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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 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


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


Dr Siu-Keung Lam

Kwong Wah Hospital, Hong Kong

Professor Terence Lao

Chinese University o Hong Kong

Dr Kwok-Yin Leung


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


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

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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

p=0.009 vs baseline

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Bifdobacterium lactisand Lactobacillus paracaseiurther increasebowel movements to target age-specic needs in growing children2

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after 28 days of feeding

M

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Publisher

Ben Yeo

Publication Manager

Marisa Lam

Deputy Managing Editor

Greg TownAssociate EditorGrace Ling

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Designer

Connie Lim

Production

Edwin Yu, Ho Wai Hung,Jasmine Chay

Circulation

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Published by:UBM Medica Pacifc Limited27th Floor, OTB Building160 Gloucester Road,Wan Chai, Hong KongTel: (852) 2559 5888

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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

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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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Vol. 38 No. 1


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


13/59

JPOG JAN/FEB 2012 6

GYNAECOLOGYGYNAECOLOGY I Peer revIewed

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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JPOG JAN/FEB 2012 7


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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JPOG JAN/FEB 2012 8


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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JPOG JAN/FEB 2012 9


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


17/59

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


18/59

JPOG JAN/FEB 2012 11


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


19/59



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-


55/59


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.


56/59


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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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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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.


59/59

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

jpog february 2012 hk

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