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Preconception Care

Dietary Intervention in Eczema

PAEDIATRICS

CME ARTICLE

JOURNAL WATCH

OBSTETRICS

Infectious Disease in Pregnancy

Newborn Stem Cells: Types, Functions and Basics

for Obstetricians

JAN/FEB 2012 Vol. 38 No. 1

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Your partner in paediatric and O&G practice

NOV/DEC 2012 Vol. 38 No. 6 Your partner in paediatric and O&G practice

NOV/DEC 2012

Vol. 38 No. 6


Journal Watch

221 • Hormonalcontraceptionandcardiovascularrisk

• Midurethralslingduringvaginalprolapsesurgerytoreduce postoperativeincontinence

• Effectofcontraceptiononmaternalmortalityrates

222 • Cumulativebirthrateswithassistedreproduction

• Urinaryprotein-to-creatinineoralbumin-to-creatinineratiotodetect significantproteinuriainpregnancy

• Reducingmeaslesmortality

223 • TheMillenniumVillagesprojectinAfrica

• Managementoftype2diabetesinchildrenandadolescents

• Treatmentforinfantsofmotherswhopresentlateinpregnancywith anuntreatedHIV-1infection

• Zidovudine,lamivudine,andritonavir-boostedlopinavirforHIV- infectedchildren

224 • Neonatalscreeningwithpulseoximetryforcriticalcongenitalheart defects:Systematicreviewandmeta-analysis

• Oralimmunotherapyforeggallergyinchildren

Board Director, Paediatrics

Professor Pik-To CheungAssociate ProfessorDepartment of Paediatrics and Adolescent MedicineThe University of Hong Kong

Board Director, Obstetrics and Gynaecology

Professor Pak-Chung HoHead, Department of Obstetrics and GynaecologyThe University of Hong Kong

Editorial Board Professor Biran AffandiUniversity of Indonesia

Dr Karen Kar-Loen ChanThe University of Hong Kong

Associate Professor Oh Moh ChayKK Women’s and Children’s Hospital, Singapore

Associate Professor Anette JacobsenKK Women’s and Children’s Hospital, Singapore

Professor Rahman JamalUniversiti Kebangsaan Malaysia

Dato’ Dr Ravindran JegasothyHospital Kuala Lumpur, Malaysia

Associate Professor Kenneth KwekKK Women’s and Children’s Hospital, Singapore

Dr Siu-Keung LamKwong Wah Hospital, Hong Kong

Professor Terence LaoChinese University of Hong Kong

Dr Kwok-Yin LeungThe University of Hong Kong

Dr Tak-Yeung LeungChinese University of Hong Kong

Professor Tzou-Yien LinChang Gung University, Taiwan

Professor Somsak LolekhaRamathibodi Hospital, Thailand

Professor Lucy Chai-See LumUniversity of Malaya, Malaysia

Professor SC NgNational University of Singapore

Professor Hextan Yuen-Sheung NganThe University of Hong Kong

Professor Carmencita D PadillaUniversity of the Philippines Manila

Professor Seng-Hock QuakNational University of Singapore

Dr Tatang Kustiman SamsiUniversity of Tarumanagara, Indonesia

Professor Perla D Santos OcampoUniversity of the Philippines

Associate Professor Alex SiaKK Women’s and Children’s Hospital, Singapore

Dr Raman SubramaniamFetal Medicine and Gynaecology Centre, Malaysia

Professor Walfrido W Sumpaico MCU-DFT Medical Foundation, Philippines

Professor Cheng Lim TanKK Women’s and Children’s Hospital, Singapore

Associate Professor Kok Hian TanKK Women’s and Children’s Hospital, Singapore

Dr Surasak TaneepanichskulChulalongkorn University, Thailand

Professor Eng-Hseon TayThomson Women’s Cancer Centre, Singapore

Professor PC WongNational University of Singapore

Dr George SH YeoKK Women’s and Children’s Hospital, Singapore

Professor Hui-Kim YapNational University of Singapore

Professor Tsu-Fuh YehChina Medical University, Taiwan

221

224

JPOG NOV/DEC 2012 • i

JPOG_NovDec_2012_TOC.indd 1 12/11/12 3:54 PM

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NOV/DEC 2012

Vol. 38 No. 6


Enquiries and Correspondence

225

JPOG NOV/DEC 2012 • ii

Publisher Ben YeoPublication Manager Marisa LamManaging EditorGreg TownAssociate Editor Grace LingDesignersAgnes Chieng, Sam ShumProduction Edwin Yu, Ho Wai Hung, Steven Cheung Circulation Christine ChokAccounting Manager Minty KwanAdvertising CoordinatorJenny Lim

Published by: UBM Medica Pacific Limited27th Floor, OTB Building160 Gloucester Road, Wan Chai, Hong KongTel: (852) 2559 5888Email: [email protected]

PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is published 6 times a year by UBM Medica, a division of United Business Media. CIRCULATION: JPOG is a controlled circulation for medical practitioners in South East Asia. It is also available on subscription to members of allied professions. SUBSCRIPTION: The price per annum is US$42 (surface 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 by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great care has been taken in compiling and checking the information 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 way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. COPYRIGHT: © 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, in any language, without written consent of copyright owner. Permission to reprint must be obtained from the publisher. ADVERTISEMENTS are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Philippine edition: Entered as second-class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.

ChinaYang XuanTel: (86 21) 6157 3888Email: [email protected]

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Review ArticlePaediatrics

225 DietaryInterventioninEczema

Eczema is a chronic inflammatory dermatosis that usually manifests in early childhood. The precise aetiology and pathogenesis of eczema are not yet fully understood, but a complex interaction between genetic and environmental factors has been implicated in the predisposition and development of the disease.

Jackelina Pando Kelly, Jonathan Hourihane

Review ArticleObstetrics

234 InfectiousDiseaseinPregnancy

Most infections during pregnancy will not cause long-term harm, but those that do should be recognized and treated. This review outlines prevention and screening for infections, maternal infection syndromes, important organisms with their clinical effects and management in pregnancy, and those infections that may lead to congenital abnormalities.

Sarah Logan, Laura Price

234


NOV/DEC 2012

Vol. 38 No. 6


JPOG NOV/DEC 2012 • iii

ReviewArticlesComprehensive reviews providing the latest clinical information on all aspects of the management of medical conditions affecting children and women.

CaseStudiesInteresting cases seen in general practice and their management.

PictorialMedicineVignettes of illustrated cases with clinical photographs.

For more information, please refer to the Instructions for Authors on our website www.jpog.com, or contact:The EditorUBM Medica Asia Pte Ltd, 6 Shenton Way, #15-08 DBS Building Tower 2, Singapore 068809Tel: (65) 6290 7400 Fax: (65) 6290 7401 E-mail: [email protected]

The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence from UBM Media LLC. The articles appearing on pages 49–53, and pages 67–80 are reprinted with permission of Consultant for Pediatricians. Copyright © 2011 UBM Media LLC. All rights reserved.

Review ArticleObstetrics

247 NewbornStemCells:Types,FunctionsandBasicsforObstetricians

This article provides a basic knowledge of newborn stem cells and their potential clinical and cryopreservation opportunities, to assist obstetricians in their important role of educating expectant mothers.

Jennifer Sze Man Mak, Juan Bolaños, Wing Cheong Leung, Richard Boyd, Robert Kien Howe Chin

Continuing Medical Education

257 PreconceptionCare

The evidence for the effectiveness of commonly practised preconception care will be examined in this article. A practical checklist for preconception care in the primary health care setting will also be provided. Lee Chin Peng

264 2012AnnualIndex

3 SKP

Lisa Low, Illustrator

The Cover:Infectious Disease in Pregnancy

© 2012 UBM Medica

247

257

Indonesia


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Journal Watch

JPOG NOV/DEC 2012 • 221

Peer reviewed

GYNAECOLOGY

Hormonal contraception and

cardiovascular risk

A Danish registry study has provided more data

about cardiovascular risks associated with hor-

monal contraception.

Data were obtained from four national reg-

istries over a 15-year period about non-pregnant

women aged 15–49 with no history of cardiovascu-

lar disease or cancer. The data included 1,626,158

women with 14,251,063 person-years of observa-

tion, during which there were 3,311 thrombotic

strokes and 1,725 myocardial infarctions. The rate

of thrombotic stroke was 21.4 per 100,000 per-

son-years and of myocardial infarction, 10.1 per

100,000 person-years. Among women using oral

contraceptives including ethinyl oestradiol at a

dose of 30–40 µg, the risk of thrombotic stroke was

increased 1.5- to 2.2-fold according to progestin

type, compared with non-users. The risk of myocar-

dial infarction was increased 1.3- to 2.3-fold. At an

ethinyl oestradiol dose of 20 µg, the increase in risk

was less in general, and there was no increased

risk with drospirenone as the progestin. Transder-

mal patches were not associated with significantly

increased risk for either thrombotic stroke or myo-

cardial infarction. Vaginal ring was associated with

a significant 2.5-fold increase in risk of thrombotic

stroke but a non-significant increase in risk of myo-

cardial infarction.

Although hormonal contraception may in-

crease the risks of thrombotic stroke and myocar-

dial infarction, the absolute risks are low. An edito-

rialist concludes that they are ‘safe enough’.

Lidegaard Ø et al. Thrombotic stroke and myocardial infarction with hormonal contraception. NEJM 2012; 366: 2257–2266; Petitti DB. Hormonal contraceptives and arterial thrombosis – not risk-free but safe enough. Ibid: 2316–2318 (editorial).

Midurethral sling during vaginal prolapse surgery to reduce post-operative incontinence

About a quarter of women undergoing surgery for

pelvic organ prolapse who had no urinary incon-

tinence before surgery will develop incontinence

after surgery. The prophylactic insertion of a mi-

durethral sling during prolapse surgery has become

popular without good evidence of its effectiveness.

A multicentre US trial has been reported.

A total of 337 women undergoing prolapse

surgery but without a history of stress incontinence

were randomized to insertion of a midurethral sling

or a control group (sham incisions) and 327 women

were followed up for 1 year. At 3 months, there

was a significant reduction in urinary incontinence

in the urethral sling group (23.6% vs 49.4%). At 12

months, the rates of incontinence were 27.3% vs

43.0%. The number needed to treat to prevent one

case of urinary incontinence at 12 months was 6.3.

Bladder perforation occurred in 6.7% of the ure-

thral sling group but in none of the control group.

There were significant increases in the sling group

in urinary tract infection (31.0% vs 18.3%), major

bleeding (3.1% vs 0%), and incomplete bladder

emptying 6 weeks after surgery (3.7% vs 0%).

The insertion of a midurethral sling was ef-

fective in reducing the risk of postoperative urinary

incontinence but at the expense of increased risk

of complications.

Wei JT et al. A midurethral sling to reduce incontinence after vaginal prolapse repair. NEJM 2012; 366: 2358–2367; Iglesia CB. Vaginal prolapse repair – place midurethral sling now or later: Ibid: 2422–2424 (editorial).

Effect of contraception on maternal mortality rates The Safe Motherhood Initiative begun in 1987 has

four strategies to reduce maternal mortality: family

planning, antenatal care, safe delivery, and postna-

tal care. Now, the effects of contraceptive use on

maternal mortality worldwide have been estimated

from three international databases.

Data were analysed from 172 countries for

2008. The number of deaths from maternal causes

in 2008 was estimated at 342,203 (data from 172

countries). The estimated number of maternal

deaths averted by contraception was 272,040, a

44% reduction of the potential total. It was also

estimated that expansion of contraceptive use

could avert another 104,000 maternal deaths each

year. The number of deaths averted increased with

increased contraceptive use. In countries with high

(> 65%) contraceptive use, almost 60% of potential

maternal deaths were averted, whereas in sub-Sa-

haran Africa (22% contraceptive use), only 32% of

potential maternal deaths were averted.

Increased use of contraception could prevent

many maternal deaths in developing countries.

Ahmed S et al. Maternal deaths averted by contraceptive use: an analysis of 172 countries. Lancet 2012; 380: 111–125; Gilmore K, Gebreyesus TA. What will it take to eliminate preventable maternal deaths? Ibid: 87–88 (comment).

JPOG_NovDec_2012_COMBINE.indd 221 12/11/12 4:43 PM


Cumulative birth rates with

assisted reproduction

Rates of live birth with assisted reproductive tech-

nology have usually been reported per cycle, but for

women undergoing continuous treatment, cumula-

tive live-birth rates are more relevant. A national

US database has been used to estimate cumulative

rates.

Data were available for 246,740 women

(471,208 cycles, 140,859 live births). Live-birth

rates decreased with increasing maternal age and

increasing cycle number with autologous, but not

with donor, oocytes. Conservative and optimal es-

timates of live-birth rates by the third cycle with

autologous oocytes were 63.3% and 74.6% for

women < 31 years old, 18.6% and 27.8% at ages 41

and 42, and 6.6% and 11.3% at age 43 or older. Us-

ing donor oocytes, the corresponding figures were

60% and 80% at all ages. Rates were higher with

blastocyst embryos (transfer at day 5 or 6) than

with cleavage embryos (day 2 or 3).

Live-birth rates similar to natural fecundity

can be achieved with favourable maternal and

embryo characteristics. The use of donor oocytes

eliminates the decline in live-birth rates with age

seen when autologous oocytes are used.

Luke B et al. Cumulative birth rates with linked assisted reproductive technology cycles. NEJM 2012; 366: 2483–2491.

Urinary protein-to-creatinine or

albumin-to-creatinine ratio to

detect significant proteinuria in

pregnancy

A systematic review and meta-analysis has ad-

dressed the use of spot urine protein-to-creatinine

or albumin-to-creatinine ratio to detect significant

proteinuria in pregnancy in the diagnosis of pre-

eclampsia.

The analysis included 20 studies (2,978

women). Threshold values for protein-to-creatinine

ratio ranged from 0.13 to 0.5 with sensitivity val-

ues between 0.65 and 0.89 and specificity of 0.63

to 0.87 for the detection of 24-hour urinary protein

> 0.3 g/day. The optimum threshold values for pro-

tein-to-creatinine ratio appeared to be 0.30–0.35.

There was insufficient evidence about the use of

albumin-to-creatinine ratio. One study suggested

that a value of > 2 mg/mmol was associated with

a sensitivity and a specificity both of 0.94. There is

insufficient evidence about the use of either test to

predict adverse pregnancy outcome.

Urinary protein-to-creatinine ratio may be

useful in the diagnosis of pre-eclampsia, but there

is insufficient evidence about the use of albumin-

to-creatinine ratio for this purpose or about the

use of either test to predict adverse pregnancy

outcome.

Morris RK et al. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis. BMJ 2012; 345: (July 21): 14 (e4342).

Reducing measles mortality

One global goal was to halve measles deaths be-

tween 1999 and 2005, and that was achieved. A

new goal was then set to reduce measles mortality

by 90% between 2000 and 2010. There has been no

endemic measles virus transmission in the Ameri-

cas since 2002, and only the southeast Asia region

of the World Health Organization has not set an aim

of measles elimination by 2020. Measles mortality

fell by an estimated 74% between 2000 and 2010,

from 535,300 to 139,300 deaths. All regions except

southeast Asia achieved a reduction of > 75%. In

India, measles deaths fell by 25% from 88,000 to

65,500. In 2010, almost half (47%) of all deaths

from measles were in India and 56% were in Africa.

Achievement of the 2000–2010 goal was impeded

by delayed implementation of disease control in

India and outbreaks of measles in Africa. Greater

political and financial commitment are needed.

Simons E et al. Assessment of the 2010 global measles mortality reduction goal: results from a model of surveillance data. Lancet 2012; 379: 2173–2178; Orenstein WA, Hinman AR. Measles: the burden of preventable deaths. Ibid: 2130–2131 (comment).

OBSTETRICS

PAEDIATRICS


Journal Watch


Peer reviewedPeer reviewed

The Millennium Villages project in

Africa

The Millennium Villages project began in nine

African countries (Nigeria, Mali, Senegal, Ghana,

Uganda, Kenya, Rwanda, Tanzania, and Malawi)

in 2006. In each country, a rural population (aver-

age, 35,000 people) with high levels of poverty and

undernutrition was selected. Finance amounting to

around US$120 per person was provided annually

to support agriculture, the environment, business

development, education, infrastructure, and health,

in partnership with communities and local govern-

ments. Average spending per person was $27 at

baseline and $116 by year 3. There were improve-

ments in water supplies and sanitation, poverty

levels, food security, stunting, and malaria preva-

lence at Millennium Village sites after 3 years.

Under-5s mortality fell by 22% in these sites and

by 33% relative to matched comparison sites. Pro-

vision of many maternal–child health interventions

was improved.

The multifaceted intervention was beneficial

in several ways including reduced child mortality.

Pronyk PM et al. The effect of an integrated multisector model for achieving the Millennium Development Goals and improving child survival in rural sub-Saharan Africa: a non-randomised controlled assessment. Lancet 2012; 379: 2179–2188; Malenga G, Molyneux M. The Millennium Villages project. Ibid: 2131–2133 (comment).

Management of type 2 diabetes

in children and adolescents

The increased prevalence of obesity in children and

adolescents has led to an increased incidence of

type 2 diabetes. The physical and emotional chal-

lenges of adolescence, together with the increased

frequency of obesity and diabetes in underprivi-

leged communities, add to the difficulties of diabe-

tes control. Three treatment approaches have been

compared in a US multicentre trial.

who have not received antiretroviral therapy in

pregnancy is uncertain. Three regimens have been

compared in an international trial.

A total of 1,684 bottle-fed infants of moth-

ers who received a diagnosis of HIV-1 infection late

in pregnancy were randomized within 48 hours of

birth in Brazil, South Africa, Argentina, or the USA

to one of three treatment regimens: zidovudine for

6 weeks (Z6), zidovudine for 6 weeks plus three

doses of nevirapine in the first 8 days (Z6 + Nev), or

zidovudine for 6 weeks plus nelfinavir and lamivu-

dine for 2 weeks (Z6 + Nelf L). The overall rate of in

utero HIV transmission was 5.7% and was the same

in all three groups. Transmission during labour oc-

curred in 4.8% (Z6), 2.2% (Z6 + Nev), and 2.4% (Z6

+ Nelf L). Overall, 8.5% of infants were infected by

3 months, 11.0% in the Z6 group, 7.1% in the Z6

+ Nev group, and 7.4% in the Z6 + Nelf L group,

a significantly greater rate in the zidovudine-only

group compared with the other two groups. HIV-1

transmission was significantly associated with zi-

dovudine monotherapy, higher maternal HIV load,

and maternal use of illegal substances. Neutrope-

nia occurred in 16.4%, 14.9%, and 27.5% of the

three groups, respectively.

The Z6 + Nev and Z6 + Nelf L regimens were

more effective than the Z6 regimen, and the Z6 +

Nev was less toxic than Z6 + Nef L.

Nielsen-Saines K et al. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. NEJM 2012; 366: 2368–2379.

Zidovudine, lamivudine, and

ritonavir-boosted lopinavir for

HIV-infected children

For mothers and infants, who have previously been

exposed to nevirapine, treatment of human immu-

nodeficiency virus (HIV)-1 infection with a regimen

including ritonavir-boosted lopinavir is better than

A total of 699 patients aged 10–17 years

with type 2 diabetes (mean duration, 7.8 months)

and obesity (body mass index, 85th percentile or

higher for age and sex) were randomized to metfor-

min alone (M), metformin plus rosiglitazone (MR),

or metformin plus a weight-loss lifestyle interven-

tion (MW). Over an average follow-up of 3.9 years,

loss of glycaemic control (glycated haemoglobin at

least 8% for 6 months or sustained metabolic de-

compensation needing insulin) occurred in 45.6%

of participants overall. The group rates for this

outcome were 51.7% (M), 38.6% (MR), and 46.6%

(MW). MR was significantly better than M, but MW

was not significantly different from M or MR.

MR was the best of the three options. Most

young people with type 2 diabetes will probably

need combination drug therapy or insulin within a

few years of diagnosis.

TODAY Study Group. A clinical trial to maintain glycemic control in youth with type 2 diabetes. NEJM 2012; 366: 2247–2256; Allen DB. TODAY – a stark glimpse of tomorrow. Ibid: 2315–2316 (editorial).

Treatment for infants of mothers

who present late in pregnancy

with an untreated HIV-1 infection

The best treatment for infants of mothers with

human immunodeficiency virus (HIV)-1 infection



treatment with a nevirapine-based combination.

The best treatment for children not previously ex-

posed to nevirapine is uncertain. Now, a trial in

six countries in sub-Saharan Africa and India has

shown that a ritonavir-boosted lopinavir-based reg-

imen is better than a nevirapine-based regimen for

young children who are nevirapine-naive.

A total of 287 nevirapine-naive HIV-infected

children aged 2–36 months were randomized to zi-

dovudine and lamivudine with either nevirapine or

ritonavir-boosted lopinavir. The median proportion

of CD4+ T-cells was 15% and median plasma HIV-1

RNA level 5.7 log10 copies/mL. Virological failure or

treatment discontinuation by week 24 occurred in

significantly more children in the nevirapine group

(40.8% vs 19.3%). Drug resistance was present in

19 of 32 children in the nevirapine group tested at

the time of virological failure. Mortality was great-

er in the nevirapine group (10/147 vs 3/140), and

drug toxicity was also greater.

The results were better with the ritonavir-

boosted lopinavir-based regimen, but these re-

searchers point to difficulties in introducing this

avoidance may be difficult. Now, a multicentre

US trial of oral immunotherapy has given positive

results.

The trial included 55 children aged 5–11

years with egg allergy without a history of severe

anaphylaxis. All had raised levels of egg-specific

IgE. Randomization was to oral immunotherapy (40

children) or placebo (15 children). Immunotherapy

consisted of giving egg white powder in three

phases, in increasing doses up to 2 g per day. Chal-

lenges with egg white were performed at 10 and

22 months. After a 5-g challenge at 10 months,

no allergic symptoms (or mild symptoms) occurred

in 55% (immunotherapy) vs none (placebo). At 22

months, 75% of children in the immunotherapy

group passed a 10-g challenge. At 24 months, 29

of the 30 children who passed the 22 months’ chal-

lenge were re-challenged and 11 passed. All of

the children who passed the 24 months’ challenge

were able to eat egg at 30 and 36 months.

Oral immunotherapy may be successful in

some children with egg allergy.

Burks AW et al. Oral immunotherapy for treatment of egg allergy in children. NEJM 2012; 367: 233–243.

treatment: the liquid formulation is unpleasant to

taste and deteriorates in hot temperatures, and the

cost is twice that of the nevirapine-based regimen.

New drug formulations are needed urgently.

Violari A et al. Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children. NEJM 2012; 366: 2380–2389.

Neonatal screening with pulse

oximetry for critical congenital

heart defects: Systematic review

and meta-analysis

Babies with congenital heart defects may be dis-

charged from hospital before a diagnosis is made

and may subsequently become suddenly and criti-

cally ill. A new systematic review and meta-anal-

ysis has confirmed that pulse oximetry screening

of asymptomatic newborn babies is highly specific

and moderately sensitive for the detection of criti-

cal congenital heart defects.

The review included 13 studies (229,421 ba-

bies). The sensitivity of pulse oximetry was 76.5%

and the specificity 99.9%. The false-positive rate

was 0.50% in the first 24 hours after birth and

0.05% when done later.

It is concluded that pulse oximetry screening

should be introduced widely.

Thangaratinam S et al. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379: 2459–2464; Kemper AR, Martin GR. Screening of newborn babies: from blood spot to bedside. Ibid: 2407–2408 (comment); The Lancet. A new milestone in the history of congenital heart disease. Ibid: 2401 (editorial).

Oral immunotherapy for egg

allergy in children

By the age of 2.5 years, around 2.5% of children

have developed egg allergy. Complete dietary


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Imaging Paediatric Brain Tumours

Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology

PAEDIATRICS I Peer revIewed


INTRODUCTION

Eczema, also known as atopic dermatitis has been proposed as a cutaneous manifes-

tation of a systemic disorder that also gives rise to asthma, food allergy, and allergic

rhinitis. It is a common, chronic, pruritic, and relapsing inflammatory dermatosis that

typically manifests during early childhood.

The current prevalence of eczema in developed countries is about 20%, represent-

ing a twofold to threefold increase during the past decades. The reason for this increase

remains unclear.

PATHOGENESIS

The pathophysiology of eczema is not yet fully understood. An interaction between

genetic and environmental factors has been implicated in the predisposition and

development of the disease. Eczema is associated with abnormalities in genes encod-

ing skin barrier molecules (filaggrin), markers, and cells of the inflammatory response;

immunoregulatory abnormalities; increased serum immunoglobulin E (IgE); impaired

delayed hypersensitivity reaction; and infectious agents.

Research has demonstrated that a combination of food allergy, defects in the gut

mucosal barrier, and increased intestinal permeability may be complicit in the pathogen-

esis of eczema. Therefore, dietary manipulation could be of use in controlling or prevent-

ing the disease, but this still remains controversial.

It is important to remember that food allergy and eczema coexist due to their com-

mon origins as manifestations of an allergic diathesis, but that one may not automatically

be implicated as a cause of the others.

Dietary Intervention in Eczema

Jackelina Pando Kelly, MMSc, MRCPCH; Jonathan Hourihane, MB, DM, FRCPCH

PAEDIATRICS i Peer reviewed



PAEDIATRICSPAEDIATRICS I Peer revIewed

We will briefly review the association between

food allergy and eczema and some of the dietary

strategies that have been proposed in eczema.

FOOD ALLERGY AND ECZEMA

Patients or parents of children with eczema com-

monly perceive that specific foods, more commonly

cow’s milk, cause flare-ups of their child’s eczema.

Other foods that have been implicated in hypersen-

sitivity reactions in eczema include citrus, nuts, and

fish. Families may wish to change their diet in the

erroneous belief that an external trigger is causing

their child’s eczema, rather than using prescription

medications that they have been told, also errone-

ously, have major toxic side effects.

Food-allergic sensitization. Allergic sensiti-

zation to food allergens is frequent in infants and

children with eczema. The highest rates of food-

allergic sensitization occur during the first 2 years

of life, and they closely parallel the onset of eczema.

There is a direct correlation between eczema

severity and food allergen sensitization. The dem-

onstration of food allergen-specific IgE in infancy

is predictive not only of eczema severity, as shown

by the fact that sensitization to food and inhalant

allergens is present in 70–80% of patients with

moderate-to-severe eczema, but also of eczema per-

sistence and of the onset of allergic airways disease

later in childhood.

Food-allergic disease in patients with

eczema. Ingested food allergens are able to acti-

vate cutaneous mast cells and skin-associated lym-

phoid tissue, and in the sensitized host, they can

produce intense pruritus, causing scratching and

rubbing that lead to typical eczematous lesions.

At a cellular level, positive oral food challenges

in patients with eczema result in a sharp increase in

plasma histamine concentrations, activation of eo-

sinophils, and clonal expansion of allergen-specific

skin homing T-cells.

It has been reported that approximately one-

third of children with moderate-to-severe eczema

have food allergy and up to two-thirds of infants < 2

years with severe or refractory eczema. Only 10%

of infants with mild eczema are affected by food

allergy.

The defective epithelial skin barrier as a

route for allergic sensitization. It has been pro-

posed that allergen sensitization occurs as a sec-

ondary consequence of a defective skin barrier in

which the penetration of microbes and allergens is

enhanced. The recent identification of loss-of-func-

There is no convincing evidence that delaying the introduction of solid foods, including those considered to be highly allergic, beyond 6 months of age has a significant protective effect on the development of eczema.




tion mutations in the epidermal structural protein

filaggrin appears to be a major risk factor for severe

eczema, peanut allergy, multiple atopic sensitiza-

tion, and coexisting asthma.

Phenotypes of food allergy in patients with

eczema. Food-allergic reactions have been broadly

classified into allergic (IgE or non-IgE-mediated)

and non-allergic hypersensitivity reactions. The al-

lergic reactions may be immediate IgE-mediated or

delayed non-IgE-mediated. Intolerance is defined as

a non-allergic reaction to a food and includes food

aversion, and toxic, enzymatic or pharmacological

reactions to foods.

There is considerable overlap between IgE-

mediated and non-IgE-mediated reactions, and most

of these phenotypes can coexist in patients with

eczema (Table 1). Therefore, it is important to under-

stand the natural history and clinical presentation of

food allergy in order to make or refute a diagnosis of

such in patients with eczema.

IgE-mediated reactions to specific foods cause

stereotyped symptoms typically within 0–2 hours

(but nearly always within 30 minutes) of ingestion,

affecting the skin, gastrointestinal tract, and res-

piratory and cardiovascular systems. These acute

allergic reactions are often followed by a delayed

flare of eczema.

Non-IgE-mediated reactions are typified by

symptoms that involve also the skin, gastrointes-

tinal tract, and respiratory tract (eczematous reac-

tions, vomiting, diarrhoea or constipation, cough,

wheeze). Delayed reactions to food allergens in the

gastrointestinal tract predominate in infancy and

early childhood and tend to improve with age.

The most common food triggers of eczema are

shown in Table 2.

In infants with moderate-severe eczema, the

relationship between milk ingestion and the devel-

opment of eczema is likely to be more obvious. A

high index of suspicion is required when evaluating

an infant with the combination of infantile eczema

and features of altered gut motility (colic, reflux,

persistent crying, etc).

The diagnosis of food allergy in patients

with eczema. An accurate diagnosis of food aller-

gy is important as it allows for a targeted approach

to allergen avoidance, but also for a relaxation of

dietary restrictions when it has erroneously been

imposed on children.

The gold standard test for food allergy

diagnosis is the double-blind, placebo-controlled

food challenge, but as this is not accessible to many

patients, the diagnosis of food allergy needs to rely

on a stepwise approach which includes a detailed

allergy-focused history and food-specific allergy

Table 1. Food allergy phenotypes

IgE-mediated IgE/non-IgE-mediated Non-IgE-mediated

Immediate food allergy/Anaphylaxis

Oral allergy syndrome

Eczema

Allergic eosinophilic gastritis

Allergic eosinophilic gastroenteritis

Food protein–induced enterocolitis

Food protein–induced proctitis

Food protein–induced enteropathy

Coeliac diseaseEczema

Any time, peak in early life Infancy–adolescence Usually infancy

Cox H, Hourihane J. 2011.

Table 2. Common food triggers of eczema

Food-allergic triggers of eczema

Non-allergic food triggers of eczema

MilkEggPeanutSoyaWheat

TomatoCitrusAcidic fruits and kiwiYeast extractOthers




tests. If in doubt after this, oral provocations tests

are needed after a trial period of dietary elimination

to make the diagnosis of food allergy.

The history. A detailed allergy-focused his-

tory should focus on the following areas:

• Family history of atopy: The risk of atopy in

creases if a parent or sibling has atopic dis-

ease (20–40% and 25–35%, respectively), and

is higher still if both parents are atopic (40–

60%).

• Infantfeeding:

– A history of breast vs formula feeding,

detailing period of exclusive breastfeed-

ing, and taking into account that the onset

of severe eczema during a period of exclu-

sive breastfeeding may be secondary to

food proteins excreted in breast milk.

– The relationship of eczema onset to the in-

troduction of formula feeds.

– The type of formula feed.

• Gastrointestinal symptoms: The presence of

gastrointestinal symptoms, such as colic, ab-

dominal pain, vomiting, reflux, feeding aver-

sion, diarrhoea, constipation, blood or mucus

in stools, and failure to thrive, in a patient with

eczema should raise the possibility of food

allergy.

• Historyofimmediatereactionstospecificfoods:

A history of immediate reactions to food is

important to ascertain. This should explore the

time of onset in relation to ingestion, the

quantity of food required to cause a reaction,

The diagnosis of food allergy in children with eczema includes taking a detailed allergy-focused history.




any previous reaction or prior tolerance of that

food, and whether the reaction was of suffi-

cient severity to cause anaphylaxis. It is neces-

sary to determine reactions to foods in infancy

as well as current reaction to establish a mean-

ingful picture of the child’s allergic status, tak-

ing in account that the natural history is for

children to acquire tolerance to most food al-

lergens over time.

• Historyofeczematousorgastrointestinal reac-

tions to specific foods: A history of food caus-

ing an eczematous flare in patients with per-

sistent eczema is frequently absent. In a place-

bo-controlled study which demonstrated a

60% improvement in eczema patients adhering

to milk- and egg-free diet, there was no corre-

lation between the parents’ suggestions that

milk and/or eggs triggered their child’s eczema.

• Current diet and prior history of tolerance to

foods:

– Which of the main allergenic foods are in-

cluded within the current diet?

– Has there been any previous attempt to

eliminate foods from the patient’s diet?

• Ageofonsetofeczema:Eczemaonset inearly

infancy is far more likely to be associated with

food allergy than eczema onset in a child >5

years.

• Eczemaseverity:Theprobabilityoffoodallergy

is greater in young children, infants, and those

with severe disease. When associated with

symptoms of gut dysmotility, the association be-

tween food allergy and eczema is strengthened.

• Co-morbidassociations:Foodallergyandecze-

ma can coexist with other diseases such as

asthma.

Asthma is a risk factor for anaphylaxis, and

children, who will have food challenges, should first

have their asthma well controlled.

Allergy-specific test. When the index of sus-

picion is high, the tests are useful for confirming al-

lergy, and conversely when the index of suspicion is

low, the tests are useful for ruling out a diagnosis of

allergy. When there is a lack of correlation between

the history and tests of specific IgE or when the his-

tory and tests are equivocal, confirmation by way

of an open or blinded provocative challenge test is

usually required to make the diagnosis.

Tests for the diagnosis of food allergy include

skin prick tests, specific IgE tests, and the atopy

patch test. None of these tests, however, confirms

or refutes the diagnosis of food allergy in the ab-

sence of an individual patient history which seeks to

establish the prior probability of the allergen being

causal. The selection of allergens for testing should

be based on the clinical history and patients’ age.

It is difficult to prove that specific foods induce

the eczema because clinical cases do not always

correlate well with skin prick testing and IgE levels.

Clinical history is the most important tool to help

with the diagnosis.

Oral food challenges (OFCs). OFC testing

remains the gold standard for diagnosing food al-

lergy, and the aim is to accurately identify causative

allergens.

It is difficult to prove

that specific foods

induce the eczema

because clinical cases

do not always

correlate well

with skin prick

testing and IgE levels




Only children with severe eczema with a histo-

ry of possible reactivity to food should have allergy

testing done, and this should be done by specialists

in the field. Avoidance of multiple foods is poten-

tially hazardous; therefore, OFC should be done only

when needed and interpreted with care.

Severe eczema is an indication for hospital-

based OFC.

It is imperative to achieve control of the ec-

zema prior to challenge testing.

Patients with eczema need their skin treat-

ment optimized before any reliable conclusions can

be drawn about a specific food being a specific trig-

ger of their eczema. This may require a referral to a

dermatologist and an intensive treatment, including

moisturizers, topical steroids, and in some cases an-

tibiotics. The aim is to gain control of their eczema-

tous inflammation so that the skin is relatively clear

at the time of challenge.

A clarification of the presence or absence of

food allergy is important, as a positive diagnosis

can empower the child and family to safely proceed

with an appropriate management plan and advice on

specific allergen avoidance. Conversely, a negative

diagnosis allows for removal of unnecessary dietary

restrictions.

DIETARY MANAGEMENT IN CHILDREN WITH ECZEMA

Although there is a lack of robust studies on dietary

avoidance in well-defined populations of children

with eczema and food allergy, confirmed on double-

blind, placebo-controlled food challenge testing,

available studies support the concern that food al-

lergy may play an important role in severe eczema,

particularly when the onset is within the first few

months of life. Furthermore, dietary elimination of

specific food allergens proven by allergy tests and

oral provocation tests result in improvement in ec-

zema in most of such cases. There is no case for

unselected elimination diets in patients with no

prior diagnosis of food allergy and no case for few-

foods or elemental diets. Elimination diets there-

fore need to be food allergen–specific, based on a

proper diagnosis of food allergy which is reached by

reviewing the allergy tests within the context of a

comprehensive clinical allergy history.

It is important to remember that the overall nu-

tritional health of patients on diets, especially chil-

dren, should be carefully looked at. There is concern

for nutritional deficiencies that may lead to adverse

growth and development outcomes in young chil-

dren consuming very strict diets.

Oral food challenge should only be used when the child suspected of having food allergy has severe eczema.




Current data do not support prolonged dietary

elimination for most children with eczema. In situa-

tions where special diets are attempted, the recom-

mendation is to do so for 4–8 weeks and then return

to a normal diet to assess the efficacy of the dietary

intervention. A dietician should be involved during

the process, as prolonged unsupervised dietary re-

strictions in children can have severe nutritional

consequences.

PRACTICAL APPROACH TO SPECIFIC DIETARY ALLERGEN EXCLUSION IN ECZEMA

An approach to the dietary elimination of foods

causing reactions was proposed by a European task

force in 2007 and a German guideline task force in

2009. These parameters rely on initial treatment

of eczema prior to dietary elimination and OFC. If

treatment of eczema leads to sustained periods of

eczema clearance with minimal need for topical

corticosteroids, no further dietary intervention is

required unless there is a specific history of imme-

diate reactions to food. The guidelines recommend

allergy testing in all patients with suspected food

allergy (Box 1).

OTHER DIETARY STRATEGIES PROPOSED IN ECZEMA

Maternal dietary restriction during pregnancy.

Dietary allergens, including peanuts, cow’s milk

protein and egg, are known to cross the placenta,

can be detected in breast milk, and therefore, may

interact with the mucosal immune system. But giv-

en the weak support for maternal dietary restriction

and the possibility of harmful effects of maternal

dietary exclusions to the developing foetus, it is not

recommended that pregnant women pursue elimi-

nation diets with the aim to prevent or alleviate

eczema in their children.

Breastfeeding. Breast milk has well docu-

mented immunologic activity, including antibod-

ies that act to neutralize foreign proteins, protect

against infection, enable the establishment of a

favourable intestinal microflora, and help induce

tolerance.

For infants at high risk of developing atopic dis-

ease, there is evidence that exclusive breastfeeding

for at least 4 months compared with feeding intact

cow’s milk protein formula decreases the cumulative

incidence of atopic dermatitis and cow’s milk allergy

in the first 2 years of life. Some studies have con-

Box 1. Consensus statements from the NICE guideline on atopic eczema for children aged 0–12 years

• A diagnosis of food allergy should be considered in children with atopic eczema who have reacted previously to a food with immediate symptoms, or in infants and young children with moderate or severe atopic eczema that has not been controlled by optimum management, particularly if associated with gut dysmotility (colic, vomiting, altered bowel habit) or failure to thrive.

• A 6–8 week trial of an extensively hydrolyzed protein formula or amino acid formula in place of cow’s milk formula for bottle-fed infants aged less than 6 months with moderate or severe atopic eczema that has not been controlled by optimal treatment with emollients and mild topical corticosteroids.

• Children with atopic eczema who follow a cow’s milk–free diet for longer than 8 weeks should be referred for specialist dietary advice.

• Diets based on unmodified proteins of other species’ milk (ie, goat’s milk) or partially hydrolyzed formulas should not be used in children with atopic eczema for the management of suspected cow’s milk allergy. Diets including soya protein can be offered to children aged 6 months or over with specialist dietary advice.

NICE = National Institute for Health and Clinical Excellence.




tradicted these findings and have found an increase

risk of eczema in breastfed infants compared with

formula-fed infants, but there is speculation that

these findings may be real, a result of reverse cau-

sation; mothers who know that their children are at

increased risk of developing atopy may be more like-

ly to breastfeed and do it for longer, in an attempt

to reduce the risk of the disease in their children.

On the other hand, some studies have shown a

decreased incidence of eczema in breastfed infants

of mothers who followed a diet that restricted milk,

egg or fish.

Overall, the results of several studies sug-

gest that exclusive breastfeeding for a minimum

of 4 months could be recommended as a potential

method of eczema prophylaxis, at least for mothers

of infants with a first-degree family history of atopy.

Hydrolyzed formula. The implication that

cow’s milk allergy may have a role in the pathogen-

esis of eczema has led to the investigations of the

use of partially and extensively hydrolyzed formulas.

Although there is some evidence that hydro-

lyzed infant formulas have a positive effect on the

prevention of eczema, there is no evidence that

these formulas offer advantages over breast milk.

Delayed introduction of solid foods. The

World Health Organization and the Department of

Public Health (UK) recommend that introduction of

solid foods should be delayed until 6 months of age.

There is no current convincing evidence that

delaying the introduction of solid foods beyond 6

months of age has a significant protective effect

on the development of atopic disease, including

eczema. This includes delaying the introduction of

foods that are considered to be highly allergic, such

as fish, eggs and food containing peanut protein.

Studies of the timing of introduction of solid

foods into the infant’s diet have yielded results that

are difficult to interpret.

Essential fatty acids. In recent years, the

incidence of eczema in Western cultures has in-

creased, and at the same time, the intake of essen-

tial fatty acids, such as omega-3, has decreased.

Although there is no clear evidence to support

dietary supplementation with omega-3 and omega-6

fatty acids as a means of preventing eczema, they

may have some benefits in decreasing the severity

of the disease. Infants and pregnant and lactating

women may be important populations to target for

supplementation with essential fatty acids.

Probiotics. Probiotics are living microorgan-

isms that enhance the microflora of the gastroin-

testinal tract. Some strains of Lactobacillus and

bifidobacteria can influence the immune system.

Gut microflora helps reduce local inflammation in

Practice points

• Eczema is a heavy burden in many children and their families.• A defective skin barrier may be implicated in the development

of food allergy.• Appropriate early intervention can impact significantly on

eczema severity, infant growth, and quality of life.• Maternal dietary restrictions during pregnancy or lactation do

not appear to have any prophylactic effect on the incidence or severity of eczema, but breastfeeding itself may reduce the incidence of eczema, especially in high-risk infants.

• Breastfed babies, who develop eczema and gastrointestinal disturbances, may respond to a trial of maternal dietary exclusion of usually milk, wheat, egg and soya; but this should be done with the guidance of a dietician.

• Hydrolyzed formulas, although not superior to breast milk, may be superior to cow’s milk formulas in preventing eczema.

• Food allergy is frequently present in a subset of patients with severe eczema who present with symptoms in early infancy.

• In those patients, avoidance of the dietary allergen is recommended provided an accurate diagnosis has been made.

• Some nutritional interventions might have an effect on eczema, and ongoing studies provide hope for future developments.




the gastrointestinal tract, and certain strains are in-

volved in maintaining the integrity of the intestinal

barrier in children with eczema. Breastfeeding has

been shown to promote the colonization of Lacto-

bacillus and bifidobacteria in the intestinal tract of

infants, and this might partially explain the benefits

of breastfeeding on atopic disease.

In animal models, probiotics have shown to

reduce dietary antigen load by degradation of mac-

romolecules, reducing subsequent development of

dietary antigen hypersensitivity, as it is known that

antigen degradation is necessary to develop toler-

ance to dietary antigens.

The hygiene hypothesis may explain the ben-

efits of probiotic therapy at the same time that

explains the increased burden of atopic disease in

industrialized countries, where the prevalence is

about 20% compared with only 5% in non-indus-

trialized nations. This hypothesis sustains that de-

creased microbial exposure, as a result of extensive

use of antiseptics and vaccinations in the developed

world, has led to an altered immune response (TH2-

skewed) that ultimately increases the risk of atopy.

Probiotics have not been proven to be a viable

treatment for established eczema yet, and there is

conflicting evidence of their clinical effectiveness in

the prevention of eczema.

Nutritional intervention to impact eczema is a

complete new field, and further studies are needed

to better guide patients and physicians in this area.

FURTHER READING

Cox H, Hourihane J. Food allergy and eczema. In: Irvine A, Hoeger P, Yan A, eds. Textbook of Pediatric Dermatology. 3rd ed. Blackwell Publishing Ltd; 2011:chap 31.

Finch J, Munhutu MN, Whitaker-Worth D. Atopic dermatitis and nutrition. Clin Dermatol 2010;28:605–614.

Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-Sponsored Expert Panel. Allergy Clin Immunol 2010;6:S1–S58.

Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions for improving established atopic eczema in adults and children: systematic review. Allergy 2009;64:258–264.

Greer F, Sicherer S, Burks W, the Committee on Nutrition and Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediat-rics 2008;121:183–191.

Muraro A, Dreborg S, Halken S, et al. Dietary prevention of aller-gic diseases in infants and small children, part III: criti-cal review of published peer-reviewed observational and interventional studies and final recommendations. Pediatr Allergy Immunol 2004;15:291–307.

von Berg A, Koletzko S, Grübl A, et al. The effect of hydrolyzed cow’s milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial. J Allergy Clin Immunol 2003;111:533–540.

© 2011 Elsevier Ltd. Initially published in Paediatrics and Child Health 2011;21(9):406–410.

About the AuthorsJackelina Pando Kelly is Clinical Lecturer in the Department of Paediatrics, University College Cork, Ireland. Jonathan Houri-hane is Professor of Paediatrics and Child Health in the Depart-ment of Paediatrics, Cork University Hospital, Cork, Ireland.

The results of several

studies suggest that

exclusive breastfeeding

for a minimum of 4 months

could be recommended

as a potential method of

eczema prophylaxis


TATA LAKSANA REGURGITASI PADA BAYI

Gastroesofageal refluks (GER) adalah keluarnya isi

lambung secara pasif ke dalam tenggorokan (esofagus)

karena adanya relaksasi sementara atau menahun

(kronis) dari otot sfingter bawah esofagus. Regurgitasi

atau gumoh merupakan gejala dari GER yang paling

sering ditemukan pada bayi. Jika keadaan GER ini

mempunyai komplikasi maka disebut dengan GERD

yang jika berat akan mengalami kesulitan menelan

(disfagi). Gejala GERD antara lain muntah, sakit perut,

bermasalah dengan makan, gagal tumbuh, rewel dan

nyeri dada.

Salah satu studi mengenai regurgitasi yang dilakukan

oleh Hegar B dkk (2009) pada 163 bayi, dan 130

bayi yang di-follow up selama 1 tahun menunjukkan,

kejadian tertinggi regurgitasi dijumpai pada bulan-

bulan pertama kehidupan (73%) dan secara bertahap

akan berkurang 50% pada usia 5 bulan. Selama 2 bulan

pertama, 20% bayi mengalami regurgitasi lebih dari 4

kali per hari. Namun setelah usia 12 bulan, yang masih

mengalami regurgitasi setiap hari berkisar 4%.

Pada mayoritas bayi, regurgitasi ini tidak menimbulkan

komplikasi, akan sembuh sendiri (self-limiting),

dan secara umum akan berhenti pada usia 12

bulan. Namun sekitar 20% orang tua menganggap

regurgitasi yang dialami bayinya adalah masalah yang

mengkhawatirkan.

Penanganan regurgitasiPemberian ASI tetap dilanjutkan, karena kejadian

regurgitasi pada bayi yang mendapat ASI lebih sedikit

dibandingkan dengan bayi yang mendapatkan susu

formula.

Parental reassurance merupakan langkah awal yang

perlu dilakukan. Posisi bayi setelah diberi minum juga

perlu diperhatikan. Posisi yang dianjurkan adalah posisi

telentang dengan garis punggung-bokong membentuk

sudut 60 derajat dengan alasnya. Posisi ini diharapkan

dapat mengurangi aliran balik dari lambung ke esofagus.

Langkah selanjutnya adalah pemberian nutrisi.

Pemberian thickening agent formula atau susu

formula anti regurgitasi (AR) dapat dipertimbangkan

karena telah terbukti dapat mengurangi regurgitasi,

meningkatkan berat badan, membuat bayi tidur

menjadi lebih lelap dan jarang menangis.

Hegar B dkk (2008) melakukan penelitian prospektif,

acak, intervensi selama 1 bulan pada 60 bayi dengan

regurgitasi ≥ 4 kali/hari dalam seminggu. Intervensi

dibagi menjadi 3 grup: A (formula standar), B (formula

standar + sereal beras) dan C (formula dengan locust

bean gum). Setelah 1 bulan, penambahan berat badan

pada bayi yang mendapat formula dengan locust bean

gum (AR) secara signifikan lebih tinggi dibandingkan

dua grup lainnya (gambar 1).

Gambar 1. Hubungan antara jenis formula dan kenaikan berat badan pada bayi dengan regurgitasi.

Orenstein SR dkk (1987) dalam Vandenplas (1988)

melakukan penelitian yang menilai pemberian formula

yang dikentalkan pada bayi dengan regurgitasi. Hasilnya

menunjukkan pemberian formula yang dikentalkan

dapat mengurangi waktu menangis dan meningkatkan

waktu tidur pada bayi (gambar 2).

Namun pada kasus yang lebih berat (esofagitis,

pneumonia berulang, asma, penurunan berat badan)

hendaknya dipertimbangkan untuk memberikan

farmakoterapi.

Referensi 1. Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J. Pediatr 110: 181-186, 1978 in Vandenplaz Y, Lifshitz, Orenstein MD, et al.

Nutritional management of regurgitation in infants. Journal of the American College of Nutrition. 1998. Vol 17, No 4; 308-316.2. Hegar B, Regurgitasi suatu keadaan normal atau hal yang perlu diperhatikan, www.idai.or.id. Diakses Agustus 2012 3. Hegar B, Dewanti NR, Kadim M, Alatas S, Firmansyah A, Vandenplas Y. Natural evolution of regurgitation in healthy infants, Acta Paediatr. 2009 Jul;98(7):1189-93 4. Hegar B, Rantos R, Firmansyah A, et al. Natural evolution on infantile regurgitation versus efficacy of thickened formula. JPGN. 2008;47:26-30.

© 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher.

’Air Susu Ibu adalah yang terbaik untuk bayi dan memberikan banyak manfaat. Adalah penting bahwa dalam persiapan untuk dan selama menyusui, Anda melakukan diet yang sehat dan seimbang. Menggabungkan pemberian ASI dan botol pada minggu pertama kehidupan dapat mengurangi suplai ASI Anda, dan sulit untuk dapat menyusui kembali bila telah berhenti. Implikasi sosial dan keuangan perlu dipertimbangkan bila akan memberikan susu formula. Penggunaan formula bayi yang tidak benar atau pemberian makanan dan cara pemberian yang tidak benar dapat menyebabkan bahaya terhadap kesehatan. Kalau Anda menggunakan formula bayi, Anda harus mengikut petunjuk penggunaannya dengan seksama – kegagalan mengikuti petunjuk dengan benar dapat membuat bayi sakit. Selalu berkonsultasi dengan dokter, bidan atau ahli medis lainnya untuk nasihat pemberian makan bayi Anda.

Gambar 2. Pengaruh formula yang dikentalkan terhadap waktu menangis dan waktu tidur pada bayi.

Hanya untuk kalangan medis



PAEDIATRICSOBSTETRICS i Peer reviewed


INTRODUCTION

All infectious diseases can occur in pregnant women. There are some that occur more

frequently in this group owing to the immunosuppressive nature of pregnancy. There

are others that cause increased concern in pregnancy owing to their potential fetal

complications. In this article, we will focus on some of the general principles for man-

agement of any infection in pregnant women and then discuss some of the diseases in

more detail.

PHYSIOLOGICAL CHANGES

Physiological and immune changes occur in pregnancy, making women more susceptible

to infections, and these are still not fully understood. A shift from cell-mediated to

humoral immunity occurs, which may affect susceptibility to and severity of some infec-

tious diseases, including an increased incidence of certain intracellular pathogens, such

as toxoplasmosis, listeriosis, influenza, and varicella.

Urinary tract infections are more common, related to progesterone effects and me-

chanical compression by the gravid uterus, as well as higher urinary glucose and pH

facilitating bacterial growth.

Respiratory infections may be more severe for several reasons. Diaphragmatic el-

evation reduces secretion clearance and functional residual capacity, and with the in-

creased oxygen demand, reduces tolerance to hypoxia, particularly in the third trimester.

Gastric acid aspiration is more common, and increased interstitial lung water is seen,

increasing the risk of acute lung injury.

Infectious Disease in PregnancySarah Logan, FRCP; Laura Price, FRCP

OBSTETRICS i Peer reviewed



OBSTETRICS I Peer revIewed



ANTENATAL SCREENING AND PREVENTION

Screening

Since 2003, the UK Department of Health has rec-

ommended screening for hepatitis B, human immu-

nodeficiency virus (HIV), rubella and syphilis early

in pregnancy with a single blood sample, as well as

asymptomatic bacteriuria (ASB) with a urine sam-

ple. There is currently no clear evidence of benefit

from screening for other infections, although wom-

en may request additional screening, particularly if

they have experience of health care systems over-

seas. Whilst the current guidance in the UK is not

to screen women for group B Streptococcus (GBS),

cytomegalovirus (CMV) and toxoplasmosis, each

case should be considered on an individual basis,

and consultation with local infectious diseases/

virology services may be required. For women at

high-risk for HIV, it is important to repeat the HIV

test in the third trimester. A negative test at book-

ing can be falsely reassuring, and seroconversion

during pregnancy carries a higher risk of mother-to-

child transmission.

Primary Prevention

Mothers are advised about primary prevention

measures to avoid toxoplasmosis infection such as

thorough hand washing, cooking raw meats, and

avoiding contact with cat litter and soil. Listeria

avoidance includes not eating unpasteurized dairy

products or pate and washing salads thoroughly.

immunization

Ideally, women should be immunized prior to con-

ception, but there are a few situations where im-

munization of a pregnant woman is indicated. Live

vaccines are usually avoided though, owing to the

risk of fetal infection.

UK immunization programmes for rubella in

childhood should protect during childbearing years.

The single vaccine has been in place since 1970,

and the measles-mumps-rubella (MMR) since 1988.

Until recently, the UK childhood immunization rates

were 92%. Following the 2003 negative press cov-

erage, rates dropped to 80%, although they have

started to increase again. Women planning a family

should ensure immunity.

Live varicella vaccines are available pre-preg-

nancy, and zoster immune globulin (IG) should be

given to pregnant women non-immune to varicella

and up to 10 days following exposure. Varicella se-

rology is also available, although immunity is usu-

ally assumed from the history of typical rash.

Pregnant women should take precaution to prevent toxoplasmosis infection.




Influenza vaccination (inactivated) may be

considered and is deemed safe throughout preg-

nancy. In light of the recent outbreak of H5N1 influ-

enza and its increased severity in pregnant women,

all women should be offered the seasonal vaccine

which will give protection to the most common cir-

culating strains.

INVESTIGATION AND MANAGEMENT

Principles

A good history is essential, considering the preg-

nancy, gestational age, prior ASB, sexually trans-

mitted infections (STIs), travel, occupation, HIV risk

factors, contacts with infectious diseases, and prior

tuberculosis (TB) infection. There may only be non-

specific symptoms and signs, but these are impor-

tant to consider, as obstetric sepsis can present this

way before rapid deterioration.

Involvement of the feto-maternal multidisci-

plinary team is essential, including clinical micro-

biologists/virologists/infectious diseases, local TB

services, and the critical care team when appropri-

ate. With evidence of STIs, genitourinary physi-

cians should be involved, and screening for other

STIs should be undertaken.

Antibiotic Use in Pregnancy

In general, penicillins, cephalosporins, and mac-

rolides such as erythromycin (although less data on

clarithromycin) are safe. Clindamycin is also prob-

ably safe although clinical experience is limited.

Penicillins are only 50% protein-bound and can

cross the placenta to achieve fetal concentrations

that are therefore 50% of maternal levels. Amoxi-

cillin has increased renal clearance in pregnancy,

therefore theoretically higher doses are needed,

although in clinical practice, doses are used as out-

side pregnancy. Augmentin was shown to increase

the risk of neonatal necrotizing enterocolitis in one

study of preterm premature rupture of membranes

(PROM) prevention, and although no animal studies

have shown harm, further human studies are need-

ed. Cephalosporins cross the placenta less com-

monly and appear to have no adverse fetal effects.

Other antibiotics are relatively contraindicat-

ed in pregnancy, but their use may be appropriate

depending on the clinical situation. Nitrofurantoin

is generally considered safe but should be avoided

at term because of the risk of haemolytic anaemia

in the neonate. There are reports of ciprofloxacin

causing an arthropathy in animal studies, but no ad-

verse human effects have been reported. Trimetho-

prim has also caused adverse effects in animals,

so should be used with caution in pregnancy, espe-

cially as it may interfere with folic acid metabolism.

It should be avoided near term when used as co-

trimoxazole in combination with a sulfonamide, as

the later can cause fetal kernicterus. Tetracyclines

increase the risk of fulminant maternal hepatitis in

the third trimester and may stain fetal teeth after

20 weeks’ gestation. Chloramphenicol should be

used with caution because of the association with

the ‘grey baby syndrome’ (characterized by cyano-

sis, flaccidity and cardiovascular collapse) when

used in newborn infants. Aminoglycoside use (eg,

gentamicin) risks fetal ototoxicity and should only

be used if there is evidence of serious gram-neg-

ative infection. Similarly, vancomycin has been as-

sociated with fetal nephrotoxicity and ototoxicity.

MATERNAL INFECTION SYNDROMES

Sepsis

Obstetric sepsis is the most important cause of UK

maternal mortality; in the most recent confidential

enquiry, the mortality related to sepsis increased

from 0.85 deaths per 100,000 mortalities in 2003–

2005 to 1.13 deaths in 2006–2008, making sepsis




the most common cause of direct maternal death.

The commonest source is the genital tract, notably

from Streptococcus pyogenes (group A Streptococ-

cus, GAS), although it is important to remember

that any systemic infections can present as sepsis

or septic shock.

Sepsis can present at any time before, during

or following delivery, and is important to recognize

and treat early, for example using early warning

score systems for ward patients, and with commu-

nity midwives being astute for signs of infection.

Mothers often present with vague symptoms and

signs, but it is important to recognize these early, as

the course can be fulminant. Management of septic

shock is similar to that outside pregnancy. Preven-

tative measures include good perineal hygiene.

Most obstetric sepsis occurs post partum,

and may relate to genital tract infections, mastitis,

thrombophlebitis, episiotomy, and perineal tear in-

fections, caesarean section (CS) wound infections,

gastric acid aspiration, or post-general anaesthesia

pneumonia.

Antepartum infections include chorioamnio-

nitis which may follow prolonged PROM (pPROM)

and prolonged labour. pPROM complicates only

2% of pregnancies but is associated with 40% of

preterm deliveries, and is suspected with a sug-

gestive maternal history and on a sterile speculum

examination. Mothers should be observed 12-hour-

ly for signs of clinical chorioamnionitis. First-line

prophylaxis for pPROM is erythromycin. Diagnosis

of chorioamnionitis is suggested by fever late in

pregnancy, uterine tenderness, offensive vaginal

discharge, and fetal tachycardia. Consequences in-

clude PROM and premature labour, increased risk of

neonatal pneumonia, bacteraemia, meningitis, and

death. Treatment is with broad-spectrum antibiotics

(ampicillin and gentamicin) and delivery.

Endometritis is a spectrum of endometrial,

myometrial and parametrial infections, all of which

can be serious, especially when associated with

GAS and Streptococcus agalatiae (GBS). GAS ne-

crotizing fasciitis and toxic shock syndrome can

occur unexpectantly following an uncomplicated

pregnancy and delivery, and management includes

antibiotic therapy with broad-spectrum antimicro-

bials according to local policy and early surgical

intervention. Thirty percent of the fevers seen in

women who have just delivered are due to endome-

trial infection. The risk is higher post CS and after

a PROM, prolonged delivery or in the presence of

retained products of conception. Infections are of-

ten polymicrobial, with aerobes and anaerobes, and

Chlamydia can cause late endometritis. Endometri-

tis can also result from CS wound incisions (more

commonly seen following emergency CS), which

is important to recognize, as utero-cutaneous fis-

tulae may result requiring surgery. Late endometri-

tis more typically follows vaginal delivery. A 2002

Cochrane review concluded that a single dose of

ampicillin or first-generation cephalosporins was

sufficient to reduce puerperal infections related to

uncomplicated CS, given as a single dose after cord

clamping.

For an excellent summary of sepsis see chap-

ter 16 of the recent 2006–2008 confidential enquiry

into maternal deaths.

Urinary Tract infections

Urinary tract infections (UTIs) are divided accord-

ing to the site of bacterial proliferation into ASB,

cystitis, and pyelonephritis.

ASB is defined as urine colonization greater

than 105 colony-forming units per mL on two con-

secutive clean-catch urine samples (without ni-

trites or leucocytes on dipstick). It occurs in 4–7%

of pregnant women and is important to recognize,

as symptomatic UTIs develop in 20–40% of cases,

and there is an increased incidence of preterm de-

livery and low-birth-weight infants. This has lead to




UK screening being recommended (see NICE guide-

lines). ASB is due to Escherichia coli in 75–90% of

cases, and cephalosporins are more appropriate

than amoxicillin, given the 60% E coli beta-lactam

resistance seen. Up to 15% will require a further

course later in pregnancy.

Cystitis or bladder infection occurs in 1–4% of

pregnancies and pyelonephritis, where the kidney

is the focus in 2% of all pregnancies.

Pyelonephritis is a serious medical condition

in pregnancy, associated with fetal and maternal

morbidity, and leads to an increased risk of pre-

mature labour. Two-thirds of cases present in the

second or third trimester, and 27% post partum.

The right kidney is most often affected owing to

dextro-rotation of the uterus. The common present-

ing features are fever, loin pain, rigors, and less of-

ten with symptoms of cystitis. Pyelonephritis is the

most common cause of septic shock in pregnancy,

and adult respiratory distress syndrome (ARDS) oc-

curs in 1–8% of cases, so patients should be closely

monitored. Diagnosis is based on the presence of

significant bacteriuria following mid-stream urine

culture, and the history and clinical signs. A renal

tract ultrasound scan should be performed to ex-

clude hydronephrosis and structural abnormalities.

Organisms are similar to those in lower tract UTIs,

with E coli in 70–80%, and Klebsiella pneumonia

and Proteus species less commonly, but important

in recurrent cases. Antibiotic choice reflects local

guidelines, usually with a first-generation cephalo-

sporin or combination ampicillin with gentamicin.

Most will be afebrile and asymptomatic following

48 hours of appropriate antibiotic treatment, and

intravenous therapy is then continued until the

patient has been afebrile for 48 hours. Failure to

respond after the initial 72 hours usually indicates

a resistant organism, renal tract stone, or anatomi-

cal obstruction. When discharged home, the mother

should be more closely watched for recurrence with

monthly urine cultures. Fetal effects of untreated

pyelonephritis include preterm delivery and low

birth weight. If GBS is detected in maternal urine,

it should be treated and appropriate intra-partum

prophylaxis administered (see later).

Cranberry juice has been used traditionally

to prevent and treat UTIs. It contains proanthocy-

anidins which prevent the adherence of bacterial

pathogens to the uroepithelium. A recent Cochrane

review showed a significant reduction in UTIs com-

pared with placebo, although this was not specific

to pregnancy.

respiratory Tract infections

Bacterial pneumonia has a similar incidence and

outcome in pregnancy, although viral pneumonias

are more common and run a more severe course

Studies showing the prevention of urinary tract infections in pregnancy with cranberry juice ingestion are lacking.




in pregnancy. Investigation and management are

similar, although delay in obtaining a chest X-ray is

common; remember that the radiation exposure is

only 0.05% that of the maximum recommended 0.2

rad. Influenza and varicella pneumonia in pregnant

women have historically been associated with a

higher rate of morbidity and mortality. Some impor-

tant pathogens are considered below, and others,

including TB, in later sections.

Respiratory Pathogens in Pregnancy

Upper respiratory tract infection – pregnant

women often find that they have a persistent cold

in the last trimester. Whilst this may be due to any

of the common viral pathogens such as rhinovirus,

there is no treatment and in the absence of lower

respiratory tract symptoms does not need investi-

gation.

Bacterial pneumonia – the most common

cause of pneumonia in pregnant women remains

the same as in the general population – Strepto-

coccus pneumoniae. This is usually fully sensitive

to amoxicillin (with some decreased susceptibility

in strains from abroad).

Influenza pneumonia – influenza infection

presents with similar self-limiting symptoms, but if

they last more than 5 days, complications are not

unusual. Pneumonia has a greater mortality rate (up

to 50%) in pregnancy and may result from a second-

ary bacterial pneumonia (Staphylococcus aureus,

Pneumococcus, or Haemophilus influenzae) or viral

parenchymal infection.

Complications from pandemic influenza A

(H1N1) are more common in pregnancy, notably

severe ARDS. Treatment is with the neuraminidase

inhibitor oseltamivir, which should be started as

soon as possible until clinical improvement occurs,

although data are limited in pregnancy. See World

Health Organization guidelines for further details.

In cases that remain hypoxic despite maximal in-

vasive mechanical ventilation, veno-venous extra-

corporeal membrane oxygenation may be required.

This is a form of ‘lung bypass’ to rest the lungs

while they recover, and successful cases have been

reported during pregnancy and immediately post

partum.

Varicella pneumonia – primary varicella in-

fections are more severe in pregnancy, and progres-

sion to varicella pneumonia is more common (10–

20% of those infected). Maternal mortality from

varicella pneumonia is higher in pregnancy (35%

versus 11%), thus prevention of primary infections

is of great importance. Oral mucosal ulceration is

common, and respiratory illness ranges from cory-

zal symptoms to severe respiratory failure requiring

mechanical ventilation. Classically, the chest X-ray

shows bilateral miliary nodular shadowing, and

later pulmonary calcification.

Other causes of pneumonia – Pneumocystis

jiroveci pneumonia (PCP, previously called P cari-

nii pneumonia) in HIV-positive patients is associ-

ated with adverse obstetric outcome, and should

be treated with co-trimoxazole. PCP is also increas-

ingly being seen in immunocompetent hosts, previ-

Primary varicella

infections are more

severe in pregnancy,

and progression to

varicella pneumonia

is more common




ously only associated with immunodeficiency. One

study showed that asymptomatic nasal carriage

of P jiroveci is more common in pregnancy, and

another that PCP is more severe in pregnancy. In

HIV-positive women, P jiroveci may be transmitted

perinatally.

Chlamydia psittaci is an unusual cause of

atypical pneumonia, (ie, those organisms not caus-

ing a ‘typical’ lobar pneumonia). It is usually trans-

mitted via infected birds and may cause a severe ill-

ness during pregnancy, but recovery is usually full.

Fungal pneumonia, although unusual, may also run

a more severe course in pregnancy, especially in the

final trimester.

Hepatitis

Viruses causing hepatitis include the hepatitis

viruses A–E, as well as Epstein-Barr virus, CMV,

toxoplasmosis, and herpes simplex virus.

Overall, the clinical course of hepatitis A, B,

C and D viruses is unchanged in pregnancy, but

prevention of vertical transmission is important.

Vertical transmission with maternal hepatitis A

virus infection is rare, and the neonate should be

given IG at birth. Hepatitis B virus is screened for

antenatally as the risk of vertical transmission from

asymptomatic mothers is high; rates are up to 95%

if mothers are hepatitis B surface antigen- and e-

antigen-positive. Vertical transmission usually oc-

curs at delivery and is more likely if the hepatitis B

virus infection is associated with a high viral load.

Several strategies including vaccination and use of

hepatitis B virus specific IG are in place to decrease

the chance of transmission. There is sometimes a

need to treat newly diagnosed pregnant women

with oral anti-viral agents for her own health. All

new diagnoses should be referred urgently to the

local hepatitis service. There is clear guidance on

management available through the Department of

Health Green Book (see Further Reading).

At least 6% of hepatitis C–positive pregnant

women will transmit this to their baby perinatally.

This risk is increased in the presence of co-infec-

tion with HIV to 15%. Elective CS may reduce the

transmission risk. There is no role for treatment of

HCV in pregnancy, and there is no vaccine available.

Screening is not routinely carried out but should be

considered in high-risk groups – mainly those with

a history of injecting drug use.

Hepatitis E virus is water-borne and transmit-

ted faeco-orally, usually causing a mild self-limiting

infection. However, in pregnancy, there is a sixfold

increase in maternal mortality, especially in the

third trimester, with 15% of cases leading to fulmi-

nant hepatic failure where the mortality is 5%. The

mechanism may relate to immunologic imbalance

associated with a predominant T helper subtype

2 cell response and suppression of cell-mediated

immunity seen in pregnancy. There is no specific

treatment.

Herpes simplex virus (usually herpes simplex

virus type 2) can also lead to fulminant hepatic

failure in pregnancy, often with associated pneu-

monitis or encephalitis. Diagnosis is made on liver

biopsy and serology, and specific treatment for the

mother and infant with acyclovir is available.

rash

There are comprehensive guidelines on the man-

agement of rashes in pregnancy from the Health

Protection Agency (www.hpa.org.uk).

The important infections to consider in the dif-

ferential diagnosis include rubella, parvovirus B19,

varicella, measles, enteroviruses, and infectious

mononucleosis. The first three are discussed in a

later section.

Measles infection in pregnancy can lead to in-

trauterine death and preterm delivery, although not

congenital infection or damage. Indigenous measles

is rare in the UK following introduction of the MMR




vaccine, although it is endemic in some countries.

Human normal IG may attenuate measles, but there

is no evidence that it prevents intrauterine death or

preterm delivery.

Enteroviruses (including coxsackievirus A, B

and echovirus) can cause a wide range of manifes-

tations such as meningitis and myocarditis. Neona-

tal infection, especially with echoviruses, can have

multisystem life-threatening complications. No

vaccines are available except for poliovirus, and IG

is advised for prophylaxis in exposed neonates.

Infectious mononucleosis is caused by primary

Epstein-Barr virus infection with no specific risk to

the fetus.

SPECIFIC PATHOGENS

Tuberculosis

The UK and worldwide TB infection rates are rising.

Incidence peaks in the childbearing years (25–34

years). In the UK, infection is most common in

Asian and West-African populations. Pregnancy is

thought not to change the course of TB, although it

does increase preterm births, especially in the de-

veloping world. As in the non-pregnant population,

transmission of Mycobacterium tuberculosis is via

respiratory droplets. Overall 10% of those infected

(initial infection is usually asymptomatic) will de-

velop active TB, usually 1–2 years after infection.

More extra-pulmonary TB is being seen with HIV

co-infection, and 5–10% of pregnant women have

extra-pulmonary disease (similar to the non-preg-

nant population). Pregnancy and the peri-partum

period is a common time for latent TB to reactivate.

Diagnosis is by usual methods, and tuberculin skin

testing is safe in pregnancy.

Management is similar to in non-pregnant pa-

tients. All four first-line drugs are thought safe and

have been used for many years, including etham-

butol and isoniazid. Pyridoxine should be added to

isoniazid therapy to prevent peripheral neuropathy.

Streptomycin, however, should be avoided, as fetal

eighth nerve damage has been associated in a sig-

nificant number of cases. Infants born to mothers

with smear-positive TB should be treated with iso-

niazid syrup for 6 weeks as chemoprophylaxis, and

then a tuberculin skin test performed. Breastfeeding

can continue as normal, as minimal anti-tuberculous

agents are secreted in breast milk.

Malaria

Malaria contributes significantly to maternal

mortality and morbidity in the developing world. In

the UK, 2,000 cases are reported annually, mostly

in travellers from endemic areas. Untreated falci-

parum malaria is life-threatening in any population,

and pregnant women are more susceptible; anaemia

can be severe, and there is an increase in maternal

mortality, preterm birth, miscarriage, and stillbirth.

Immunity to malaria is altered by pregnancy,

especially in primiparous women with high parasite

loads, although the risk is reduced with successive

pregnancies. Drugs are used for prevention in en-

demic areas, with effective reduction in maternal

anaemia, birth weight and possibly perinatal death.

In the UK, women with malaria in pregnancy should

be admitted as there is an increased risk of severe

disease and hypoglycaemia. Suitable regimes de-

pend on the type of malaria and local resistance

patterns, and chloroquine is the choice for Plasmo-

dium vivax, P malariae, P ovale, and quinine for P

falciparum. All regimes should be supplemented

with folic acid.

Malaria prophylaxis: travel to a malarial

area in pregnancy should be avoided; getting malar-

ia whilst pregnant increases the risk of miscarriage

as well as being life-threatening to the mother. No

antimalarial is 100% effective, and women should

seek advice from a local travel clinic. There are

guidelines available on the choice of agent to use




The common vaginal

commensal, group B

Streptococcus, can lead

to life-threatening

neonatal effects

if travel is unavoidable from the Royal College of

Obstetrics and Gynaecology (see Further Reading).

Mefloquine is first line for prophylaxis after the

first trimester.

Human immunodeficiency virus

HIV worldwide infection is increasing. UK sero-

prevalence in pregnant women is 0.21%, with over

300 HIV-infected women giving birth annually.

There is an increased risk of preterm delivery, low-

birth-weight infants and miscarriage with maternal

HIV infection, worse in mothers with advanced

disease and poor nutrition. Antenatal screening is

done routinely in the UK.

The mother-to-child transmission rate in the

UK is now less than 1%. This has been achieved

through a variety of interventions, notably the use

of antiretroviral combination therapy, a multidisci-

plinary approach to both the timing and method of

delivery, post-exposure prophylaxis for the infant,

and an avoidance of breastfeeding. Management

of each case is highly individualized and should

be done in conjunction with a team of health care

professionals including a midwife, obstetrician,

HIV specialist, and a neonatologist and paediatric

nurse. Some antiretroviral drugs are safe in preg-

nancy although currently very few are licensed.

Guidelines are available (see Further Reading).

Group B Streptococcus

This common vaginal commensal can lead to

life-threatening neonatal effects. Of the 20%

of mothers that carry it, 40–70% of infants be-

come colonized in the first week of life. Neonatal

infection can be early or late, presenting with pneu-

monia, sepsis, meningitis, and death in up to 10%

(higher in preterm infants). As the overall UK infec-

tion rate in infants is 1%, routine screening is not

currently offered. Neonatal disease is reduced by

administration of intra-partum intravenous penicil-

lin to high-risk mothers. These are identified for-

tuitously by high vaginal swabs performed for a va-

riety of reasons during pregnancy, including those

women complaining of vaginal discharge, those

with possible preterm membrane rupture, women

in preterm labour, temperature greater than 38°C in

labour, preterm PROM, ROM for more than 18 hours

prior to delivery, or a previously affected child.

Chlamydia trachomatis

Genital tract infection with Chlamydia trachomatis

is common in the UK and may lead to ectopic preg-

nancy, preterm labour, puerperal infection, and oph-

thalmia neonatorum. Erythromycin is the advised

treatment.

Bacterial vaginosis

This STI, caused by Gardnerella vaginalis, may

cause chorioamnionitis, preterm delivery, and post-

partum fevers. Treatment is with erythromycin or

metronidazole.

Herpes Simplex virus

Maternal genital herpes is more virulent in preg-

nancy. Early miscarriage (but not fetal abnormali-

ties) may occur, and late maternal primary infec-

tion can lead to severe neonatal infection. Genital

lesions, especially in primary infection, contain




Varicella is also

important to recognize

and treat in pregnancy

as maternal complications

are more severe

high viral concentrations, and transmission at de-

livery may exceed 41%. Neonatal herpes carries a

high mortality rate. Disease can be (1) localized to

skin, eyes and mouth, where death when treated

is uncommon, (2) encephalitis, or (3) disseminated

infection with multi-organ involvement, with mor-

tality up to 30% often with long-term neurological

manifestations. Maternal infection is confirmed

using viral culture or polymerase chain reaction,

and serology differentiates between primary and

recurrent infections. Primary infections should be

treated with oral or intravenous acyclovir. In the

UK, caesarean section is the recommended mode

of delivery following primary infections in the late

second and third trimesters, and discussion should

be with women presenting in labour with recurrent

(secondary) herpes attacks regarding the small risk

of perinatal transmission associated with vaginal

birth in this situation. The risk is low, but some may

choose caesarean delivery.

INFECTIONS WITH SIGNIFICANT FETAL MALFORMATION RISKS

Many infections, as detailed previously, risk fetal

infection, and all maternal infections may lead to

preterm delivery, but there are several important

maternal infections that can lead to congenital ab-

normalities. These are discussed below, and sum-

marized in Table 1.

rubella

Symptoms of primary maternal rubella infection fol-

low viraemia are mild and include fever, headache,

joint pains, sore throat, and a maculopapular rash

usually appearing shortly after glandular enlarge-

ment. These non-specific symptoms make clinical

diagnosis unreliable. The fetus is at high-risk of

congenital rubella syndrome from infection during

maternal viraemia, and significant malformations

are common, seen in 80–90% survivors infected

in the first trimester. Fetal abnormalities due to

rubella infection in the second trimester are less

common (in 15% survivors) – usually sensorineural

hearing loss, and infection prior to conception or af-

ter 20 weeks carries minimal risk. Maternal rubella

reinfection is mostly subclinical and is diagnosed

by a rising antibody titre.

Suspected cases of rubella should be inves-

tigated promptly with serology testing for rising

antibody titre and rubella-specific IgM as clinical

diagnosis is limited.

Before rubella vaccine became available,

200–300 babies were born each year with congeni-

tal rubella syndrome in the UK. Routine rubella vac-

cination for schoolgirls was introduced in England

and Wales in 1970, and subsequently for suscepti-

ble women post partum. It is a live attenuated vac-

cine, so is contraindicated in pregnancy, but should

be offered to non-immune mothers 1 month post

partum and preconceptually.

varicella

Varicella is highly infectious from 2 days prior un-

til 5 days following the typical vesicular rash. Fe-




Table 1. Fetal risks associated with certain maternal infections

Infection Rubella Varicella Cytomegalovirus Parvovirus B19 Toxoplasmosis

Congenital defects

Ocular defects, heart (PDA), SNHL, mental retardation

Fetal varicella syndrome: skin scars, eye defects, limb hypoplasia, developmental delay, microcephaly

IUGR, HSM, micro-cephaly, jaundice, chorioretinitis, intracranial calcification, 20% mortality. Late microcephaly, SNHL, and developmental delay (15%)

Fetal hydrops, IUD (1st trimester). Rarely persistent neonatal infection and anaemia

Hydrocephalus, mental retardation, chorioretinitis

Trimester most at risk (% risk of defects)

First – abnormali-ties in 80–90% survivors; risk 13–16 weeks of SNHL

All trimesters, espe-cially 13–20 weeks (2%)

All trimesters First trimester Malformations high-est in first trimester. More infections near term (2% at 8 weeks vs 75% at term)

Maternal effects

Arthritis Pneumonia; increased mortality

Asymptomatic or IM syndrome

Febrile illness, erythema infectiosum, aplastic anaemia

Mostly asymptomatic or flu-like; lymphadenopathy

Available treatment

TOP offered ZIG to mother and neonate. Acyclovir within 24 h of rash onset for mother and for infected neonates

None Intrauterine transfusion. No vaccine

Spiramycin (cycled pyrimethamine, sulfadiazine, and folinic acid)

HSM = hepatosplenomegaly; IM = infectious mononucleosis; IUGR = intrauterine growth retardation; PDA = patent ductus arteriosus; SNHL = sensorineural hearing loss; TOP = termination of pregnancy; ZIG = zoster immune globulin.

tal varicella syndrome occurs in 1% of fetuses in-

fected before 20 weeks, especially 13–20 weeks.

Note that this is less than the 85% risk of rubella

fetal damage, hence there is currently no UK rou-

tine screening policy. Varicella is also important to

recognize and treat in pregnancy as maternal com-

plications are more severe.

Treatment in pregnancy is safe with acyclovir.

If delivery is imminent and infection occurs within

10 days of delivery, it is advisable to wait 5–7 days

for passive transfer of maternal IG if possible. If

not, the neonate should be given zoster IG, as there

is a 20% neonatal infection risk if the mother devel-

ops clinical chickenpox in the period 5 days prior to

birth until 2 days after. Neonatal infection carries a

high mortality rate.

Shingles (dermatomal reactivation of latent

virus) when localized carries no apparent risk to the

fetus. However, it is uncertain whether dissemina-

tion, for example in an immunocompromised pa-

tient, carries a fetal/neonatal risk.

Cytomegalovirus

Fetal CMV infection is the second most prevalent

cause of mental retardation after Down syndrome.

Childhood infection is common in developing coun-




Practice points

• Most maternal infections do not harm the fetus• All rash illnesses should be referred for specialist assessment• Maternal obstetric sepsis may present with non-specific symp-

toms and signs, and run a fulminant course• Obstetric sepsis remains a significant cause of maternal mortal-

ity and should be identified early and managed aggressively• The investigation of infections that can affect the fetus should

be appropriate for both mother and fetus, usually in or in consultation with a feto-maternal medicine unit

• Screening is important for HIV as interventions exist to reduce vertical transmission

tries, hence leads to herd immunity, however only

50–60% of women in developed counties have

positive serology. Primary maternal infection in

adults may be asymptomatic or lead to infectious

mononucleosis-like syndrome. Primary infection,

reactivation, or reinfection with a different strain

of CMV may lead to intrauterine infection, although

the fetus is rarely affected in cases of reactivation.

Primary infection leads to transplacental fetal

infection in 40% of cases, and fetal sequelae may

occur over a wide timescale. Up to 7% will present

at birth with defects (see Table 1). The mortality

is 20% in this group, and a further 15% will have

abnormalities found later at follow-up.

In cases of suspected maternal infection,

blood serology is helpful, ideally with a paired sam-

ple from booking to compare rising antibody titre,

noting that circulating IgM may persist for months.

When confirmed, fetal infection should be proven

by culture and polymerase chain reaction of amni-

otic fluid at amniocentesis. Serial fetal ultrasound

is available to identify suggestive features such as

ventriculomegaly and intracranial calcification, al-

though no findings are specific. It must be remem-

bered that most infected neonates will in fact be

unaffected. There is no specific treatment, although

a vaccine is in development, and screening for ma-

ternal immunity is therefore not routine in the UK.

Parvovirus B19

Parvovirus B19 infection is common, with 50–60%

of adults having been infected. Infection in the first

20 weeks of pregnancy can lead to intrauterine

death and fetal hydrops. These consequences usu-

ally occur 3–5 weeks after the onset of maternal

infection, but can be later. There is no evidence to

suggest that reinfection is a risk to the fetus. No

vaccine or preventive measures are available, and

an increased incidence occurs every 3–4 years, of-

ten in schoolchildren.

Toxoplasmosis

Maternal infection is rare (2 per 1,000 in the UK;

more common in France), and flu-like symptoms

and lymphadenopathy occur in up to 15% of in-

fected women. Fetal infection probably depends on

the gestational age at maternal seroconversion. A

French study showed that there were more congeni-

tal abnormalities (see Table 1) with early maternal

infections, and more fetal infections with serocon-

version at term.

Diagnosis is confirmed by amniocentesis, cho-

rionic villus sampling or fetal blood sampling, and

ultrasound findings of intracranial calcification, he-

patomegaly and placental thickening are late and

non-specific. Treatment with spiramycin from time

of maternal infection may reduce fetal infection

and, therefore, congenital abnormalities. In late

(after 32 weeks) high-risk fetal infections, 3-week

cycled courses of pyrimethamine, sulfadiazine and

folinic acid may be added.

Syphilis

Maternal infection with the spirochaete Treponema

pallidum has increased in recent years. Fetal infec-

tion can occur at any stage, but most often in pri-

mary (90%), secondary and early latent infections.




Most infected women are asymptomatic, and posi-

tive serology is detected at antenatal screening.

Maternal infections treated with high-dose penicil-

lin will reduce the risk of fetal infection. Twenty-five

percent of fetal infections result in preterm labour

and 25% in fetal loss. In survivors, congenital syph-

ilis may result with polyhydramnios, hepatomegaly,

osteochondritis, purpura, and late interstitial kera-

titis. Fetal infection is suggested by antigen testing

of amniotic fluid or fetal blood, although these have

a poor negative predictive value.

Listeria monocytogenes

Listeriosis is caused by Listeria monocytogenes,

a gram-positive bacillus, and although an unusual

infection, may have serious adverse outcome in

pregnancy. There are about 20 cases of Listeria as-

sociated with pregnancy in the UK per year. It is

food-borne, from unpasteurized dairy products, and

pregnant women should avoid such high-risk foods.

It can survive at low temperatures (such as the

fridge) on raw vegetables, hence the importance of

washing food in pregnancy. Maternal symptoms can

be asymptomatic or with flu-like symptoms, and can

range from mild to severe with ARDS. The diagnosis

is based on a high index of clinical suspicion, and

on positive Gram stain from maternal blood, liquor

or neonatal samples.

Maternal infection can lead to miscarriage,

premature labour, and if the infant survives, to

perinatal listeriosis. Congenital listeriosis has also

been reported following transplacental passage

and can lead to fetal hydrops. Treatment is with

high-dose ampicillin and gentamicin.

CONCLUSION

Infections during pregnancy are usually self-

limiting; however, awareness is needed to iden-

tify those leading to significant maternal and fetal

morbidity and mortality. Screening and vaccination

programmes are important. Investigation and man-

agement of infection may be complex and the mul-

tidisciplinary approach is essential, involving the

obstetric team, as well as fetal medicine, genitou-

rinary and critical care physicians.

FURTHER READING

National Institute for Clinical Excellence. Antenatal care: routine care for the healthy pregnant woman, Clinical Guideline 6. London: National Institute for Clinical Excellence; October 2003.

Hepatitis guidelines: http://www.dh.gov.uk/prod_consum_dh /groups/dh_digitalassets/@dh/@en/documents/digital asset/dh_108820.pdf.

HIV guidelines: www.bhiva.org.Mackenzie I, Lever A. Management of sepsis. BMJ

2007;335:929–932. Malaria prophylaxis: http://www.nathnac.org/pro/misc/pdfs

/RCOGPreventionMalariaPregnancy0410.pdf.Maternal mortality. Saving Mothers Lives: Reviewing maternal

deaths to make motherhood safer: 2006–2008. The eighth report of the Confidential Enquiries into Maternal Deaths in the UK, 118. London: BJOG; 2011:1–203.

Nelson-Piercy C. Handbook of Obstetric Medicine. 4th ed. Obstet Med 2011;4:87. doi:10.1258/om.2011.110023.

Royal College of Obstetricians and Gynecologists. Chickenpox in pregnancy: Guideline No 17. London: RCOG; September 2007.

Royal College of Obstetricians and Gynecologists. Genital herpes in pregnancy: Guideline No 30. London: RCOG; September 2007.

Royal College of Obstetricians and Gynecologists. HIV in preg-nancy: Guideline No 39. London: RCOG; April 2004.

Royal College of Obstetricians and Gynecologists. Preterm prela-bour rupture of membranes: Guideline No 44. London: RCOG; November 2006.

Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria pregnancy. Cochrane Database Syst Rev 2007;(2):CD000490.

Tookey P. Rubella in England, Scotland and Wales. Euro Surveill 2004;9:21–23.

WHO guidelines for treatment of severe H1N1 influenza A: http://www.who.int/csr/resources/publications/swine flu/h1n1_guidelines_pharmaceutical_mngt.pdf.

© 2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology and Reproductive Medicine 2011;21(12):331–338.

About the AuthorsSarah Logan is a Specialist Registrar in Infectious Diseases at Royal Free Hospital, London, UK. Laura Price is a Specialist Registrar in Respiratory and Intensive Care Medicine at Royal Brompton Hospital, London, UK.


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Perinatal Case Management—Caring for Mothers as They Care

for BabiesCh’ng Ying Chia, MA (Applied Social Studies); Jemie Biwen Wang, Bachelor of Psychology (Hons);

Helen Chen, MBBS, M Med (Psych), Dip. Psychotherapy



INTRODUCTION

There is a major unmet clinical need of millions of patients globally suffering many ma-

jor diseases, which, in all cases, severely compromise the quality of life and frequently

lead to death. While advances are being made with more traditional drug-based thera-

pies, it is now clear that a major new impetus is required. The potential revolution in sci-

ence and medicine that stem cells represent is rapidly emerging as the new frontier in

clinical therapies. Given that stem cells are ‘regenerative medicine factories’, they may

be delivered as ‘stand-alone treatments’; but more likely, they will be potent adjuvants

and be combined with current strategies. Clearly, a great deal of preclinical and clinical

research on stem cells is required not only to capitalize on their treatment potential

but also to ensure that safety and ethical requirements are met. It is also imperative to

select the most appropriate source of stem cells for the variety of treatments. Ideally,

these stem cells should be derived from the patients themselves to overcome any issues

of immune rejection. It is now evident that the time of birth is a remarkable once-in-a-

lifetime opportunity to collect and cryopreserve a panel of stem cells, which effectively

represent nature’s ‘body repair kit’ for the duration of the newborn’s life. There are also

stem cells available for maternal utility.

Once regarded as medical waste, the umbilical cord, based on extensive ground-

breaking research, has now been revealed as an invaluable source of haematopoietic

stem cells (HSCs) and pluripotent mesenchymal cells (MSCs) both of which now have

increasing application in regenerative medicine. In addition, the amnion membrane is a

very rich source of pluripotential MSCs which, being equivalent to embryonic stem cells

(ESCs), are able to differentiate into many different types of tissues.

Accordingly, these advances in stem cell research, coupled with the ever-increas-

ing clinical efficacy, have led to the fast-growing establishment of cord blood banks

Newborn Stem Cells: Types, Functions and

Basics for Obstetricians Jennifer Sze Man Mak, MBChB; Juan Bolaños, BSc (Biotechnology); Wing Cheong Leung, MBBS, MD, FRCOG, FHKCOG, FHKAM (O&G);

Richard Boyd, BSc (Hons), PhD; Robert Kien Howe Chin, MBBS, FRCOG, FHKCOG, FHKAM (O&G)

OBSTETRICS i Peer reviewed




worldwide, which store umbilical cord blood (UCB)

for future use and are of either a public or private

nature. This affluence of stem cell banks started in

the mid to late 1990’s in response to the potential

use of cord blood transplants for the treatment of

various disorders. However, the knowledge of stem

cells and cord blood banking are scarce among

pregnant women as shown by many studies, while

most of them would like to be informed by health

care professionals specifically and especially in

early pregnancy so that they would have time to

contemplate the virtues or otherwise of cryopreser-

vation of their babies stem cells.1,2 This article will

therefore review the background on stems cells and

UCB banking (UCBB) as well as patients’ knowledge

on this issue, and the role of obstetricians in con-

veying adequate information to patients. Present

development on stem cells will also be discussed.

BACKGROUND (HISTORY) OF STEM CELLS

Stem cells are one of nature’s most powerful ‘build-

ing blocks’. They have the unique ability to both

self-renew to replenish their availability and differ-

entiate into a variety of different cell types. Hence,

they not only create the organs and tissues in the

body but also maintain them and assist in the repair

following damage or disease.

There are two broad types of stem cells: ESCs

and adult stem cells.

Human eSCs

Human ESCs are isolated from 4- to 5-day-old post-

fertilized blastocysts (Figure 1). Human ESCs are

capable of indefinite ex vivo proliferation and can

differentiate into any specialized cell in the hu-

man body. Adult stem cells are located in tissues

throughout the body and function as a reservoir to

replace damaged or ageing cells;3,4 they differenti-

ate only into the cell lineage of the organ system in

which they are located (Figure 2). UCB is a source

of adult stem cells, in particular MSCs (or stromal

cells), which not only have the normal capacity to

differentiate into structural tissue (bone, muscle,

cartilage, fat) but also have the important property

of being anti-inflammatory.5

ESCs have great potential in generating tis-

sues and organs, yet there are several major prob-

lems with them. The generation of ESCs requires

destruction of discarded embryos from in vitro ferti-

lization, which is ethically challenging if it involves

destruction of life. Furthermore, by virtue of the way

ESCs are produced by long-term replicative culture

in vitro, there is a major safety issue: because of

their rapid proliferation, ESCs form teratomas upon

transplantation.6 Most importantly, we do not have

our own ESCs, and therefore any ESC transplant

will be allogeneic. An accessible and ethically

Figure 1. Stages of development of human embryos.

Single-cell embryo

5- to 7-day embryo

3-day embryo

Zygote

Embryonic stem cells (pluripotent)

6-week embryo

4-week embryo

• Embryonicgermcells (pluripotent)• Fetaltissuestemcells (pluripotent or multipotent)




Figure 2. The cell lineage of each organ system in the human body.

Bone marrow (mesenchymal cells and haematopoietic stem cells)

• Invasive method for collection

Breast milk (mesenchymal cells)

• Easiest way to collect stem cells• Breast milk can be obtained

without assistance by doctors or hospitals

• Non-invasive method for collection

Fat (mesenchymal cells)

• Invasive method for collection

Organ/tissue

• Tissue/organ-specific stem cells

• Eg, eyes, heart, lung

sound alternative is adult stem cells, which exist in

virtually every tissue, albeit being difficult to iden-

tify and isolate. Adult stem cells also possess lim-

ited differentiation potential, but one of their major

advantages is that they pose no risk of rejection as

they are used in autologous transplants.

Newborn Stem Cells

Given the difficulty in settling the dilemmas as-

sociated with the use of human ESCs legally, with

regard to the public perception of the ethical issues

and the safety concerns, alternate sources of stem

cells were sought after. In 1983, Edward Boyse pro-

posed the idea of using UCB as a potential source

of stem cells for haematopoietic transplantation,

thereby highlighting research on placental/new-

born stem cells. This was followed by experiments

in irradiated mice revealing that murine blood from

near-term and neonatal mice contained adequate

numbers of HSCs to effect bone marrow recovery.7




Obstetricians can educate pregnant women about umbilical cord blood banking.

The first pioneering haematopoietic cord blood

transplant was performed to treat a 6-year-old boy

with Fanconi anaemia in 1988 in Paris, France,8

with the first successful unrelated UCB transplant

performed in the United States in 1994.9

In vitro cultures of CD34+ cells (as a marker of

HSC) from umbilical cord yielded a higher rate of

proliferation than similar cells from marrow.10 Be-

sides, UCB HSCs may also have a greater capacity

for self-renewal and long-term growth in culture.11

However, although UCB is proportionally rich in

HSCs, its use is limited because of the relatively

low volume of blood and hence total HSC dose.

The transplanted cell dose is approximately 10%

of a marrow transplant.12 HSCs can be used in al-

logeneic and autologous settings. In the allogeneic

setting, they can be used to treat neoplastic con-

ditions (eg, leukaemia), non-neoplastic conditions

such as inherited disorders (eg, thalassaemia ma-

jor), immunodeficiency, osteoporosis, and acquired

conditions (eg, aplastic anaemia). In the autologous

setting, they can be used to treat autoimmune dis-

orders like aplastic anaemia; but in advance-stage

solid tumours, their use is currently limited. HSCs

are also being investigated for efficacy in treat-

ing cerebral palsy, stroke, and as a means of gene

therapy. Autologous cord blood stem cells are not

suitable for treating inborn errors of metabolism or

some genetic diseases such as childhood leukae-

mia in which chromosomal translocations in fetal

blood were detected in children who finally devel-

oped leukaemia.13,14 The use of autologous stem

cells would also negate the beneficial graft-versus-

leukaemic effect that occurs with allogeneic stem




cell transplants by its residual T lymphocytes in the

haematopoietic progenitor cell product.15

UCB as a source of HSC for transplant is more

superior than, for example, bone marrow, as it ap-

pears to have a higher tolerability of HLA mismatch,

which may be explained by its high content of im-

mune suppressing cells called regulatory T cells,

which are able to suppress immune responses; ac-

cordingly, they have been used for treating type 1

diabetes and multiple sclerosis. This is an impor-

tant and often unrecognized value of UCB.16

THE PATIENT’S KNOWLEDGE OF STEM CELLS AND UCBB

In 2003, Fernandez et al1 examined pregnant wom-

en’s knowledge and attitudes relating to UCB and

UCBB; 70% reported poor or very poor knowledge

about UCB; 66% expected the physician to talk to

them about cord blood collection and said they

would specifically like to receive such information

from health care professionals or in prenatal class

(70%). Twenty-five percent overestimated the risk

of a child needing a bone marrow transplant before

his or her 10th birthday—the risk is reported as be-

tween 1 in 200,000 and 1 in 10,000.17 Eighty-three

percent expected to be asked about UCBB before

30 weeks of pregnancy. In a post hoc analysis, this

level of knowledge was not associated with the

choice between public and private banking.1

In 2006, Perlow et al demonstrated that among

the 425 patients recruited in the survey in USA,

37% had no knowledge of UCBB. Older patients and

those more educated were more aware of UCBB.

Among patients familiar with UCBB, only 2.6% felt

extremely knowledgeable while 74% felt ‘minimal-

ly informed’. Seventy-one percent of patients were

not planning UCBB with the main reasons of ex-

pense and insufficient knowledge. Only 14% were

educated about UCBB by the nurse or obstetrician,

and 90% expected their obstetrician to answer

their questions on UCBB.18 Similar results were also

reported by Fernandez et al1 and Dinç and Sahin.2

In one study, almost one-third of the partici-

pants did not realize that they had the option to

retain their cord blood at delivery; only 50% were

aware that they could store their cord blood in a pri-

vate bank and half of the respondents thought cord

blood donation to the public bank was to protect

their child’s future health.19

A recent research article about our Hong Kong

locality showed that among 2,000 women recruited,

93.3% completed the questionnaire. The majority

(78.2%) had no idea about the chance of using self-

stored stem cells. Most were unclear about which

diseases other than leukaemia are amenable to

treatment with UCB stem cells. This is not taking

into account that if the child developed leukaemia,

their UCB would not be used for haematological

rescue because autologous stem cells lack the

graft-versus-leukaemia effect as well as because

of the fear of cancer contaminants within the UCB.

Only 20.3% of women knew that stem cells are

available from the Red Cross (a local public cord

blood bank) in case their children needed haemat-

opoietic cell transplantation. Hence, most patients

have inadequate knowledge about stem cells and

UCBB, creating an obstacle to UCBB. They would

like to receive more information from health care

providers, especially their obstetricians, and be

provided with the relevant knowledge accordingly

in early pregnancy so that they can have adequate

time to contemplate their choices.20

THE OBSTETRICIAN’S ROLE IN CONVEYING DETAILED AND ACCURATE INFORMATION TO THE PUBLIC

Given this background, it is imperative that the ob-




stetrician be well educated of the pros and cons of

stem cells so that appropriate advice to expecting

parents can be given.

Advantages and disadvantages of Cord

Haematopoietic Progenitor Cells

Being an alternative to bone marrow as a source of

HSCs for allergenic transplantation, cord blood has

both advantages and disadvantages.21,22

The advantages are as follows:

• Fasteravailability:patientsonaveragereceive

cord blood transplantation earlier than those

receiving conventional bone marrow grafts23

• Ethnicdiversityallowsextensionofdonorpool:

with a greater tolerability of HLA mismatch,

this allows a higher availability of specimen

for transplantation

• As a result of greater tolerability of HLA mis-

match, there is lower incidence and severity of

acute graft-versus-host disease with a relative

risk of 0.66 24

• Lowerincidenceofviraltransmission, ie,cyto-

megalovirus and Epstein-Barr virus

• Nodonorattritioncomparedwithbonemarrow

registry

• Highproliferativecapacity

• Painlesscollectionofstemcells

The disadvantages are as follows:

• Low numbers of haematopoietic progenitor

cells and stem cells (approximately 10% of a

marrow transplant12) in each cord blood unit,

which may delay engraftment; this is hereby

addressed by experimental procedures like ex

vivo expansion of the cells and use of multiple

UCB units in the same recipient to expand the

progenitor pool

• Inability to obtain addition stem cells and/

or lymphocytes from the graft donor for second

transplantation in case of graft failure or dis-

ease relapse

indication

HSC use is recommended especially in at-risk fami-

lies for which there is a known genetic or haema-

tological disease amenable to HSC transplantation

for the affected child if HLA-compatible.25

Collection

There are two techniques of cord blood collection:

in vivo with placenta in utero, and in vitro with pla-

centa ex utero.

A comparison of the two techniques has

shown larger unit volumes and higher total nucleat-

ed cells counts with in vivo collection.26 It is recom-

mended that collection should be done by a trained

third party (ie, not by the attending obstetrician or

midwife) using methods and facilities appropriate

to meet the European Tissues and Cells Directive.

The collection procedure must be undertaken ei-

ther during the third stage or shortly after, a time

when there is a risk of postpartum haemorrhage.21

It is not guaranteed that sufficient volume can be

collected; successful transplantation of cord blood

HSCs is related to the volume and cell dose col-

lected. Stringent antiseptic technique is needed to

avoid bacterial contamination.27

ethical issues

The use of stem cells has generated lots of debate

on bioethics, focusing on the principle of autonomy.

It is suggested that the cord blood belongs to the

property of the child, as the placenta or cord blood

stem cells is biologically and genetically developed

by the child.28,29 On the other hand, one would sug-

gest that it is the mother’s property once the cord

is cut. However, legal rights of property are not

generally founded on genetic identity. Although

based on the ontological status of the fetus, once

it is outside the mother’s body, it is recognized as

a legal individual by law but is unable to have full

understanding and thus unable to give consent.




Therefore, the mother, who shares the prenatal au-

thority, would be the one to give consent on behalf

of the baby. If the cord blood is stored for the child’s

use, then the mother will hold in trust till the child

attains the age of 18 years, by which time the use

of stem cells will be decided by the child.21 If the

cord blood is donated, this may then be considered

as a manipulation of human body parts without the

individual’s knowledge.30 In order to translate the

ethical debate from the speculative level into prac-

tice, it is important to get good informed consent

for stem cells use.

Consent

Obstetricians should not be obligated to obtain con-

sent for private UCBB.31

A report by the Institute of Medicine has rec-

ommended that cord blood centres establish clear

policies as to who must provide consent for dona-

tion with consideration of paternal objection to do-

nation and for public cord blood banking. The con-

sent process should not include a promise that the

cells may be available at a later date for use by the

family. The consent should be obtained before la-

bour, preferably in late third trimester. The consent

process should also include disclosure for units that

do not meet quality standards.32

It is recommended by the Royal College of

Obstetricians and Gynaecologists that the service

should not be made available for cases in which

the attending clinician believes it to be contrain-

dicated. Details of the hospital’s policy should be

made available to all patients.

Cost and Choice of Banking

Broxmeyer et al, in a study, suggested that UCB can

be frozen and stored for at least 15 years with high-

ly efficient recovery of viable and highly functional

human stem cells.33 Data suggested that longer-

term storage is feasible and does not compromise

the quality of the engraftment ability of UCB unit.34

The great therapeutic potential of UCB and the

demonstration of the feasibility of cryopreserving

collected units and their utility for up to 15 or more

years led to the development of cord blood banks. A

cord blood bank is an establishment for collection,

processing, and storage of cord blood. There has

been an emergence of public and private banking in

the past two decades.

Public banks, being community-based, pro-

mote allogeneic donation of both related and unre-

lated cord blood, which is subsequently accessible

by the general population. Patients should be in-

formed that they relinquish property rights to the

cord blood units after donation.

Private banks, which are commercially based,

store cord blood for autologous use with cost as-

sociated with specimen processing and storage for

the harvested cord blood as a family biological in-

A report by the

Institute of Medicine

has recommended that

cord blood centres

establish clear policies as

to who must provide

consent for donation with

consideration of paternal

objection to donation

and for public cord

blood banking.




surance, which can also be used for other family

members.

It is recommended that balanced information

for both autologous and allogeneic donation should

be provided to pregnant patients in the antenatal

period.32

In public banks, the donated cord blood is not

assured of being banked or being made available

to donors if required in the future. Safety is a con-

cern as the donated cord blood may carry genetic

defects for disorders, such as congenital anaemia

or immunodeficiency, that are not apparent in the

donor for months or years, by which time all iden-

tifying information has been removed while the re-

cipient could have developed these disorders.

Private banks provide a life insurance by having

the cord blood available for the lifetime, depending

on its commercial viability of the enterprises,35 and

the estimated utility of autologous UCB is approxi-

mately 1 in 20,000 28 to 37 in 100,000 (1 in 2,700).20

regulatory issues

To establish a uniform standard for collection and

quality assurance, it is important that establish-

ments provide standardization of procurement, test-

ing, processing, storage, distribution, documenta-

tion, labelling, equipment control, and cord blood

bank operations.

Figure 3. A variety of progenitor cells in umbilical cord, cord blood, amnion, and placenta/chorion.

Amnion (epiblast stem cells)

• Amnion has been used for the treatment of burns since many years ago

• It can form soft tissue, such as skin and cornea, and have the potential to differenti-ate into hepatic, pancreatic and neural cells

• High requirement for extraction technology

Cord blood (haematopoietic stem cells)

• Since 1988, doctors have used these cells to treat more than 20,000 patients suffering from over 80 diseases

• There are more annual transplant cases than bone marrow transplantation

Umbilical cord (mesenchymal cells and epiblast stem cells)

• The number of cells that can be extracted is less than that from the placenta and amnion

• The new technology provided by Monash Immu-nology and Stem Cell Laboratories, Australia, can extract and store two different stem cells separately

Placenta/chorion (mesenchymal cells)

• Richest source of newborn stem cells• High requirement for extraction technology




In the United Kingdom, cord blood collection

is regulated by the Human Tissue Authority (HTA);

for an HTA-licensed establishment, a third party

agreement is required. The HTA stresses on four

aspects of cord blood collection: safety, quality,

consent, and lawfulness. The HTA does not regu-

late or provide advice about the effectiveness of

treatments using cord blood.36

In the United States, many cord blood banks

have undergone voluntary accreditation through

the American Association of Blood Banks or the

NetCord Foundation for the Accreditation of Cel-

lular Therapy. In our locality, we do not have an

establishment as such, and there is currently no

guideline available on cord blood collection or

use of collected stem cells. Therefore, health

care providers, especially obstetricians, should

help in conveying detailed and balanced informa-

tion on stem cells to couples to ensure thorough

understanding and aid their decisions.

FUTURE DEVELOPMENT

Stem cell research has heralded a new horizon

in clinical medicine. While appreciating the value

of cord blood, it is recognized that there is a va-

riety of progenitor cells, besides HSCs, in cord

blood and placenta; they are the MSCs in umbili-

cal cord, chorion, and placenta, namely, MSCs in

umbilical cord tissue (Wharton’s jelly), amniotic

MSCs, and amniotic epithelial stem cells (Figure

3), which may be a new platform for tissue trans-

plant, ie, bone, cartilage, fat, myocardial muscle,

and neural tissue, owing to its anti-inflammatory,

immunosuppressive, and pro-reparative proper-

ties (Table 1).

As addressed above, allogeneic transplanta-

tion with UCB in adult recipients is limited by a

low CD34+ cells from UCB in vitro. However, hu-

man placenta can now serve as a novel source of

human mesenchymal progenitor cell for in vitro

expansion. Human placenta-derived mesenchy-

mal progenitor cells support culture expansion of

long-term culture-initiating cells from cord blood

CD34+ cells.44

Besides placenta and cord blood, more focus

has been put on the amnion, which is made by

the baby and therefore is a safe and effective al-

ternative to ESCs. Amniotic epithelial stem cells

have remarkable potential to form virtually all

cells in the body and have strong anti-inflamma-

tory properties, and can be considered for repair

of tissues. They have been used for over 15 years

to treat burns and cornea. Currently, there is re-

search on stems cells in adult lung disease like

pulmonary fibrosis and the immune system. The

immune system degenerate drastically with age

and causes problems like being at high risk for

opportunistic infections, poor vaccine responses,

higher incidence and complications of cancer, risk

of death from infection and relapse after chemo-

therapy and radiotherapy, and failure to recover

from human immunodeficiency virus infections.

Therefore, this generates immense research on

using amniotic epithelial stem cells to reverse the

ageing process to restore the thymus function.

Therefore, newborn cells can be regarded

as a natural body repair kit. Yet this novel infor-

mation is scarce to the public, thus limiting the

Table 1. Conditions for the use of mesenchymal cells for repair

Lung fibrosis, chronic obstructive pulmonary disease37,38

Heart and vascular damage39

Spinal disc injury40

Suppress graft-versus-host disease in allogeneic bone marrow transplantInhibit autoimmunity, eg, multiple sclerosis, diabetes, arthritis41

Ageing tissues: tendon, muscle, cartilage, bone (hips, joints)42

Sporting injuries43




1. Fernandez CV, Gordon K, Van den Hof M, Taweel S, Baylis F. Knowledge and attitudes of pregnant women with regard to collection, test-ing and banking of cord blood stem cells. CMAJ 2003;168:695–698.2. Dinç H, Sahin NH. Pregnant women’s knowl-edge and attitudes about stem cells and cord blood banking. Int Nurs Rev 2009;56:250–256.3. van der Kooy D, Weiss S. Why stem cells? Sci-ence 2000;287:1439–1441.4. Pittenger MF, Mackay AM, Beck SC, et al. Mul-tilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.5. Fadel H. Cord blood banking: ethical con-siderations. J Islam Med Assoc N Am North America 2010;42. http://jima.imana.org/article /view/5197.6. Sell S. Stem Cells Handbook. New Jersey: Hu-mana Press; 2004.7. Broxmeyer HE, Kurtzberg J, Gluckman E, et al. Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplanta-tion. Blood Cells 1991;17:313–329.8. Gluckman E, Broxmeyer HA, Auerbach AD, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1989;321:1174–1178.9. Kurtzberg J, Graham M, Casey J, Olson J, Ste-vens CE, Rubinstein P. The use of umbilical cord blood in mismatched related and unrelated he-mopoietic stem cell transplantation. Blood Cells 1994;20:275–283.10. Lansdorp PM, Dragowska W, Mayani H. Ontogeny-related changes in proliferative po-tential of human hematopoietic cells. J Exp Med 1993:178:787–791.11. Hao QL, Shah AJ, Thiemann FT, Smogorze-wska EM, Crooks GM. A functional comparison of CD34+CD38– cells in cord blood and bone marrow. Blood 1995;86:3745–3753.12. Rocha V, Labopin M, Sanz G, et al. Transplants

of umbilical-cord blood or bone marrow from un-related donors in adults with acute leukemia. N Engl J Med 2004;351:2276–2285.13. Rowley JD. Backtracking leukemia to birth. Nat Med 1998;4:150–151.14. Greaves MF, Wiemels J. Origins of chromo-some translocations in childhood leukaemia. Nat Rev Cancer 2003;3:639–649.15. Johnson FL. Placental blood transplantation and autologous banking—caveat emptor. J Pedi-atr Hematol Oncol 1997;19:183–186.16. Rainaut M, Pagniez M, Hercend T, Daffos F, Forestier F. Characterization of mononuclear cell subpopulations in normal fetal peripheral blood. Hum Immunol 1987:18:331–337.17. Kline RM. Whose blood is it, anyway? Sci Am 2001:284:42–49.18. Perlow JH. Patients’ knowledge of umbilical cord blood banking. J Reprod Med 2006;51:642–648.19. Sugarman J, Kurtzberg J, Box TL, Horner RD. Optimization of informed consent for um-bilical cord blood banking. Am J Obstet Gynecol 2002;187:1642–1646.20. Work Group on Cord Blood Banking. Cord blood banking for potential future transplanta-tion: subject review. American Academy of Pedi-atrics. Pediatrics 1999;104:116–118.21. Royal College of Obstetricians and Gynae-cologists. Umbilical cord blood banking. Scien-tific Advisory Committee Opinion Paper 2, revised June 2006. Available at: http://www.rcog.org.uk /files/rcog-corp/uploaded-files/SAC2Umbilical CordBanking2006.pdf.22. Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol 2005;106:1393–1407.23. Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ. Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002;8:257–260.24. Laughlin MJ, Eapen M, Rubinstein P, et al.

Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351:2265–2275.25. Hows JM. Status of umbilical cord blood transplantation in the year 2001. J Clin Pathol 2001;54:428–434.26. Solves P, Moraga R, Saucedo E, et al. Com-parison between two strategies for umbilical cord blood collection. Bone Marrow Transplant 2003;31:269–273.27. Armitage S, Warwick R, Fehily D, Navarrete C, Contreras M. Cord blood banking in London: the first 1000 collections. Bone Marrow Transplant 1999;24:139–145.28. Annas GJ. Waste and longing—the legal status of placental-blood banking. N Engl J Med 1999;340:1521–1524.29. Munzer SR. The special case of property rights in umbilical cord blood for transplantation. Rutgers Law Rev 1999;51:493–568.30. Carlo Petrini. Umbilical cord blood collection, storage and use: ethical issues. Blood Transfus 2010;8:139–148.31. Committee on Obstetric Practice; Committee on Genetics. ACOG Committee Opinion No. 399: umbilical cord blood banking. Obstet Gynecol 2008;111:475–477.32. Institute of Medicine. Cord blood: establish-ing a national hematopoietic stem cell bank program. Institute of Medicine Web site. http://www.iom.edu/Reports/2005/Cord-Blood-Estab lishing-a-National-Hematopoietic-Stem-Cell-Bank-Program.aspx.33. Broxmeyer HE, Srour EF, Hangoc G, et al. High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years. Proc Natl Acad Sci USA 2003;100:645–650.34. Scaradavou A, Stevens CE, Dobrila L, Sung D, Rubinstein P. National Cord Blood Program. “Age” of cord blood (CB) unit: impact of long-term cryo-

preservation and storage on transplant outcome. American Society of Hematology 49th Annual Meeting and Exposition; December 8–11, 2007; Atlanta, GA. Abstract 2033.35. Fisk NM, Roberts IA, Markwald R, Mironov V. Can routine commercial cord blood banking be scientifically and ethically justified? PLoS Med 2005;2:e44.36. Stem cells and cord blood. Human Tissue Au-thority Web site. http://www.hta.gov.uk/licensin gandinspections/sectorspecificinformation/stem cellsandcordblood.cfm. Updated November 2010.37. Moodley Y, Ilancheran S, Samuel C, et al. Human amnion epithelial cell transplantation ab-rogates lung fibrosis and augments repair. Am J Respir Crit Care Med 2010;182:643–651.38. Murphy S, Lim R, Dickinson H, et al. Human amnion epithelial cells prevent bleomycin-in-duced lung injury and preserve lung function. Cell Transplant 2011;20:909–923.39. Minguell JJ, Erices A. Mesenchymal stem cells and the treatment of cardiac disease. Exp Biol Med (Maywood) 2006;231:39–49.40. Goldschlager T, Jenkin G, Ghosh P, Zannettino A, Rosenfeld JV. Potential applications for using stem cells in spine surgery. Curr Stem Cell Res Ther 2010;5:345–355.41. Sykes M, Nikolic B. Treatment of severe au-toimmune disease by stem-cell transplantation. Nature 2005;435:620–627.42. Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Bio-chem 1994;56:283–294.43. Quintero AJ, Wright VJ, Fu FH, Huard J. Stem cells for the treatment of skeletal muscle injury. Clin Sports Med 2009;28:1–11.44. Zhang Y, Li C, Jiang X, et al. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp Hematol 2004;32:657–664.

potential clinical use of invaluable pluripotent stem

cells. Health care providers should serve as an im-

portant channel to convey such invaluable informa-

tion to the public.

CONCLUSION

This article reviews the current trends in UCB stor-

age, as well as recent consensus in the ethical and

commercial activities related to private and public

UCBB. Adult stem cells offer a new and realistic

approach for the treatment of diseases, without the

ethical and medical risks associated with the use

of ESCs.

About the AuthorsDr Mak is Resident Trainee in the Department of Obstetrics and Gynaecology, Kwong Wah Hospital, Hospital Authority, Hong Kong. Mr Juan Bolaños is Research Fellow at ProStemCell Ltd, Hong Kong. Dr Leung is Chief of Service in the Department of Obstetrics and Gynaecology, Kwong Wah Hospital, Hospital Authority, Hong Kong. Dr Boyd is Professor and Director in the Monash Immunology and Stem Cell Laboratories, Monash University, Australia. Dr Chin is Honorary Consultant in the Department of Obstetrics and Gynaecology, Kwong Wah Hospi-tal, Hospital Authority, Hong Kong.

REFERENCES


SGM BBLR dengan formula yang disempurnakan memberikan dukungan nutrisi

pada periode kejar tumbuh untuk bayi prematur atau

berat lahir rendah.

“Karena Anda Mengerti yang Terbaik untuk Ananda”

Informasi Penting :ASI adalah makanan terbaik untuk bayi. ASI menyediakan nutrisi terbaik serta memberikan perlindungan terhadap penyakit. ASI sebaiknya diberikan secara eksklusif selama 6 bulan pertama kehidupan bayi dan dianjurkan sampai anak berusia 2 tahun dengan pemberian makanan tambahan yang sesuai.Susu formula dapat diberikan atas rekomendasi dokter / bidan, hanya bila ibu tidak bisa memberikan ASI. Sebelum memutuskan untuk menggunakan susu formula, seorang ibu hendaknya diperingatkan tentang implikasi sosial maupun ekonomi dari keputusannya. Ikuti petunjuk penyiapan dengan baik. Cara menyiapkan susu formula yang tidak benar bisa membuat bayi sakit. Peganglah bayi anda dan jangan pernah meninggalkan bayi sendirian pada saat minum susu botol.

ASI adalah nutrisi terbaik bagi Ananda. Namun jika terdapat indikasi medis dan dalam kondisi spesifik (prematur / berat badan lahir rendah), SGM BBLR dengan formula yang disempurnakan hadir memberikan solusi untuk Ananda berkebutuhan khusus agar tetap tumbuh kembang optimal.

Mendukung periode kejar tumbuh. 12 Asam Amino Esensial, termasuk Arginin yang tidak dapat disintesis oleh bayi prematur.1

Mendukung perkembangan otak yang pesat.

Mendukung pembentukan sel darah merah yang diperlukan untuk perkembangan otak, fungsi otot maupun fungsi jantung.

Tinggi energi mendukung periode kejar tumbuh.

1Wu, G.; et al. (August 2004.Journal of Nutritional Biochemistry 15 (8): 332-451)

“Karena Anda Mengertiyang Terbaik untuk Ananda”

Informasi Penting :ASI adalah makanan terbaik untuk bayi. ASI menyediakan nutrisi terbaik serta memberikan perlindungan terhadap penyakit. ASI sebaiknya diberikan secara eksklusif selama 6 bulan pertama kehidupan bayi dan dianjurkan sampai anak berusia 2 tahun dengan pemberian makanan tambahan yang sesuai.Susu formula dapat diberikan atas rekomendasi dokter / bidan, hanya bila ibu tidak bisa memberikan ASI. Sebelum memutuskan untuk menggunakan susu formula, seorang ibu hendaknya diperingatkan tentang implikasi sosial maupun ekonomi dari keputusannya. Ikuti petunjuk penyiapan dengan baik. Cara menyiapkan susu formula yang tidak benar bisa membuat bayi sakit. Peganglah bayi anda dan jangan pernah meninggalkan bayi sendirian pada saat minum susu botol.

ASI adalah nutrisi terbaik bagi Ananda. Namun jika terdapat indikasi medis dan dalam kondisi spesifik (prematur/berat badan lahir rendah), SGM BBLR dengan formula yang disempurnakan hadir memberikan dukungan untuk Ananda berkebutuhan khusus agar tetap tumbuh kembang optimal.

Bayi BBLR memiliki kesempatan untuk tumbuh kembang optimal di periode emasnya

Bayi BBLR memiliki kesempatan untuk tumbuh kembang optimal di periode emasnya

EnergiProtein

Rasio Whey : KaseinAsam Amino Esensial

ESPGHAN1

ESPGHAN1

Codex Alimentarius2

110-135 kkal/kg/hari3-3,6 g/100 kkal

11 jenis AAE

Kejar Tumbuh Rekomendasi

Mengejar pertumbuhan bayi normal.

120 kkal/kg/hari3,1 g/100 kkal

60 : 4012 jenis AAE

SGM BBLR

1

Rasio AA : DHAKolin

LA : ALA

ESPGHAN1

ESPGHAN1

ESPGHAN1

1-2 : 17-50 mg/100 kkal

10-15 : 1

Perkembangan Otak Rekomendasi

1 : 1, 0,2% TFA20 mg/100 kkal

15 : 1

SGM BBLR

Mendukung perkembangan otak yang sesuai dengan tahapan usianya.2

MCTMaltodekstrin

ESPGHAN1 < 40% TFA

Mudah Diserap Rekomendasi

34% TFA100%

SGM BBLR

Mempermudah pencernaan dalam absorbsi.3

Level Zat Besi Codex Alimentarius2 Min 0,45 mg/100 kkal

Pembentukan Sel Darah Rekomendasi

1 mg/100 kkal

SGM BBLR

Pembentukan sel darah.4

Bayi prematur membutuhkannutrisi khusus untuk :

1. ESPGHAN 20102. Codex Alimentarius 2007



Family planning is an important part of preconception care.

Preconception Care

Lee Chin Peng, MBBS, FRCOG, FHKAM(O&G)

INTRODUCTION

Pregnancy is usually confirmed after

the missed menstrual period, a few

weeks after the conception. In early

pregnancy, the embryo is susceptible

to teratogens. Furthermore, the health

of the pregnant woman may not be op-

timally suited to pregnancy. Therefore,

it seems logical that care should begin

before conception. Most women do not

visit the obstetricians before pregnancy

has been confirmed. Family doctors or

other primary health care providers are

in a better position to provide precon-

ception care. Some of the preconcep-

tion care can even be introduced in the

community and in schools, in the form

of health education and public health

measures. Although the impact of pre-

conception care for women with signifi-

cant pre-existing health problem, such

as diabetes, may be more obvious than

for women without, preconception care

should not be confined to the former

group of women. Offering preconception

care, such as folic acid supplementa-

tion to prevent neural tube defect, to all

women may have a significant impact on

the whole population. The evidence for

the effectiveness of commonly practised

preconception care will be examined

in this article. A practical checklist for

preconception care in the primary health

care setting will also be provided.

OBJECTIVES OF PRECONCEPTION CARE

The objectives of preconception care are

to improve the physical and psychologi-

cal health of the mother (decrease ma-

ternal mortality and morbidity) and the

father, and to improve the health of the

offspring (decrease perinatal morbid-

ity and mortality). The major causes of

perinatal morbidity and mortality are low

birth weight and congenital abnormali-

ties. Therefore, preconception interven-

tion strategies are targeted at reducing

these.

PLANNED PARENTHOOD

Family planning is an important part of

preconception care. In developing coun-

tries, maternal deaths are associated

with high multiparity and closely spaced

pregnancies.1 In developed countries, es-

pecially in metropolitan cities, delayed

parenthood, single parenthood and lack

of support from the extended family may

pose special problems. For example, post-

partum depression occurs more often in

unplanned pregnancies, while subfertility

and miscarriages occur more often with

older maternal age.2 Women and their

partners should be given information on

contraception, and they should also be

encouraged to discuss when it is best for

them to have children.

DIETARY AND VITAMIN SUPPLEMENTATION

Folic acid supplement use before concep-

3 SKP

JPOG_NovDec_2012_CME_ID.indd 257 12/11/12 2:56 PM


tion and continued to 12 weeks’ gestation

has been found to be effective in reducing

neural tube defects in offspring of women

in the general population (low-risk) and

also offspring of women with previous af-

fected babies, and women on antiepileptic

drugs (high-risk).3 For low-risk women, 400

µg of folic acid daily is adequate, but for

high-risk women, 5 mg of folic acid daily is

usually prescribed.

In Southeast Asia where thalassae-

mia trait is common, an increased inci-

dence of neural tube defect has been found

in thalassaemia trait carriers.4 It is logical

to use the higher dose of folic acid for tha-

lassaemia trait carriers for this purpose,

even though the 400 µg and 5 mg daily dos-

es have not been compared in randomized

controlled trials in this group of women.

Since up to 50% of pregnancies are

unplanned, mandatory fortification of food

(mainly flour) has been used in many coun-

tries and has been found to be effective in

reducing the prevalence of neural tube de-

fects.5 However, there are some concerns

that mandatory fortification exposing the

whole population to increased intake of

folic acid may lead to some adverse ef-

fects in susceptible individuals. For exam-

ple, degenerative neurological diseases in

the elderly may potentially be worsened.6

The effectiveness of folic acid sup-

plementation in preventing congenital ab-

normalities other than neural tube defect

has not been well established.3

Other dietary supplementations have

not been well studied or have not been

found to significantly reduce congenital

abnormalities. It must also be remembered

that high-dose vitamin A is teratogenic.7

Women with iron deficiency anaemia

should be given iron supplement to correct

the anaemia.

GOOD PRACTICE IN DRUG PRESCRIBING

Women in the reproductive age group

should avoid teratogens unless they are

practising effective contraceptive methods.

Most drugs are of low teratogenic-

ity, but a good prescription practice is

not to prescribe unless necessary and

only to prescribe drugs that are proven

to be effective.8 Many commonly used

drugs are assigned to US Food and Drug

Administration (FDA) pregnancy risk cate-

gory C, which means that these drugs have

been found to be teratogenic or embryo-

cidal in animal studies but there are no

controlled studies in women or animals.

These drugs can be used if the potential

benefits outweigh the potential risks and

if no alternatives are found. However,

some drugs used commonly for treatment

of symptoms (eg, codeine, promethazine,

NSAIDs) are category C drugs. For symp-

tomatic treatment only, their use is hardly

justifiable in women who are pregnant

or who are potentially pregnant. Doctors

should be particularly cautious when pre-

scribing treatment for women presenting

with upper gastrointestinal tract symp-

toms or urinary symptoms, as these can be

symptoms of early pregnancy.

Special caution must be taken when

prescribing categories D and X drugs.

Category D means that there is positive

evidence of human fetal risk but the ben-

efits from use in pregnant women may be

acceptable despite the risk. A common

example are antiepileptic drugs, most of

which are category D. Stopping antie-

pileptic drugs in some women may result

in recurrence of epileptic attacks, which

is even more detrimental than antiepi-

leptic drugs to the mother and the baby.

Therefore, their use may be unavoidable in

some women. Folic acid supplement 5 mg

daily should be given together with antie-

pileptic drugs for women who may become

pregnant.

Category X drugs are those that have

been demonstrated to be teratogenic

in humans and their associated risks in

pregnancy clearly outweigh any possible

benefits. An example is isotretinoin, a

highly teratogenic drug, which is used for

skin conditions. When category X drugs

are prescribed, women should be advised

against pregnancy and appropriate contra-

ception should be provided. In some coun-

tries, medical practitioners are required

by law to ask female patients to sign a

consent agreeing to take category X drugs

and to use effective contraception while

on these drugs. Irrespective of the local

legal requirement, it is a good practice to

document in the medical record that this

has been explained to the patient.

Women in the reproductive age group

should also be educated to be cautious

when they use over-the-counter drugs,

which may include some category C drugs.

Precautions regarding their use in preg-

nancy are usually stated on the package.

They should also be educated to inform

doctors if they are not practising contra-

ception and to ask if the prescribed drugs

are safe for pregnancy, even if they do not




suspect that they are pregnant.

AVOIDANCE OF IRRADIATION

Diagnostic X-ray should be avoided during

the luteal phase of the menstrual cycle

and deferred to the follicular phase if pos-

sible. However, most diagnostic X-rays,

except those done under fluoroscopy, have

irradiation doses below the estimated ter-

atogenic threshold (0.1 Gy).9 Therefore, ur-

gent diagnostic X-ray should not be withheld

if there is a strong indication or if alterna-

tive non-irradiation tests are not available.

Abdominal shield should be used.

Therapeutic irradiation, including ra-

dioactive iodine, is absolutely contraindi-

cated during pregnancy.

ADVICE AGAINST LIFESTYLE SUBSTANCE USE

Alcohol consumption is associated with

increased risk of miscarriages and fetal

malformation. However, whether a low in-

take (less than 5 units per week) is safe is

uncertain.10 Therefore, women planning to

get pregnant should be advised to abstain

from alcohol.

Cigarette smoking is not teratogenic

but doubles the risk of intrauterine growth

restriction and increases the risk of miscar-

riages and perinatal mortality by one-third.11

Women should be encouraged and be

helped to stop smoking before pregnancy.

There is an association between use

of recreational drugs and fetal congenital

abnormalities, in particular, gastroschi-

sis.12 Cocaine use is associated with in-

creased incidence of placental abruption.

PREVENTION OF INFECTIONS

Some maternal infections can be transmitted

to the baby during pregnancy and/or delivery,

causing grave consequences to the baby.

Rubella infection in pregnancy can

cause major congenital abnormalities.

Vaccination against rubella is part of the

vaccination programme for children and

adolescents in many countries. However,

even in countries with such vaccination

programmes, doctors must be aware that

immigrants may not have been vaccinated

in their original country. Therefore, check-

ing the immune status and providing the

vaccination to women is an important part

of preconception care. Chickenpox infec-

tion during pregnancy can also cause scar-

ring and deformity in the baby in a small

proportion of cases. Vaccination against

chickenpox in susceptible women before

pregnancy can be an option.13

Hepatitis B vaccination should be

provided to susceptible health care work-

ers and non-immune women whose part-

ners are carriers. However, women who

are hepatitis B carriers should not be un-

duly worried, because effective prevention

of perinatal transmission is available.14

Screening for HIV and syphilis are

part of routine antenatal care. However,

it can be done before pregnancy. Syphilis

can be effectively treated before preg-

nancy. This also allows time for contact

tracing and for more effective prevention

of re-infection during pregnancy. There is

no curative treatment for HIV, but carriers

can remain healthy with monitoring and

early antiretroviral treatment. Prevention

of perinatal transmission with antepartum

HAART (highly active antiretroviral ther-

apy with multiple agents) together with

intrapartum and postnatal zidovudine for

the baby is highly effective.15 Therefore,

it may not be necessary to advise against

pregnancy in carriers. With compliance,

perinatal transmission rate can be reduced

to less than 1%, but in rare instances the

baby can still be infected. Knowing the HIV

status before pregnancy may change the

reproduction plan for some women or may

help HIV-positive individuals to be better

prepared to start a family. However, nega-

tive screening before pregnancy does not

mean that the individual is not susceptible

to infection after the screening or during

the pregnancy.

TREATMENT FOR OBESITY

It has increasingly been shown that obe-

sity has adverse effects on pregnancy.

The association of obesity with maternal

mortality and morbidity is well proven.

There is also evidence suggesting that

fetal congenital abnormalities and peri-

natal morbidities are also increased in

obese mothers.16 Weight reduction may

potentially be harmful during pregnancy.

Therefore, weight reduction should ideally

be achieved before pregnancy.17

ATTENTION TO DENTAL HYGIENE

Periodontal disease in pregnant women

has been found to be associated with in-

creased risk of preterm delivery.18 However,

treatment of the disease during pregnancy

has been shown to be ineffective in reduc-



ing premature deliveries. Effectiveness of

treatment before pregnancy in improving

pregnancy outcome has not been stud-

ied.19 Provision of dental care as part of

general health care is a good practice, but

its role in preconception care has yet to

be determined. However, for women with

medical diseases such as valvular heart

disease, good dental hygiene is a very im-

portant part of preconception care.

CERVICAL SCREENING

Cervical smears should be taken before

pregnancy in women planning to get preg-

nant, if they are not already in a regular

screening programme. Hormonal changes

in pregnancy may lead to problems in in-

terpretation of cervical cytology. Cervical

biopsy and treatment of cervical intraepi-

thelial neoplasia during pregnancy are

also associated with a higher incidence

of heavy bleeding and are generally not

advisable unless there is a suspicion of

invasive disease. With experience, colpo-

scopic examination during pregnancy to

detect invasive lesions is effective.20 If in-

vasive disease is detected, full treatment

cannot be given without terminating the

pregnancy. Therefore, screening before

pregnancy is more ideal than screening

during pregnancy.

WOMEN WITH MEDICAL DISEASES

Women with significant medical dis-

eases, such as diabetes, active thyroid

diseases, epilepsy, autoimmune diseas-

es, renal diseases, cardiac diseases and

post transplantation, should be referred

to a maternal medicine specialist for pre-

conception care. Preconception care for

women with diabetes is the best known

model for preconception care in women

with significant chronic medical illness.

It is well known that the incidence of

congenital abnormalities in fetuses of

diabetic women is directly proportional

to periconception glycosylated haemo-

globin A1C, which reflects the glycaemic

control.21 Therefore, achieving good gly-

caemic control before pregnancy is im-

portant. Women with diabetes should

also be screened for diabetic retinopa-

thy, nephropathy and ischaemic heart

disease before pregnancy, as these com-

plications greatly increase the maternal

risks and perinatal mortality and morbid-

ity. However, good glycaemic control is

difficult to achieve and intervention pro-

grammes have, so far, fallen short of the

expectation.22

Hypertension is often asymptomatic,

and blood pressure should be checked

even in women without a history of hyper-

tension.

WOMEN WITH MAJOR PSYCHIATRIC DISEASES

Women with major depression, bipolar

disorders and schizophrenia should be

under the care of a psychiatrist to ensure

that the disease is well controlled before

pregnancy. Many psychotropic drugs are

FDA category C or D. However, their use

may be unavoidable, as relapse during

pregnancy may be more detrimental to the

mother and the baby.

WOMEN AND MEN WITH MALIGNANT DISEASES

Many malignant diseases can be suc-

cessfully treated with modern medicine.

Women and men may want to start a fam-

ily after treatment of malignant diseases.

Some treatment may affect the future fer-

tility of men and women. Storage of se-

men or even cryopreservation of ovarian

tissues before these treatments may be

an option.23 After treatment, some women

may be concerned about the risk of recur-

rence of the malignancy during pregnancy

because of altered hormonal and immune

status. Pregnancy does not affect the re-

currence risk of most malignant diseases

if the woman is disease-free before em-

barking on a pregnancy. It is best to con-

sult an oncologist on this.

SCREENING FOR GENETIC DISEASES

For families with no history of genetic

diseases, screening for carrier status of

any genetic disease before pregnancy is

only advisable if (1) the particular genetic

disease is common in the population, (2)

reliable screening methods are avail-

able, and (3) the affected individual has

poor quality of life or a major handicap.

An example is α- and β-thalassaemia in

Southeast Asia. In Hong Kong, the prev-

alence of α-thalassaemia carriers and

β-thalassaemia is 5.0% and 3.4%, respec-

tively.24 A simple complete blood picture

with mean corpuscular volume above 80 fL

effectively exclude α- and β-thalassaemia

trait.24 (However, it does not exclude car-





riers of haemoglobin E, which is preva-

lent in Thailand, and haemoglobin E–β-

thalassaemia heterozygous may have

transfusion-dependent anaemia.) Further

investigations, such as haemoglobin pat-

tern analysis and DNA studies may be

needed after excluding iron deficiency.

Iron deficiency can be excluded by iron

profile studies, but a simple and practi-

cal way to exclude iron deficiency is a

therapeutic trial of iron supplement for 4

weeks. If red cell microcytosis is due to

iron deficiency alone, it should be cor-

rected by supplement. Which genetic dis-

eases to screen for and how they should

be screened for should be determined to

suit the local population. In general, it

is important that a screening test should

have a high sensitivity with a low false-

positive rate. There is some controversy

as to whether screening should be done

before or during pregnancy. If prenatal

diagnosis is readily available and accept-

able to the couple and early antenatal care

is accessible, antenatal screening may be

more cost-effective than preconception

screening. Preconception screening has

the advantage of allowing more time for

couples to understand and consider the

options of prenatal diagnosis before the

pregnancy. Screening for genetic diseas-

es, whether before pregnancy or during

pregnancy, should only be done with in-

formed consent. Individuals should not be

coerced into undergoing genetic testing or

screening.

It is also a good practice to obtain a

genetic history from couples planning to

get pregnant. If there are any genetic dis-

eases in the family (eg, the woman’s broth-

er has haemophilia, if the couple already

have a child with genetic disease, or one

potential parent has a genetic disease),

referral to a geneticist for preconception

counselling and testing is recommended.

Many tests to confirm the diagnosis and

Preconception care checklist for primary care physicians

History• Family history, including genetic diseases• Past health• Past obstetric history, including all pregnancy losses• Use of alcohol, cigarette, and recreational drugs• Psychological readiness for pregnancy and child rearing

Physical examination• Weight and height• Blood pressure• Urine (for glucose and albumin)• Examination of the cardiovascular system

Investigations• Rubella immune status• Varicella immune status (if no known history of chickenpox or varicella zoster)• Hepatitis B surface antigen (HBsAg)• HIV screening• Syphilis screening• Complete blood count (to screen for anaemia and thalassaemia)• Cervical smear (if not already in a screening programme)

Advice and treatment• Contraception advice if needed• Provide necessary vaccinations• Body weight control if needed• Folic acid supplementation if planning to get pregnant• Appropriate use of drugs, avoid unnecessary drugs• Avoid unnecessary irradiation• Cessation of smoking, drinking, or recreational drugs

Referrals• Most couples do not need referrals to specialists • Refer to obstetricians or fetomaternal medicine specialists ~ Women with significant medical illnesses or poor obstetric history• Refer to medical geneticist ~ Couple with suspected genetic diseases or are potential carriers



REFERENCES

1. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066–1074.2. Nybo Anderson AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ 2000;320:1708–1712.3. De-Regil LM, Fernandez-Gaxiolo AC, Dowsell T, Pena-Rosas JP. Effects and safety of pericon-ceptional folate supplementation for prevent-ing birth defects. Cochrane Database Syst Rev 2010;(10):CD007950.4. Lam YH, Tang MH. Risk of neural tube defects in the offspring of thalassaemia carriers in Hong Kong Chinese. Prenat Diagn 1999;19:1135–1137. 5. Blencowe H, Cousens S, Modell B, Lawn J. Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol 2010;39(Suppl 1):i110–i121.6. Finglas PM, de Meer K, Molloy A, et al. Research goals for folate and related B vitamin in Europe. Eur J Clin Nutr 2006;60:287–294.7. Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vita-min A intake. N Engl J Med 1995;333:1369–1373.

8. Rayburn WF, Amanze AC. Prescribing medica-tions safely during pregnancy. Med Clin North Am 2008;92:1227–1237.9. Valentin J. ICRP Publication 84: Pregnancy and Medical Radiation. Annals of the ICRP Volume 30/1. Elsevier 2000;1–39.10. Royal College of Obstetricians and Gynaecolo-gists. Alcohol consumption and outcomes of preg-nancy. RCOG Statement No. 5; 2006.11. Walsh RA. Effects of maternal smoking on adverse pregnancy outcomes: examination of the criteria of causation. Hum Biol 1994;66:1059–1092.12. Draper ES, Rankin J, Tonks AM, et al. Recre-ational drug use: a major risk factor for gastroschi-sis? Am J Epidemiol 2008;167:485–491.13. Royal College of Obstetricians and Gynaeco-logists. Chickenpox in pregnancy. RCOG Green-top Guideline No. 13; 2007.14. Wong VC, Ip HM, Reesink HW, et al. Preven-tion of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet 1984;323:921–926.

15. European Collaborative Study. Mother-to-child transmission of HIV Infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2005;40:458–465.16. Nuthalapaty FS, Rouse DJ. The impact of obesity on obstetrical practice and outcome. Clin Obstet Gynecol 2004;47:898–913.17. Davies GA, Maxwell C, McLeod L, et al; Society of Obstetricians and Gynaecologists of Canada. SOGC clinical practice guidelines: obesity in preg-nancy. No. 239, February 2010. Int J Gynecol Obstet 2010;110:167–173.18. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP, Goldenberg RL, Hauth JC. Periodontal infection and preterm birth: results of a prospective study. J Am Dent Assoc 2001;132:875–880.19. Polyzos NP, Polyzos IP, Zavos A, et al. Obstetric outcomes after treatment of periodontal disease during pregnancy: systematic review and meta-analysis. BMJ 2010;341:c7017.20. Fader AN, Alward EK, Neiderhauser A, et al. Cervical dysplasia in pregnancy: a multi-institutional evaluation. Am J Obstet Gynecol 2010;203:113.e1–e6.21. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA,

Ratner RE. Preconception care of diabetes, congeni-tal malformations, and spontaneous abortions. Diabetes Care 1996;19:514–541.22. Tieu J, Middleton P, Crowther CA. Preconcep-tion care for diabetic women for improving mater-nal and infant health. Cochrane Database Syst Rev 2010;(12):CD007776.23. Schmidt KT, Rosendahl M, Ernst E, et al. Auto-transplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience. Fertil Steril 2011;95:695–701.24. Lau YL, Chan LC, Chan YY, et al. Prevalence and genotypes of alpha- and beta-thalassemia carriers in Hong Kong—implications for population screen-ing. N Engl J Med 1997;336:1298–1301.25. Geraedts JP, De Wert GM. Preimplantation genetic diagnosis. Clin Genet 2009;76:315–325.26. Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collabora-tive randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 1992;166:1318–1323.

future. Preconception care can be in the

form of careful prescription and careful

ordering of investigations which are po-

tentially teratogenic. Preconception care

can be provided on specific request from

patients or actively promoted to all women

and men of the reproductive age group.

History taking and advice giving are very

important components of preconception

care. Some standard investigations are

useful, but these cannot replace a care-

fully taken history. The box on page 174 is

a summary of this review and can be used

as a checklist for primary care physicians

in providing preconception care.

About the AuthorDr Lee is Consultant in the Department of Obstetrics

and Gynaecology, University of Hong Kong, Queen Mary

Hospital, Hong Kong.

then to determine the mutation of rarer

genetic diseases are lengthy. Therefore, it

is better if these can be confirmed before

the pregnancy rather than during pregnan-

cy, as the window for prenatal diagnosis

is short. In some cases, prenatal diagnosis

may not be possible and couples may need

to change their reproductive plans.

For couples who cannot accept ter-

mination of pregnancy following prenatal

diagnosis, preimplantation genetic diag-

nosis, if available, can be an option if they

are known to carry mutations which may

affect the baby.25

WOMEN WITH BAD OBSTETRIC HISTORY

Women with recurrent miscarriages (three

or more) in the first trimester, one or more

pregnancy loss after the first trimester,

history of severe early onset pre-eclamp-

sia, or history of severe early onset in-

trauterine fetal growth restriction should

be referred to an obstetrician or maternal

fetal medicine specialist for preconcep-

tion care. Investigations for treatable or

preventable causes (eg, antiphospholipid

syndrome)26 can be undertaken, and appro-

priate management may optimize the out-

come of future pregnancies in some cases.

SUMMARY

Preconception care can be provided in

primary health care. Doctors should also

be aware that whenever they are treating

women in the reproductive age group, they

are treating someone who may be preg-

nant or may become pregnant in the near


CME Questions

1. Preconception folic acid supplement use prevents neural tube defects.

2. Folic acid 5 mg daily should be prescribed to all women who are planning to get pregnant.

3. Antiepileptic drugs must be stopped in women who are planning to get pregnant.

4. Women planning to get pregnant should be advised to abstain from alcohol.

5. Women who are HIV carriers should be advised against pregnancy.

6. Obesity is associated with higher maternal mortality and morbidity.

7. Treatment of periodontal disease during pregnancy improves the pregnancy outcome.

8. Cervical screening cannot be done during pregnancy.

9. All women should be referred to obstetricians for preconception care.

10. Blood pressure should be checked during preconception care.

JPOG advanced online publication; 1 July 2012 • 263 JPOG NOV/DEC 2012 • 263

Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh Medical Progress Institute, sebuah institusi yang didedikasikan untuk pembelajaran CME, bekerjasama dengan Ikatan Dokter Indonesia.

Setelah membaca artikel ‘Preconception Care’, jawab pertanyaan berikut kemudian kirimkan dengan menggunakan formulir jawaban yang sudah disediakan ke CME Medical Progress/ Journal of Paediatrics, Obstetrics & Gynaecology, untuk mendapatkan 3 SKP.

Artikel CME:

Preconception Care

Jawab pertanyaan di bawah ini dengan Benar atau Salah

3 SKP

Answers

1 2 3 4 5 6 7 8 9 10

T F F T F T F F F T


JPOG NOv/Dec 2012 • 264

JPOG 2012 Annual Index

Section First Author Issue Page

GynAecOlOGy

Analgesia, analgesics, combined oral contraceptives, diagnosis, dysmenorrhoea, physiopathology Clinical Review Kolhe S Jul/Aug 147

Anovulation, ovulation induction Clinical Review Yeung WYT Jan/Feb 5

Atopobium, bacterial vaginosis, biofilms, Gardnerella, metronidazole Clinical Review Hay P Mar/Apr 60

Chronic pain, dysmenorrhoea, endometriosis, pelvic pain Clinical Review Raffi F May/Jun 93

Contraceptive agents, contraceptive failure, intrauterine devices, postcoital contraception, unplanned pregnancy CME Li HWR Jul/Aug 169

Early detection of cancer, ovarian neoplasms, randomized controlled trial CME Chan KKL Mar/Apr 81

Hormone replacement therapy, risks and benefits Clinical Review Farrell E Jul/Aug 157

ObstetrIcs

Abruptio placentae, antepartum haemorrhage, caesarean section, Doppler ultrasonography, placenta praevia, resuscitation Clinical Review Athana sias PK Sep/Oct 193

Acute fatty liver of pregnancy, HELLP syndrome, hepatitis, hyperemesis gravidarum, inflammatory bowel diseases, obstetric cholestasis, pancreatitis, pregnancy Clinical Review Cuckson C May/Jun 105

Aetiology, antenatal hydronephrosis, fetal magnetic resonance imaging, prenatal ultrasonography CME Yap TL May/Jun 125

Breastfeeding, emollients, lactation, nipple eczema, topical corticosteroids In Practice Fischer G Sep/Oct 201

Caesarean section, pregnancy outcome, second labour stage CME TK Lo Jan/Feb 37

Congenital abnormalities, maternal mortality, vertical infectious disease transmission Clinical Review Logan S Nov/Dec 234

Fetal blood; health knowledge, attitudes, practice; obstetrics; stem cells Clinical Review Mak JSM Nov/Dec 247

Folic acid, non-prescription drugs, preconception care, primary health care, reproductive history, vaccination CME Lee CP Nov/Dec 257

Four-dimensional ultrasonography, three-dimensional ultrasonography, obstetrics CME Lau B Sep/Oct 213

PAedIAtrIcs

Adolescent, child, diabetic ketoacidosis, haemoglobin A1c, hypoglycaemia, type 1 diabetes mellitus Clinical Review Shulman RM Mar/Apr 49

Analgesics, child, diagnosis, headache, migraine disorders, prevention and control Clinical Review McShane MA Jul/Aug 164

Anaphylaxis, child, food hypersensitivity, immediate hypersensitivity Clinical Review Joshi P Jan/Feb 26

Atopic dermatitis, emollients, food allergy, topical calcineurin inhibitors, topical corticosteroids Clinical Review Shekariah T Mar/Apr 68

Biological therapy, child, Psoriasis Area and Severity Index, plaque, paediatric psoriasis Clinical Review Sharma V Jul/Aug 137

Child, differential diagnosis, limping, primary health care Clinical Review Cox A May/Jun 117

Child, genetic testing, hydroxymethylglutaryl-CoA reductase inhibitors, hyperlipidaemias, hyperlipoproteinaemia type II Clinical Review Datta BN Sep/Oct 202

Childhood, eczema, food allergy Clinical Review Kelly JP Nov/Dec 225

Dental caries, preschool child, prevention and control In Practice Wooley S Mar/Apr 59

Gastro-oesophageal reflux, infant, oesophagitis, vomiting Clinical Review Bhavsar H Sep/Oct 181

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