infection; urinary tract infection; vaginal infection infectious vaginitis  359–360 infertility  401 aetiology of  401–402, 402f causes of  404–412 anovulation and  405–406 cervical mucus quality and  410 male factor infertility in  404–405 multifactorial  411 oocyte quality and  410 sexual intercourse in  408 tubal factors in  406–408 uterine factors in  409–410 endometriosis and  408, 516 evaluation of  402–404, 402t–403t induction of labour and  244b procedures for COH  411 complications with  412 GIFT  411

ICSI  411–412 IUI  411 IVF  411–412 oocyte freezing  412 ovarian tissue freezing  412 ZIFT  411 termination of pregnancy and  464 unexplained  401b, 410–411 see also male factor infertility inflammatory breast cancer  533f influenza  153t–154t, 161, 336 infundibulation  344 infundibulopelvic ligament  7 inguinal hernia  612 inheritance patterns  664b inherited anomalies of coagulation factors  167 inhibited ejaculation  446 injectable gonadotrophin therapy  422–423 insomnia in pregnancy  211–212 instrumental delivery  250, 253 adverse effects of  265–266 fetal  265–266 intracranial haemorrhage as  265 maternal  265 shoulder dystocia as  265–266 skull fracture as  265 soft tissue injury as  265 sub-aponeurotic haematoma as  265 vaginal, cervical and perineal tears as  265 consent to  261 failed  264–265 forceps and  260–261, 260f incidence of  258 indications for  258–259 aftercoming head and  258–259 bearing down and  258 fetal compromise and  258 prolonged second stage of labour in  258 instrument choice in  257–258, 258t non-vertex presentations and  264 procedure of  261–265 mid-cavity forceps delivery  261–263 outlet and low forceps delivery  261 prerequisites to  261 technique in  261–264, 262f–263f vacuum birth  264 station prior to  259 trial of  264 vacuum extraction device and  261 insulin  188–189 intellectual disability gestational age and  688t menstrual management with  375, 383 in preterm newborns  687–688, 688t intensive care nursery  684f intermittent positive pressure ventilation (IPPV)  646 internal genitalia (female)  4–7, 6f internal iliac ligation  304 internal pudendal vessels  10 internal rotation  223 internal sphincter  254 International Federation of Gynecology and Obstetrics (FIGO)  558

711

Index

interstitial pregnancy  62 intervillous space  21 intracranial haemorrhage  193, 265, 641 intracytoplasmic sperm injection (ICSI)  411–412 intrapartum care  101, 193b intrapartum fetal compromise see fetal compromise intrauterine adhesions  409–410 intrauterine contraceptive device (IUD)  454–455, 455f copper  455 contraindications to  455 emergency contraception with  461 failure rate of  453t see also levonorgestrel intrauterine system intrauterine growth restriction (IUGR)  651–653 dichorionic twins and  115 monochorionic twins and  117 preeclampsia and  135f intrauterine insemination (IUI)  411 intrauterine pregnancy  55 intrauterine resuscitation  280 intravascular volume  136–137 intravenous fentanyl  316 intravenous infusion  271 intravenous nutrition  625 intraventricular haemorrhage  683–685, 686f introital tears  308 involution  323, 523–524 iodine  36, 48 iodine deficiency  48 IPPV see intermittent positive pressure ventilation iron deficiency of anaemia and  164 assessment of  165 diagnosis of  164 incidence of  164 physiology of  164 predisposing factors  164 treatment of  165 pregnancy and  36, 47–48 supplementation with  47–48, 392 ischial spine  229f isoantibody  176 isoimmunisation  176 ITP see immune thrombocytopenic purpura IUD see intrauterine contraceptive device IUGR see intrauterine growth restriction IUI see intrauterine insemination IVF see in vitro fertilisation

J jaundice  169–170 breast milk  634 causes of  169b obstructive  634 in preterm newborn  682 see also neonatal jaundice Johnson, Virginia  442–443 jugular venous pressure  312

K kangaroo care see skin-to-skin contact kernicterus  634–635

712

kidneys cystic  664t development of  19 of fetus  586 preeclampsia and  132, 137 Kielland forceps  260f Klumpke  641t knots see true knots

L labia majora  3 labia minora  3 labial fusion  542 labour  216b with breech presentation  124–126 cardiac disorders and  143 complications with  227 diagnosis of  226b epilepsy and  192 first stage of  221 active phase  221 deflexed vertex presentation and  297 latent phase  221, 221f, 289 maternal assessment in  231 with genetic or structural abnormalities  81 initiation of  217–220 amniotic and chorionic membranes and  217–219 cervix and  217–219, 218f ligaments and  219 myometrium and  217–219 perineum and  219 positive feedback loops in  217 uterus and  217, 218t, 219, 220f vagina and  219 multiple sclerosis and  192 onset of  219 pain of  315–316 second stage of  221–225 bearing-down reflex in  224 deflexed vertex presentation and  297 duration of  224 fetal compromise in  224 instrumental delivery indications and  258 normal birth mechanisms and  221–224, 222f pelvic floor tissue damage in  224–225 perineal tears and  253 recognition of  235–236 secondary powers in  224 spurious  227 stages of  220–225 third stage of  225 true  227 with twins  117–118 uterine contractions in cervical dilation and  220 pain of  219–220 strength, duration and frequency of  219 see also augmentation of labour; induction of labour; obstructed labour; parturition; preterm labour; prolonged labour; trial of labour after caesarean section labour analgesia see analgesia labour assessment  226b abdominal station and  231

Index

cardiotocograph in  229–230 clinical  227–230 examination in  227–229, 228f–229f fetal membranes and  232 fetal wellbeing and  227 gestational age and  227 history in  227 investigations in  229–230 issues in  227 uterine contractions and  231 vaginal examination and  231–232 labour management fetal growth restriction and  94–95 fetal wellbeing assessment in  232–233 first stage  226b, 230–235 alternative birthing centres and  230 antibiotics in  235 bladder and bowels in  235 caregivers in  230–231 homebirth and  230 hospital admission and  230 location and  230 maternal assessment in  231 nutrition and fluid intake in  235 obstetricians and midwives in  230 partner, family and friends in  230–231 psychological support in  231 unregulated birth attendants in  230 second stage  235–237 third stage  226b, 237–241 active  238–240 clamping of cord in  237–238 cord blood and  238 delivery of placenta and membranes in  239–240 oxytocin administration in  238 passive  240 placental separation and descent and  238 uterine contractions and  238 lactation breast infection and  527 failure of  326–327 nutrition and  325 physiology of  325–328, 618–619 prolactin and  523–524 relactation and  623–624 suppression of  623 lactation consultant  327b lactational amenorrhoea  462 lactogenesis II  338 lamotrigine  192 language  346 lanugo  598, 681 laparoscopy applications of  369 consent to  369 endometriosis investigation with  516 in gynaecological investigations  368–369 instrumentation for  368 pelvic pain and  511, 511t pelvis viewed by  369f port site placement in  369f recovery from  369 technique of  368–369

large for gestational age  651, 653–654 laryngeal airway mask  588 laser ablation  557 last normal menstrual period  33 late pregnancy  204–205, 216–220 lateral palpation  41 laxatives  204 LBC see liquid-based cytology LeFort colpocleisis  490 legs  125, 205f, 510 leiomyoma  365f, 547, 564f leiomyosarcoma  564 Leopold’s manoeuvres  41–42 lesbians  443 let-down reflex  620 leucomalacia  683–685 leucoplakia  536–537 leucorrhoea  210 levator ani  10 levator plate  484 levonorgestrel emergency contraception  461 levonorgestrel intrauterine system  394–395, 395f, 455 endometriosis management with  518t failure rate of  453t fibromyoma treatment with  565 libido  381 lice, pubic  473 lichen planus  537–538, 538f lichen sclerosus  536–537, 537f lichen simplex chronicus  537, 538f lie see oblique lie; transverse lie ligaments broad  7 infundibulopelvic  7 pelvic  10 round  7, 204 limb reduction defects  664t lipid profile  435–437 lips  609 liquid-based cytology (LBC) in cervical intraepithelial neoplasia screening  361 Pap smear compared to  364f, 554f technique for  363f lissencephaly  637t Listeria monocytogenes  148 listeriosis  36, 48, 48b, 148 lithium carbonate  200t lithotomy position  236 liver development of  20 preeclampsia and  132, 134f, 137 see also acute fatty liver of pregnancy liver bud  20 locally advanced  532–533 lochia  323, 333 loop excision of cervix  557 loss of consciousness aetiology of  313–314 clinical features of  314 management of  314 neurological causes of  313–314 Lövset’s manoeuvre  125f low forceps delivery  261

713

Index

low station  259 lower genital tract infection  466b lower uterine segment  6 breech presentation and  123 descent and  221–223 fibromyoma in  286 junction of  217f placenta in  121 placenta praevia and  86, 88, 305 thinning of  246, 287 transcervical balloon catheter and  247 lower uterine segment caesarean section (LUSCS)  268, 268f lumbar puncture  659 lumbosacral joint  9–10 lung aeration of  644 air in  585–586 blood flow in  644 fluid in  585–586, 643–644 gas exchange in  644 morphology of  643–644 of newborn  585–586 physiology of  643–644 structure of  644f see also chronic lung disease lung bypass  584–585 lung surfactants  644, 647–648, 687 LUSCS see lower uterine segment caesarean section luteal phase, of menstrual cycle  10–11, 380f luteinised unruptured follicle syndrome  406 luteinising hormone  416–418 luteinising hormone releasing agonists  531 lymph nodes  524, 524f, 529–530 lymphadenectomy  559–560 lymphadenopathy  524 lymphatic spread  514 lymphocytes  676 lymphogranuloma venereum  472

M macroadenoma  420–421, 421f macrosomia  108, 108t magnesium hydroxide  204 magnesium sulphate  87, 101 magnetic resonance imaging (MRI)  364–365, 487, 525 malaria  153t–154t, 160–161 male factor infertility hypothalamo-pituitary dysfunction and  404 obstructive disorders and  404–405 semen analysis and  404–405 testicular function and  404 male sexual problems see sexual dysfunction male sterilisation  453t, 462 malformation  662–663 see also congenital abnormalities malformation sequence  663 malignant disorders of uterine body  566–568 malnutrition  473, 651, 652t, 653 malposition  294b malpresentation  253–254, 270, 294b see also breech presentation mammary gland see breast mammary Paget disease see Paget’s disease of the breast

714

mammography  524–525, 525f, 532 Manchester repair  488–490 manipulative delivery  250 mastalgia  527 mastectomy  530, 531f Masters, William  442–443 mastitis  336, 338, 621 maternal age  29–30, 267–268 maternal antibodies  677–678 maternal circulation  22–24 maternal collapse  310 aetiology of  310 classification of  311b diagnosis of  311f hypotensive  310–313 maternal fetal medicine subspecialist  38 maternal hypotension  277, 278b maternal infection with HIV  158–159 with HSV  158 with rubella  156 with toxoplasmosis  160 with varicella  157 maternal mortality  287 from cervical cancer  343–344 contraception and  343 global public health and  341–342 from HIV  343 obstructed labour and  287, 340b prevention of  341–342 prolonged labour and  340b rate of  340b, 341, 341f from termination of pregnancy  342–343 from vesicovaginal fistula  342 maternal oxygenation  277 maternal serum screening  71–74 maternal support  40 maternal trauma  292 maternal vascular disease  132 maternal weight  40–41 maternity blues  197–198 mature teratoma  581 Mauriceau–Smellie–Veit technique  126f maximum urethral closure pressure  498–499 McCall culdoplasty  490 McRobert’s position  292 measles  153t–154t, 158 meconium  649 meconium aspiration syndrome  649 investigations of  649 outcomes of  649 resuscitation and  649 treatment of  649 meconium ileus  667 meconium staining  281–282 meconium-stained liquor  649 medical eligibility criteria  452, 453t medical history  34, 354 medical termination of pregnancy (MTOP)  463–464 medico-legal issues  586 mediolateral episiotomy  250 meiosis  11–12, 16 melanocytic naevus  604–605, 605f

Index

membranes, amniotic and chorionic delivery of  239–240, 239f labour initiation and  217–219 see also artificial rupture of the membranes; prelabour rupture of the membranes; premature rupture of the membranes memory  315 men  402–404 menarche  378 delayed  374–375 androgen excess and  375 atypical pubertal development with  374–375 normal pubertal development with  374 pubic hair and  374 early  373 post-  375–376 meningitis  660 meningomyelocele see spina bifida menopause  13, 434 assessment of  435–436 average age of  434b hormone replacement therapy for  436–438 management of  435–438 physiology and  434–435 see also climacteric; premature menopause menorrhagia  379f in adolescence  375 fibromyomas and  564 investigations for  359t menstrual cup  381–383, 383f menstrual cycle  10–13 breast physiology and  523–524 duration of  379f follicular phase of  10, 380f hormonal changes during  11f luteal phase of  10–11, 380f menstrual phase of  11 normal  377b–378b ovulation  10 problems with  377b–378b, 378 uterine contractions in  381 menstrual history  354–355 menstrual hygiene  381–383 menstrual pad  381–383, 382f menstrual phase  11 menstruation  378–379 adolescent problems with  375 average blood loss during  379 climacteric and  435 cultural attitudes to  383 duration of  378–379 endocrine control of  415f features associated with  381 hypothalamic-pituitary-ovarian-uterine interrelationships in  12f intellectual disability and  375, 383 normal  379f process of  379–381, 380f see also heavy menstrual bleeding mental illness  196 identification and assessment of  197 induction of labour and  244b management of  198–200 electroconvulsive therapy in  199–200

pharmacological  199 psychological therapies in  199 mentoposterior position  301f mercury  48 mesodermal layer  18–19 metabolic syndrome  432 metabolism bilirubin  628–629, 629f of newborn  586 prostaglandin  386f puerperium and  325 metastatic breast cancer  533 metformin  422 methotrexate  63 metronidazole  146, 473, 475, 479 metrorrhagia  379f microadenoma  421f microarray  75 microbiological gynaecological investigations  358–360 microcephaly  664t, 666–667 micromastia  522–523 micronutrients  619 microscopy  469 micturition  493 mid-cavity delivery  261–263 mid-cavity station  259 midgut  20 midline episiotomy  250 mid-pelvic plane  9 midstream urine for microscopy, culture and sensitivities (MSU MCS)  35 mid-urethral sling (MUS)  502,  503f midwife  38, 230 mifepristone (RU486)  464 migraines  193, 381 milia  601, 603f military position see deflexed vertex presentation milk see breast milk; cow’s milk milk of magnesia  204 Millennium Development Goals  340b, 341 Mirena  455 miscarriage  55–60 aetiology of  56–57 from amniocentesis  70b anti-D and  58 assessment of  57 bleeding and  57 classification of  57, 58t clinical features of  57 complete  58–59, 58t incomplete  58t, 59, 59f inevitable  58t, 59 management of  57–58, 60, 60t missed  58t, 59–60 pain and  57 passage of products of conception and  57 pregnancy symptoms and  57 recurrent  57, 60–61, 359t resuscitation and  58 second-trimester  60 septic  60 threatened  58, 58t misoprostol  238, 246, 463–464

715

Index

missed miscarriage  58t, 59–60 mitosis  11–12 Mongolian spot  604–605 monochorionic twins see twins monocytes  676 mons pubis  2 mood, abnormal  333 mood stabilisers  200t Moro reflex  606–607, 607f motherhood  329, 331 mothers assessment of  231 breastfeeding benefits to  327b breastfeeding problems of  621–622 caesarean section preference in  269–270 influenza and  336 instrumental delivery adverse effects on  265 neonatal thrombocytopenia and  679 observation of  330, 332f prolonged labour complications and  289 seronegative  155, 155b motor vehicle accidents  171, 172f, 307 moulding  227, 607 mouth  609–610 movement limitation  598 MRI see magnetic resonance imaging MSU MCS see midstream urine for microscopy, culture and sensitivities MTOP see medical termination of pregnancy mucinous ovarian tumours  575 mucus  410, 461 mucus plug  220f Müllerian system anomalies of  409 congenital disorders of  170 epithelial ovarian tumours and  574 multichannel urodynamics  498 multidisciplinary care  38 multifactorial inheritance  664b multiple pregnancy  111 caesarean section indications and  270 comparative risk of  116t high-order  118–119 induction of labour and  244b placental abruption and  89 see also twins multiple sclerosis  191–192 multivitamin supplementation  36 MUS see mid-urethral sling muscle cramps  208–209 muscles bulbocavernosus  5f pelvic diaphragm  223f pelvic floor  324, 485f perineal  5f, 253 see also uterine muscle myasthenia gravis  177t, 179, 194 Mycoplasma genitalium  477–478 mycoplasmal infection  149–150 myelination  637 myeloid cells  676 myelomeningocele  77, 77f myocarditis  312–313

716

myomectomy  172, 565 myometrial hypertrophy  323 myometrium  217–219 myotonic dystrophy  194

N nabothian cysts  546, 546f nabothian follicles  5–6 Naegele’s rule  33 naevus flammeus  604–605 naevus simplex  604f NAIT see neonatal alloimmune thrombocytopenia nasal continuous positive airway pressure (nCPAP)  645–646, 645f, 648 National Cervical Screening Program (NCSP)  553, 555f nausea and vomiting of pregnancy  52 adjuvant therapies for  53 aetiology of  52 assessment of  53 clinical features of  52 treatment of  53 nCPAP see nasal continuous positive airway pressure NCSP see National Cervical Screening Program neck cord around  236 fistulas of  610 masses of  610 neonatal assessment of  610–612 sternomastoid tumours and  610–612 neck extension  300f necrotising enterocolitis  624, 685, 687f Neisseria gonorrhoea  360, 476–477 neonatal abstinence syndrome  641–642 neonatal alloimmune neutropenia  184 neonatal alloimmune thrombocytopenia (NAIT)  184, 679 neonatal assessment  616 of abdomen  612 achondroplasia and  606, 606f of arms  606–607 arthrogryposis and  606 of breasts  612 of cardiovascular system  606, 612 of chest wall  612 of clitoris and vagina  612–613 of ears  609 encephalocele and  608–609 of eyes  609 of face  609–610 of feet  615 general observations in  598–605 of genitalia and anus  612–613 of grasp and Moro reflexes  606–607, 607f haematoma and  608 of hands  605–606 of head  607–609 hepatomegaly and  612 of hips  613–615 inguinal hernia and  612 of lips  609 measurement in  598, 599f–601f of mouth  609–610 of neck  610–612

Index

of nipples  612 of nose  610 of penis and scrotum  613 physical examination in  597–615 of respiration  612 of skin  610 splenomegaly and  612 of thorax  612 of umbilical cord  612 neonatal care  592 bathing and  593 behaviour and sleep and  594 bonding and  594–596 domicile and  594 family and siblings and  595–596 general  592–594 for preterm newborn  688–689 routine  592b skin-to-skin contact in  593f, 594 structural abnormalities and  81 thermal environment and  594 umbilical cord and  593 urine and stools and  593 vaccinations in  595 weighing and  594 neonatal cholestasis  634 neonatal death  597b from anti-Ro and anti-La syndromes  180 bipolar disorder and schizophrenia and  198 birth weight and  95f, 680b from infections  655b from malaria  160–161 from preterm birth  688f neonatal feeding and nutrition  617b, 625–626 neonatal gynaecological problems  372–373 neonatal haematology  675b neonatal heel-prick screening  594–595, 595b, 595f neonatal infection antenatally acquired  655–657 candidiasis  657, 658f conjunctivitis  657–658 cytomegalovirus  656 in developing world  661 Group B streptococcus  660, 660t hepatitis  634, 660–661 HIV/AIDS  661 HSV  158, 601–604, 603f, 656–657 meningitis  660 in neonatal intensive care units  661 omphalitis  658 osteomyelitis  660 perinatally acquired  657–659 pneumonia  660 rubella  157, 656 septic arthritis  660 of skin  658 superficial  657–658 syphilis  657 systemic  658–659 toxoplasmosis  656, 656f varicella  158 neonatal intensive care units  661 neonatal jaundice  628b

causes of  629–631, 630b early presentation of  630 investigations of  629–630 prolonged  630 treatment of  631–633 exchange transfusion  633 phototherapy  631–633, 631f–632f neonatal labial fusion  542 neonatal pustular melanosis  604f neonatal respiratory depression Apgar score and  590–591, 590t causes of  586b hypoxia and  586–587 small for gestational age and  653 neonatal resuscitation  584b, 586–591 adrenaline in  590 algorithm  587, 588f assisted ventilation in  588–589 cessation of  591, 591b chest compression in  590 equipment for  589f oxygen concentration with  589–590 prematurity and  591, 591b procedure of  587–591 response to  591 training for  591b neonatal seizures see seizures neonatal sepsis  658–659 neonatal tetanus  634f neonatal thrombocytopenia  679 neonatal vaginal bleeding  373 NeoPuff device  588f nerve palsies  640–641 nerves of bladder  506t of breast  522 of cervix  506t of fallopian tubes  506t of genitalia  506, 506t, 508f of ovaries  506t pain and  505–506 of pelvis  506, 506t, 507f pudendal  10, 324 of rectum  506t of uterus  506t of vagina  506t of vulva  506t nervous system central  664t, 666–667 development of  16–17 pain and  506 neural tube defects  666 neuraxial blockade  317 neuro-anatomical abnormalities  637t neurodevelopmental outcomes  687–688 neurogenic shock  312–313 neuroimaging  194 neurological conditions  191b, 636b, 637–642, 681–682 neuromodulation  502 neuronal differentiation  637 neuronal migration  636–637 neuronal proliferation  636 neuropathies  194, 207

717

Index

neutropenia  676 see also neonatal alloimmune neutropenia newborn alertness of  586 behaviour of  586, 594 bladder function in  493 blood volume in  676 breastfeeding benefits to  327b breastfeeding difficulties of  622–623 cardiopulmonary system of  585–586 close physical contact with  329 colour of  598 constipation in  626 dysmorphic features of  598 floppy  639–640, 640f fluid requirements of  683t growth charts for  599f–600f haemoglobin value in  675 haemolytic disease of  180t, 633 haemorrhage in  678–679 haemorrhagic disease of  625, 678 hair of  604 head circumference of  598, 601f hearing of  609f heart of  585–586 immune system of  655 Indigenous  652b length of  598, 601f lungs of  585–586 metabolism of  586 movement limitation of  598 respiratory rate of  598 skin of  598–605 sleep of  594, 622–623 suck of  326 transient tachypnoea of  649 vomiting in  625–626 weight of  594, 598, 626 see also preterm newborn nifedipine  100 nipple accessory  522–523 anatomy of  521 cracked  622 flat or inverted  622 neonatal assessment of  612 sensitivity of  338 sore  622 nipple discharge  527 nitric oxide  101 nitrous oxide  316 nocturia  211 non-enteral feeding  625 non-gestational choriocarcinoma  582 non-steroidal anti-inflammatory drugs (NSAIDs) dysfunctional uterine bleeding treatment with  392 dysmenorrhoea treatment with  385 endometriosis management with  518t fibromyoma treatment with  565 patent ductus arteriosus treatment with  687 non-vertex presentation  264 Norwegian scabies  473 nose  610

718

NSAIDs see non-steroidal anti-inflammatory drugs nuchal translucency screening  73, 73f nulliparity  254 nutrition in first-stage labour management  235 for Indigenous women  347 intravenous  625 lactation and  325 neonatal  617b, 625–626 pregnancy and  36 puerperium and  325

O obesity caesarean section incidence and  267–268 among Indigenous women  347 PCOS and  431–432 postdates pregnancy and  107 prevalence of  49 oblique lie  127–128 aetiology of  128 caesarean section with  128 diagnosis of  127 external cephalic version with  128 management of  128 predisposing factors  127 obstetric forceps see forceps obstetric history  354 obstetrician  38, 230 obstructed labour caesarean section and  269 cephalopelvic disproportion and  286–288 consequences of  286–287 fetal death in  286 genital tract fistula in  286 sepsis in  286 maternal mortality and  287, 340b signs of  287–288, 288b uterine rupture and  287, 307 vesicovaginal fistula and  342 obstructive disorders  404–405, 663t–664t obstructive jaundice  634 occipital lobe  132–133, 134f occipitoposterior position  295–297, 297f–298f occipitotransverse position  297 occiput  72f, 222f, 236, 294b, 301f OCP see oral contraceptive pill oedema gross pitting  207f management of  207 pathophysiology of  207 vulvar  540 oesophageal reflux  53, 203–204, 625–626 oesophagus  668 oestradiol  426 oestradiol valerate  456 oestrogen anti-oestrogens and  422 bone loss and  435 as breast cancer risk factor  529 breastfeeding and  323 candidiasis and  540–541 in hormone replacement therapy regimen  437

Index

topical vaginal  437 unopposed  568b oestrogen efficacy  217 oligohydramnios  41b, 108t omphalitis  658 omphalocele  669 oocyte  15f, 16, 410, 412 oophorectomy  389, 531 see also salpingo-oophorectomy operculum see mucus plug ophthalmia  657–658 ophthalmological assessment  683 opisthotonus  634, 634f oral combined hormonal contraception advantages of  456 contraindications to  456 disadvantages of  456 medications  457t side effects of  456 types of  456 oral contraceptive pill (OCP) dysfunctional uterine bleeding treatment with  395 dysmenorrhoea treatment with  385–386 endometriosis management with  518t failure rate of  453t fibromyoma treatment with  565 hirsutism treatment with  428–429 PCOS treatment with  432 PMS and PMDD treatment with  389 orgasm  446 osteogenesis imperfecta  673, 673f osteomyelitis  660 osteoporosis  438 outlet forceps delivery  261 outlet station  259 ovarian cancer abdominal distension and  573f incidence and characteristics of  578–579 management of  579 pathology of  578–579 presentation of  578 protective factors for  578 risk factors for  578 risk-reducing bilateral salpingo-oophorectomy for  579 screening for  358, 578 ovarian cystadenoma  576 ovarian cystectomy  575 ovarian cysts  172–173 antenatal  372 clinical features of  173 dermoid  581 functional  573–574 history and  572–573 management of  173 pelvic pain and  376 ovarian dermoids  581 ovarian endometrioma  577 ovarian follicles  434–435 ovarian hyperthecosis  427 ovarian tissue freezing  412 ovarian torsion  376, 574 ovarian tumours  172–173 antenatal  372

benign  574–577 borderline  574–578, 576b clear cell  575 clinical features of  173 endometrioid  575 epithelial  574–579 germ cell  580–582 history and  572–573 imaging for  573 malignant  574–576, 576b management of  173, 575–576 markers of  359t, 573 mucinous  575 pelvic pain and  376 presentation of  572 serous  575 staging of  576b ovaries  7 amenorrhoea and  416–419, 417t anovulation and  406 delayed puberty and  374 dysfunction of  406 failure of  416–419, 417t innervation of  506t pathology of  572, 572b diagnosis of  572–573 examination of  573 history and  572–573 presentation of  572 veins of  217f see also polycystic ovarian syndrome overflow incontinence  496 overweight  49, 431–432 ovulation  10, 380f body temperature and  405f hypothalamic-pituitary-ovarian-uterine interrelationships in  12f PCOS and  429 see also anovulation ovulation induction  414b, 421–423 injectable gonadotrophin therapy for  422–423 oral agents for  422 anti-oestrogen  422 bromocriptine  422 clomiphene citrate  422 letrozole  422 metformin  422 tamoxifen  422 surgical approach to  423 ovum  14, 15f, 57 oxygen  277, 584–585, 589–590 oxygen therapy  646, 648, 683 oxytocin administration of  238, 245 breastfeeding and  325–326 infusion of adverse effects of  247–248 excessive uterine muscular activity with  247–248 hypotension with  248 induction of labour with  247–248 postpartum haemorrhage with  248 regimen for  247 water intoxication with  248 oxytocin receptor antagonists  101

719

Index

P pachygyria  637t paclitaxel  579 paediatric and adolescent gynaecology  372b paediatric candidiasis  542 paediatric pruritus vulvae  542 paediatric vaginal discharge  542 paediatric vulvovaginal disorders  542 Paget’s disease of the breast  528, 528f pain in breast  521b, 527 characteristics of  506–507 function of  506 gynaecological  505–506 labour  315–316 miscarriage and  57 nerve pathways of  505–506 nervous system response to  506 physiology of  505–506 round ligament  204 sacroiliac  208 sexual intercourse  446–447 somatic  506–507 uterine contraction  219–220 visceral  506–507 vulvar  538–539, 539b see also abdominal pain; pelvic pain painful coitus see dyspareunia palpation  41–42, 42f pancreas  20 Pap smear see Papanicolaou smear Papanicolaou smear (Pap smear)  357, 357t liquid-based cytology compared to  364f, 554f in prepregnancy consultation  30 recommendations for  553 sampling devices for  361f slide preparation for  361 technique for  362f papillomas  547 paracolpos  483–484 parametrium  7 paraphilias  447 parathyroid glands  20 paraurethral ducts  3 paravaginal haematoma  308 parents  673–674, 692 parity caesarean section and  269 high  127 nulliparity  254 uterovaginal prolapse in pregnancy and  171 partners  230–231, 244b parturition  216b parvovirus  153t–154t Patau syndrome  71, 72f, 664t patent ductus arteriosus  686–687 patient controlled epidural analgesia (PCEA)  317 Pawlik’s grip  41–42, 42f PCEA see patient controlled epidural analgesia PCOS see polycystic ovarian syndrome Pearl index  452–453 pelvic brim  8f pelvic cavity  9, 507f

720

pelvic diaphragm  5, 223f pelvic diaphragm muscles  223f pelvic examination in gynaecological examination  355–357 pelvic inflammatory disease and  478 pelvic organ prolapse and  485–486 pelvic pain and  510 urinary incontinence evaluation and  498 pelvic floor  224–225, 324, 485f, 501 pelvic inclination  9 pelvic inflammatory disease (PID) aetiology of  478–480 diagnosis of  478–479 examination and  478 history and  478 investigations of  478 management of  479–480 post-abortal  480 tuberculosis  480 pelvic inlet  8f, 9 pelvic joints  9–10 pelvic ligaments  10 pelvic lymphadenectomy  559–560 pelvic mass decision algorithm for  570f differential diagnosis of  568–569 fibromyomas and  564 origins of  569t pelvic ultrasound and  569 in young women  571 pelvic MRI  364–365 pelvic organ prolapse aetiology of  485 anatomy and  483–484 apex  483 levator plate  484 paracolpos  483–484 perineal body  484 anterior compartment  486f apical compartment  486f classification of  486 clinical presentation of  485–490 evaluation of  487 management of  486–487 conservative  488 surgical  488–490 vaginal pessaries for  488 physical examination of  485–486 POP-Q terminology and  486–487 posterior compartment  487f predisposing factors for  485b severity of  487 Pelvic Organ Prolapse Quantification System (POP-Q)  486–487, 487f pelvic organs  3f pelvic outlet  8f, 9 pelvic pain  505b acute  509b adolescent  376 chronic  508t, 511t clinical aspects of  507–511 differential diagnosis of  508t, 509b examination for  510

Index

gynaecological history and  355 history and  507–510, 510b investigations for  510–511 laparoscopy and  511, 511t management of  511 mechanisms of  507b ovarian cysts and tumours and  376 ovarian torsion and  376, 574 pelvic reconstructive surgery  488–490 pelvic soft tissue  10 pelvic ultrasound  361–364 heavy menstrual bleeding and  391, 391f–392f in hirsutism investigation  427–428, 428t pelvic mass and  569 pelvic organ prolapse evaluation with  487 postmenopausal bleeding assessment with  398 pelvic viscera  506, 506t pelvis  7–10 dystocia and  286 frozen  509f laparoscopic view of  369f measurements of  9t nerves of  506, 506t, 507f renal, obstructive defects of  663t–664t sagittal view of  9f shapes of  9t support for  483–484 penicillin  472 penis  613 perimenopause see climacteric perinatal mortality fetal compromise and  279 gestational age and  107t TOLAC and  274 perinatal period  197–198, 199b, 338, 657–659 perineal body  484 perineal membrane  492–493 perineal muscles  5f, 253 perineal pad  227 perineal tears classification of  253, 253t complications with  254 episiotomy and  249 instrumental delivery and  265 postpartum haemorrhage and  308 predisposing factors to  253–254 inelastic perineum as  254 large presenting part as  253–254 rapid second stage of labour as  253 repair and management of  254 scarring from  254 perineum  4 examination of  510 inelastic  254 labour initiation and  219 post-birth inspection of  241 support for  484f period  33, 354–355 periorbital haematoma  266f peripartum cardiomyopathy  143 peripheral neuropathies  194 peritoneal factors  408f periventricular leucomalacia  683–685

permethrin  473 pertussis  161 pessary  489f cervical insufficiency management with  103, 105f pelvic organ prolapse management with  488 prostaglandin E2 slow-release  246 petechiae  598–601, 602f Pfannenstiel incision  271–272, 271f pH, vaginal  466–467, 469 phenobarbital  192 phenylketonuria  594–595 phenytoin  192 phototherapy  631–633, 631f–632f physiological changes in pregnancy cardiac disorders  141 respiratory disease  144 urinary system  173–174 see also puerperium physiological hydronephrosis of pregnancy  173, 173f physiology of anaemia  163 of breast  523–524 of breastfeeding  325–328, 523–524 diabetes mellitus and  186 of genital tract  466–467 genital tract infection and  466–467 hyperprolactinaemia and  419 of iron deficiency  164 of lung  643–644 menopause and  434–435 of pain  505–506 pulmonary  643–644 see also lactation physiotherapy  324, 337, 501 PID see pelvic inflammatory disease PIEB see programmed intermittent epidural bolus pituitary amenorrhoea and  416, 417t anovulation and  406 delayed puberty and  373–374 male factor infertility and  404 menstruation and  12f pituitary apoplexy of Sheehan  326–327 placenta  20–25 at 8 weeks’ gestation  22f antibodies crossing  176 blood volume in  676 circumvallate  241f delivery of  239–240, 239f development of  20–22 fundal expression of  240 incomplete  240 inspection of  240, 240f in lower uterine segment  121 manual removal of  309, 309f oxygen diffusion in  584–585 preeclampsia and  133–134, 133f retained  308–309 separation and descent  238 structure of  22–25 fetal placental units and  22 placental calcification and  25 at term  23f–24f

721

Index

placenta accreta  88 caesarean section and  269, 273–274, 274t clinical presentation of  306 management of  306 pathology of  305 postpartum haemorrhage and  305–306 predisposing factors of  306 placenta membranacea  241f placenta praevia  86–88, 87f asymptomatic  87 caesarean section and  88, 274, 274t clinical features of  86–87 degrees of grades of  86f diagnosis of  87 management of  87–88 postpartum haemorrhage and  305 predisposing factors  86 symptomatic  87–88 placental abruption  88–90 classification of  89 clinical features of  89 fetal compromise and  278 incidence of  88 management of  89–90 predisposing factors  88–89 multiple pregnancy and  89 placental bed ischaemia and  88–89 polyhydramnios and  89 uterine trauma and  89 placental bed  323 placental bed ischaemia  88–89 placental calcification  25 placental circulation  585–586 placental insufficiency diagnosis of  40 fetal compromise and  278 induction of labour and  244b postdates pregnancy and  107–108, 108t placentation  112f, 131 plantar creases  681 plasma cell vulvitis  538 plasma volume  163 platelets  676, 679 platinum-based chemotherapy  560 platypelloid pelvic shape  9t PMB see postmenopausal bleeding PMC see pontine micturition centre PMDD see premenstrual dysphoric disorder PMS see premenstrual syndrome pneumonia  646–647, 660 pneumothorax  646–649, 647f polycystic ovarian syndrome (PCOS)  425b anovulation and  405–406 cardinal features of  429 clinical presentation of  430 diagnosis of  430–431, 431t hirsutism and  426, 432 investigations for  359t, 431t management of  431–432 endometrial protection and  432 metabolic syndrome assessment in  432 oral contraceptive pill in  432

722

outcomes of  432t weight loss in  431–432 pathogenesis of  429, 430f prevalence of  429 surgical ovulation induction and  423 polycythaemia  630b, 653, 678 polydactyly  605–606, 606f polygenic inheritance  664b polyhydramnios  89 polymastia  522–523 polyps cervical  90 endocervical  546–547, 547f endometrial  565 uterine  367f polythelia  522–523 Pomeroy sterilisation  272, 273f pontine micturition centre (PMC)  493 POP see progesterone only pill POP-Q see Pelvic Organ Prolapse Quantification System port-wine stain  604–605 position of the woman  236 positive pressure ventilation see assisted ventilation post-abortal endometritis  146–147 post-abortal PID  480 postdates pregnancy  106–108 aetiology of  107 anencephaly and  107 antenatal management of  108–109 fetal wellbeing assessment and  108 gestational age assessment and  108 induced labour and  109 cardiotocography and  108 clinical features of  107–108 fetal movements and  108 fundal height and  108 incidence of  106–107 macrosomia and  108, 108t obesity and  107 perinatal mortality and  107t placental insufficiency and  107–108, 108t ultrasound and  108 posterior position  296 posterior vaginal repair  488 postmenopausal bleeding (PMB)  378, 396, 438 aetiology of  396 assessment of  397–398 clinical features of  397–398 treatment of  398 postmenopausal period  13 postnatal care  241 0 to 6 hours after birth  329–331 1 to 6 weeks  334 6 hours to 7 days after birth  331–333 epilepsy and  192–193 first week  333–334 routine  330b of twins  118 postnatal depression  197b, 198 postpartum endometritis  146 postpartum haemorrhage  248, 302 aetiology of  303, 303b

Index

incidence of  302 management of  303–304 assistance in  303 balloon tamponade in  304, 304f birth canal and  303 birth suite  303 compression sutures in  304, 304f contracting the uterus in  303–304 emptying the uterus in  303 exploring the uterus in  303 hysterectomy in  304 internal iliac ligation in  304 operating theatre  303–304 radiological embolisation in  304 resuscitation in  303 placental site  304–307 coagulation defect and  307 placenta accreta and  305–306 placenta praevia and  305 retained products of conception and  305 uterine atony and  304–305 uterine inversion and  306 prolonged labour and  289 in puerperium  336–337 secondary  309 traumatic site  307–308 introital tears and  308 perineal tears and  308 uterine rupture and  307–308 vaginal wall tears and  308 vulval and paravaginal haematoma and  308 post-term birth  651 postural hypotension syndrome  278f post-void residual  496 pouch of Douglas  514–516 precipitate birth  253 precocious puberty  373 preconceptual folic acid  31 preeclampsia amniotomy and  137 blood pressure control with  136 caesarean section indications and  270 classification of  135 clinical features of  132–134 cardiovascular  132 haematological  132, 137 hepatic  132, 134f, 137 neurological  132–133, 134f placental  133–134, 133f renal  132, 137 convulsion prophylaxis and  136 delivery with  137 development of  42 diagnosis of  40 differential diagnosis of  134–135 ‘factor X’ in  131 fetal surveillance and therapy with  137 intravascular volume status and  136–137 IUGR and  135f management of  135–138 mild  135–136 pathophysiology of  131, 132f

predisposing factors  131–132 deficient placentation in  131 hyperplacentosis in  132 maternal vascular disease in  132 pregnancy-induced  115 prophylaxis and  137–138 puerperium and  137 severe  135b, 136 thrombocytopenia and  166 pregnancy  13 abdominal  62 abdominal pain in  204 alcohol and  37 autoimmune disease in  177–180, 177t bacterial vaginosis and  474 breast changes during  618 caregivers  38 cerebrovascular disease in  193–194 cervical cancer during  561 chlamydial infection and  476 clinical condition management with  36 complications of  40 cornual/interstitial  62 dating of  33 diabetes mellitus and  187–188 diagnosing  32–33 diet in  36, 46–47, 47t early  11, 113–114 emotional wellbeing in  196–197 employment during  37 exercise and  36–37 fibromyomas and  564 general advice on  36–37 headache in  193 hepatitis management and  159 heterotopic  62 HSV and  158, 470 illicit drugs and  37 of Indigenous women  345–349 insomnia in  211–212 intrauterine  55 iron, iodine and calcium and  36 late  204–205, 216–220 listeriosis and  36, 48 maternal age and  29–30 medications and  37 mercury and  48 multidisciplinary care in  38 multiple sclerosis in  191–192 neuroimaging in  194 nutrition and  36 physiological hydronephrosis of  173, 173f plan for  38 problems in  203b prolactin-producing tumours and  421 prolonged  244b after renal transplant  175 secondary amenorrhoea and  415–416 sexual intercourse during  37 singleton  116t skin conditions in  209 smoking and  37

723

Index

pregnancy (cont.) timing of  29–31 travel during  37 trichomoniasis and  475 uterine scar  62, 63f viability of  55 weight gain in  48–50, 49t see also early pregnancy bleeding; ectopic pregnancy; miscarriage; multiple pregnancy; physiological changes in pregnancy; postdates pregnancy; termination of pregnancy pregnancy risk  452–453 pregnancy screening and investigations  34, 34t antibody screen in  34–35 blood group and  34–35 cervical screening in  35 clinical examination in  34 full blood examination in  34 Hb electrophoresis  35 medical history in  34 microbiological serology in  35 MSU MCS in  35 thyroid function and  35 vitamin D and  35 pregnancy test  33 pregnancy-induced hypertension and preeclampsia  115 pre-implantation development  16 pre-implantation genetic diagnosis  411 pre-invasive disease of the cervix classification of  550–553, 551t, 552f progression of  552f treatment of  556–557 prelabour rupture of the membranes  244b premature ejaculation  446 premature menopause  434 aetiology of  438 clinical features of  438 diagnosis of  438 management of  438 premature newborn see preterm newborn premature rupture of the membranes (PROM) preterm  19f, 101–103 diagnosis of  102 epidemiology of  101 management of  102–103 risks from  101–102 term  109 clinical consequences of  109 management of  109 prevalence of  109 prematurity  680–681 apnoea of  685 neonatal resuscitation and  591, 591b problems with  682–687 retinopathy of  683 see also preterm newborn premenstrual dysphoric disorder (PMDD) aetiology of  387, 389f clinical features of  386–387 daily record of severity of  388f diagnostic criteria for  387 spectrum of  387f treatment of  387–389 premenstrual syndrome (PMS)  377–378

724

aetiology of  387, 389f clinical features of  386–387 daily record of severity of  388f incidence of  386 spectrum of  387f treatment of  387–389 prenatal genetic diagnosis  74 prepregnancy cardiac disorder management and  142 diabetes mellitus and  186, 188 epilepsy and  192 multiple sclerosis and  191 prepregnancy consultation  29–31 clinical problem management and  30–31 diagnostic assessment in  30 prognostic advice in  31 treatment optimisation in  30–31 general advice in  31 pharmacological advice and  31 preconceptual folic acid and  31 sexual intercourse timing and  31 smoking, alcohol and illicit drugs and  31 screening in  30 history and examination in  30 investigations in  30 Pap smear in  30 rubella and varicella vaccination status and  30 prepuberty  13 presentation cephalic  294, 295t compound  287f cord  282–283, 282f non-vertex  264 shoulder  127–128 vertex  294, 295t see also breech presentation; brow presentation; deflexed vertex presentation; face presentation presenting parts, station of  227, 229f preterm birth  651 anaemia and  676b dichorionic twins and  114 neonatal death from  688f preterm labour  98–101 aetiology of  98–99 epidemiology of  98 examination and  99–100 history and  99 prevention of  100 treatment of  100–101 antibiotics in  100 beta-adrenergic agonists in  101 calcium channel blockers in  100 corticosteroids in  100 intrapartum care in  101 magnesium sulphate in  101 neuroprotection in  101 nitric oxide donors in  101 oxytocin receptor antagonists in  101 prostaglandin synthase inhibitors in  101 STATIN acronym for  100 tocolytics in  100–101 transfer and admission in  100 preterm newborn  680b

Index

apnoea of prematurity in  685 cerebral palsy in  688 chronic lung disease in  682, 682f fluid requirements of  683t growth of  688–689 hypoglycaemia in  682 intellectual disability in  687–688, 688t in intensive care nursery  684f intraventricular haemorrhage in  683–685, 686f jaundice in  682 necrotising enterocolitis in  685 neonatal care for  688–689 neurodevelopmental outcomes of  687–688 neurological conditions of  681–682 parents of  692 patent ductus arteriosus in  686–687 periventricular leucomalacia in  683–685 physical features of  681, 681f postnatal retrieval of  689–692 prenatal transport of  689–692, 689t, 691b prognosis of  687–689 recognition of  681–682 respiratory distress syndrome in  682 retinopathy of prematurity in  683 survival rates of  687, 687t, 688f thermoregulation of  683 viability of  682 progesterone cervical insufficiency management with  103 dysfunctional uterine bleeding treatment with  392–394 efficacy of  217 PMS and PMDD treatment with  389 serum levels of  428t progesterone only pill (POP)  458 advantages of  458 contraindications to  458 disadvantages of  458 types of  458 progestin  518t progestogens endometriosis management with  518t in hormone replacement therapy regimen  437 programmed intermittent epidural bolus (PIEB)  317 prolactin breastfeeding and  326 lactation and  523–524 serum levels of  419 prolactin-producing tumours  421 prolonged labour  285b complications of  289–290 management of  290 assessment in  290 first stage of labour and  290 second stage of labour and  290 maternal mortality and  340b vesicovaginal fistula and  342 prolonged pregnancy  244b PROM see premature rupture of the membranes prostaglandin E2 gel  246 prostaglandin E2 slow-release pessary  246 prostaglandin synthase inhibitors  101, 246 prostaglandins adverse effects of  246

contraindications to  246–247 excessive uterine muscular activity and  246 fetal surveillance and  247 induction of labour with  246–248 inhibition of synthesis of  516 metabolism of  386f uterine activity and quiescence and  218t proteases  218t protein  619 proteinuria  42 protozoal infections  152, 153t–154t, 160–161 pruritic urticarial papules and plaques of pregnancy (PUPPP)  209, 210f pruritus  209, 355 pruritus vulvae  209–210, 542 pseudomyxoma peritonei  579 psoriasis, of vulva  538 psychological history  354 psychological issues breastfeeding and  622 disparate sexual desire and  445 termination of pregnancy and  464–465 psychological support  230–231 psychological therapy  199 puberty  13 atypical development of  374–375 breast physiology and  523–524 delayed  373–374 hypothalamic-pituitary causes of  373–374 ovarian causes of  374 gender identity and  443 menarche and  374–375 normal development of  373–375 precocious  373 stages of  374f pubic hair  374 pubic lice  473 public health  341–342, 452–453 pudendal nerve  10, 324 puerperal disorders  335, 335b puerperal psychosis  198 puerperium bowel problems in  337 cardiac disorder management and  143 complications in  333 constipation in  333, 337 diabetes mellitus management in  190 duration of  323b haemorrhoids in  333, 337 incontinence in  333, 338 infections in  333, 336, 337b perineal tear care in  254 physiological changes in  323–324, 324f caesarean section recovery and  324 cardiovascular  324 gastrointestinal system  325 genital tract  323–324 haematological  325 immune system  325 metabolism  325 nutritional  325 renal system  324–325 respiratory system  325

725

Index

puerperium (cont.) post-episiotomy care in  253 postpartum haemorrhage in  336–337 preeclampsia and  137 thromboembolism in  333, 335–336 urinary retention in  333, 337 urinary system and  324–325, 337 varicose vein management and  206 pulmonary blood flow  644 pulmonary embolism  141 pulmonary physiology  643–644 pulmonary system see cardiopulmonary system punch biopsy  556f PUPPP see pruritic urticarial papules and plaques of pregnancy purpuric rash  291, 291f purulent discharge  610f pustular melanosis  604f pustules  604 pyelonephritis  147, 174 pyometra  480, 566 pyridoxine  53

Q Quick Start methodology  456b see also contraception

R radiation therapy  421, 529–531 radical abdominal hysterectomy  559–560 radiofrequency electrothermal ablation  395–396, 396f radiological embolisation  304 radiological myomectomy  565 raloxifene  437 ranitidine  53 rape  447–448 RDS see respiratory distress syndrome rectal examination  498 rectovaginal fistula  254 rectum  506t recurrent miscarriage  57, 60–61, 359t recurrent vulvovaginal candidiasis  540 red blood cells  675–676 abnormalities of  634 destruction of  677–678 production failure  678 see also anti-red blood cell antibodies red cell antigens  180t red cell isoimmune disease antigens and  180–181 pathophysiology of  180 prevention of blood transfusion compatibility and  181 passive anti-D administration and  181–182, 181f see also anti-red blood cell antibodies red degeneration of uterine fibromyoma  204 red reflex  609f regional analgesia  271 relactation  623–624 relaxation techniques  316 remifentanil  316 renal agenesis/dysgenesis  664t renal insufficiency see chronic renal insufficiency

726

renal pelvis, obstructive defects of  663t–664t renal system  132, 137, 324–325 renal transplant  175 reproductive health  345b reproductive life, phases of  13 reproductive system (female)  10–13 anatomy of  2–10 external genitalia in  2–4, 7 internal genitalia in  4–7, 6f function of  2b problems with  170–173 reproductive tract infection  145–147 respiration  612 respiratory depression see neonatal respiratory depression respiratory disease  140b, 144 respiratory distress  643b, 644 causes of  644, 645b investigations of  646–647 management of  645–646 respiratory distress syndrome (RDS)  643b, 647–648 in preterm newborn  682 prevention of  648 treatment of  648 respiratory hypoxia aetiology of  313 clinical features of  313 management of  313 respiratory rate  598 respiratory system  20, 325 respiratory tract infection, upper  205 restitution see external rotation resuscitation in APH management  85 intrauterine  280 meconium aspiration syndrome and  649 miscarriage and  58 in postpartum haemorrhage management  303 see also neonatal resuscitation retained placenta  308–309 retained products of conception  305, 464 retinopathy of prematurity (ROP)  683 retrieval  689–692 re-useable menstrual pad  382f revised American Fertility Society scoring system  516, 517f Rh genes  182–183 Rh haemolytic disease  181, 633 rhythm method  461–462 rigid hysteroscope  367 risk tolerance  244, 267–269 rooming-in  333, 594 rooting reflex  620 ROP see retinopathy of prematurity rotation  223, 223f, 292–293 round ligaments  7, 204 RU486 see mifepristone rubella  153t–154t, 155–157 congenital rubella syndrome and  155–156, 156f fetal infection with  156–157 maternal infection with  156 neonatal infection with  157, 656 pregnancy microbiological serology and  35 vaccination for  30, 161

Index

rupture of the membranes see artificial rupture of the membranes; prelabour rupture of the membranes; premature rupture of the membranes

S sacral neuromodulation  502 sacrococcygeal joint  9–10 sacrococcygeal teratoma  287f sacrocolpopexy  490 sacroiliac joints  9–10 sacroiliac pain  208 sacrospinous fixation  490 salpingectomy  64, 64f salpingitis  477f salpingo-oophorectomy endometrial cancer treatment with  568 ovarian cancer treatment with  579 ovarian tumour surgical management with  575–576 salpingostomy  64 Sampson’s theory  513 scabies  473 scar from caesarean section  307, 307f from episiotomy  254 from perineal tears  254 uterine  269, 307, 307f schizophrenia  198 scleral haemorrhage  610f sclerosis  526 screening for anaemia  165 for aneuploidy  71–75, 76f antibody  34–35, 43–44 for breast cancer  532 cervical intraepithelial neoplasia  360–361 for congenital abnormalities  114 cystic fibrosis  75 for endometrial cancer  567 for GDM  186–187, 186t for genetic conditions  76 for gestational diabetes mellitus  186–187, 186t in gynaecological examination  357, 357t haemoglobinopathies  75–76 maternal serum  71–74 neonatal heel-prick  594–595, 595b, 595f nuchal translucency  73, 73f for ovarian cancer  358, 578 see also cervical intraepithelial neoplasia; cervical screening; Down syndrome; pregnancy screening and investigations; prepregnancy consultation scrotum  613 second-trimester miscarriage  60 seizures epilepsy and  192 neonatal  639 causes of  639, 639b clinical manifestations of  639 investigations of  639 outcomes of  639 treatment of  639 selective oestrogen receptor modulators (SERM)  531 selective serotonin reuptake inhibitor (SSRI)  387–389 self-hypnosis  316

semen analysis  404–405 semirecumbent position  236 senna  204 sensate focus  446b sepsis acute vasodilation and  312 antisepsis and  236 neonatal  658–659 obstructed labour and  286 urinary tract  336 septic arthritis  660 septic miscarriage  60 septicaemia see sepsis septicaemic shock  312 SERM see selective oestrogen receptor modulators seroconversion  155 serotonin and noradrenaline reuptake inhibitor (SNRI)  387–389 serous ovarian tumours  575 Sertoli-Leydig cell tumours  580 sex  441 sex chromosome abnormalities  673 sex hormone binding globulin (SHBG)  426 sex hormones  325, 443 sex-cord stromal tumours  579–580 clinical features of  580 fibromas and  580 granulosa cell tumours and  580 management of  580 Sertoli-Leydig cell tumours and  580 thecoma and  580 sexual activity, in adolescence  375–376 sexual assault  447–448 aftercare planning  448 childhood  447 consent and  447–448 disclosure of previous  448 forensic examination after  448 incidence of  447–448 medical care after  447–448 reporting of  447 sexual aversion disorder  446 sexual desire  445 sexual development  443 sexual dysfunction assessment of  444–445, 445b classification of  444–445, 444t disparate sexual desire and  445 female difficulty or inability to orgasm and  446 dyspareunia and  446–447 female sexual arousal disorder and  446 sexual aversion disorder and  446 vaginismus and  227, 447 incidence of  444 male delayed ejaculation and  446 erectile dysfunction and  446 premature ejaculation and  446 medications causing  445b sexual health  441–442 sexual history  468 sexual intercourse

727

Index

sexual intercourse (cont.) infertility and  408 painful  446–447 during pregnancy  37 timing of, for pregnancy  31 sexual orientation  443–444 sexual relationships  443 sexual response cycle  442f sexuality  441–443, 441b sexually transmitted infection (STI)  541 cervicitis and  475–478 gonorrhoea and  476–477 high risk groups  358–359 HPV  470–471 HSV  469–470 investigations for  359t list of  469–480 Mycoplasma genitalium and  477–478 syphilis and  471–472 trichomoniasis and  475 of vulva  469–473 SGA see small for gestational age SHBG see sex hormone binding globulin shock anaphylactic  312 cardiogenic  312–313 neurogenic  312–313 septicaemic  312 toxic  382–383 short cervix  103 short cord  284 shoulder dystocia  250, 290–293 adverse consequences of  291–292 birth asphyxia in  291–292 brachial plexus injury in  291, 291f facial purpuric rash in  291, 291f fractured clavicle in  291, 293f maternal trauma in  292 instrumental delivery and  265–266 large for gestational age and  653 management of  292–293, 293b caesarean section in  293 cleidotomy in  293 McRobert’s position in  292 posterior arm delivery in  293 shoulder rotation in  292–293 suprapubic pressure in  292, 292f symphysiotomy in  293 pathophysiology of  291 predisposing factors  292, 292b shoulder presentation  127–128 shoulders  125, 237 siblings  595–596 sickle cell haemoglobin  165 Sims’ speculum  486f single gene testing  75 singleton pregnancy  116t sitting position  236 Sjögren’s syndrome  177t skeletal dysplasias  673 skeletal system  78–79 Skene’s ducts see paraurethral ducts skin

728

conditions in pregnancy  209 neonatal assessment of  610 neonatal infection of  658 of newborn  598–605 of preterm newborn  681 skin-to-skin contact  593f, 594 skull  265, 295f SLE see systemic lupus erythematosus sleep breastfeeding and  328 co-sleeping  594 of newborn  594, 622–623 small for gestational age (SGA)  92, 651–653 hypoglycaemia and  653 hypothermia and  653 neonatal respiratory depression and  653 polycythaemia and  653 prognosis of  653 tests for  94t see also fetal growth restriction (FGR) smoking by Indigenous women  348 pregnancy and  37 prepregnancy consultation and  31 SNRI see serotonin and noradrenaline reuptake inhibitor social history  354 social wellbeing  347–348 socioeconomic factors  327, 347 soft tissue  286 somatic pain  506–507 speculum  357f, 486f sperm ICSI and  411–412 number ejaculated  14 obstruction of  404–405 spermatogenesis  404 spermicide  453t spina bifida  77, 637t, 664t, 666b, 666f spinal anaesthesia  312, 320 spinal cord injury  194 spinal epidural see combined spinal epidural spironolactone  428–429 splenomegaly  612 spurious labour  227 squatting position  236 SSRI see selective serotonin reuptake inhibitor standing position  236 Staphylococcus infection  658 STATIN acronym  100 station abdominal  231 of head  229f high  259 instrumental delivery and  259 low  259 mid-cavity  259 outlet  259 of presenting parts  227, 229f stem cell storage  238 sterilisation caesarean section and  272, 273f failure rate of  453t female  453t, 462

Index

male  453t, 462 Pomeroy  273f sternomastoid tumours  610–612 STI see sexually transmitted infection stillbirth birth weight and  95f fetal movements and  41 FGR and  91–95 stools  593, 679 STOP see surgical termination of pregnancy storage reflex  495f stork bite  604f straight leg-raising test  510 strawberry naevus  604–605, 605f streptococcus  146 see also Group B streptococcus stress  218t stress incontinence  175 stress urinary incontinence  495, 502 structural abnormalities  76–80 cardiovascular system  77 central nervous system  77–78 detection of  77–80 face  78 fetal tumours  79–80 gastrointestinal system  78 genitourinary system  78 hydrops fetalis and  80, 80f, 677–678 pregnancy management with  80–83 adoption and  82 counselling in  81–82 history and examination in  81 imaging in  81 invasive testing in  81 labour and delivery in  81 lethal abnormalities and  82 neonatal care and  81 ongoing care and  82 post-termination care in  82–83 risk of recurrence and  82 termination of pregnancy and  82 prevention of  76–77 skeletal system  78–79 sub-aponeurotic haematoma  265 subfertility  359t, 401b subgaleal haematoma  608, 608f subgaleal haemorrhage see sub-aponeurotic haematoma submucous fibromyoma extrusion  564 sucking  326, 622 suckling  325–328 suction  588 sudden infant death syndrome  330f, 594 sulphonamides  679 supernumerary toe  615 supine hypotension  208 supplementation  47–48 calcium  48 folate  47 iodine  48 iron  47–48, 392 multivitamin  36 vitamin D  48 surfactant see lung surfactants

surgical history  353–354 surgical myomectomy  565 surgical termination of pregnancy (STOP)  464–465 surgical transplantation  513 survival rates  99f, 687, 687t, 688f sutures (head)  607–608 symphysiotomy  293 symphysis pubis  9–10 syncope  208 syndrome  663 syphilis diagnosis of  148, 472 epidemiology of  148 among Indigenous women  348–349 management of  148 neonatal infection with  657 in pregnancy microbiological serology  35 sequelae of  148 STIs and  471–472 treatment of  472 systemic lupus erythematosus (SLE)  177t, 179

T tachypnoea see transient tachypnoea of the newborn talipes  615 tamoxifen  422, 531–532 tampon  381–383, 382f Tanner stages  374f temperature, in neonatal care  594 see also body temperature TENS  316 tension headache  193 teratogenesis  37, 192 teratoma  287f, 581–582 term birth  651 termination of pregnancy at 8 weeks  21f in Australia  463–465 first-trimester  463–464 medical  463–464 surgical  464 genetic conditions and structural abnormalities and  82 legality of  342–343 maternal mortality from  342–343 safety of  463–465 second-trimester  464–465 complications with  464–465 medical  464 surgical  464–465 testes, undescended  669–670 testicular failure  404 testicular function  404 testosterone in hormone replacement therapy regimen  437–438 serum levels of  404, 428, 428t tetanus  161, 634f thalassaemia  164–165 theca lutein cysts  574 thecoma  580 therapeutic hypothermia  638 thermoregulation  683 thiazide diuretics  679 Thin Prep Pap Test see liquid-based cytology

729

Index

thorax  612 threatened miscarriage  58, 58t thrombocytopenia  166 causes of  166b fetal sequelae of  166 gestational  166 neonatal  679 preeclampsia and  166 TTP  166 see also immune thrombocytopenic purpura; neonatal alloimmune thrombocytopenia thromboembolism  140b clinical features of  141 deep vein thrombosis and  141 diagnosis of  141 predisposing factors for  141t prevention of  141 in puerperium  333, 335–336 pulmonary embolism and  141 symptoms of  336b treatment of  141 venous  437 thrombophilia  56 thrombophlebitis  206 thrombotic thrombocytopenic purpura (TTP)  166 thrush see candidiasis thymus glands  20 thyroid disease  56 thyroid glands  20, 35 tibolone  437 tinea, of vulva  541 tocolytics  100–101 toe  615 TOLAC see trial of labour after caesarean section topical vaginal oestrogen  437 TORCH organisms  655–657 toxic shock syndrome  382–383 toxins  57 toxoplasmosis  153t–154t fetal infection with  160 maternal infection with  160 neonatal infection with  656, 656f prevention of  160b treatment of  160 trachelectomy  559, 560f tracheo-oesophageal fistula  668, 668f traction  239, 259f traction force reduction  250 TRAM flap see transverse rectus abdominis myocutaneous flap tranexamic acid  392 transcervical balloon catheter adverse effects of  247 induction of labour with  247 infection with  247 trans-coelomic spread  514 transcription factors  218t, 219f transformation zone  550f transfusion blood  180–181 exchange  633 feto-maternal  677 twin-to-twin  677, 677f see also twin-twin transfusion syndrome

730

transgender  443 transient tachypnoea of the newborn  649 transplacental infection  147–149 transport  689–692, 689t, 691b transposition of great arteries  665 transvaginal repair high uterosacral vault suspension in  490 LeFort colpocleisis in  490 Manchester repair in  488–490 McCall culdoplasty in  490 sacrospinous fixation in  490 transverse arrest  296 transverse lie  127–128, 127f aetiology of  128 caesarean section with  128 diagnosis of  127 external cephalic version with  128 management of  128 predisposing factors  127 transverse rectus abdominis myocutaneous flap (TRAM flap)  530, 531f trastuzumab  531 trauma birth  190, 485b, 678–679 fetal  289–290 maternal  292 in miscarriage aetiology  57 uterine  89 uterine rupture and  307 see also postpartum haemorrhage travel  37 Treponema pallidum  471 trial of labour after caesarean section (TOLAC) decision equation for  274 likelihood of  274 management of  275 first stage  275 place of birth and  275 second stage  275 perinatal mortality and morbidity and  274 uterine rupture and  274 trichomonal vaginitis  541 trichomoniasis  359–360, 475 triplets  116t trisomy 13 see Patau syndrome trisomy 18 see Edwards syndrome trisomy 21 see Down syndrome trophoblast  14b, 20–22, 20f see also gestational trophoblastic disease tropical genital ulcer disease  472 true hermaphrodism  670f true knots  283–284 true labour  227 trunk  125, 223–224, 237 TTP see thrombotic thrombocytopenic purpura tubal abortion  61 tubal disease  407–408 tubal dysfunction  407 tubal ectopic pregnancy  61–62, 61f–63f tubal hydrosalpinx  407, 407f tubal infection  407 tubal missed abortion  62 tubal rupture  61–62

Index

tuberculosis  150–151, 595 tuberculosis PID  480 tumour markers  573 tumours benign cervical  546–547 Brenner  577 endodermal sinus  582 fetal  79–80 granulosa cell  580 prolactin-producing  421 Sertoli-Leydig  580 sternomastoid  610–612 yolk sac  582 see also ovarian tumours; sex-cord stromal tumours Turner’s syndrome  673, 673f twins aetiology of  111–112 chorionicity and amnionicity of  112–113 classification of  112–113 comparative risk of  116t diagnosis of  113 dichorionic  113–115 congenital abnormality screening with  114 death of one twin and  115 Down syndrome screening with  114 early pregnancy management and  113–114 growth of  114–115 IUGR and  115 pregnancy-induced hypertension and preeclampsia with  115 preterm birth with  114 incidence of  111–112 intrapartum management of  119b labour and delivery of  117–118 monochorionic  115–117 abnormality of one twin and  117 death of one twin and  116–117 monoamniotic  117 selective IUGR and  117 twin-twin transfusion syndrome and  115–116, 116f placentation of  112f postnatal care of  118 presentation of  118f zygosity of  112 twin-to-twin transfusion  115–116,  116f,  677, 677f twin–twin transfusion syndrome  115–116, 116f,  677, 677f

U ulcers  468, 472, 539 ultrasound breast assessment with  525 Down syndrome screening with  74 endometriosis investigation with  516 fetal growth assessment with  93 fetal wellbeing assessment with  96–97 gestational age assessment with  33 in GTD diagnosis  66 ovarian tumour imaging with  573 postdates pregnancy and  108 see also pelvic ultrasound umbilical cord  25 accidents  282–284 blood  238 clamping of  237–238

controlled traction of  239 cord presentation and  282–283, 282f entanglement  283–284 fetal compromise and  278–279 knotting of  283f around neck  236 neonatal assessment of  612 neonatal care and  593 short  284 velamentous insertion of  24f see also cord prolapse; true knots umbilicus  19 unconjugated bilirubin  629 unconjugated hyperbilirubinaemia see haemolytic disease underweight  347 undescended testes  669–670 United Kingdom  452 unregulated birth attendants  230 upper genital tract infection  466b upper respiratory tract infection  205 ureaplasmal infection  149–150 urethra  492–493 urethral diverticulum  496, 501f urethral meatus  3 urgency urinary incontinence  495 urinalysis  42 urinary frequency  211 urinary incontinence  492b aetiology of  494–496 urethral diverticulum and  496 urogenital fistula and  496 classification of  494–496 clinical evaluation of  496–501, 497t management of  501–502 fluid management in  501 medication in  501–502 neuromodulation in  502 pelvic floor physiotherapy in  501 surgical  502 mixed  496 overflow  496 stress  495, 502 urgency  495 voiding dysfunction and  496 urinary pregnancy test  33 urinary retention incarceration with  175, 564 intrapartum  175 postpartum  175 in puerperium  333, 337 urinary system  78 anatomy of  492–493 neurophysiology of  493 physiological changes in pregnancy  173–174 problems with  173–175 puerperium and  324–325, 337 urinary tract infection (UTI) acute pyelonephritis and  147 clinical features of  174 lower  174 management of  174 pathogenesis of  147 urinary tract sepsis  336

731

Index

urine MSU MCS and  35 neonatal care and  593 neonatal sepsis and  659 urinary incontinence and  498 urodynamics  498–499, 500t uroflow  496 urogenital atrophy  398, 435 urogenital development  19 urogenital diaphragm  10 urogenital fistula  496 urogenital sinus  670f ursodeoxycholic acid  209 uterine activity  217, 218t, 285, 288f uterine atony  225, 304–305 uterine bleeding  379f see also dysfunctional uterine bleeding; heavy menstrual bleeding uterine body  6 uterine cervix  5–6 uterine contractions cervical dilation and  220 labour assessment and  231 of late pregnancy  204–205 in menstrual cycle  381 pain of  219–220 strength, duration and frequency of  219 third-stage labour management and  238 uterine disorders amenorrhoea and  417t, 418 benign  563–566 malignant  566–568 uterine fibroid embolisation  395f uterine fibromyoma clinical features of  172, 564 incarceration with urinary retention in  564 leiomyosarcoma in  564 menorrhagia in  564 pelvic mass in  564 submucous fibromyoma extrusion in  564 diagnosis of  564 dystocia and  286 epidemiology of  563 examination of  564 investigations of  564 in lower uterine segment  286 management of  172 pathology of  563–564 pregnancy and  564 red degeneration of  204 treatment of  565 hysterectomy  565 medical  565 observation only  565 radiological myomectomy  565 surgical myomectomy  565 uterine fundus  324f uterine hyperstimulation  246, 246t, 278 uterine incision, in caesarean section  268, 268f uterine inertia  285–286 uterine inversion clinical features of  306 management of  306

732

pathophysiology of  306, 306f postpartum haemorrhage and  306 uterine muscle  246–248, 285–286 uterine perforation  566 uterine polyp  367f uterine quiescence  217, 218t uterine rupture augmentation of labour and  289 caesarean section and  273–274, 307, 307f cervical lacerations and  308 clinical features of  308 obstructed labour and  287, 307 postpartum haemorrhage and  307–308 predisposing factors of  307–308 trauma in  307 uterine scar in  307, 307f prolonged labour and  289 TOLAC and  274 treatment of  308 uterine sarcoma  568 uterine scar  269, 307, 307f uterine scar pregnancy  62, 63f uterine trauma  89 uterine tubes  6–7 uterine veins, distended  217f uterovaginal prolapse in pregnancy  171, 171f uterus  5–6 bicornuate  365f, 409, 409f contracting  303–304 emptying  303 exploration of  303 infertility and  409–410 innervation of  506t labour initiation and  217, 218t, 219, 220f leiomyoma in  564f menstruation and  12f miscarriage aetiology and  57 postpartum haemorrhage management and  303–304 structural changes in  216–217 termination of pregnancy and  464 upper segment of  216–217, 217f see also lower uterine segment uterus didelphys  170f, 286 UTI see urinary tract infection

V vaccinations cervical cancer  561–562 hepatitis B  595 HPV  361, 470–471, 547–550, 561–562 influenza  161 in neonatal care  595 rubella  30, 161 tetanus, diphtheria and pertussis  161 tuberculosis  595 varicella  30, 161 vacuum birth  257–258, 258t, 264 vacuum extraction device  261 vagina  4–5 amenorrhoea and  417t bleeding from, neonatal  373 congenital cysts of  540 dryness of  324, 435

Index

duplication of  540 foreign bodies in  541 innervation of  506t labour initiation and  219 neonatal assessment of  612–613 pH of  466–467, 469 post-birth inspection of  241 sphincter around  5f stretching of  323–324 support for  484f vaginal adenosis  540 vaginal agenesis  540 vaginal birth with breech presentation  122–127, 123b, 123t caesarean section compared to  269, 269f contraindications to  244 female genital mutilation and  170 hospital discharge after  333–334 vaginal birth after caesarean section see trial of labour after caesarean section vaginal breech delivery see breech delivery vaginal discharge age and  467 assessment of  210–211 from bacterial vaginosis  473–474 causes of  473–478 characteristics of  468 from chlamydial infection  467 diagnosis of  210, 467–469 examination for  468 gynaecological history and  355 history and  467–468 investigations of  469 paediatric  542 pathological causes of  467 vaginal epithelium  252–253 vaginal examination brow presentation diagnosis in  299 deflexed vertex presentation diagnosis and  296 face presentation diagnosis in  300 in gynaecological examination  355–357 labour assessment and  231–232 for vaginal infection  468 vaginal haematoma  255–256 vaginal infection  473–478 diagnosis of  467–469 examination for  468 investigations of  469 pathological causes of  467 vaginal intraepithelial neoplasia  557–558 vaginal nodule  514f vaginal orifice  3–4 vaginal pessary see pessary vaginal radical trachelectomy  560f vaginal repair  252–253, 488 see also transvaginal repair vaginal ring  456–458 vaginal septum  227, 286 vaginal sponge  460 vaginal surgery  490 vaginal tears  265, 308 vaginismus  227, 447 vaginitis

atrophic  541 desquamative inflammatory  541–542 infectious  359–360 trichomonal  541 vulvovaginitis  373 vaginosis  541 valproate  192 varicella  153t–154t fetal infection with  157 maternal infection with  157 neonatal infection with  158 pregnancy microbiological serology and  35 vaccination for  30, 161 varicella zoster virus  157 varicose veins clinical consequences of  206 of leg  205f management of  206 antenatal  206 intrapartum  206 puerperium  206 pathophysiology of  205 of vulva  205f vas deferens  404–405 vasa praevia  25f, 88, 88f blood loss and  677 clinical consequences of  88 diagnosis of  88 incidence of  88 management of  88 vasectomy  462, 463f vasodilation  312, 585 vasomotor symptoms  435–436, 438 vasovagal see neurogenic shock velamentous insertion, of cord  24f venous thromboembolism  437 ventilation  587–588 see also assisted ventilation ventouse see vacuum extraction device ventral induction  636 ventricular septal defect  663t, 665 ventriculomegaly  78 vernix  598, 602f version see external cephalic version vertex presentation  294, 295t see also deflexed vertex presentation vesicles  601–604 vesicovaginal fistula  289, 342 vesiculobullous rash  604f vestibule  3 video urodynamics  499 villi  21, 22f violence, against women  344 viral infections  152, 153t–154t visceral pain  506–507 vitamin B12 deficiency  164–165 vitamin D  35, 48 vitamin K  625, 678 vitamins  389 voiding dysfunction  496 voiding reflex  495f vomiting  625–626 see also nausea and vomiting of pregnancy

733

Index

Von Willebrand’s disease  167 vulsellum forceps  486f vulva disorders of  536–540 examination of  468, 510 innervation of  506t painful conditions of  538–539, 539b post-birth inspection of  241 psoriasis of  538 STIs of  469–473 stretching of  323–324 tinea of  541 ulcers, fissures and abscesses of  539 varicose veins of  205f warts of  541 vulval haematoma  255–256, 255f, 308 vulval tear  250f vulvar cancer  542–544 vulvar dermatitis  542 vulvar dermatoses  536–538 vulvar HSV  469–470 vulvar intraepithelial neoplasia  542–543 vulvar oedema  540 vulvar Paget’s disease  543 vulvitis  538, 541 vulvodynia  539–540, 539b vulvovaginal candidiasis see candidiasis vulvovaginal disorders  540–542 vulvovaginitis  373

W warts, vulvar  541 water intoxication  248 weight

734

gain  48–50, 49t, 626 loss  431–432 maternal  40–41 of newborn  594, 598, 626 overweight  49, 431–432 underweight  347 see also birth weight; obesity wet preparation  469 white blood cells  676 white cell and platelet isoimmune disease in pregnancy  184 withdrawal  453t women dietary guidelines for  47t pelvic mass in  571 violence against  344 see also Indigenous women; mothers women’s health  340–341 World Health Organisation  452 wounds  253, 331, 336

X X-linked recessive inheritance  664b

Y yolk sac tumour  582 Yuzpe method  461

Z ZIFT see zygote intra-fallopian transfer zona pellucida  14, 15f Zoon’s vulvitis see plasma cell vulvitis zygosity, of twins  112 zygote formation  16 zygote intra-fallopian transfer (ZIFT)  411