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www.jpog.com
JAN/FEB 2012 Vol. 38 No. 1
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
Your partner in paediatricand O&G practice
www.jpog.comwww.jpog.com
JAN/FEB 2012 Vol. 38 No. 1 Your partner in paediatricand O&G practice
ISSN 1012-8875(HONG KONG)
Management ofPregnancies With
Previous Caesarean Section
CME ARTICLE
JOURNAL WATCH
GYNAECOLOGY
HKCOG
Guidelines
Induction o
Ovulation
Does
My Child
Have a
Food Allergy?
PAEDIATRICS
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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
Journal Watch
1 Asthmainpregnancy:TreatmentguidedbyFENO measurement
WomenexposedtoDES in utero:Moreonadversehealthoutcomes
HospitaldeliverypolicyinChinaandneonatalmortality
2 Polycysticovarysyndrome:Adversepregnancyoutcomes
VitaminAsupplementsforchildrenindevelopingcountries:
Systematicreviewandmeta-analysis AdenoidectomyforrecurrentURTIsinchildren:Negativetrial
3 BenetsofroutinerotavirusvaccinationforUSchildren
MillenniumDevelopmentGoals4and5:Anupdateonprogress
Immunoglobulinforneonatalsepsis:Noteffective
Acyclovirsuppressivetherapyaftertreatmentofneonatalherpes
4 Malariaandbacteraemiainchildren
Adjuvantedinuenzavaccineforchildren
Board Director, Paediatrics
Professor Pik-To CheungAssociate ProessorDepartment o Paediatricsand Adolescent Medicine
The University o Hong Kong
Board Director, Obstetrics and Gynaecology
Professor Pak-Chung HoHead, Department oObstetrics and GynaecologyThe University o Hong Kong
Editorial Board Professor Biran AffandiUniversity o Indonesia
Dr Karen Kar-Loen Chan
The University o Hong Kong
Associate Professor Oh Moh Chay
KK Womens and Childrens Hospital,Singapore
Associate Professor Anette Jacobsen
KK Womens and Childrens Hospital, Singapore
Professor Rahman Jamal
Universiti Kebagsaan Malaysia
Dato Dr Ravindran Jegasothy
Hospital Kuala Lumpur, Malaysia
Associate Professor Kenneth Kwek
KK Womens and Childrens Hospital, Singapore
Dr Siu-Keung Lam
Kwong Wah Hospital, Hong Kong
Professor Terence Lao
Chinese University o Hong Kong
Dr Kwok-Yin Leung
The University o Hong Kong
Dr Tak-Yeung Leung
Chinese University o Hong Kong
Professor Tzou-Yien LinChang Gung University, Taiwan
Professor Somsak LolekhaRamathibodi Hospital, Thailand
Professor Lucy Chai-See LumUniversity o Malaya, Malaysia
Professor SC NgNational University o Singapore
Professor Hextan Yuen-Sheung NganThe University o Hong Kong
Professor Carmencita D PadillaUniversity o the Philippines Manila
Professor Seng-Hock QuakNational University o Singapore
Dr Tatang Kustiman SamsiUniversity o Tarumanagara, Indonesia
Professor Perla D Santos OcampoUniversity o the Philippines
Associate Professor Alex Sia
KK Womens and Childrens Hospital, Singapore
Dr Raman SubramaniamFetal Medicine and Gynaecology Centre, Malaysia
Professor Walfrido W SumpaicoMCU-DFT Medical Foundation, Philippines
Professor Cheng Lim TanKK Womens and Childrens Hospital, Singapore
Associate Professor Kok Hian TanKK Womens and Childrens Hospital, Singapore
Dr Surasak TaneepanichskulChulalongkorn University, Thailand
Professor Eng-Hseon Tay
Thomson Womens Cancer Centre, Singapore
Professor PC WongNational University o Singapore
Dr George SH YeoKK Womens and Childrens Hospital, Singapore
Professor Hui-Kim YapNational University o Singapore
Professor Tsu-Fuh YehChina Medical University, Taiwan
1
4
JPOG JAN/FEB 2012 i
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The Friso Gold range with * comprises a key prebiotic and two probiotics to
support a healthy stool pattern, a prerequisite or optimal intestinal health in children
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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
Publisher
Ben Yeo
Publication Manager
Marisa Lam
Deputy Managing Editor
Greg TownAssociate EditorGrace Ling
Design Manager
Rowena Sim
Designer
Connie Lim
Production
Edwin Yu, Ho Wai Hung,Jasmine Chay
Circulation
Christine Chok
Accounting Manager
Minty Kwan
Advertising Coordinator
Jenny Lim
Published by:UBM Medica Pacifc Limited27th Floor, OTB Building160 Gloucester Road,Wan Chai, Hong KongTel: (852) 2559 5888
Email: [email protected]
PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) ispublished 6 times a year by UBM Medica, a division o United Business Media.CIRCULATION: JPOG is a controlled circulation or medical practitionersin South East Asia. It is also available on subscription to members o alliedproessions. SUBSCRIPTION: The price per annum is US$42 (surace mail,students US$21) and US$48 (overseas airmail, students US$24); back issues
US$8 per copy. EDITORIAL MATTER published herein has been prepared byproessional editorial sta. Views expressed are not necessarily those o UBMMedica. Although great care has been taken in compiling and checking theinormation given in this publication to ensure that it is accurate, the authors,the publisher and their servants or agents shall not be responsible or in any wayliable or the continued currency o the inormation or or any errors, omissionsor inaccuracies in this publication whether arising rom negligence or otherwisehowsoever, or or any consequences arising thererom. The inclusion or exclusiono any product does not mean that the publisher advocates or rejects its useeither generally or in any particular eld or elds. COPYRIGHT: 2012 UBMMedica. All rights reserved. No part o this publication may be reproduced, storedin a retrieval system or transmitted in any orm or by any means, electronic,mechanical, photocopying, recording or otherwise, in any language, withoutwritten consent o copyright owner. Permission to reprint must be obtainedrom the publisher. ADVERTISEMENTS are subject to editorial acceptance andhave no infuence on editorial content or presentation. UBM Medica does notguarantee, directly or indirectly, the quality or ecacy o any product or servicedescribed in the advertisements or other material which is commercial in nature.Philippine edition: Entered as second-class mail at the Makati Central PostOce under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by FortunePrinting International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee ChungStreet, Chai Wan, Hong Kong.
ChinaTeo Wai Choo
Tel: (86 21) 6157 3888Email: [email protected]
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Enquiries and Correspondence
5
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JPOG JAN/FEB 2012 ii
ReviewArticles
Gynaecology
5 HKCOGGuidelinesInductionofOvulation
This guideline by The Hong Kong College o Obstetricians and Gynaecologists (HKCOG) coversthe classiication o ovulation disorders, treatment options o various ovulation disorders, and their
associated risks.
Yeung Wing Yee Tracy, Lee Chi Yan Vivian, Li Hang Wun Raymond, Ng Hung Yu Ernest;for The Hong Kong College of Obstetricians and Gynaecologists
Paediatrics
33 DoesMyChildHaveaFoodAllergy?
Avoidance, education about management o an acute reaction and optimal treatment o other atopicconditions, particularly asthma, are the mainstays o treatment o ood allergy in children.
Preeti Joshi
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JAN/FEB 2012
Vol. 38 No. 1
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
JPOG JAN/FEB 2012 iii
ReviewArticlesComprehensive reviesproviing the latest clinicalinformation on all aspectsof the management of meicalconitions affecting chilrenan omen.
CaseStudiesInteresting cases seen in generalpractice an their management.
PictorialMedicineVignettes of illustrate casesith clinical photographs.
For more information, please refer to the Instructions for Authors on our ebsite www.jpog.com, or contact:The EditorUBM Meica Asia Pte Lt, No 3 Lim Teck Kim Roa, Genting Centre, Singapore 088934
Tel: (65) 6223 3788 Fax: (65) 6221 4788 E-mail: [email protected]
The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence rom UBM Media LLC. The articlesappearing on pages 4953, and pages 6780 are reprinted with permission o Consultant for Pediatricians. Copyright 2011UBM Media LLC. All rights reserved.
ReviewArticle
Continuing Medical Education
45 ManagementofPregnanciesWithPreviousCaesareansection
This article reviews the recommendations on vaginal birth ater previous caesarean section (VBAC)by dierent proessional societies, the avourable and unavourable actors in considering VBAC,
the associated maternal and etal beneits and risks, as well as the non-medical concerns that
play a role in the decision-making process.
Yung WK, Lau WL, Leung WC
257
The Cover:Does My Child Have
a Food Allergy 2012 UBM Medica
Rowena Sim, Art DirectorConnie Lim, Illustrator
45
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JPOG JAN/FEB 2012 1
OBSTETRICS
Asthmainpregnancy:Treatment
guidedbyFENO measurement
Fraction o exhaled nitric oxide (FENO) is a measure
o airway inlammation. A study at two hospitals
in Australia has shown that the management o
asthma in pregnancy might be improved by using
measurements o FENO to guide therapy.
A total o 220 pregnant, non-smoking women
with asthma were randomized at 1220 weeks
gestation to management using a clinical symp-
toms algorithm or an FENO algorithm. With the lat-
ter, the dose o inhaled steroid was increased at
FENO > 29 ppb and reduced at F
ENO < 16 ppb, at
monthly visits to the antenatal clinic. The rate o
asthma exacerbations was 0.288 per pregnancy in
the FENO group and 0.615 per pregnancy in the con-
trol group, a signiicant 50% reduction in the F ENO
group. The number-needed-to-treat was 6. Qual-
ity o lie was improved signiicantly in the FENO
group; the mean daily dose o steroid was less
and more women received long-acting 2
agonist
therapy. Neonatal outcomes tended to be better in
this group.
Use o the FENO algorithm could improve the
management o asthma in pregnancy.
Powell H et al. Management o asthma in pregnancy guided bymeasurement o raction o exhaled nitric oxide: a double-blind,
randomised controlled trial. Lancet 2011; 378: 983990; Szefer SJ.
Personalised medicine or asthma management in pregnancy. Ibid:
963964 (comment).
WomenexposedtoDES in utero:
Moreonadversehealthoutcomes
It has been known or 40 years that diethylstil-
bestrol (DES) given to mothers during pregnancy
induces clear-cell adenocarcinoma o the vagina
and cervix in their daughters in adolescence and
early adulthood. Later, developmental deects othe genital tract and complications o pregnancy
were added to the long-term eects. Now, three
US cohort studies combined have provided more
long-term data.
Altogether, the three studies, with ollow-
up to an average age o 48 years, included 4,653
women exposed to DES in utero and 1,927 unex-
posed controls. The risks o 12 outcomes were
assessed in exposed women and controls up to
the age o 45 or reproductive outcomes and 55
or other outcomes. The risks or all 12 outcomes
were increased in exposed women compared with
controls. The rates or exposed women versus
controls and hazard ratios were: inertility, 33.3%
vs 15.5% (2.37); spontaneous abortion, 50.3% vs
38.6% (1.64); ectopic pregnancy, 14.6% vs 2.9%
(3.72); loss o second-trimester pregnancy, 16.4%
vs 1.7% (3.77); preterm delivery, 53.3% vs 17.8%
(4.68); preeclampsia, 26.4% vs 13.7% (1.42); still-
birth, 8.9% vs 2.6% (2.45); neonatal death, 2.4%
vs 0.56% (8.12); early menopause 5.1% vs 1.7%
(2.35); cervical intraepithelial neoplasia grade 2 or
greater, 6.9% vs 3.4% (2.28); breast cancer at age
40 years or older, 3.9% vs 2.2% (1.82); and clear-
cell adenocarcinoma, 0.09% vs 0.0% (ininity).
Vaginal epithelial changes at baseline increased
the risk o most outcomes.
The daughters o women who took DES inpregnancy have increased lietime risks or a wide
range o adverse outcomes.
Hoover RN et al. Adverse health outcomes in women exposed in utero to
diethylstilbestrol. NEJM 2011; 365: 13041314.
HospitaldeliverypolicyinChina
andneonatalmortality
In many countries, a major obstacle to reducing
mortality in children < 5 years old is reractoriness
o neonatal mortality. In China, home births have
been discouraged and birth in hospital is now the
rule. Less than hal o all births were in hospital
in 1988, but in 2008 almost all babies were born
in hospital. This policy appears to have been ac-
companied by a marked all in neonatal mortality.
A population-based epidemiological study was
carried out at 116 surveillance sites (37 urban, 79 ru-
ral) between 1996 and 2008; during this time, neona-
tal mortality ell by 62% (rom 24.7 to 9.3 per 1,000
live births). Most neonatal deaths (82%) occurred in
the rst week o lie and more than hal were in the
rst 2 days. Neonatal mortality was lower in urban
than in rural areas and highest in the most deprived
rural areas. Neonatal mortality declined in almost all
regions and rom almost all causes.These researchers attribute the reduction in
neonatal morality to the policy o hospital births
and improvements in obstetric and neonatal care.
Commentators advise caution in the interpretation
o these results.
Feng XL et al. Chinas acility-based birth strategy and neonatal mortality:
a population-based epidemiological study. Lancet 2011; 378: 14931500;
Bassini DG, Roth DE. Chinas progress in neonatal mortality. Ibid: 1446
1447 (comment).
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JPOG JAN/FEB 2012 2
Polycysticovarysyndrome:
Adversepregnancyoutcomes
The incidence o polycystic ovary syndrome has
been reported as 315% o women o reproduc-
tive age. The eatures include hyperandrogenism,
anovulation, and polycystic ovaries. Meta-analyses
have shown that the condition is associated with
increased risks o gestational diabetes, pre-ec-
lampsia, preterm birth, and perinatal mortality. It
has been unclear, however, whether the risks are
due to the polycystic ovary syndrome itsel or to
the associated eatures such as obesity or ertility
treatments with increased risk o multiple preg-
nancy. Now, a study in Sweden has shown that
polycystic ovary syndrome is associated with ad-
verse pregnancy outcomes irrespective o the use
o assisted reproductive technology.
Using national birth and patient registers,
data were obtained or all singleton births in Swe-
den between 1995 and 2007. There were 1,195,123
births, and in 3,787 cases the mother had polycys-
tic ovary syndrome. The risks o adverse pregnancy
outcomes (gestational diabetes, pre-eclampsia,
low Apgar score, meconium aspiration, small or
large or gestational age, macrosomia) were ad-
justed or maternal characteristics, socioeconomic
actors, and use o assisted reproductive technol-
ogy. Comparing women with polycystic ovarian syn-
drome with women without the syndrome, aectedwomen were more likely to be obese (61% vs 35%)
and to have used assisted reproductive technology
(14% vs 2%). They were 45% more likely to have
pre-eclampsia, 2.2 times more likely to have very
preterm delivery, and 2.3 times more likely to have
gestational diabetes. Among their inants, there
was a 39% increase in largeness or gestational
age, a twoold increase in meconium aspiration,
and a 40% increase in low Apgar score at 5 min-
utes.
Women with a diagnosis o polycystic ovary
syndrome are at increased risk o adverse preg-
nancy outcomes irrespective o whether they have
used assisted reproductive technology or not.
Roos N et al. Risk o adverse pregnancy outcomes in women with
polycystic ovary syndrome: population based cohort study. BMJ 2011;
343: 835 (d6309); Macklon NS. Polycystic ovary syndrome. Ibid: 804805
(d6407) (editorial).
PAEDIATRICS
VitaminAsupplementsfor
childrenindevelopingcountries:
Systematicreviewandmeta-
analysis
A systematic review and meta-analysis has con-
irmed the value o vitamin A supplements given to
children in developing countries.
The study included 16 trials (194,483 chil-
dren aged 6 months to 5 years). Vitamin A supple-
mentation was associated with a 24% reduction in
mortality. There was a signiicant 28% reduction
in diarrhoea mortality and a non-signiicant 20%
reduction in measles mortality. There were signii-
cant reductions in prevalence o Bitots spots o the
bulbar conjunctiva (by 55%), night blindness (by
68%), and xerophthalmia (by 69%).
Vitamin A supplementation or children aged
6 months to 5 years reduces the incidence o di-arrhoea and overall mortality. It also results in
signiicant reductions in the eatures o vitamin A
deiciency and might prevent blindness rom this
cause.
Mayo-Wilson E et al. Vitamin A supplements or preventing mortality,
illness, and blindness in children aged under 5: systematic review and
meta-analysis. BMJ 2011; 343: 519 (d5094); Thorne-Lyman A, Fawzi
WW. Improving child survival through vitamin A supplementation. Ibid:
487488 (d5294) (editorial).
Adenoidectomyforrecurrent
URTIsinchildren:Negativetrial
It has long been suspected that early adenoidec-
tomy is not beneicial or children with recurrent
upper respiratory tract inections (URTIs). A trial in
the Netherlands has conirmed these suspicions.
A total o 111 children aged 116 years se-
lected or adenoidectomy by ear, nose and throat
surgeons because o recurrent URTIs were random-
ized to adenoidectomy (with or without myringoto-
my) within 6 weeks or a strategy o wait-and-see.
Follow-up was or up to 24 months. The rate o
URTIs was 7.91 episodes per child-year (adenoid-
ectomy) versus 7.84 episodes per child-year (con-
trols). The rate o new URTIs was similar over time
in the two groups, with a gradual decrease. The
groups did not dier signiicantly on ollow-up in
the rate o ever with ear symptoms or in quality-
o-lie measures. The adenoidectomy group had
more days with ever during ollow-up (20 vs 16
days per child-year). During the trial, 40% o the
control group underwent adenoidectomy, but their
presurgery URTIs were not more severe than those
o the 60% who did not undergo surgery and they
ared no better than those 60% ater surgery.
Early adenoidectomy does not beneit young
children with recurrent URTIs.
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JPOG JAN/FEB 2012 3
PEER REVIEwEd
Van den Aardweg MTA et al. Eectiveness o adenoidectomy in children
with recurrent upper respiratory tract inections: open randomised
controlled trial. BMJ 2011; 343: 520 (d5154); Kvaerner KJ. Adenoidectomy
in children with recurrent upper respiratory inections. Ibid: 488489
(d5274) (editorial).
Benetsofroutinerotavirus
vaccinationforUSchildren
Routine inant vaccination with pentavalent rotavi-
rus vaccine (RV5) was introduced in the USA in Feb-
ruary 2006. Beore that, there were an estimated
400,000 visits o children < 5 years old nationally
to physicians oices or rotavirus diarrhoea, with
200,000 visits to emergency departments, 55,000
hospital admissions, and 2060 deaths each year.
MarketScan databases (containing inormation
rom insurance claims) were used to obtain inor-
mation about RV5 coverage and diarrhoea-associ-
ated health problems in children < 5 years old in
the periods July 2001 to June 2006 and July 2007
to June 2009. By the end o December 2008, 73%
o children < 1 year old had received at least one
dose o RV5. Rates o hospital admission or diar-
rhoea in this age group were 52 per 10,000 person-
years in 20012006, 35 per 10,000 person-years
in 20072008, and 39 per 10,000 person-years in
20082009. Rates o hospital admission or rota-
virus diarrhoea in these periods were 14, 4, and 6
cases per 10,000 person-years, respectively. Indi-
rect beneit rom the vaccine (among unvaccinated
children) was shown by reductions o diarrhoea ill-
ness in January to June 2008 but not in the same
period in 2009. Nationally in 20072009, there were
an estimated 64,855 ewer hospital admissions or di-
arrhoea among children < 5 years old with a saving in
health-care costs o US$278 million.
The introduction o routine inant vaccination
with RV5 was ollowed by substantial reduction in
diarrhoea among the under-5s and substantial sav-
ing in health-care costs.
Cortes JE et al. Rotavirus vaccine and health care utilization or diarrhoea
in US children. NEJM 2011; 365: 11081117.
MillenniumDevelopmentGoals
4and5:Anupdateonprogress
The targets or Millennium Development Goals
(MDGs) 4 and 5 are a reduction in under-5 mortal-
ity by two-thirds and in maternal mortality ratio by
three-quarters between 1990 and 2015. A urther
update on progress has been reported using recent
surveys, censuses, vital registration, and verbal
autopsy data.
It is estimated that under-5 deaths will have
allen to 7.2 million in 2011 with 2.2 million early
neonatal deaths, 0.7 million late neonatal, 2.1 mil-
lion postneonatal inantile, and 2.2 million o chil-
dren aged 14 years. The rate o decline o under-5
mortality was greater in 20002011 than in 1990
2000 in 106 countries. There has been no progress
towards MDG-4 in our countries. Maternal mor-
tality has allen rom 409,100 in 1990 to 273,500
in 2011. In 2011, it is estimated that 56,100 ma-
ternal deaths will be human immunodeiciency vi-
rusrelated. Twenty developing countries show no
progress towards MDG-5. Current estimates sug-
gest that 31 countries will achieve MDG-4, 13 will
achieve MDG-5, and nine will achieve both targets.
Fourteen countries are likely to achieve both tar-
gets by 2020. Lancet commentators question the
value o requent, diering estimates o progress.
Most developing countries will not achieve the tar-
gets o MDG-4 and MDG-5 until many years ater
2015.
Lozano R et al. Progress towards Millennium Development Goals 4 and 5
on maternal and child mortality: an updated systematic analysis. Lancet
2011; 378: 11391165; Byass P, Graham WJ. Grappling with uncertainties
along the MDG trail. Ibid: 11191120 (comment).
Immunoglobulinforneonatal
sepsis:Noteffective
The results o trials o immunoglobulin as prophy-
laxis or treatment or neonatal sepsis have been
variable, and there is still no consensus about its
value. A large international trial has shown no ben-
eit o intravenous immunoglobulin or the treat-
ment o neonatal sepsis.
At 113 centres in nine countries, a total o
3,493 newborn inants (birth weight < 1,500 g) re-
ceiving antibiotic treatment or proved or suspect-
ed sepsis were randomized to polyvalent IgG immu-
noglobulin 500 mg/kg, or placebo, repeated ater
48 hours. The primary outcome (death or major
disability at age 2 years, adjusted or gestational
age) occurred in 39% o each group. Death beore
hospital discharge occurred in 17% o each group,
and there were no dierences between the groups
in other secondary outcomes.
Treatment with intravenous immunoglobulin
did not aect outcomes.
The INIS Collaborative Group. Treatment o neonatal sepsis with
intravenous immunoglobulin. NEJM 2011; 365: 12011211.
Acyclovirsuppressivetherapy
after treatment of neonatal
herpes
Ater neonatal herpes simplex virus (HSV) inec-
tion, the risk o sequelae depends on the initial
clinical picture. Supericial disease (skin, eye, and
mouth) is associated with a low risk o neurological
impairment, although there may be skin recurrenc-
es. With disseminated disease, there is a 30% mor-
tality rate and a 20% risk o neurological damage in
survivors. Central nervous system (CNS) inection
carries a 6% mortality and a 70% risk o permanent
neurological sequelae. Two paralleled multicentre
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JPOG JAN/FEB 2012 4
trials in the USA, reported together, have shown
that 6 months o oral acyclovir ater initial paren-
teral treatment may be beneicial.The two trials together included 74 neonates
with HSV inection, 29 with supericial disease,
and 45 with CNS involvement. They were treated
with parenteral acyclovir or 14 days (supericial
disease) or 21 days (CNS disease). Randomization
was then to oral acyclovir or placebo three times
daily or 6 months. Acyclovir suppressive therapy
prolonged the time to two cutaneous recurrences
in the CNS disease group but not in the supericial
disease group. Among the 45 inants with initial
CNS disease, three had a CNS recurrence within 12
months o entering the study, one assigned to acy-
clovir and two to placebo. On the Mental Develop-
ment Index o the Bayley Scales o Inant Develop-
ment, perormed at 12 months o age on 28 o the
45 inants, the mean score was signiicantly lower
in the placebo group (68.12) than in the acyclovir
group (88.24). There was a trend towards more neu-
tropenia in the acyclovir group.
Six months o oral suppressive therapy with
acyclovir ater initial parenteral therapy may im-
prove neurodevelopmental outcomes ater neona-
tal HSV inection. An editorialist avours treating
all children with either supericial or CNS disease.
Kimberlin DW et al. Oral acyclovir suppression and neurodevelopment
ater neonatal herpes. NEJM 2011; 365: 12841292; Gershon AA.
Neonatal herpes simplex inection and the three musketeers. Ibid: 1338
1339 (editorial).
Malariaandbacteraemiain
children
Bacteraemia is common in children in sub-Saharan
Arica. Human immunodeiciency virus (HIV) inec-
tion, malnutrition, and sickle-cell disease all con-
tribute to the susceptibility. Malaria is also thought
to make children susceptible to invasive bacterial
inections. Sickle-cell trait (HbAs), however, pro-
vides protection against malaria, and researchers
in Kenya have taken advantage o this to perorm amendelian randomization study.
First, they studied 292 children aged 3
months to 13 years with bacteraemia and 528
control children. Bacteraemia was associated with
sickle-cell disease, HIV inection, undernutrition,
and leukocyte haemozoin pigment. Sickle-cell trait
was associated with a 64% reduction in risk o
bacteraemia. Next, they perormed a longitudinal
case-control study with 1,454 cases (children with
bacteraemia) and 10,749 controls. Between 1999
and 2007, the rate o hospital admission or malaria
ell rom 28.5 to 3.45 admissions per 1,000 child-
years because o more eective malaria control. At
the same time, the protection provided by sickle-
cell trait against bacteraemia ell and hospital
admissions or bacteraemia, largely Gram-negative
bacteraemia including cases due to non-typhoidal
salmonella, decreased in parallel with those or
malaria, rom 2.59 to 1.45 per 1,000 child-years.
Malaria parasitaemia increased the risk o bacte-
raemia 6.7-old. In 1999, the prevalence o para-
sitaemia in the community was 29%, and 62% o
cases o bacteraemia were attributed to malaria.
Malaria control should reduce the preva-
lence o bacteraemia.
Scott JAG et al. Relation between alciparum malaria and bacteraemia
in Kenyan children: a population-based, case-control study and a
longitudinal study. Lancet 2011; 378: 13161323; Obaro S, Greenwood B.
Malaria and bacteraemia in Arican chil dren. Ibid: 12811282 (comment).
Adjuvantedinuenzavaccinefor
children
Many countries recommend seasonal inluenza
vaccination or children, but the trivalent inactivat-
ed vaccine (TIV) produces poor immune responses
in young children. Now, the addition o MF59, an
oil-in-water emulsion, as an adjuvant to TIV, has
been shown to increase the immunogenicity o TIV
and to give greater eicacy.
A total o 4,707 children aged 6 to < 72
months were randomized to TIV without adju-
vant, TIV with adjuvant (ATIV), or a control (non-
inluenza) vaccine. The vaccines were given as
two doses, with an interval o 28 days, during the
inluenza seasons o 20072008 and 20082009 in
Germany and 20082009 in Finland. The rates o
inluenza-like illness were 0.7% (ATIV), 2.8% (TIV),
and 4.7% (controls), and the vaccine eicacy rates
against all inluenza strains were 86% (ATIV) and
43% (TIV). Among children aged 6 to < 36 months,
the eicacy was 79% (ATIV) and 40% (TIV). Among
children aged 36 to < 72 months, the corresponding
eicacies were 92% and 45%. The antibody titres
achieved were greater with ATIV. There were more
systemic reactions with ATIV in the older children.
The rate o adverse reactions was similar in all
three groups.
ATIV was more eicacious than TIV in in-
ants and young children.
Vesikari T et al. Oil-in-water emulsion adjuvant with infuenza vaccine in
young children. NEJM, 2011; 365: 14061416.
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GYNAECOLOGY I PEER REVIEwEd
JPOG JAN/FEB 2012 5
PURPOSE AND SCOPE
This guideline covers the classiication o ovulation disorders, treatment options o vari-
ous ovulation disorders, and their associated risks.
INTRODUCTION
Ovulation disorders account or 20% o the causes o subertility.1 The goal o ovulation
induction is to achieve development o a single ollicle and subsequent ovulation in
women with anovulation. The selection o the most appropriate treatment or ovula-
tion disorders depends upon reaching the correct diagnosis. Patients should be ully
inormed o the treatment options available, the success o each treatment option, and
the associated risks.
CLASSIFICATION
Ovulation disorders can be classiied according to the anatomical site where the hypo-
thalamic-pituitary-ovarian axis is deicient (Table 1). The corresponding World Health
Organization (WHO) classiication2 is also given or reerence (Figure 1).
Adequate history and physical examination are essential. Further investigations
are necessary to pinpoint where the deect in the hypothalamic-pituitary-ovarian axis is
occurring. Based on the results o the investigation, the causes o anovulation can be
divided into our distinct categories.3
HKCOGGuidelinesInductionofOvulation
Yeung Wing Yee Tracy, MBBS (HK), MRCOG, FHKCOG, FHKAM (O&G); Lee Chi Yan Vivian, MBBS (HK), MRCOG, FHKCOG, FHKAM (O&G); Li Hang Wun Raymond, MBBS (HK),
MMedSc (HK), MRCOG, FHKCOG, FHKAM (O&G), Cert RCOG (Reproductive Medicine), Cert HKCOG (Reproductive Medicine);
Ng Hung Yu Ernest, MBBS (HK), MD (HKU), FRCOG, FAMHK (O&G);
for The Hong Kong College of Obstetricians and Gynaecologists
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Hyperprolactinaemia
Hyperprolactinaemia can be ound in 15% o wom-en with anovulation, and in 75% o women with
both anovulation and galactorrhoea.4 It intereres
with the pulsatile secretion o gonadotrophin-re-
leasing hormone (GnRH) and impairs normal ovarian
unction. Causes o hyperprolactinaemia include a
prolactin-producing adenoma, other tumours o the
pituitary region blocking the inhibitory control o
the hypothalamus, primary hypothyroidism, chronic
renal ailure, and a variety o drugs.
Prolactin molecules orm irregular high-
molecular-weight polymers to produce a bio-
logically inactive orm called macroprolactin.
Macroprolactinaemia has no clinical signiicance
and does not require any treatment. It should be
considered in patients with no apparent hyperpro-
lactinaemic symptoms.5 The correct diagnosis can
be made using prolactin chromatography and poly-
ethylene glycol immunoprecipitation. It has been
suggested that routine screening or macroprolactin
Table 1: Classifcation o ovulation disorders
1. Intrinsic ovarian ailure (WHO group III) Genetic, autoimmune, ollowing chemotherapy or
radiotherapy
2. Secondary ovarian dysunction
a. Disorders o gonadotrophin regulation
Specifc Hyperprolactinaemia Kallmanns syndrome (WHO group I)
Functional (WHO group I)
Weight loss, exercise, drugs, idiopathicb. Gonadotrophin defciency (WHO group I)
Pituitary tumour, pituitary necrosis or thrombosis
c. Disorders o gonadotrophin action (WHO group II)
Polycystic ovary syndrome
WHO = World Health Organization.
in sera rom subjects with suspected hyperprolacti-
naemia is cost-eective and should be perormedto prevent inaccurate diagnosis and unnecessary
intervention or hyperprolactinaemia.6
Asymptomatic patients with hyperprolactinae-
mia may not require treatment, and periodic obser-
vation should then suice. When a woman with a
macroprolactinoma wishes to become pregnant, it
is necessary to plan conception to occur ater se-
rum prolactin is normalized and the tumour volume
is signiicantly reduced in order to avoid or reduce
the risk o compression o the optic chiasm during
pregnancy.7
The irst-line treatment is the use o dopa-
mine agonists, which lower prolactin concentration
and cause shrinkage o a prolactinoma i present.
Surgery in the orm o trans-sphenoidal pituitary ad-
enomectomy is seldom indicated in the presence o
a prolactinoma because o high recurrence rate and
possibility o panhypopituitarism.8,9 Radiotherapy
is used very inrequently and is considered onlyi both medical and surgical treatments ail or are
contraindicated.
Hypergonaotrophic Hypogonaism (wHO
Group III)
Hypergonadotrophic hypogonadism or ovarian ail-
ure may be due to chromosomal abnormalities, au-
toimmune disorders, inection (mumps oophoritis),
and irradiation or cytotoxic drugs. Many cases,
however, are idiopathic even ater extensive in-
vestigations. These women present with primary
or secondary amenorrhoea with low endogenous
oestrogen and highly elevated ollicle-stimulating
hormone (FSH) levels. There is no advantage in
perorming laparoscopy and ovarian biopsy to de-
tect the presence o ollicles in the resistant ovary
syndrome because o the invasive nature and the
doubtul value o the procedure.10,11
About hal o young women with spontane
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Figure 1: Flowchart o diagnosis and treatment
ous hypergonadotrophic hypogonadism experienceintermittent and unpredictable ovarian unction,
and spontaneous pregnancies have been reported
in approximately 510% o cases subsequent to
the diagnosis.12 Although there have been case re-
ports o successul ovulation induction treatment,
any orm o ovulation induction is not advisable
in these women. The only realistic treatment or
these patients is the use o donor eggs in an in
vitro ertilization setting. In addition, they should
be oered long-term hormone replacement therapy
to protect their bones rom the deleterious eects
o hypooestrogenism.
Hypogonaotrophic Hypogonaism (wHO
Group I)
These patients present with primary or secondary
amenorrhoea. They have very low serum oestradiol
concentration due to low FSH and luteinizing hor-
mone (LH) secretion rom the pituitary gland (hypog-
onadotrophic hypogonadism). It can be due to eithercongenital causes such as Kallmanns syndrome
(isolated gonadotrophin deiciency and anosmia) or
acquired causes such as pituitary tumour, pituitary
necrosis (Sheehans syndrome), stress, and exces-
sive weight loss (anorexia nervosa).
Surgery is clearly indicated in patients with
central nervous system tumours. Patients with ano-
rexia nervosa may beneit rom psychotherapy and
weight gain ater extensive counselling. Pulsatile
GnRH or gonadotrophins containing both FSH and
LH13 are oered to patients with other hypogonado-
trophic causes or with persisting anovulation de-
spite weight gain.
Normogonaotrophic Anovulation (wHO
Group II)
This includes a heterogeneous group o patients
who can present either with regular cycles, oli-
gomenorrhoea, or even amenorrhoea. The mid-
FSH = follicle-stimulating hormone; GnRH = gonadotrophin-releasing hormone; TSH = thyroid-stimulating hormone.
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luteal serum progesterone is low, FSH levels are in
the normal range, and prolactin is normal. Most othese patients are likely to have polycystic ovary
syndrome (PCOS). Other causes include congenital
adrenal hyperplasia, adrenal tumours, and andro-
gen-producing ovarian tumours. In these conditions,
the patient may have clinical symptoms or signs o
hyperandrogenism such as hirsutism, which should
require more detailed investigations such as meas-
urement o dehydroepiandrosterone sulate and
17-hydroxyprogesterone.
Obese PCOS women will beneit rom weight
loss, as this might lead to resumption o sponta-
neous periods and ovulation and will also improve
their response to ovulation induction. They usu-
ally respond well to clomiphene citrate (CC) or aro-
matase inhibitors, ailing that, to gonadotrophins
or ovulation induction. Insulin-sensitizing agents
or laparoscopic ovarian drilling may be considered
in those not responding to CC. Speciic causes, such
as adrenal or ovarian tumours, should be treated by
removing the cause. Congenital adrenal hyperpla-
sia beneits rom corticosteroid therapy.
TREATMENT
Eective use o ovulation induction agents requires
understanding o their mechanism o action, proper
indications, dierent regimens, monitoring meth-
ods, and potential complications.
weight Reuction
Body mass index (BMI) is more representative o
body at and is calculated as weight in kilogrammes
divided by height in metres squared. Overweight is
deined as BMI 25 kg/m2 and obesity is BMI
30 kg/m2.14 Overweight and obese women have a
higher incidence o menstrual disturbance, ovula-
tion disorders, and subertility.15 They may require
higher dosage o ovulation drugs to achieve suc-
cessul ovulation but have lower ovulation rates
and delayed responses to various treatments oovulation induction, i needed.
Ovulation induction with CC in overweight and
obese women results in lower ovulation rates16 and
lower cumulative live birth rates or women with
a BMI > 30 kg/m2.17 The dose o CC required to
achieve ovulation is positively correlated with body
weight.18 Ovulation rates ollowing gonadotrophin
therapy in overweight women are lower owing to
higher cancellation rates,19,20 but this decreased
success rate is not ound in all studies.21 Women
with BMI o 2528 need a gonadotrophin dose 50%
higher than normal-weight women.22 Obese women
are also more prone to pregnancy complications
such as miscarriage,23 gestational diabetes, hyper-
tension, macrosomia, and diicult delivery.24
Multiple observational studies report that
weight loss is associated with improved spontane-
ous ovulation rates in women with PCOS, 15 even a-
ter losing < 5% o body weight.25 Weight loss
Patients seeking treatment or ovulation disorders should beully inormed o the treatment options available, the success
o each treatment option, and the associated risks.
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is thereore recommended as irst-line therapy in
obese women with and without PCOS seeking preg-nancy. This recommendation is based on extrapola-
tion rom the beneits o weight loss seen in medi-
cal conditions, such as diabetes and cardiovascular
disease. There is a paucity o studies suggesting
that weight loss prior to conception improves live
birth rate in obese women with or without PCOS. 26
The guidelines or dietary and liestyle inter-
vention in PCOS have been proposed.26 Liestyle
modiication is the irst orm o therapy, combining
behavioural (reduction o psychosocial stressors),
dietary, and exercise management. Reduced-energy
diets (5001,000 kcal/day reduction) are eective
options or weight loss and can reduce body weight
by 710% over a period o 612 months . Structured
exercise is an important component o a weight-
loss regime; aim or > 30 minutes per day. These in-
terventions should be conducted prior to pregnancy
and not during ovulation induction, as the eects o
calorie restriction and increased physical activity inthe periconceptional period are unknown.27
Meical Inuction of Ovulation
Dopamine Agonists
Three dopamine agonists, bromocriptine, cabergo-
line and quinagolide, are licensed or treatment o
hyperprolactinaemia. Experience with bromocrip-
tine is ar more extensive, and thereore or women
undergoing ovulation induction this drug remains
the treatment o choice, with cabergoline and quin-
agolide as acceptable second-line drugs in patients
who are intolerant o bromocriptine.28
Mechanism of action. The secretion o
prolactin rom the lactotroph cells in the anterior
pituitary gland is mainly regulated by the tonic
inhibitory control o a prolactin inhibiting actor,
which in humans is predominantly dopamine. Drugs
with dopaminomimetic activity lower prolactin
secretion, restore gonadal unction, and shrink a
prolactinoma, i present.
Regimen and monitoring. Bromocriptine isgiven at a daily dosage o 2.520 mg in divided dos-
es 23 times a day. Serum prolactin concentrations
are regularly measured, and ovulation is checked
by mid-luteal progesterone concentrations. Other
orms o monitoring or ovarian response are not
required, as its use is not associated with multiple
pregnancy or ovarian hyperstimulation syndrome
(OHSS).
Cabergoline and quinagolide have longer bio-
logical hal lives than bromocriptine. Cabergoline
can be taken once or twice weekly and quinagolide
once daily.
In patients who do not ovulate even when
prolactin concentrations are within normal range,
dopamine agonists can be combined with anti-oes-
trogen or gonadotrophin as appropriate.
Results. Bromocriptine can normalize serum
prolactin concentrations in 8090% o patients
with microprolactinomas and about 70% o those
with macroprolactinomas, together with a decrease
in tumour size.7,9 Dopamine agonist therapy restores
ovulation in about 90% o women with anovulation
related to hyperprolactinaemia.
A prospective study suggested that the overall
Experiencewithbromocriptineis
farmoreextensive,andtherefore
forwomenundergoingovulation
inductionthisdrugremains
the treatment of choice
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Period free HRT
Rapid... Symptom relief1
Recommend low dose HRT... Activelle
When its timefor period free HRT
You can trustfirst line, first choice.
Additive... Effect of NETA
1
Reliable... Freedom from periods2
Easy... to switch to3
References:
1) Notelovitz et al, Poster NAMS 1998
2) Johnson et al, Menopause 2002; 9(1):16-22
3) Data on file
Further information is available on request : DKSH Hong Kong Limited Tel : (852) 2895 9668 Fax : (852) 2895 9548 H R T D
2 0 1 0 0 1
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estimated rates o remission at 5 years in patients
treated with bromocriptine were 76% among pa-tients with non-tumoural hyperprolactinaemia, 67%
among those with microprolactinomas, and 57%
among those with macroprolactinomas.29
Cabergoline 30,31 and quinagolide32,33 are shown
to be signiicantly more eective than bromocrip-
tine in restoring normal prolactin concentrations
and ovulatory cycles. Quinagolide is probably less
eective than cabergoline in hyperprolactinaemic
patients.28
It is recommended that the minimal length o
dopamine agonist therapy in patients with prolacti-
noma should be 1 year.7 Normalization o magnetic
resonance imaging prior to the withdrawal o do-
pamine agonists and longer duration o the drug
therapy are signiicant predictors o remission.34 I
a patient has normal prolactin concentrations ater
dopamine agonist therapy or at least 3 years and
the tumour volume is markedly reduced, a trial o
tapering and discontinuation o these drugs maybe initiated. Long-term ollow-up is essential with
close monitoring or recurrent hyperprolactinaemia
and renewed tumour growth.
Side-effects. Side-eects with bromocrip-
tine are common and include nausea, vomiting,
abdominal cramps, vertigo, postural hypotension,
headaches, and drowsiness. Although they are
usually transient and mild, around 12% o pa-
tients discontinue the treatment or this reason.28
The side-eects can be minimized by increasing
the dose gradually rom a low starting dose given
with a meal in the evening, or by administering
vaginal bromocriptine. A slow-release oral prepara-
tion may also reduce the incidence o side-eects.
Signiicantly lesser side eects were reported in
patients taking cabergoline and quinagolide when
compared with bromocriptine.28
There is no increase in the incidence o mul-
tiple pregnancy, OHSS and spontaneous abortion
with dopamine agonists.
Bromocriptine, cabergoline or quinagolide hasnot been associated with any detrimental eect on
pregnancy or etal development.28 It is still recom-
mended that patients with microprolactinomas or
idiopathic hyperprolactinaemia stop bromocriptine
treatment once pregnancy has been conirmed
in order to avoid any potential harmul eects.
Continuation o bromocriptine therapy during preg-
nancy may be considered in cases o macroprolacti-
noma or where there is evidence o tumour expan-
sion.7,9
While there is considerable experience o
bromocriptine use in women undergoing ovula-
tion induction and during pregnancy, data on oth-
er dopamine agonists used in pregnancy are still
limited.
The European Medicines Agency has recom-
mended new warnings and contraindications or
ergot-derived dopamine agonists as a result o the
risk o ibrosis, particularly cardiac ibrosis, associ-ated with chronic use. Cardiac valvulopathy should
be excluded by echocardiography beore treatment
with cabergoline or bromocriptine, and patients
should be monitored during treatment.35 Women
who are planning pregnancy are urther advised to
stop taking cabergoline 1 month beore they try to
conceive.
Anti-oestrogens
Clomiphene citrate
Clomiphene citrate is commonly used as the irst-
line drug in women who suer rom normogonado-
trophic anovulation (WHO group II).
Mechanism of action. It is an orally active
non-steroidal compound with both oestrogenic and
anti-oestrogenic properties with its primary mecha-
nism o action based on the anti-oestrogenic prop-
erty. It displaces endogenous oestrogen rom oes-
trogen receptors in the hypothalamic-pituitary axis,
which diminishes its negative eedback and
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increases the secretion o GnRH and thus gonado-
trophins. The increase in FSH and LH stimulate theproduction o ovarian ollicles and subsequent ovu-
lation.
Regimen and monitoring. CC should be
started at 50 mg per day or 5 days ollowing a
spontaneous or progestin-induced withdrawal
bleeding. The recommended maximum dose is 150
mg per day as there was no clear evidence o e-
icacy at higher doses and the US Food and Drug
Administration (FDA) recommended a maximum o
750 mg per treatment cycle.27 Starting rom day 2,
3, 4 or 5 o the cycle was not shown to inluence
the results.36
Ovulation usually occurs within 510 days
ater the last tablet. I there is no ovulation, the
dose is increased at increments o 50 mg per cycle
until ovulation occurs, or a maximum dose o 150
mg daily is reached.
While 50 mg per day is the recommended dose
in the irst cycle, a meta-analysis o 13 publishedreports suggests that only 46% will ovulate at this
dose, a urther 21% will respond to 100 mg and
another 8% will ovulate with 150 mg per day. 37
Although results o large trials suggest that
monitoring by ultrasound or progesterone is not
mandatory to ensure good outcome,17 it is recom-
mended to monitor the response at least during the
irst treatment cycle to ensure that an appropriate
dose is received.38 Transvaginal pelvic ultrasound
should be used to monitor ollicular growth and
endometrial thickness. Patients who have no or
excessive response to the current dose o CC and
show reduced endometrial thickness can be identi-
ied. Serum progesterone concentrations could also
be measured in mid-luteal phase to check or ovula-
tion.
Duration of treatment. Treatment should
generally be limited to six (ovulatory) cycles. 39 A
course o six ovulatory cycles is usually suicient
to know i pregnancy will be achieved. Studies have
reported that 7187.5% o pregnancies achieved
with CC occur within the irst three cycles o treat-
ment.16,40,41
Further cycles (with a maximum o 12 in to-tal) may be considered on an individual basis ater
discussion with the patient. However, second-line
treatment should be considered or patients not
conceiving ater six ovulatory cycles o CC.
Further use o CC beyond 12 cycles has been
ound to be associated with an increased risk o
ovarian cancer (relative risk [RR], 11.1; 95% coni-
dence interval [CI], 1.582.3)42 and is thus not rec-
ommended.
Results. A compilation o published results
rom 5,268 patients revealed an ovulation rate o
73% per patient, pregnancy rate o 36% per pa-
tient, and live birth rate o 29% per patient.39
A Cochrane meta-analysis43 o three stud-
ies 4446 comparing CC versus placebo in patients
with anovulatory subertility showed a large and
consistent beneit o CC compared with placebo
(odds ratio [OR], 5.77; 95% CI, 1.5521.48; P 4 cm, > 75% eacement) in spon-
taneous labour have a twoold increase in
success rate.1315
Induction o labour or maternal or
etal condition is increasingly common in
obstetric practice. Labour induction and
augmentation in women with previous
caesarean delivery is associated with an
increased risk o uterine rupture. The risk
is highest with misoprostol (6%), ollowed
by prostaglandin E2
(2%) and lowest with
oxytocin (1.1%).16 All the three organiza-
tions discouraged the use o misoprostol
and prostaglandins in most women with
previous caesarean delivery.
Studies on mechanical cervical ripen-
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ing and labour induction with transcervical
catheter were limited and retrospective. The
risk on uterine rupture was inconclusive.1
Induced labour is also associated
with lower success rate o VBAC com-
pared with spontaneous labour. I oxytocin
was used alone or induction or augmen-
tation, the vaginal delivery rate was 62%
(95% conidence interval, CI, 5370%) and
68% (95% CI, 6472%), respectively.17
Although induction o labour is not
contraindicated in women with prior cae-
sarean delivery, the act o lower success
rate together with higher rupture risk
should be considered in the counselling.
Nonetheless, individual circumstanc-
es must be considered in all cases. For ex-
ample, i a patient, who may not otherwisebe a candidate or planned VBAC, presents
in advanced labour, obstetricians may judge
it best to proceed with vaginal delivery.
MATERNAL BENEFIT AND
RISK
Both planned VBAC and ERCS carry mater-
nal and neonatal risks. The risks o either
approach include maternal haemorrhage,
inection, operative injury, thromboembo-
lism, hysterectomy, and death. The risk
o uterine rupture is essentially limited
to the VBAC group. As successul VBAC
is associated with the least complications
while a ailed one with more complica-
tions, careul selection o women who
would most likely deliver vaginally is the
key to management o pregnancy aterprior caesarean section.
Short term
Successul VBAC oers several distinct,
consistently reproducible short-term ad-
vantages compared with ERCS, such as
ewer hysterectomies, ewer thromboem-
bolic events, lower blood transusion rate,
and shorter hospital stay. However, when
VBAC ails, emergency caesarean section
is associated with increased uterine rup-
ture, hysterectomy, operative injury, blood
transusion, endometritis, and longer hos-
pital stay.18 At present, clinical prediction
o the optimal candidate or planned VBAC
remains imprecise.
Long term
It is well-known that caesarean delivery
increases the risk o long-term problems.
Chronic pain is a common condition expe-rienced by some women ater caesarean
delivery. The risk appears to be higher
with increasing number o operations
perormed. A group in Denmark ollowed
up 244 women or chronic pain ater cae-
sarean section. O those women, 18.6%
had pain ater 3 months and 12.3% still
suered rom pain at 10 months ater de-
livery. Furthermore, 5.9% o the women
characterized their pain as being present
daily or almost daily.19 One o the causes
o moderate to severe pelvic pain was
neuropathic pain caused by entrapment o
iliohypogastric or ilioinguinal nerves.20
As with chronic pain, pelvic adhe-
sions increase with the number o cae-
sarean sections. Dense adhesions make
subsequent operation more diicult, and
increase the operating time, blood lossand the risk o injury to the surrounding or-
gans.20 Adhesions were assessed in a co-
hort study involving 3,190 women in Saudi
Arabia.21 Adhesions were described as se-
vere i they were dense or causing usion
o uterus to the abdominal wall or blad-
der. In that study, severe adhesions were
present in 0.2%, 11.5%, 26.0%, 44.8%,
54.5% and 50.6% o women having their
irst, second, third, ourth, ith, and sixth
or more caesarean sections, respectively.
A strong association exists between
previous caesarean delivery and abnormal
placentation. A meta-analysis perormed
by Ananth et al22 showed that a woman
with at least one previous caesarean
was at 2.6 times greater risk o placenta
previa in her subsequent pregnancy. The
risk increased with the number o prior
Both planned vaginal birth after previouscaesarean section and elective repeatcaesarean section carry maternal andneonatal risks.
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Continuing MedicalEducation
caesarean sections.
The most signiicant long-term risk ocaesarean delivery is placenta accreta oc-
curring in subsequent pregnancies. As the
placenta does not properly separate rom
the uterus ater delivery, it may result in
massive bleeding, leading to disseminated
intravascular coagulopathy, multi-organ
ailure and maternal mortality. Even i cae-
sarean hysterectomy is to be perormed as
the lie-saving procedure, the operation
could be diicult with its own set o com-
plications and results in permanent loss o
ertility.20 As with previa, it is certain that
the risk o placental accreta increases with
the number o prior caesarean sections.
The combination o placenta previa and
previous caesarean delivery dramatically
increases the risk urther. In a cohort study
o 723 women with placenta previa, ac-
creta occurred in 3%, 11%, 40%, 61% and67% o those having their irst, second,
third, ourth, and ith or more caesarean
sections, respectively.23
FETALBENEFITANDRISK
Perinatal morbidity and mortality are other
concerns when considering the option o
delivery. The largest population-based
evaluation o perinatal mortality was per-
ormed by Smith et al.24 The rate o deliv-
ery-related perinatal death was signii-
cantly greater in the VBAC group than in the
ERCS group (12.9 vs 1.1 per 10,000 births).
The marked excess o perinatal deaths was
mainly due to uterine rupture in the VBAC
group. What urther complicated the rela-
tive risk is that elective caesarean delivery
at 39 weeks gestation would prevent two
etal deaths per 1,000 live births compared
with expectant management.As with perinatal death, asphyxia-
related injury in VBAC usually occurs a-
ter uterine rupture. In a study by Landon
et al,25 the incidence o hypoxic ischemic
encephalopathy was 0.08% in the VBAC
group compared with 0% in the ERCS
group, at a background uterine rupture rate
o 0.7%.
Sepsis is a requent indication or
admission to the neonatal intensive care
unit. Both maternal ever and prolonged
rupture o membrane greater than 18 hours
are more common in the VBAC group.
Neonates who were born ater ailed VBAC
requiring emergency caesarean delivery
had a signiicantly greater rate o suspect-
ed sepsis.26
Although the evidence suggests an
increased perinatal risk or women un-dergoing VBAC, the absolute numbers o
serious morbidity and mortality remain
low. One should also note that a large
proportion o women undergoing VBAC
would deliver successully. In act, there
are numerous beneicial eects o labour
and vaginal delivery to the newborn. Even
at term gestation, babies born vaginally
are at lower risk o respiratory morbidity
(respiratory distress syndrome or transient
tachypnoea o newborn) compared with
those born by prelabour caesarean sec-
tion.27,28 This inding was demonstrated by
a large cohort study29 in Denmark involving
34,458 babies over 9 years. The risk o res-
piratory morbidity or inants delivered by
elective caesarean section was increased
compared with that by the vaginal route at
37 weeks gestation (odds ratio, OR, 3.9;
95% CI, 2.46.5), 38 weeks gestation (OR,
3.0; 95% CI, 2.14.3) and 39 weeks gesta-tion (OR, 1.9; 95% CI, 1.23.0). A same
pattern was observed or risk o serious
respiratory morbidity at an even higher
odds ratio at 37 weeks gestation (OR 5.0;
95% CI, 1.616.0). This is the reason why
most authorities recommend that ERCS be
perormed ater 39 weeks gestation. Other
potential beneits o vaginal delivery are
the lower risk o hypothermia and hypoten-
sion at birth, higher likelihood o success-
ul breasteeding, and lower incidence o
asthma in childhood.28
NON-MEDICALFACTORS
Despite the numerous research-based evi-
dence on the saety o trial o labour ater
caesarean section, the VBAC rate remains
low in some developed countries such asthe United States (8.5% in 2006). It is ap-
parent that some non-clinical actors play
a role in the decision-making.
The actors which might aect VBAC
rate in an institution include administrative
policies, medicolegal pressures, proes-
sional society guidelines, and patient and
obstetrician preerences.
According to a survey by Wells30 in the
United States, reasons or obstetricians
not oering VBAC included (1) them be-
ing unwilling to accept the risk o adverse
outcome, (2) them not believing that VBAC
is sae, (3) medico-legal liability concerns,
and (4) lack o immediate availability o a-
cilities or laparotomy.
The decision may also be aected by
non-clinical patient priorities, such as pa-
tients desire or a vaginal delivery, her
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JPOG JAN/FEB 2012 50
wish to experience (or avoid) labour, her
need or scheduling the delivery, and herpositive or negative eeling about the pre-
vious delivery.31 It is important to discuss
with the women their risk perception and
priorities when considering the mode o
delivery.
COUNSELLING AND
DECISION-MAKING
Depending on the clinical situation, either
planned VBAC or ERCS is usually appropri-
ate or most women with prior caesarean
delivery. Understanding the womens be-
lies and values o the process and out-
come is essential in providing evidence-
based, patient-centred care.32 Discussing
the options in early pregnancy allows the
women and their amily to evaluate the
risks and beneits based on their ownperception. While patient pamphlets play
an important role in general inormation-
giving, the obstetricians advice should
be more speciic to the individuals condi-
tion. The decision made in early pregnancy
should never be considered inal, as medi-
cal and social circumstances continue to
evolve. For instance, women who intend to
deliver by ERCS might present with spon-
taneous labour beore the scheduled date.
I labour progresses well and the chance
o a successul VBAC is high, she might
change her preerence to vaginal delivery.
According to the international guidelines,
ERCS should be scheduled ater 39 weeks
gestation in an otherwise uncomplicated
pregnancy.1
I a woman does not show any strong
preerence regarding the mode o delivery
in early pregnancy, planned VBAC could be
encouraged with the lexibility o a laterchange o plan. A local study has been
conducted to assess the psychological im-
pact o women being assigned to the mode
o delivery.33 It involved 298 women, who
showed no preerence or VBAC or ERCS,
being randomly assigned to either option
with lexibility. Women in the planned
VBAC group achieved high success rate o
vaginal delivery (73%) without an increase
in the psychological stress and morbidity.
EXPERIENCE FROM A PUBLIC
OBSTETRIC UNIT
Kwong Wah Hospital is one o the eight
public hospitals in the Hong Kong terri-
tory providing obstetric service. There are
almost 6,000 deliveries annually. Women
receive obstetric service at minimal per-
sonal cost, as the service is largely unded
by the government. Obstetricians and mid-
wives are salaried, and the advices given
are thereore not inluenced by personal
inancial gain. Women with history oprior caesarean deliveries are assessed by
obstetricians at the booking visit. The pre-
vious operation records are traced via the
electronic system o the public hospitals
or by an enquiry letter to the correspond-
ing obstetricians/hospitals. Planned VBAC
is oered to women with one previous
uncomplicated transverse lower segment
caesarean delivery. Inormation pamphlets
on planned VBAC and ERCS are given out
during antenatal visits. The pregnancy
conditions are continuously reviewed. The
mode o delivery is discussed beore 37
weeks gestation and documented in the
record. Women who have no strong pre-
erence or either option are encouraged to
consider planned VBAC when the pregnan-
cy conditions are avourable. Women who
intend to undergo ERCS are orewarned oa possible re-evaluation o the mode o
delivery i they present themselves in an
advanced stage o labour. All women at-
tempting VBAC receive electronic continu-
ous etal heart monitoring during labour.
Labour progress is assessed regularly by
the obstetricians. Facilities and expertise
or emergency operation are available in
the delivery suite. The authors experience
over a 4-year period is shown in the Table.
CONCLUSION
At present, there is no reliable ormula
to calculate the best mode o delivery
in women with prior caesarean section.
This should be a shared decision made by
the obstetricians and the women, in-
corporating medical actors, social
Successful VBAC carries
thelowestrisk,
followedbyERCS,
andtheriskishighest
withfailedVBAC,
requiring caesarean
delivery.
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JPOG JAN/FEB 2012 51
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circumstances and patients preerences.
Successul VBAC carries the lowest risk,ollowed by ERCS, and the risk is high-
est with ailed VBAC, requiring caesarean
delivery.
Although uterine rupture increases
the risk o adverse outcome, it is still a rare
complication in high-resource settings.
The incidence has remained the same
(< 1%) in UK, where the rate o primary
caesarean section has increased over thepast decade. Moreover, the resulting seri-
ous adverse outcome ater uterine rupture
is very low in absolute number.
Given the high success rate o VBAC
in careully selected pregnancies, obste-
tricians should not overstate the risk and
consequence o uterine rupture so as to
turn women away rom attempting VBAC
without balancing the short- and long-term complications o ERCS.
AbouttheAuthorsDr Yung is Associate Consultant, Dr Lau is Consultant, and
Dr Leung is Chie o Service at the Department o Obstet-
rics and Gynaecology, Kwong Wah Hospital, Hong Kong.
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CME Questions
This continuing medical education service is brought to you by the Medical Progress Institute, an institutededicated to CME learning. Read the article Management of Pregnancies With Previous Caesarean
Section and answer the following questions. This JPOGarticle has been accredited for CME by the Hong
Kong College of Obstetricians and Gynaecologists.
CME Answers for JPOG Nov/Dec 2011Name in BLOCK CAPITALS:
CME Article
Management of Pregnancies With Previous Caesarean Section
Answer True or False to the questions below.
1. Previous classical caesarean section is a contraindication to planned vaginal birth ater previouscaesarean section (VBAC).
2. Patients with unknown type o previous caesarean scar should not be oered planned VBAC.
3. Obese patients (body mass index, BMI, > 30) should not be oered planned VBAC, as high BMI isassociated with a low success rate.
4. Spontaneous labour increases the likelihood o successul VBAC.
5. Continuous electronic etal monitoring should be oered to all women attempting VBAC.
6. Labour induction and augmentation by oxytocin are associated with increased risk o uterine rupture in
patients with prior caesarean delivery.
7. The risk o placenta previa/placenta accreta is directly related to the number o previous caesareandeliveries.
8. Perinatal mortality and asphyxia-related etal injury are more signifcant in the VBAC group comparedwith the elective repeat caesarean section (ERCS) group.
9. Babies who are born vaginally are at lower risk o respiratory morbidity in both the short and long term.
10. Women who decline planned VBAC should be oered ERCS at 37 weeks gestation in order to avoidspontaneous labour beore the scheduled operation.
True False