JPOG December 2012

JAN/FEB 2012
nov/dec
2012Vol.
Vol.38
38No.
No.16
Your partner in paediatric

and O&G practice
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
ISSN 1016-0124
(INDONESIA)
JOURNAL WATCH
PAEDIATRICS
Dietary Intervention
in Eczema
OBSTETRICS
Infectious Disease in Pregnancy

Newborn Stem Cells: Types,
Functions and Basics
for Obstetricians

P
3 SK
CME ARTICLE
Preconception Care
www.jpog.com
Get your copy of JPOG and Medical Progress today and earn SKP IDI
NO V/DEC 2 0 1 2
Vol. 38
No. 6
Journal Watch
221 Hormonal contraception and cardiovascular risk

Midurethral sling during vaginal prolapse surgery to reduce
postoperative incontinence

Effect of contraception on maternal mortality rates
221
222 Cumulative birth rates with assisted reproduction

Urinary protein-to-creatinine or albumin-to-creatinine ratio to detect
significant proteinuria in pregnancy
Reducing measles mortality

223 The Millennium Villages project in Africa

Management of type 2 diabetes in children and adolescents
Treatment for infants of mothers who present late in pregnancy with

an untreated HIV-1 infection
Zidovudine, lamivudine, and ritonavir-boosted lopinavir for HIV-
infected children
224 Neonatal screening with pulse oximetry for critical congenital heart
defects: Systematic review and meta-analysis
Oral immunotherapy for egg allergy in children

224
Editorial Board
Professor Biran Affandi

University of Indonesia
Dr Tak-Yeung Leung
Chinese University of Hong Kong
Dr Raman Subramaniam
Fetal Medicine and Gynaecology Centre, Malaysia
Board Director, Paediatrics
Dr Karen Kar-Loen Chan

The University of Hong Kong
Professor Tzou-Yien Lin

Chang Gung University, Taiwan
Professor Walfrido W Sumpaico

MCU-DFT Medical Foundation, Philippines
Associate Professor Oh Moh Chay

KK Womens and Childrens Hospital,
Singapore
Professor Somsak Lolekha

Ramathibodi Hospital, Thailand
Professor Cheng Lim Tan

KK Womens and Childrens Hospital, Singapore
Professor Lucy Chai-See Lum

University of Malaya, Malaysia
Associate Professor Kok Hian Tan

Professor SC Ng
National University of Singapore
Dr Surasak Taneepanichskul
Chulalongkorn University, Thailand
Professor Hextan Yuen-Sheung Ngan

Professor Eng-Hseon Tay

Thomson Womens Cancer Centre, Singapore
Professor Carmencita D Padilla

University of the Philippines Manila
Professor PC Wong
Professor Seng-Hock Quak

Dr George SH Yeo
Dr Tatang Kustiman Samsi

University of Tarumanagara, Indonesia
Professor Terence Lao

Chinese University of Hong Kong
Professor Hui-Kim Yap

Professor Perla D Santos Ocampo

University of the Philippines
Professor Tsu-Fuh Yeh

China Medical University, Taiwan
Dr Kwok-Yin Leung
Associate Professor Alex Sia

Professor Pik-To Cheung

Associate Professor
Department of Paediatrics
and Adolescent Medicine
Board Director, Obstetrics and Gynaecology
Professor Pak-Chung Ho
Head, Department of
Obstetrics and Gynaecology
Associate Professor Anette Jacobsen

Professor Rahman Jamal
Universiti Kebangsaan Malaysia
Dato Dr Ravindran Jegasothy
Hospital Kuala Lumpur, Malaysia
Associate Professor Kenneth Kwek
Dr Siu-Keung Lam
Kwong Wah Hospital, Hong Kong
JPOG NOV/DEC 2012 i
JPOG_NovDec_2012_TOC.indd 1
12/11/12 3:54 PM
Protein Whey dan Casein

terhidrolisat parsial dengan
alerginisitas rendah untuk
mengurangi risiko dermatitis atopi.
CM
MY
CY
CMY
Isolat Protein Kedelai berkualitas

yang diperkaya L-Methionine,
Karnitin untuk mengatasi alergi
susu sapi.
NO V/DEC 2 0 1 2
Vol. 38
No. 6
Review Article
Paediatrics
225 Dietary Intervention in Eczema

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.

225
Jackelina Pando Kelly, Jonathan Hourihane
Review Article
Obstetrics
234 Infectious Disease in Pregnancy

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
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JPOG NOV/DEC 2012 ii
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Indonesia
NO V/DEC 2 0 1 2
Vol. 38
No. 6
Review Article
Obstetrics
247 Newborn Stem Cells: Types, Functions and Basics for Obstetricians

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.

247
Jennifer Sze Man Mak, Juan Bolaos, Wing Cheong Leung, Richard Boyd, Robert Kien Howe Chin
Continuing Medical Education
P
3 SK
257 Preconception Care

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 2012 Annual Index
257
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Dengan locust bean gum sebagai thickening agent
Diperkaya dengan AA dan DHA

Dengan Nukleotida
Referensi:
Peer Reviewed
GYNAECOLOGY
Hormonal contraception and
cardiovascular risk
Journal Watch
ethinyl oestradiol dose of 20 g, the increase in risk
There were significant increases in the sling group
was less in general, and there was no increased
in urinary tract infection (31.0% vs 18.3%), major
risk with drospirenone as the progestin. Transder-
bleeding (3.1% vs 0%), and incomplete bladder
mal patches were not associated with significantly
emptying 6 weeks after surgery (3.7% vs 0%).
increased risk for either thrombotic stroke or myo-
The insertion of a midurethral sling was ef-
cardial infarction. Vaginal ring was associated with
fective in reducing the risk of postoperative urinary
a significant 2.5-fold increase in risk of thrombotic
incontinence but at the expense of increased risk
stroke but a non-significant increase in risk of myo-
of complications.
cardial infarction.
Although hormonal contraception may in-
Wei JT et al. A midurethral sling to reduce incontinence after vaginal

prolapse repair. NEJM 2012; 366: 23582367; Iglesia CB. Vaginal prolapse
repair place midurethral sling now or later: Ibid: 24222424 (editorial).
crease the risks of thrombotic stroke and myocardial infarction, the absolute risks are low. An editorialist concludes that they are safe enough.
Lidegaard et al. Thrombotic stroke and myocardial infarction with
hormonal contraception. NEJM 2012; 366: 22572266; Petitti DB.
Hormonal contraceptives and arterial thrombosis not risk-free but safe
enough. Ibid: 23162318 (editorial).
Effect of contraception on
maternal mortality rates
The Safe Motherhood Initiative begun in 1987 has
four strategies to reduce maternal mortality: family
Midurethral sling during vaginal

prolapse surgery to reduce postoperative incontinence
planning, antenatal care, safe delivery, and postnatal care. Now, the effects of contraceptive use on
maternal mortality worldwide have been estimated
from three international databases.
About a quarter of women undergoing surgery for
Data were analysed from 172 countries for
A Danish registry study has provided more data
pelvic organ prolapse who had no urinary incon-
2008. The number of deaths from maternal causes
about cardiovascular risks associated with hor-
tinence before surgery will develop incontinence
in 2008 was estimated at 342,203 (data from 172
monal contraception.
after surgery. The prophylactic insertion of a mi-
countries). The estimated number of maternal
Data were obtained from four national reg-
durethral sling during prolapse surgery has become
deaths averted by contraception was 272,040, a
istries over a 15-year period about non-pregnant
popular without good evidence of its effectiveness.
44% reduction of the potential total. It was also
women aged 1549 with no history of cardiovascu-
A multicentre US trial has been reported.
estimated that expansion of contraceptive use
lar disease or cancer. The data included 1,626,158
A total of 337 women undergoing prolapse
could avert another 104,000 maternal deaths each
women with 14,251,063 person-years of observa-
surgery but without a history of stress incontinence
year. The number of deaths averted increased with
tion, during which there were 3,311 thrombotic
were randomized to insertion of a midurethral sling
increased contraceptive use. In countries with high
strokes and 1,725 myocardial infarctions. The rate
or a control group (sham incisions) and 327 women
(> 65%) contraceptive use, almost 60% of potential
of thrombotic stroke was 21.4 per 100,000 per-
were followed up for 1 year. At 3 months, there
maternal deaths were averted, whereas in sub-Sa-
son-years and of myocardial infarction, 10.1 per
was a significant reduction in urinary incontinence
haran Africa (22% contraceptive use), only 32% of
100,000 person-years. Among women using oral
in the urethral sling group (23.6% vs 49.4%). At 12
potential maternal deaths were averted.
contraceptives including ethinyl oestradiol at a
months, the rates of incontinence were 27.3% vs
dose of 3040 g, the risk of thrombotic stroke was
43.0%. The number needed to treat to prevent one
increased 1.5- to 2.2-fold according to progestin
case of urinary incontinence at 12 months was 6.3.
type, compared with non-users. The risk of myocar-
Bladder perforation occurred in 6.7% of the ure-
dial infarction was increased 1.3- to 2.3-fold. At an
thral sling group but in none of the control group.
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: 111125; Gilmore K, Gebreyesus TA.
What will it take to eliminate preventable maternal deaths? Ibid: 8788
(comment).
JPOG NOV/DEC 2012 221
JPOG_NovDec_2012_COMBINE.indd 221
12/11/12 4:43 PM
with cleavage embryos (day 2 or 3).
OBSTETRICS
Live-birth rates similar to natural fecundity

can be achieved with favourable maternal and
Cumulative birth rates with

assisted reproduction
a sensitivity and a specificity both of 0.94. There is

insufficient evidence about the use of either test to
predict adverse pregnancy outcome.
embryo characteristics. The use of donor oocytes
Urinary protein-to-creatinine ratio may be
eliminates the decline in live-birth rates with age
useful in the diagnosis of pre-eclampsia, but there
seen when autologous oocytes are used.
is insufficient evidence about the use of albumin-
Luke B et al. Cumulative birth rates with linked assisted reproductive

technology cycles. NEJM 2012; 366: 24832491.
to-creatinine ratio for this purpose or about the

use of either test to predict adverse pregnancy
outcome.
Urinary protein-to-creatinine or
albumin-to-creatinine ratio to
detect significant proteinuria in
pregnancy
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).
PAEDIATRICS
Reducing measles mortality

One global goal was to halve measles deaths between 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 AmeriRates of live birth with assisted reproductive tech-
cas since 2002, and only the southeast Asia region
nology have usually been reported per cycle, but for
of the World Health Organization has not set an aim
women undergoing continuous treatment, cumula-
of measles elimination by 2020. Measles mortality
tive live-birth rates are more relevant. A national
A systematic review and meta-analysis has ad-
fell by an estimated 74% between 2000 and 2010,
US database has been used to estimate cumulative
dressed the use of spot urine protein-to-creatinine
from 535,300 to 139,300 deaths. All regions except
rates.
or albumin-to-creatinine ratio to detect significant
southeast Asia achieved a reduction of > 75%. In
proteinuria in pregnancy in the diagnosis of pre-
India, measles deaths fell by 25% from 88,000 to
eclampsia.
65,500. In 2010, almost half (47%) of all deaths
Data were available for 246,740 women

(471,208 cycles, 140,859 live births). Live-birth
rates decreased with increasing maternal age and
The analysis included 20 studies (2,978
from measles were in India and 56% were in Africa.
increasing cycle number with autologous, but not
women). Threshold values for protein-to-creatinine
Achievement of the 20002010 goal was impeded
with donor, oocytes. Conservative and optimal es-
ratio ranged from 0.13 to 0.5 with sensitivity val-
by delayed implementation of disease control in
timates of live-birth rates by the third cycle with
ues between 0.65 and 0.89 and specificity of 0.63
India and outbreaks of measles in Africa. Greater
autologous oocytes were 63.3% and 74.6% for
to 0.87 for the detection of 24-hour urinary protein
political and financial commitment are needed.
women < 31 years old, 18.6% and 27.8% at ages 41
> 0.3 g/day. The optimum threshold values for pro-
and 42, and 6.6% and 11.3% at age 43 or older. Us-
tein-to-creatinine ratio appeared to be 0.300.35.
ing donor oocytes, the corresponding figures were
There was insufficient evidence about the use of
60% and 80% at all ages. Rates were higher with
albumin-to-creatinine ratio. One study suggested
blastocyst embryos (transfer at day 5 or 6) than
that a value of > 2 mg/mmol was associated with
Simons E et al. Assessment of the 2010 global measles mortality

reduction goal: results from a model of surveillance data. Lancet 2012;
379: 21732178; Orenstein WA, Hinman AR. Measles: the burden of
preventable deaths. Ibid: 21302131 (comment).
12/11/12 4:44 PM
Peer Reviewed
The Millennium Villages project in

Africa
Journal Watch
who have not received antiretroviral therapy in

pregnancy is uncertain. Three regimens have been
compared in an international trial.
The Millennium Villages project began in nine
A total of 1,684 bottle-fed infants of moth-
African countries (Nigeria, Mali, Senegal, Ghana,
ers who received a diagnosis of HIV-1 infection late
Uganda, Kenya, Rwanda, Tanzania, and Malawi)
in pregnancy were randomized within 48 hours of
in 2006. In each country, a rural population (aver-
birth in Brazil, South Africa, Argentina, or the USA
age, 35,000 people) with high levels of poverty and
to one of three treatment regimens: zidovudine for
undernutrition was selected. Finance amounting to
6 weeks (Z6), zidovudine for 6 weeks plus three
around US$120 per person was provided annually
doses of nevirapine in the first 8 days (Z6 + Nev), or
to support agriculture, the environment, business
zidovudine for 6 weeks plus nelfinavir and lamivu-
development, education, infrastructure, and health,
dine for 2 weeks (Z6 + Nelf L). The overall rate of in
in partnership with communities and local govern-
A total of 699 patients aged 1017 years
utero HIV transmission was 5.7% and was the same
ments. Average spending per person was $27 at
with type 2 diabetes (mean duration, 7.8 months)
in all three groups. Transmission during labour oc-
baseline and $116 by year 3. There were improve-
and obesity (body mass index, 85th percentile or
curred in 4.8% (Z6), 2.2% (Z6 + Nev), and 2.4% (Z6
ments in water supplies and sanitation, poverty
higher for age and sex) were randomized to metfor-
+ Nelf L). Overall, 8.5% of infants were infected by
levels, food security, stunting, and malaria preva-
min alone (M), metformin plus rosiglitazone (MR),
3 months, 11.0% in the Z6 group, 7.1% in the Z6
lence at Millennium Village sites after 3 years.
or metformin plus a weight-loss lifestyle interven-
+ Nev group, and 7.4% in the Z6 + Nelf L group,
Under-5s mortality fell by 22% in these sites and
tion (MW). Over an average follow-up of 3.9 years,
a significantly greater rate in the zidovudine-only
by 33% relative to matched comparison sites. Pro-
loss of glycaemic control (glycated haemoglobin at
group compared with the other two groups. HIV-1
vision of many maternalchild health interventions
least 8% for 6 months or sustained metabolic de-
transmission was significantly associated with zi-
was improved.
compensation needing insulin) occurred in 45.6%
dovudine monotherapy, higher maternal HIV load,
of participants overall. The group rates for this
and maternal use of illegal substances. Neutrope-
outcome were 51.7% (M), 38.6% (MR), and 46.6%
nia occurred in 16.4%, 14.9%, and 27.5% of the
(MW). MR was significantly better than M, but MW
three groups, respectively.
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: 21792188; Malenga G, Molyneux M. The Millennium
Villages project. Ibid: 21312133 (comment).
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.
Management of type 2 diabetes

in children and adolescents
adolescents has led to an increased incidence of
lenges of adolescence, together with the increased

frequency of obesity and diabetes in underprivi-
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: 23682379.
TODAY Study Group. A clinical trial to maintain glycemic control in youth

with type 2 diabetes. NEJM 2012; 366: 22472256; Allen DB. TODAY a
stark glimpse of tomorrow. Ibid: 23152316 (editorial).
The increased prevalence of obesity in children and
type 2 diabetes. The physical and emotional chal-
The Z6 + Nev and Z6 + Nelf L regimens were
Treatment for infants of mothers

who present late in pregnancy
with an untreated HIV-1 infection
leged communities, add to the difficulties of diabe-
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-
tes control. Three treatment approaches have been
The best treatment for infants of mothers with
nodeficiency virus (HIV)-1 infection with a regimen
compared in a US multicentre trial.
human immunodeficiency virus (HIV)-1 infection
including ritonavir-boosted lopinavir is better than
12/11/12 4:44 PM
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 HIVinfected children. NEJM 2012; 366: 23802389.
Neonatal screening with pulse

oximetry for critical congenital
heart defects: Systematic review
and meta-analysis
Babies with congenital heart defects may be discharged from hospital before a diagnosis is made
and may subsequently become suddenly and critically ill. A new systematic review and meta-anal-
avoidance may be difficult. Now, a multicentre
treatment with a nevirapine-based combination.
ysis has confirmed that pulse oximetry screening
US trial of oral immunotherapy has given positive
The best treatment for children not previously ex-
of asymptomatic newborn babies is highly specific
results.
posed to nevirapine is uncertain. Now, a trial in
and moderately sensitive for the detection of criti-
six countries in sub-Saharan Africa and India has
cal congenital heart defects.
The trial included 55 children aged 511

years with egg allergy without a history of severe
shown that a ritonavir-boosted lopinavir-based reg-
The review included 13 studies (229,421 ba-
anaphylaxis. All had raised levels of egg-specific
imen is better than a nevirapine-based regimen for
bies). The sensitivity of pulse oximetry was 76.5%
IgE. Randomization was to oral immunotherapy (40
young children who are nevirapine-naive.
and the specificity 99.9%. The false-positive rate
children) or placebo (15 children). Immunotherapy
was 0.50% in the first 24 hours after birth and
consisted of giving egg white powder in three
0.05% when done later.
phases, in increasing doses up to 2 g per day. Chal-
A total of 287 nevirapine-naive HIV-infected

children aged 236 months were randomized to zidovudine and lamivudine with either nevirapine or
ritonavir-boosted lopinavir. The median proportion
of CD4 T-cells was 15% and median plasma HIV-1
It is concluded that pulse oximetry screening

should be introduced widely.
RNA level 5.7 log10 copies/mL. Virological failure or

treatment discontinuation by week 24 occurred in
significantly more children in the nevirapine group
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: 24592464; 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).
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
(40.8% vs 19.3%). Drug resistance was present in
of the 30 children who passed the 22 months chal-
19 of 32 children in the nevirapine group tested at
lenge were re-challenged and 11 passed. All of
the time of virological failure. Mortality was great-
the children who passed the 24 months challenge
er in the nevirapine group (10/147 vs 3/140), and

drug toxicity was also greater.
Oral immunotherapy for egg

allergy in children
were able to eat egg at 30 and 36 months.

Oral immunotherapy may be successful in
some children with egg allergy.
The results were better with the ritonavirboosted lopinavir-based regimen, but these re-
By the age of 2.5 years, around 2.5% of children
searchers point to difficulties in introducing this
have developed egg allergy. Complete dietary
Burks AW et al. Oral immunotherapy for treatment of egg allergy in

children. NEJM 2012; 367: 233243.
12/11/12 4:44 PM
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Imaging Paediatric
Brain Tumours
Dietary Intervention
in Eczema
Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology
Jackelina Pando Kelly, MMSc, MRCPCH; Jonathan Hourihane, MB, DM, FRCPCH
INTRODUCTION
Eczema, also known as atopic dermatitis has been proposed as a cutaneous manifestation 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%, representing 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 encoding 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 pathogenesis of eczema. Therefore, dietary manipulation could be of use in controlling or preventing the disease, but this still remains controversial.
It is important to remember that food allergy and eczema coexist due to their common origins as manifestations of an allergic diathesis, but that one may not automatically
be implicated as a cause of the others.
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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.
their childs eczema, rather than using prescription

medications that they have been told, also erroneously, have major toxic side effects.
Food-allergic sensitization. Allergic sensitization to food allergens is frequent in infants and
children with eczema. The highest rates of foodallergic 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 demonstration 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 7080% of patients with
moderate-to-severe eczema, but also of eczema persistence and of the onset of allergic airways disease
later in childhood.
Food-allergic disease in patients with
eczema. Ingested food allergens are able to activate cutaneous mast cells and skin-associated lymphoid 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 eosinophils, and clonal expansion of allergen-specific
We will briefly review the association between

food allergy and eczema and some of the dietary
strategies that have been proposed in eczema.
skin homing T-cells.

It has been reported that approximately onethird of children with moderate-to-severe eczema
have food allergy and up to two-thirds of infants < 2
FOOD ALLERGY AND ECZEMA
years with severe or refractory eczema. Only 10%

of infants with mild eczema are affected by food
Patients or parents of children with eczema com-
allergy.
monly perceive that specific foods, more commonly
The defective epithelial skin barrier as a
cows milk, cause flare-ups of their childs eczema.
route for allergic sensitization. It has been pro-
Other foods that have been implicated in hypersen-
posed that allergen sensitization occurs as a sec-
sitivity reactions in eczema include citrus, nuts, and
ondary consequence of a defective skin barrier in
fish. Families may wish to change their diet in the
which the penetration of microbes and allergens is
erroneous belief that an external trigger is causing
enhanced. The recent identification of loss-of-func-
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tion mutations in the epidermal structural protein
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Table 1. Food allergy phenotypes
filaggrin appears to be a major risk factor for severe

eczema, peanut allergy, multiple atopic sensitiza-
IgE-mediated
IgE/non-IgE-mediated
Non-IgE-mediated
tion, and coexisting asthma.
Immediate
food allergy/
Anaphylaxis
Oral allergy
syndrome
Eczema
Allergic eosinophilic
gastritis
Allergic eosinophilic
gastroenteritis
Food proteininduced
enterocolitis
Food proteininduced
proctitis
Food proteininduced
enteropathy
Coeliac disease
Eczema
Infancyadolescence
Usually infancy
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 allergic 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-
Any time, peak

in early life
Cox H, Hourihane J. 2011.
mediated and non-IgE-mediated reactions, and most

of these phenotypes can coexist in patients with
Table 2. Common food triggers of eczema
eczema (Table 1). Therefore, it is important to understand 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 02 hours
(but nearly always within 30 minutes) of ingestion,
affecting the skin, gastrointestinal tract, and res-
Food-allergic triggers
of eczema
Non-allergic food triggers

of eczema
Milk
Egg
Peanut
Soya
Wheat
Tomato
Citrus
Acidic fruits and kiwi
Yeast extract
Others
piratory and cardiovascular systems. These acute

allergic reactions are often followed by a delayed
an infant with the combination of infantile eczema
flare of eczema.
and features of altered gut motility (colic, reflux,
Non-IgE-mediated reactions are typified by
persistent crying, etc).
symptoms that involve also the skin, gastrointes-
The diagnosis of food allergy in patients
tinal tract, and respiratory tract (eczematous reac-
with eczema. An accurate diagnosis of food aller-
tions, vomiting, diarrhoea or constipation, cough,
gy is important as it allows for a targeted approach
wheeze). Delayed reactions to food allergens in the
to allergen avoidance, but also for a relaxation of
gastrointestinal tract predominate in infancy and
dietary restrictions when it has erroneously been
early childhood and tend to improve with age.
imposed on children.
The most common food triggers of eczema are

shown in Table 2.
The gold standard test for food allergy

diagnosis is the double-blind, placebo-controlled
In infants with moderate-severe eczema, the
food challenge, but as this is not accessible to many
relationship between milk ingestion and the devel-
patients, the diagnosis of food allergy needs to rely
opment of eczema is likely to be more obvious. A
on a stepwise approach which includes a detailed
high index of suspicion is required when evaluating
allergy-focused history and food-specific allergy

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The diagnosis of food allergy in children with eczema includes taking a detailed allergy-focused history.
tests. If in doubt after this, oral provocations tests
food proteins excreted in breast milk.
are needed after a trial period of dietary elimination
The relationship of eczema onset to the in-
to make the diagnosis of food allergy.
The history. A detailed allergy-focused history 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 ( 2040% and 2535%, respectively), and
is higher still if both parents are atopic (40
60%).
Infant feeding:
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
The type of formula feed.
troduction of formula feeds.
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.
History of immediate reactions to specific foods:
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,
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any previous reaction or prior tolerance of that
picion is high, the tests are useful for confirming al-
food, and whether the reaction was of suffi-
lergy, and conversely when the index of suspicion is
cient s everity to cause anaphylaxis. It is neces- low, the tests are useful for ruling out a diagnosis of
sary to determine reactions to foods in infancy
allergy. When there is a lack of correlation between
as well as current reaction to establish a mean-
the history and tests of specific IgE or when the his-
ingful picture of the childs allergic status, tak-
tory and tests are equivocal, confirmation by way
ing in account that the natural history is for
of an open or blinded provocative challenge test is
children to acquire tolerance to most food al-
usually required to make the diagnosis.
lergens over time.
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History of eczematous or gastrointestinal 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-
that specific foods
bo-controlled study which demonstrated a
induce the eczema
60% improvement in eczema patients adhering
to milk- and egg-free diet, there was no corre-
It is difficult to prove
because clinical cases
lation between the parents suggestions that
do not always
correlate well
milk and/or eggs triggered their childs eczema.
Current diet and prior history of tolerance to

foods:
Which of the main allergenic foods are in
with skin prick

testing and IgE levels
cluded within the current diet?
Has there been any previous attempt to

eliminate foods from the patients diet?
Tests for the diagnosis of food allergy include
Age of onset of eczema: Eczema onset in early
skin prick tests, specific IgE tests, and the atopy
infancy is far more likely to be associated with
patch test. None of these tests, however, confirms
food allergy than eczema onset in a child >5
or refutes the diagnosis of food allergy in the ab-
years.
sence of an individual patient history which seeks to
Eczema severity: The probability of food allergy
establish the prior probability of the allergen being
causal. The selection of allergens for testing should
is greater in young children, infants, and those
with severe disease. When associated with
be based on the clinical history and patients age.
symptoms of gut dysmotility, the association be-
It is difficult to prove that specific foods induce
tween food allergy and eczema is strengthened.
the eczema because clinical cases do not always
Co-morbid associations: Food allergy and ecze-
correlate well with skin prick testing and IgE levels.
ma can coexist with other diseases such as
Clinical history is the most important tool to help
asthma.
with the diagnosis.
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-
Oral food challenges (OFCs). OFC testing

remains the gold standard for diagnosing food allergy, and the aim is to accurately identify causative
allergens.
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Oral food challenge should only be used when the child suspected
of having food allergy has severe eczema.
dermatologist and an intensive treatment, including

moisturizers, topical steroids, and in some cases antibiotics. The aim is to gain control of their eczematous 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 doubleblind, placebo-controlled food challenge testing,
available studies support the concern that food allergy 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 ecOnly children with severe eczema with a histo-
zema in most of such cases. There is no case for
ry of possible reactivity to food should have allergy
unselected elimination diets in patients with no
testing done, and this should be done by specialists
prior diagnosis of food allergy and no case for few-
in the field. Avoidance of multiple foods is poten-
foods or elemental diets. Elimination diets there-
tially hazardous; therefore, OFC should be done only
fore need to be food allergenspecific, based on a
when needed and interpreted with care.
proper diagnosis of food allergy which is reached by
Severe eczema is an indication for hospitalbased OFC.

It is imperative to achieve control of the eczema prior to challenge testing.
reviewing the allergy tests within the context of a

comprehensive clinical allergy history.
It is important to remember that the overall nutritional health of patients on diets, especially chil-
Patients with eczema need their skin treat-
dren, should be carefully looked at. There is concern
ment optimized before any reliable conclusions can
for nutritional deficiencies that may lead to adverse
be drawn about a specific food being a specific trig-
growth and development outcomes in young chil-
ger of their eczema. This may require a referral to a
dren consuming very strict diets.
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Current data do not support prolonged dietary

elimination for most children with eczema. In situa-
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Box 1. Consensus statements from the NICE guideline on atopic

eczema for children aged 012 years
tions where special diets are attempted, the recommendation is to do so for 48 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 restrictions 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-
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 68 week trial of an extensively hydrolyzed protein formula
or amino acid formula in place of cows 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 cows milkfree
diet for longer than 8 weeks should be referred for specialist
dietary advice.
Diets based on unmodified proteins of other species milk (ie,
goats milk) or partially hydrolyzed formulas should not be
used in children with atopic eczema for the management of
suspected cows milk allergy. Diets including soya protein can
be offered to children aged 6 months or over with specialist
dietary advice.
diate reactions to food. The guidelines recommend

allergy testing in all patients with suspected food
NICE = National Institute for Health and Clinical Excellence.
allergy (Box 1).
OTHER DIETARY STRATEGIES

PROPOSED IN ECZEMA
eczema in their children.

Breastfeeding. Breast milk has well documented immunologic activity, including antibod-
Maternal dietary restriction during pregnancy.
ies that act to neutralize foreign proteins, protect
Dietary allergens, including peanuts, cows milk
against infection, enable the establishment of a
protein and egg, are known to cross the placenta,
favourable intestinal microflora, and help induce
can be detected in breast milk, and therefore, may
tolerance.
interact with the mucosal immune system. But giv-
For infants at high risk of developing atopic dis-
en the weak support for maternal dietary restriction
ease, there is evidence that exclusive breastfeeding
and the possibility of harmful effects of maternal
for at least 4 months compared with feeding intact
dietary exclusions to the developing foetus, it is not
cows milk protein formula decreases the cumulative
recommended that pregnant women pursue elimi-
incidence of atopic dermatitis and cows milk allergy
nation diets with the aim to prevent or alleviate
in the first 2 years of life. Some studies have conJPOG NOV/DEC 2012 231
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Practice points
method of eczema prophylaxis, at least for mothers

of infants with a first-degree family history of atopy.
Hydrolyzed formula. The implication that
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 cows 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.
cows milk allergy may have a role in the pathogenesis of eczema has led to the investigations of the
use of partially and extensively hydrolyzed formulas.
Although there is some evidence that hydrolyzed 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 infants diet have yielded results that
are difficult to interpret.
Essential fatty acids. In recent years, the
tradicted these findings and have found an increase
incidence of eczema in Western cultures has in-
risk of eczema in breastfed infants compared with
creased, and at the same time, the intake of essen-
formula-fed infants, but there is speculation that
tial fatty acids, such as omega-3, has decreased.
these findings may be real, a result of reverse cau-
Although there is no clear evidence to support
sation; mothers who know that their children are at
dietary supplementation with omega-3 and omega-6
increased risk of developing atopy may be more like-
fatty acids as a means of preventing eczema, they
ly to breastfeed and do it for longer, in an attempt
may have some benefits in decreasing the severity
to reduce the risk of the disease in their children.
of the disease. Infants and pregnant and lactating
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.
women may be important populations to target for

supplementation with essential fatty acids.
Probiotics. Probiotics are living microorganisms that enhance the microflora of the gastroin-
Overall, the results of several studies sug-
testinal tract. Some strains of Lactobacillus and
gest that exclusive breastfeeding for a minimum
bifidobacteria can influence the immune system.
of 4 months could be recommended as a potential
Gut microflora helps reduce local inflammation in
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the gastrointestinal tract, and certain strains are in-
world, has led to an altered immune response (TH2-
volved in maintaining the integrity of the intestinal
skewed) that ultimately increases the risk of atopy.
barrier in children with eczema. Breastfeeding has
Probiotics have not been proven to be a viable
been shown to promote the colonization of Lacto-
treatment for established eczema yet, and there is
bacillus and bifidobacteria in the intestinal tract of
conflicting evidence of their clinical effectiveness in
infants, and this might partially explain the benefits
the prevention of eczema.
of breastfeeding on atopic disease.
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Nutritional intervention to impact eczema is a
In animal models, probiotics have shown to
complete new field, and further studies are needed
reduce dietary antigen load by degradation of mac-
to better guide patients and physicians in this area.
romolecules, reducing subsequent development of

dietary antigen hypersensitivity, as it is known that
antigen degradation is necessary to develop tolerance to dietary antigens.
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
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;28:605614.
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:S1S58.
Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions
for improving established atopic eczema in adults and
children: systematic review. Allergy 2009;64:258264.
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. Pediatrics 2008;121:183191.
Muraro A, Dreborg S, Halken S, et al. Dietary prevention of allergic diseases in infants and small children, part III: critical review of published peer-reviewed observational and
interventional studies and final recommendations. Pediatr
Allergy Immunol 2004;15:291307.
von Berg A, Koletzko S, Grbl A, et al. The effect of hydrolyzed
cows 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;111:533540.
The hygiene hypothesis may explain the benefits of probiotic therapy at the same time that
explains the increased burden of atopic disease in
2011 Elsevier Ltd. Initially published in Paediatrics and Child

Health 2011;21(9):406410.
industrialized countries, where the prevalence is

about 20% compared with only 5% in non-indus-
About the Authors
trialized nations. This hypothesis sustains that de-
Jackelina Pando Kelly is Clinical Lecturer in the Department of

Paediatrics, University College Cork, Ireland. Jonathan Hourihane is Professor of Paediatrics and Child Health in the Department of Paediatrics, Cork University Hospital, Cork, Ireland.
creased microbial exposure, as a result of extensive

use of antiseptics and vaccinations in the developed
12/11/12 4:44 PM
TATA LAKSANA REGURGITASI PADA BAYI

Gastroesofageal refluks (GER) adalah keluarnya isi
perlu diperhatikan. Posisi yang dianjurkan adalah posisi
lambung secara pasif ke dalam tenggorokan (esofagus)
telentang dengan garis punggung-bokong membentuk
karena adanya relaksasi sementara atau menahun
sudut 60 derajat dengan alasnya. Posisi ini diharapkan
(kronis) dari otot sfingter bawah esofagus. Regurgitasi
dapat mengurangi aliran balik dari lambung ke esofagus.
atau gumoh merupakan gejala dari GER yang paling

sering ditemukan pada bayi. Jika keadaan GER ini
Langkah
selanjutnya
adalah
pemberian
nutrisi.
mempunyai komplikasi maka disebut dengan GERD
Pemberian thickening agent formula atau susu
yang jika berat akan mengalami kesulitan menelan
formula anti regurgitasi (AR) dapat dipertimbangkan
(disfagi). Gejala GERD antara lain muntah, sakit perut,
karena telah terbukti dapat mengurangi regurgitasi,
bermasalah dengan makan, gagal tumbuh, rewel dan
meningkatkan berat badan, membuat bayi tidur
nyeri dada.
menjadi lebih lelap dan jarang menangis.
Salah satu studi mengenai regurgitasi yang dilakukan
Hegar B dkk (2008) melakukan penelitian prospektif,
oleh Hegar B dkk (2009) pada 163 bayi, dan 130
acak, intervensi selama 1 bulan pada 60 bayi dengan
bayi yang di-follow up selama 1 tahun menunjukkan,
regurgitasi 4 kali/hari dalam seminggu. Intervensi
kejadian tertinggi regurgitasi dijumpai pada bulan-
dibagi menjadi 3 grup: A (formula standar), B (formula
bulan pertama kehidupan (73%) dan secara bertahap
standar + sereal beras) dan C (formula dengan locust
akan berkurang 50% pada usia 5 bulan. Selama 2 bulan
bean gum). Setelah 1 bulan, penambahan berat badan
pertama, 20% bayi mengalami regurgitasi lebih dari 4
pada bayi yang mendapat formula dengan locust bean
kali per hari. Namun setelah usia 12 bulan, yang masih
gum (AR) secara signifikan lebih tinggi dibandingkan
mengalami regurgitasi setiap hari berkisar 4%.
dua grup lainnya (gambar 1).
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 regurgitasi
Pemberian ASI tetap dilanjutkan, karena kejadian
regurgitasi pada bayi yang mendapat ASI lebih sedikit
dibandingkan dengan bayi yang mendapatkan susu
formula.
Gambar 1. Hubungan antara jenis formula dan kenaikan berat badan

pada bayi dengan regurgitasi.
Parental reassurance merupakan langkah awal yang
Orenstein SR dkk (1987) dalam Vandenplas (1988)
perlu dilakukan. Posisi bayi setelah diberi minum juga
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.
Gambar 2. Pengaruh formula yang dikentalkan terhadap waktu

menangis dan waktu tidur pada bayi.
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.
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.
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.
Hanya untuk kalangan medis
PAEDIATRICS
OBSTETRICS
OBSTETRICS
II
Peer
Peer Reviewed
Reviewed
Imaging Paediatric
Brain Tumours
Sarah Logan, FRCP; Laura Price, FRCP
Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology
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 management 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 infectious 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 mechanical 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 elevation reduces secretion clearance and functional residual capacity, and with the increased 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.
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OBSTETRICS
ANTENATAL SCREENING AND

PREVENTION
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Pregnant women should take precaution to prevent toxoplasmosis

infection.
Screening
Since 2003, the UK Department of Health has recommended screening for hepatitis B, human immunodeficiency virus (HIV), rubella and syphilis early
in pregnancy with a single blood sample, as well as
asymptomatic bacteriuria (ASB) with a urine sample. There is currently no clear evidence of benefit
from screening for other infections, although women may request additional screening, particularly if
they have experience of health care systems overseas. 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 booking can be falsely reassuring, and seroconversion
during pregnancy carries a higher risk of mother-tochild 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.
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 coverage, rates dropped to 80%, although they have
started to increase again. Women planning a family
Immunization
Ideally, women should be immunized prior to conception, but there are a few situations where immunization 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
should ensure immunity.

Live varicella vaccines are available pre-pregnancy, and zoster immune globulin (IG) should be
given to pregnant women non-immune to varicella
and up to 10 days following exposure. Varicella serology is also available, although immunity is usually assumed from the history of typical rash.
12/11/12 4:44 PM
OBSTETRICS
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Influenza vaccination (inactivated) may be
the risk of neonatal necrotizing enterocolitis in one
considered and is deemed safe throughout preg-
study of preterm premature rupture of membranes
nancy. In light of the recent outbreak of H5N1 influ-
(PROM) prevention, and although no animal studies
enza and its increased severity in pregnant women,
have shown harm, further human studies are need-
all women should be offered the seasonal vaccine
ed. Cephalosporins cross the placenta less com-
which will give protection to the most common cir-
monly and appear to have no adverse fetal effects.
culating strains.
Other antibiotics are relatively contraindicated in pregnancy, but their use may be appropriate
INVESTIGATION AND
MANAGEMENT
depending on the clinical situation. Nitrofurantoin

is generally considered safe but should be avoided
at term because of the risk of haemolytic anaemia
Principles
A good history is essential, considering the pregnancy, gestational age, prior ASB, sexually transmitted infections (STIs), travel, occupation, HIV risk
factors, contacts with infectious diseases, and prior
tuberculosis (TB) infection. There may only be nonspecific symptoms and signs, but these are important to consider, as obstetric sepsis can present this
way before rapid deterioration.
Involvement of the feto-maternal multidisciplinary team is essential, including clinical microbiologists/virologists/infectious diseases, local TB
services, and the critical care team when appropriate. With evidence of STIs, genitourinary physicians should be involved, and screening for other
STIs should be undertaken.
in the neonate. There are reports of ciprofloxacin

causing an arthropathy in animal studies, but no adverse human effects have been reported. Trimethoprim has also caused adverse effects in animals,
so should be used with caution in pregnancy, especially as it may interfere with folic acid metabolism.
It should be avoided near term when used as cotrimoxazole 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 cyanosis, flaccidity and cardiovascular collapse) when
used in newborn infants. Aminoglycoside use (eg,
gentamicin) risks fetal ototoxicity and should only
Antibiotic Use in Pregnancy

In general, penicillins, cephalosporins, and macrolides such as erythromycin (although less data on
clarithromycin) are safe. Clindamycin is also probably 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. Amoxicillin has increased renal clearance in pregnancy,
therefore theoretically higher doses are needed,
although in clinical practice, doses are used as outside pregnancy. Augmentin was shown to increase
be used if there is evidence of serious gram-negative infection. Similarly, vancomycin has been associated 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 20062008, making sepsis
12/11/12 4:44 PM
OBSTETRICS
the most common cause of direct maternal death.
can be serious, especially when associated with
The commonest source is the genital tract, notably
GAS and Streptococcus agalatiae (GBS). GAS ne-
from Streptococcus pyogenes (group A Streptococ-
crotizing fasciitis and toxic shock syndrome can
cus, GAS), although it is important to remember
occur unexpectantly following an uncomplicated
that any systemic infections can present as sepsis
pregnancy and delivery, and management includes
or septic shock.
antibiotic therapy with broad-spectrum antimicro-
Sepsis can present at any time before, during
bials according to local policy and early surgical
or following delivery, and is important to recognize
intervention. Thirty percent of the fevers seen in
and treat early, for example using early warning
women who have just delivered are due to endome-
score systems for ward patients, and with commu-
trial infection. The risk is higher post CS and after
nity midwives being astute for signs of infection.
a PROM, prolonged delivery or in the presence of
Mothers often present with vague symptoms and
retained products of conception. Infections are of-
signs, but it is important to recognize these early, as
ten polymicrobial, with aerobes and anaerobes, and
the course can be fulminant. Management of septic
Chlamydia can cause late endometritis. Endometri-
shock is similar to that outside pregnancy. Preven-
tis can also result from CS wound incisions (more
tative measures include good perineal hygiene.
commonly seen following emergency CS), which
Most obstetric sepsis occurs post partum,
is important to recognize, as utero-cutaneous fis-
and may relate to genital tract infections, mastitis,
tulae may result requiring surgery. Late endometri-
thrombophlebitis, episiotomy, and perineal tear in-
tis more typically follows vaginal delivery. A 2002
fections, caesarean section (CS) wound infections,
Cochrane review concluded that a single dose of
gastric acid aspiration, or post-general anaesthesia
ampicillin or first-generation cephalosporins was
pneumonia.
sufficient to reduce puerperal infections related to
Antepartum infections include chorioamnionitis which may follow prolonged PROM (pPROM)
Peer Reviewed
uncomplicated CS, given as a single dose after cord

clamping.
and prolonged labour. pPROM complicates only
For an excellent summary of sepsis see chap-
2% of pregnancies but is associated with 40% of
ter 16 of the recent 20062008 confidential enquiry
preterm deliveries, and is suspected with a sug-
into maternal deaths.
gestive maternal history and on a sterile speculum

examination. Mothers should be observed 12-hourly 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 include 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
Urinary Tract Infections

Urinary tract infections (UTIs) are divided according 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 consecutive clean-catch urine samples (without nitrites or leucocytes on dipstick). It occurs in 47%
of pregnant women and is important to recognize,
as symptomatic UTIs develop in 2040% of cases,
and there is an increased incidence of preterm delivery and low-birth-weight infants. This has lead to
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OBSTETRICS
Peer Reviewed
Studies showing the prevention of urinary tract infections in

pregnancy with cranberry juice ingestion are lacking.
ten with symptoms of cystitis. Pyelonephritis is the

most common cause of septic shock in pregnancy,
and adult respiratory distress syndrome (ARDS) occurs in 18% 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 exclude hydronephrosis and structural abnormalities.
Organisms are similar to those in lower tract UTIs,
with E coli in 7080%, and Klebsiella pneumonia
and Proteus species less commonly, but important
in recurrent cases. Antibiotic choice reflects local
guidelines, usually with a first-generation cephalosporin 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 anatomical obstruction. When discharged home, the mother
should be more closely watched for recurrence with
UK screening being recommended (see NICE guide-
monthly urine cultures. Fetal effects of untreated
lines). ASB is due to Escherichia coli in 7590% of
pyelonephritis include preterm delivery and low
cases, and cephalosporins are more appropriate
birth weight. If GBS is detected in maternal urine,
than amoxicillin, given the 60% E coli beta-lactam
it should be treated and appropriate intra-partum
resistance seen. Up to 15% will require a further
prophylaxis administered (see later).
course later in pregnancy.
Cranberry juice has been used traditionally
Cystitis or bladder infection occurs in 14% of
to prevent and treat UTIs. It contains proanthocy-
pregnancies and pyelonephritis, where the kidney
anidins which prevent the adherence of bacterial
is the focus in 2% of all pregnancies.
pathogens to the uroepithelium. A recent Cochrane
Pyelonephritis is a serious medical condition
review showed a significant reduction in UTIs com-
in pregnancy, associated with fetal and maternal
pared with placebo, although this was not specific
morbidity, and leads to an increased risk of pre-
to pregnancy.
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 presenting features are fever, loin pain, rigors, and less of-
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
12/11/12 4:44 PM
OBSTETRICS
in pregnancy. Investigation and management are
vasive mechanical ventilation, veno-venous extra-
similar, although delay in obtaining a chest X-ray is
corporeal membrane oxygenation may be required.
common; remember that the radiation exposure is
This is a form of lung bypass to rest the lungs
only 0.05% that of the maximum recommended 0.2
while they recover, and successful cases have been
rad. Influenza and varicella pneumonia in pregnant
reported during pregnancy and immediately post
women have historically been associated with a
partum.
higher rate of morbidity and mortality. Some impor-
Varicella pneumonia primary varicella in-
tant pathogens are considered below, and others,
fections are more severe in pregnancy, and progres-
including TB, in later sections.
sion to varicella pneumonia is more common (10
Peer Reviewed
20% of those infected). Maternal mortality from

Respiratory Pathogens in Pregnancy
varicella pneumonia is higher in pregnancy (35%
Upper respiratory tract infection pregnant
versus 11%), thus prevention of primary infections
women often find that they have a persistent cold
is of great importance. Oral mucosal ulceration is
in the last trimester. Whilst this may be due to any
common, and respiratory illness ranges from cory-
of the common viral pathogens such as rhinovirus,
zal symptoms to severe respiratory failure requiring
there is no treatment and in the absence of lower
mechanical ventilation. Classically, the chest X-ray
respiratory tract symptoms does not need investi-
shows bilateral miliary nodular shadowing, and
gation.
later pulmonary calcification.
Bacterial pneumonia the most common

cause of pneumonia in pregnant women remains
the same as in the general population Streptococcus 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
Primary varicella
infections are more
severe in pregnancy,
and progression to
to 50%) in pregnancy and may result from a second-
varicella pneumonia
ary bacterial pneumonia (Staphylococcus aureus,
is more common
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
Other causes of pneumonia Pneumocystis
inhibitor oseltamivir, which should be started as
jiroveci pneumonia (PCP, previously called P cari-
soon as possible until clinical improvement occurs,
nii pneumonia) in HIV-positive patients is associ-
although data are limited in pregnancy. See World
ated with adverse obstetric outcome, and should
Health Organization guidelines for further details.
be treated with co-trimoxazole. PCP is also increas-
In cases that remain hypoxic despite maximal in-
ingly being seen in immunocompetent hosts, previJPOG NOV/DEC 2012 239
12/11/12 4:44 PM
OBSTETRICS
Peer Reviewed
ously only associated with immunodeficiency. One
At least 6% of hepatitis Cpositive pregnant
study showed that asymptomatic nasal carriage
women will transmit this to their baby perinatally.
of P jiroveci is more common in pregnancy, and
This risk is increased in the presence of co-infec-
another that PCP is more severe in pregnancy. In
tion with HIV to 15%. Elective CS may reduce the
HIV-positive women, P jiroveci may be transmitted
transmission risk. There is no role for treatment of
perinatally.
HCV in pregnancy, and there is no vaccine available.
Chlamydia psittaci is an unusual cause of
Screening is not routinely carried out but should be
atypical pneumonia, (ie, those organisms not caus-
considered in high-risk groups mainly those with
ing a typical lobar pneumonia). It is usually trans-
a history of injecting drug use.
mitted via infected birds and may cause a severe ill-
Hepatitis E virus is water-borne and transmit-
ness during pregnancy, but recovery is usually full.
ted faeco-orally, usually causing a mild self-limiting
Fungal pneumonia, although unusual, may also run
infection. However, in pregnancy, there is a sixfold
a more severe course in pregnancy, especially in the
increase in maternal mortality, especially in the
final trimester.
third trimester, with 15% of cases leading to fulminant hepatic failure where the mortality is 5%. The
Hepatitis
Viruses causing hepatitis include the hepatitis
viruses AE, 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 eantigen-positive. Vertical transmission usually occurs 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).
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 pneumonitis 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 management of rashes in pregnancy from the Health
Protection Agency (www.hpa.org.uk).
The important infections to consider in the differential 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 intrauterine death and preterm delivery, although not
congenital infection or damage. Indigenous measles
is rare in the UK following introduction of the MMR
12/11/12 4:44 PM
OBSTETRICS
vaccine, although it is endemic in some countries.
isoniazid therapy to prevent peripheral neuropathy.
Human normal IG may attenuate measles, but there
Streptomycin, however, should be avoided, as fetal
is no evidence that it prevents intrauterine death or
eighth nerve damage has been associated in a sig-
preterm delivery.
nificant number of cases. Infants born to mothers
Enteroviruses (including coxsackievirus A, B
with smear-positive TB should be treated with iso-
and echovirus) can cause a wide range of manifes-
niazid syrup for 6 weeks as chemoprophylaxis, and
tations such as meningitis and myocarditis. Neona-
then a tuberculin skin test performed. Breastfeeding
tal infection, especially with echoviruses, can have
can continue as normal, as minimal anti-tuberculous
multisystem life-threatening complications. No
agents are secreted in breast milk.
Peer Reviewed
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 (2534
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 developing 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 develop active TB, usually 12 years after infection.
More extra-pulmonary TB is being seen with HIV
co-infection, and 510% of pregnant women have
extra-pulmonary disease (similar to the non-pregnant 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 patients. All four first-line drugs are thought safe and
have been used for many years, including ethambutol and isoniazid. Pyridoxine should be added to
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 falciparum 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 endemic 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 depend on the type of malaria and local resistance
patterns, and chloroquine is the choice for Plasmodium 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 malaria 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
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OBSTETRICS
Peer Reviewed
if travel is unavoidable from the Royal College of
lin to high-risk mothers. These are identified for-
Obstetrics and Gynaecology (see Further Reading).
tuitously by high vaginal swabs performed for a va-
Mefloquine is first line for prophylaxis after the
riety of reasons during pregnancy, including those
first trimester.
women complaining of vaginal discharge, those

with possible preterm membrane rupture, women
Human Immunodeficiency Virus

HIV worldwide infection is increasing. UK seroprevalence in pregnant women is 0.21%, with over
300 HIV-infected women giving birth annually.
There is an increased risk of preterm delivery, lowbirth-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 multidisciplinary 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 pregnancy 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, 4070% of infants become colonized in the first week of life. Neonatal
infection can be early or late, presenting with pneumonia, sepsis, meningitis, and death in up to 10%
(higher in preterm infants). As the overall UK infection rate in infants is 1%, routine screening is not
currently offered. Neonatal disease is reduced by
administration of intra-partum intravenous penicil-
in preterm labour, temperature greater than 38C in

labour, preterm PROM, ROM for more than 18 hours
prior to delivery, or a previously affected child.
The common vaginal

commensal, group B
Streptococcus, can lead

to life-threatening
neonatal effects
Chlamydia trachomatis
Genital tract infection with Chlamydia trachomatis
is common in the UK and may lead to ectopic pregnancy, preterm labour, puerperal infection, and ophthalmia neonatorum. Erythromycin is the advised
treatment.
Bacterial Vaginosis
This STI, caused by Gardnerella vaginalis, may
cause chorioamnionitis, preterm delivery, and postpartum fevers. Treatment is with erythromycin or
metronidazole.
Herpes Simplex Virus
Maternal genital herpes is more virulent in pregnancy. Early miscarriage (but not fetal abnormalities) may occur, and late maternal primary infection can lead to severe neonatal infection. Genital
lesions, especially in primary infection, contain
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OBSTETRICS
high viral concentrations, and transmission at de-
are common, seen in 8090% survivors infected
livery may exceed 41%. Neonatal herpes carries a
in the first trimester. Fetal abnormalities due to
high mortality rate. Disease can be (1) localized to
rubella infection in the second trimester are less
skin, eyes and mouth, where death when treated
common (in 15% survivors) usually sensorineural
is uncommon, (2) encephalitis, or (3) disseminated
hearing loss, and infection prior to conception or af-
infection with multi-organ involvement, with mor-
ter 20 weeks carries minimal risk. Maternal rubella
tality up to 30% often with long-term neurological
reinfection is mostly subclinical and is diagnosed
manifestations. Maternal infection is confirmed
by a rising antibody titre.
using viral culture or polymerase chain reaction,
Suspected cases of rubella should be inves-
and serology differentiates between primary and
tigated promptly with serology testing for rising
recurrent infections. Primary infections should be
antibody titre and rubella-specific IgM as clinical
treated with oral or intravenous acyclovir. In the
diagnosis is limited.
UK, caesarean section is the recommended mode
Before rubella vaccine became available,
of delivery following primary infections in the late
200300 babies were born each year with congeni-
second and third trimesters, and discussion should
tal rubella syndrome in the UK. Routine rubella vac-
be with women presenting in labour with recurrent
cination for schoolgirls was introduced in England
(secondary) herpes attacks regarding the small risk
and Wales in 1970, and subsequently for suscepti-
of perinatal transmission associated with vaginal
ble women post partum. It is a live attenuated vac-
birth in this situation. The risk is low, but some may
cine, so is contraindicated in pregnancy, but should
choose caesarean delivery.
be offered to non-immune mothers 1 month post
Peer Reviewed
partum and preconceptually.
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 abnormalities. These are discussed below, and summarized in Table 1.
Varicella is also
important to recognize
and treat in pregnancy
as maternal complications
Rubella
Symptoms of primary maternal rubella infection follow viraemia are mild and include fever, headache,
joint pains, sore throat, and a maculopapular rash
usually appearing shortly after glandular enlargement. 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 more severe
Varicella
Varicella is highly infectious from 2 days prior until 5 days following the typical vesicular rash. FeJPOG NOV/DEC 2012 243
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Table 1. Fetal risks associated with certain maternal infections
Infection
Rubella
Varicella
Cytomegalovirus
Parvovirus B19
Toxoplasmosis
Congenital
defects
Ocular defects,
Fetal varicella
heart (PDA), SNHL, syndrome: skin
mental retardation scars, eye defects,
limb hypoplasia,
developmental
delay,
microcephaly
IUGR, HSM, microcephaly, jaundice,

chorioretinitis,
intracranial
calcification, 20%
mortality. Late
microcephaly,
SNHL, and
developmental
delay (15%)
Fetal hydrops,
Hydrocephalus,
IUD (1st
mental retardation,
trimester).
chorioretinitis
Rarely persistent
neonatal infection
and anaemia
Trimester most
at risk (% risk
of defects)
First abnormalities in 8090%

survivors; risk
1316 weeks of
SNHL
All trimesters, espe- All trimesters

cially 1320 weeks
(2%)
First trimester
Malformations highest 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
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
Febrile illness,
erythema
infectiosum,
aplastic
anaemia
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-
ops clinical chickenpox in the period 5 days prior to
fected before 20 weeks, especially 1320 weeks.
birth until 2 days after. Neonatal infection carries a
Note that this is less than the 85% risk of rubella
high mortality rate.
fetal damage, hence there is currently no UK rou-
Shingles (dermatomal reactivation of latent
tine screening policy. Varicella is also important to
virus) when localized carries no apparent risk to the
recognize and treat in pregnancy as maternal com-
fetus. However, it is uncertain whether dissemina-
plications are more severe.
tion, for example in an immunocompromised pa-
Treatment in pregnancy is safe with acyclovir.
tient, carries a fetal/neonatal risk.
If delivery is imminent and infection occurs within

10 days of delivery, it is advisable to wait 57 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-
Cytomegalovirus
Fetal CMV infection is the second most prevalent
cause of mental retardation after Down syndrome.
Childhood infection is common in developing coun-
12/11/12 4:44 PM
OBSTETRICS
tries, hence leads to herd immunity, however only
Peer Reviewed
Practice points
5060% 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
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 symptoms and signs, and run a fulminant course
Obstetric sepsis remains a significant cause of maternal mortality 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
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 sample 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 amniotic fluid at amniocentesis. Serial fetal ultrasound
is available to identify suggestive features such as
ventriculomegaly and intracranial calcification, although no findings are specific. It must be remembered that most infected neonates will in fact be
unaffected. There is no specific treatment, although
a vaccine is in development, and screening for maternal immunity is therefore not routine in the UK.
Parvovirus B19
Parvovirus B19 infection is common, with 5060%
of adults having been infected. Infection in the first
20 weeks of pregnancy can lead to intrauterine
death and fetal hydrops. These consequences usually occur 35 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 34 years, often 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 infected women. Fetal infection probably depends on
the gestational age at maternal seroconversion. A
French study showed that there were more congenital abnormalities (see Table 1) with early maternal
infections, and more fetal infections with seroconversion at term.
Diagnosis is confirmed by amniocentesis, chorionic villus sampling or fetal blood sampling, and
ultrasound findings of intracranial calcification, hepatomegaly 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 infection can occur at any stage, but most often in primary (90%), secondary and early latent infections.
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OBSTETRICS
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Most infected women are asymptomatic, and posi-
morbidity and mortality. Screening and vaccination
tive serology is detected at antenatal screening.
programmes are important. Investigation and man-
Maternal infections treated with high-dose penicil-
agement of infection may be complex and the mul-
lin will reduce the risk of fetal infection. Twenty-five
tidisciplinary approach is essential, involving the
percent of fetal infections result in preterm labour
obstetric team, as well as fetal medicine, genitou-
and 25% in fetal loss. In survivors, congenital syph-
rinary and critical care physicians.
ilis may result with polyhydramnios, hepatomegaly,

osteochondritis, purpura, and late interstitial kera-
FURTHER READING
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 associated 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
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;335:929932.
Malaria prophylaxis: http://www.nathnac.org/pro/misc/pdfs
/RCOGPreventionMalariaPregnancy0410.pdf.
Maternal mortality. Saving Mothers Lives: Reviewing maternal
deaths to make motherhood safer: 20062008. The eighth
report of the Confidential Enquiries into Maternal Deaths
in the UK, 118. London: BJOG; 2011:1203.
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 pregnancy: Guideline No 39. London: RCOG; April 2004.
Royal College of Obstetricians and Gynecologists. Preterm prelabour 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;9:2123.
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):331338.
About the Authors

Infections during pregnancy are usually selflimiting; however, awareness is needed to identify those leading to significant maternal and fetal
Sarah 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.
12/11/12 4:44 PM
Dukung Tumbuh Kembang Optimalnya

dengan Nutrisi Tepat
sebagai investasi masa depan
Selama 50 tahun berkarya, SGM tak pernah berhenti berinovasi dalam menghadirkan
ketersediaan nutrisi presisi bagi anak Indonesia. Dengan formulasi gizi dan nutrisi
sesuai standar internasional, SGM Specialties senantiasa mendukung optimalnya tumbuh kembang
bayi Indonesia yang memerlukan nutrisi khusus agar menjadi anak yang sehat, kuat dan cerdas,
sebagai investasi kualitas hidup di masa depan.
Hanya Untuk Kalangan Medis
ASl adalah makanan terbaik untuk bayi. ASl menyediakan nutrisi terbaik serta memberikan
perlindungan terhadap penyakit. ASl sebaiknya diberikan secara eksklusif selama 6 bulan
pertama kehidupan bayi dan dianjurkan sampai anak berusia 2 tahun dengan pemberian
makanan tambahan yang sesuai.
OBSTETRICS
OBSTETRICS
II
Peer
Peer Reviewed
Reviewed
Newborn Stem Cells:

Functions and
Perinatal Types,
Case Management
for Obstetricians
Caring forBasics
Mothers
as They Care
Jennifer Sze Man Mak, MBChB; Juan Bolaos, 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)
for Babies
Chng 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 major 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 therapies, it is now clear that a major new impetus is required. The potential revolution in science 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-alifetime opportunity to collect and cryopreserve a panel of stem cells, which effectively
represent natures body repair kit for the duration of the newborns life. There are also
stem cells available for maternal utility.
Once regarded as medical waste, the umbilical cord, based on extensive groundbreaking 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-increasing clinical efficacy, have led to the fast-growing establishment of cord blood banks
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OBSTETRICS
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Figure 1. Stages of development of human embryos.
Zygote
BACKGROUND (HISTORY)
OF STEM CELLS
Stem cells are one of natures most powerful building blocks. They have the unique ability to both
self-renew to replenish their availability and differ-
Single-cell embryo
entiate into a variety of different cell types. Hence,

3-day embryo
Embryonic stem cells
(pluripotent)
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.
5- to 7-day embryo
4-week embryo
6-week embryo
Embryonic germ cells

(pluripotent)
Fetal tissue stem cells
(pluripotent or multipotent)
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 1990s 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 cryopreservation 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 conveying adequate information to patients. Present
development on stem cells will also be discussed.
Human ESCs
Human ESCs are isolated from 4- to 5-day-old postfertilized blastocysts (Figure 1). Human ESCs are
capable of indefinite ex vivo proliferation and can
differentiate into any specialized cell in the human 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 differentiate 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 tissues and organs, yet there are several major problems with them. The generation of ESCs requires
destruction of discarded embryos from in vitro fertilization, 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
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Figure 2. The cell lineage of each organ system in the human body.
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
Organ/tissue

Tissue/organ-specific stem
cells
Eg, eyes, heart, lung
Fat (mesenchymal cells)
Bone marrow (mesenchymal

cells and haematopoietic
stem cells)
Invasive method for collection
Invasive method for collection
sound alternative is adult stem cells, which exist in
regard to the public perception of the ethical issues
virtually every tissue, albeit being difficult to iden-
and the safety concerns, alternate sources of stem
tify and isolate. Adult stem cells also possess lim-
cells were sought after. In 1983, Edward Boyse pro-
ited differentiation potential, but one of their major
posed the idea of using UCB as a potential source
advantages is that they pose no risk of rejection as
of stem cells for haematopoietic transplantation,
they are used in autologous transplants.
thereby highlighting research on placental/newborn stem cells. This was followed by experiments
Newborn Stem Cells

Given the difficulty in settling the dilemmas associated with the use of human ESCs legally, with
in irradiated mice revealing that murine blood from

near-term and neonatal mice contained adequate
numbers of HSCs to effect bone marrow recovery.7
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Obstetricians can educate pregnant women about umbilical cord blood banking.
The first pioneering haematopoietic cord blood
ditions (eg, leukaemia), non-neoplastic conditions
transplant was performed to treat a 6-year-old boy
such as inherited disorders (eg, thalassaemia ma-
with Fanconi anaemia in 1988 in Paris, France,
jor), immunodeficiency, osteoporosis, and acquired
with the first successful unrelated UCB transplant
conditions (eg, aplastic anaemia). In the autologous
performed in the United States in 1994.
setting, they can be used to treat autoimmune dis-
In vitro cultures of CD34 cells (as a marker of
orders like aplastic anaemia; but in advance-stage
HSC) from umbilical cord yielded a higher rate of
solid tumours, their use is currently limited. HSCs
proliferation than similar cells from marrow. 10 Be-
are also being investigated for efficacy in treat-
sides, UCB HSCs may also have a greater capacity
ing cerebral palsy, stroke, and as a means of gene
for self-renewal and long-term growth in culture.
11
therapy. Autologous cord blood stem cells are not
However, although UCB is proportionally rich in
suitable for treating inborn errors of metabolism or
HSCs, its use is limited because of the relatively
some genetic diseases such as childhood leukae-
low volume of blood and hence total HSC dose.
mia in which chromosomal translocations in fetal
The transplanted cell dose is approximately 10%
blood were detected in children who finally devel-
of a marrow transplant. HSCs can be used in al-
oped leukaemia. 13,14 The use of autologous stem
logeneic and autologous settings. In the allogeneic
cells would also negate the beneficial graft-versus-
setting, they can be used to treat neoplastic con-
leukaemic effect that occurs with allogeneic stem
12
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OBSTETRICS
cell transplants by its residual T lymphocytes in the
and 90% expected their obstetrician to answer
haematopoietic progenitor cell product.
their questions on UCBB.18 Similar results were also
15
UCB as a source of HSC for transplant is more
Peer Reviewed
reported by Fernandez et al1 and Din and Sahin.2
superior than, for example, bone marrow, as it ap-
In one study, almost one-third of the partici-
pears to have a higher tolerability of HLA mismatch,
pants did not realize that they had the option to
which may be explained by its high content of im-
retain their cord blood at delivery; only 50% were
mune suppressing cells called regulatory T cells,
aware that they could store their cord blood in a pri-
which are able to suppress immune responses; ac-
vate bank and half of the respondents thought cord
cordingly, they have been used for treating type 1
blood donation to the public bank was to protect
diabetes and multiple sclerosis. This is an impor-
their childs future health.19
tant and often unrecognized value of UCB.16
A recent research article about our Hong Kong

locality showed that among 2,000 women recruited,
THE PATIENTS KNOWLEDGE OF

STEM CELLS AND UCBB
93.3% completed the questionnaire. The majority

(78.2%) had no idea about the chance of using selfstored stem cells. Most were unclear about which
In 2003, Fernandez et al examined pregnant wom-
diseases other than leukaemia are amenable to
ens knowledge and attitudes relating to UCB and
treatment with UCB stem cells. This is not taking
UCBB; 70% reported poor or very poor knowledge
into account that if the child developed leukaemia,
about UCB; 66% expected the physician to talk to
their UCB would not be used for haematological
them about cord blood collection and said they
rescue because autologous stem cells lack the
would specifically like to receive such information
graft-versus-leukaemia effect as well as because
from health care professionals or in prenatal class
of the fear of cancer contaminants within the UCB.
(70%). Twenty-five percent overestimated the risk
Only 20.3% of women knew that stem cells are
of a child needing a bone marrow transplant before
available from the Red Cross (a local public cord
his or her 10th birthdaythe risk is reported as be-
blood bank) in case their children needed haemat-
tween 1 in 200,000 and 1 in 10,000. Eighty-three
opoietic cell transplantation. Hence, most patients
percent expected to be asked about UCBB before
have inadequate knowledge about stem cells and
30 weeks of pregnancy. In a post hoc analysis, this
UCBB, creating an obstacle to UCBB. They would
level of knowledge was not associated with the
like to receive more information from health care
choice between public and private banking.
providers, especially their obstetricians, and be
17
In 2006, Perlow et al demonstrated that among
provided with the relevant knowledge accordingly
the 425 patients recruited in the survey in USA,
in early pregnancy so that they can have adequate
37% had no knowledge of UCBB. Older patients and
time to contemplate their choices.20
those more educated were more aware of UCBB.
THE OBSTETRICIANS ROLE IN

extremely knowledgeable while 74% felt minimal- CONVEYING DETAILED AND
ly informed. Seventy-one percent of patients were ACCURATE INFORMATION TO
not planning UCBB with the main reasons of ex- THE PUBLIC
Among patients familiar with UCBB, only 2.6% felt
pense and insufficient knowledge. Only 14% were

educated about UCBB by the nurse or obstetrician,
Given this background, it is imperative that the obJPOG NOV/DEC 2012 251
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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:
Faster availability: patients on average receive
cord blood transplantation earlier than those
receiving conventional bone marrow grafts 23
Ethnic diversity allows extension of donor pool:
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
Lower incidence of viral transmission, ie, cyto megalovirus and Epstein-Barr virus
No donor attrition compared with bone marrow
registry
High proliferative capacity
Painless collection of stem cells
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 families for which there is a known genetic or haematological 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 placenta ex utero.
A comparison of the two techniques has
shown larger unit volumes and higher total nucleated cells counts with in vivo collection.26 It is recommended 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 either 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 collected. 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 suggest that it is the mothers 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 mothers body, it is recognized as
a legal individual by law but is unable to have full
understanding and thus unable to give consent.
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OBSTETRICS
Therefore, the mother, who shares the prenatal au-
tion with consideration of paternal objection to do-
thority, would be the one to give consent on behalf
nation and for public cord blood banking. The con-
of the baby. If the cord blood is stored for the childs
sent process should not include a promise that the
use, then the mother will hold in trust till the child
cells may be available at a later date for use by the
attains the age of 18 years, by which time the use
family. The consent should be obtained before la-
of stem cells will be decided by the child. If the
bour, preferably in late third trimester. The consent
cord blood is donated, this may then be considered
process should also include disclosure for units that
as a manipulation of human body parts without the
do not meet quality standards.32
21
individuals knowledge.30 In order to translate the
It is recommended by the Royal College of
ethical debate from the speculative level into prac-
Obstetricians and Gynaecologists that the service
tice, it is important to get good informed consent
should not be made available for cases in which
for stem cells use.
the attending clinician believes it to be contrain-
Peer Reviewed
dicated. Details of the hospitals policy should be

made available to all patients.
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.
Consent
Obstetricians should not be obligated to obtain consent for private UCBB.31
A report by the Institute of Medicine has recommended that cord blood centres establish clear
policies as to who must provide consent for dona-
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 highly efficient recovery of viable and highly functional
human stem cells.33 Data suggested that longerterm 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, promote allogeneic donation of both related and unrelated cord blood, which is subsequently accessible
by the general population. Patients should be informed 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 associated with specimen processing and storage for
the harvested cord blood as a family biological inJPOG NOV/DEC 2012 253
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OBSTETRICS
Peer Reviewed
Figure 3. A variety of progenitor cells in umbilical cord, cord blood, amnion, and placenta/chorion.
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 Immunology and Stem Cell Laboratories, Australia,
can extract and store two different stem cells
separately
Amnion (epiblast stem cells)
Placenta/chorion (mesenchymal 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 differentiate into hepatic, pancreatic and neural cells
High requirement for extraction technology
Richest source of newborn stem cells

High requirement for extraction technology
surance, which can also be used for other family

members.
cipient could have developed these disorders.

Private banks provide a life insurance by having
It is recommended that balanced information
the cord blood available for the lifetime, depending
for both autologous and allogeneic donation should
on its commercial viability of the enterprises, 35 and
be provided to pregnant patients in the antenatal
the estimated utility of autologous UCB is approxi-
period.
mately 1 in 20,000 28 to 37 in 100,000 (1 in 2,700).20
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 concern 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 identifying information has been removed while the re-
Regulatory Issues
To establish a uniform standard for collection and
quality assurance, it is important that establishments provide standardization of procurement, testing, processing, storage, distribution, documentation, labelling, equipment control, and cord blood
bank operations.
12/11/12 4:44 PM
OBSTETRICS
In the United Kingdom, cord blood collection
Peer Reviewed
Table 1. Conditions for the use of mesenchymal cells for repair
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 regulate or provide advice about the effectiveness of
treatments using cord blood.36
In the United States, many cord blood banks
Lung fibrosis, chronic obstructive pulmonary disease37,38

Heart and vascular damage39
Spinal disc injury40
Suppress graft-versus-host disease in allogeneic bone marrow
transplant
Inhibit autoimmunity, eg, multiple sclerosis, diabetes, arthritis41
Ageing tissues: tendon, muscle, cartilage, bone (hips, joints)42
Sporting injuries43
have undergone voluntary accreditation through

the American Association of Blood Banks or the
NetCord Foundation for the Accreditation of Cel-
human mesenchymal progenitor cell for in vitro
lular Therapy. In our locality, we do not have an
expansion. Human placenta-derived mesenchy-
establishment as such, and there is currently no
mal progenitor cells support culture expansion of
guideline available on cord blood collection or
long-term culture-initiating cells from cord blood
use of collected stem cells. Therefore, health
CD34 + cells.44
care providers, especially obstetricians, should
Besides placenta and cord blood, more focus
help in conveying detailed and balanced informa-
has been put on the amnion, which is made by
tion on stem cells to couples to ensure thorough
the baby and therefore is a safe and effective al-
understanding and aid their decisions.
ternative to ESCs. Amniotic epithelial stem cells

have remarkable potential to form virtually all
FUTURE DEVELOPMENT
cells in the body and have strong anti-inflammatory properties, and can be considered for repair
Stem cell research has heralded a new horizon
of tissues. They have been used for over 15 years
in clinical medicine. While appreciating the value
to treat burns and cornea. Currently, there is re-
of cord blood, it is recognized that there is a va-
search on stems cells in adult lung disease like
riety of progenitor cells, besides HSCs, in cord
pulmonary fibrosis and the immune system. The
blood and placenta; they are the MSCs in umbili-
immune system degenerate drastically with age
cal cord, chorion, and placenta, namely, MSCs in
and causes problems like being at high risk for
umbilical cord tissue (Whartons jelly), amniotic
opportunistic infections, poor vaccine responses,
MSCs, and amniotic epithelial stem cells (Figure
higher incidence and complications of cancer, risk
3), which may be a new platform for tissue trans-
of death from infection and relapse after chemo-
plant, ie, bone, cartilage, fat, myocardial muscle,
therapy and radiotherapy, and failure to recover
and neural tissue, owing to its anti-inflammatory,
from human immunodeficiency virus infections.
immunosuppressive, and pro-reparative proper-
Therefore, this generates immense research on
ties (Table 1).
using amniotic epithelial stem cells to reverse the
As addressed above, allogeneic transplanta-
ageing process to restore the thymus function.
tion with UCB in adult recipients is limited by a
Therefore, newborn cells can be regarded
low CD34 + cells from UCB in vitro. However, hu-
as a natural body repair kit. Yet this novel infor-
man placenta can now serve as a novel source of
mation is scarce to the public, thus limiting the

12/11/12 4:44 PM
OBSTETRICS
Peer Reviewed
potential clinical use of invaluable pluripotent stem
ethical and medical risks associated with the use
cells. Health care providers should serve as an im-
of ESCs.
portant channel to convey such invaluable information to the public.
About the Authors
CONCLUSION
This article reviews the current trends in UCB storage, 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
Dr Mak is Resident Trainee in the Department of Obstetrics and

Gynaecology, Kwong Wah Hospital, Hospital Authority, Hong
Kong. Mr Juan Bolaos 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 Hospital, Hospital Authority, Hong Kong.
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18. Perlow JH. Patients knowledge of umbilical
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19. Sugarman J, Kurtzberg J, Box TL, Horner
RD. Optimization of informed consent for umbilical cord blood banking. Am J Obstet Gynecol
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20. Work Group on Cord Blood Banking. Cord
blood banking for potential future transplantation: subject review. American Academy of Pediatrics. Pediatrics 1999;104:116118.
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/files/rcog-corp/uploaded-files/SAC2Umbilical
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22. Moise KJ Jr. Umbilical cord stem cells. Obstet
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24. Laughlin MJ, Eapen M, Rubinstein P, et al.
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bone marrow from unrelated donors in adults
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25. Hows JM. Status of umbilical cord blood
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26. Solves P, Moraga R, Saucedo E, et al. Comparison between two strategies for umbilical
cord blood collection. Bone Marrow Transplant
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27. Armitage S, Warwick R, Fehily D, Navarrete C,
Contreras M. Cord blood banking in London: the
first 1000 collections. Bone Marrow Transplant
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28. Annas GJ. Waste and longingthe legal
status of placental-blood banking. N Engl J Med
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29. Munzer SR. The special case of property
rights in umbilical cord blood for transplantation.
Rutgers Law Rev 1999;51:493568.
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storage and use: ethical issues. Blood Transfus
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31. Committee on Obstetric Practice; Committee
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32. Institute of Medicine. Cord blood: establishing a national hematopoietic stem cell bank
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www.iom.edu/Reports/2005/Cord-Blood-Estab
lishing-a-National-Hematopoietic-Stem-CellBank-Program.aspx.
33. Broxmeyer HE, Srour EF, Hangoc G, et al. Highefficiency recovery of functional hematopoietic
progenitor and stem cells from human cord blood
cryopreserved for 15 years. Proc Natl Acad Sci
USA 2003;100:645650.
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 811, 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 Authority 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 abrogates lung fibrosis and augments repair. Am J
Respir Crit Care Med 2010;182:643651.
38. Murphy S,Lim R,Dickinson H,et al. Human
amnion epithelial cells prevent bleomycin-induced lung injury and preserve lung function. Cell
Transplant2011;20:909923.
39. Minguell JJ,Erices A. Mesenchymal stem
cells and the treatment of cardiac disease. Exp
Biol Med (Maywood)2006;231:3949.
40. Goldschlager T,Jenkin G,Ghosh P,Zannettino
A,Rosenfeld JV. Potential applications for using
stem cells in spine surgery. Curr Stem Cell Res
Ther2010;5:345355.
41. Sykes M, Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation.
Nature 2005;435:620627.
42. Bruder SP,Fink DJ,Caplan AI. Mesenchymal
stem cells in bone development, bone repair,
and skeletal regeneration therapy. J Cell Biochem1994;56:283294.
43. Quintero AJ,Wright VJ,Fu FH,Huard J. Stem
cells for the treatment of skeletal muscle injury.
Clin Sports Med2009;28:111.
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12/11/12 4:44 PM
SGM BBLR dengan
formula yang disempurnakan

memberikan dukungan nutrisi
pada periode kejar tumbuh
untuk bayi prematur atau
berat lahir rendah.
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.
Tinggi energi mendukung periode kejar tumbuh.
Mendukung perkembangan otak yang pesat.
Mendukung pembentukan sel darah merah yang diperlukan untuk
perkembangan otak, fungsi otot maupun fungsi jantung.
Mendukung periode kejar tumbuh. 12 Asam Amino Esensial, termasuk
Arginin yang tidak dapat disintesis oleh bayi prematur.1
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.
1
Wu, G.; et al. (August 2004.Journal of Nutritional Biochemistry 15 (8): 332-451)
Bayi prematur membutuhkan

nutrisi khusus untuk :
Bayi BBLR memiliki

kesempatan untuk
tumbuh kembang
optimal di periode
emasnya
Mengejar pertumbuhan bayi normal.
Kejar Tumbuh
Rekomendasi
Energi
ESPGHAN1
110-135 kkal/kg/hari 120 kkal/kg/hari
ESPGHAN1
3-3,6 g/100 kkal 3,1 g/100 kkal
Protein
60 : 40
Rasio Whey : Kasein
12 jenis AAE
Asam Amino Esensial Codex Alimentarius2 11 jenis AAE
Mendukung perkembangan otak yang

sesuai dengan tahapan usianya.
Rekomendasi
Perkembangan Otak
Rasio AA : DHA
Kolin
LA : ALA
ESPGHAN1
ESPGHAN1
ESPGHAN1
MCT
Maltodekstrin
1-2 : 1
1 : 1, 0,2% TFA
7-50 mg/100 kkal 20 mg/100 kkal
10-15 : 1
15 : 1
Rekomendasi
ESPGHAN1
< 40% TFA
SGM BBLR
34% TFA
100%
Pembentukan sel darah.

Rekomendasi
Pembentukan Sel Darah

Level Zat Besi
SGM BBLR
Codex Alimentarius2 Min 0,45 mg/100 kkal 1 mg/100 kkal
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.
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.
ESPGHAN 2010
Codex Alimentarius 2007
SGM BBLR
Mempermudah pencernaan dalam absorbsi.
Mudah Diserap
1.
2.
SGM BBLR

P
3 SK
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 optimally 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
Family planning is an important part of preconception care.
other primary health care providers are

in a better position to provide precon-
OBJECTIVES OF
tion care can even be introduced in the PRECONCEPTION CARE
tries, maternal deaths are associated
community and in schools, in the form
pregnancies.1 In developed countries, es-
ception care. Some of the preconcep-
with high multiparity and closely spaced
of health education and public health
The objectives of preconception care are
pecially in metropolitan cities, delayed
measures. Although the impact of pre-
to improve the physical and psychologi-
parenthood, single parenthood and lack
conception care for women with signifi-
cal health of the mother (decrease ma-
of support from the extended family may
cant pre-existing health problem, such
ternal mortality and morbidity) and the
pose special problems. For example, post-
as diabetes, may be more obvious than
father, and to improve the health of the
partum depression occurs more often in
for women without, preconception care
offspring (decrease perinatal morbid-
unplanned pregnancies, while subfertility
should not be confined to the former
ity and mortality). The major causes of
and miscarriages occur more often with
group of women. Offering preconception
perinatal morbidity and mortality are low
older maternal age.2 Women and their
care, such as folic acid supplementa-
birth weight and congenital abnormali-
partners should be given information on
tion to prevent neural tube defect, to all
ties. Therefore, preconception interven-
contraception, and they should also be
women may have a significant impact on
tion strategies are targeted at reducing
encouraged to discuss when it is best for
the whole population. The evidence for
these.
them to have children.
PLANNED PARENTHOOD
DIETARY AND VITAMIN

SUPPLEMENTATION
the effectiveness of commonly practised

preconception care will be examined
in this article. A practical checklist for
preconception care in the primary health
Family planning is an important part of
care setting will also be provided.
preconception care. In developing coun-
Folic acid supplement use before concepJPOG NOV/DEC 2012 257
JPOG_NovDec_2012_CME_ID.indd 257
12/11/12 2:56 PM
tion and continued to 12 weeks gestation
Women with iron deficiency anaemia
acceptable despite the risk. A common
has been found to be effective in reducing
should be given iron supplement to correct
example are antiepileptic drugs, most of
neural tube defects in offspring of women
the anaemia.
which are category D. Stopping antie-
in the general population (low-risk) and
pileptic drugs in some women may result
GOOD PRACTICE IN DRUG

fected babies, and women on antiepileptic PRESCRIBING
in recurrence of epileptic attacks, which
drugs (high-risk).3 For low-risk women, 400
leptic drugs to the mother and the baby.
also offspring of women with previous af-
is even more detrimental than antiepi-
g of folic acid daily is adequate, but for
Women in the reproductive age group
Therefore, their use may be unavoidable in
high-risk women, 5 mg of folic acid daily is
should avoid teratogens unless they are
some women. Folic acid supplement 5 mg
usually prescribed.
practising effective contraceptive methods.
daily should be given together with antie-
In Southeast Asia where thalassae-
Most drugs are of low teratogenic-
pileptic drugs for women who may become
mia trait is common, an increased inci-
ity, but a good prescription practice is
dence of neural tube defect has been found
not to prescribe unless necessary and
Category X drugs are those that have
pregnant.
in thalassaemia trait carriers. It is logical
only to prescribe drugs that are proven
been demonstrated to be teratogenic
to use the higher dose of folic acid for tha-
to be effective. 8 Many commonly used
in humans and their associated risks in
lassaemia trait carriers for this purpose,
drugs are assigned to US Food and Drug
pregnancy clearly outweigh any possible
even though the 400 g and 5 mg daily dos-
Administration (FDA) pregnancy risk cate-
benefits. An example is isotretinoin, a
es have not been compared in randomized
gory C, which means that these drugs have
highly teratogenic drug, which is used for
controlled trials in this group of women.
been found to be teratogenic or embryo-
skin conditions. When category X drugs
Since up to 50% of pregnancies are
cidal in animal studies but there are no
are prescribed, women should be advised
unplanned, mandatory fortification of food
controlled studies in women or animals.
against pregnancy and appropriate contra-
(mainly flour) has been used in many coun-
These drugs can be used if the potential
ception should be provided. In some coun-
tries and has been found to be effective in
benefits outweigh the potential risks and
tries, medical practitioners are required
reducing the prevalence of neural tube de-
if no alternatives are found. However,
by law to ask female patients to sign a
fects. However, there are some concerns
some drugs used commonly for treatment
consent agreeing to take category X drugs
that mandatory fortification exposing the
of symptoms (eg, codeine, promethazine,
and to use effective contraception while
whole population to increased intake of
NSAIDs) are category C drugs. For symp-
on these drugs. Irrespective of the local
folic acid may lead to some adverse ef-
tomatic treatment only, their use is hardly
legal requirement, it is a good practice to
fects in susceptible individuals. For exam-
justifiable in women who are pregnant
document in the medical record that this
ple, degenerative neurological diseases in
or who are potentially pregnant. Doctors
has been explained to the patient.
the elderly may potentially be worsened.6
should be particularly cautious when pre-
Women in the reproductive age group
The effectiveness of folic acid sup-
scribing treatment for women presenting
should also be educated to be cautious
plementation in preventing congenital ab-
with upper gastrointestinal tract symp-
when they use over-the-counter drugs,
normalities other than neural tube defect
toms or urinary symptoms, as these can be
which may include some category C drugs.
has not been well established.
symptoms of early pregnancy.
Precautions regarding their use in preg-
Other dietary supplementations have
Special caution must be taken when
nancy are usually stated on the package.
not been well studied or have not been
prescribing categories D and X drugs.
They should also be educated to inform
found to significantly reduce congenital
Category D means that there is positive
doctors if they are not practising contra-
abnormalities. It must also be remembered
evidence of human fetal risk but the ben-
ception and to ask if the prescribed drugs
that high-dose vitamin A is teratogenic.
efits from use in pregnant women may be
are safe for pregnancy, even if they do not
12/11/12 2:56 PM
PREVENTION OF INFECTIONS
suspect that they are pregnant.
HAART (highly active antiretroviral therapy with multiple agents) together with
AVOIDANCE OF IRRADIATION
Diagnostic X-ray should be avoided during
Some maternal infections can be transmitted
intrapartum and postnatal zidovudine for
to the baby during pregnancy and/or delivery,
the baby is highly effective.15 Therefore,
causing grave consequences to the baby.
it may not be necessary to advise against
the luteal phase of the menstrual cycle
Rubella infection in pregnancy can
pregnancy in carriers. With compliance,
and deferred to the follicular phase if pos-
cause major congenital abnormalities.
perinatal transmission rate can be reduced
sible. However, most diagnostic X-rays,
Vaccination against rubella is part of the
to less than 1%, but in rare instances the
except those done under fluoroscopy, have
vaccination programme for children and
baby can still be infected. Knowing the HIV
irradiation doses below the estimated ter-
adolescents in many countries. However,
status before pregnancy may change the
atogenic threshold (0.1 Gy). Therefore, ur-
even in countries with such vaccination
reproduction plan for some women or may
gent diagnostic X-ray should not be withheld
programmes, doctors must be aware that
help HIV-positive individuals to be better
if there is a strong indication or if alterna-
immigrants may not have been vaccinated
prepared to start a family. However, nega-
tive non-irradiation tests are not available.
in their original country. Therefore, check-
tive screening before pregnancy does not
Abdominal shield should be used.
ing the immune status and providing the
mean that the individual is not susceptible
Therapeutic irradiation, including ra-
vaccination to women is an important part
to infection after the screening or during
dioactive iodine, is absolutely contraindi-
of preconception care. Chickenpox infec-
the pregnancy.
cated during pregnancy.
tion during pregnancy can also cause scar-
ring and deformity in the baby in a small
ADVICE AGAINST LIFESTYLE

SUBSTANCE USE
TREATMENT FOR OBESITY
proportion of cases. Vaccination against

chickenpox in susceptible women before
It has increasingly been shown that obe-
pregnancy can be an option.
sity has adverse effects on pregnancy.
13
Alcohol consumption is associated with
Hepatitis B vaccination should be
The association of obesity with maternal
increased risk of miscarriages and fetal
provided to susceptible health care work-
mortality and morbidity is well proven.
malformation. However, whether a low in-
ers and non-immune women whose part-
There is also evidence suggesting that
take (less than 5 units per week) is safe is
ners are carriers. However, women who
fetal congenital abnormalities and peri-
uncertain. Therefore, women planning to
are hepatitis B carriers should not be un-
natal morbidities are also increased in
get pregnant should be advised to abstain
duly worried, because effective prevention
obese mothers.16 Weight reduction may
from alcohol.
of perinatal transmission is available.14
potentially be harmful during pregnancy.
10
Cigarette smoking is not teratogenic
Screening for HIV and syphilis are
but doubles the risk of intrauterine growth
part of routine antenatal care. However,
restriction and increases the risk of miscar-
it can be done before pregnancy. Syphilis
riages and perinatal mortality by one-third.
11
can be effectively treated before preg-
Women should be encouraged and be
nancy. This also allows time for contact
helped to stop smoking before pregnancy.
tracing and for more effective prevention
Therefore, weight reduction should ideally

be achieved before pregnancy.17
ATTENTION TO DENTAL
HYGIENE
There is an association between use
of re-infection during pregnancy. There is
Periodontal disease in pregnant women
of recreational drugs and fetal congenital
no curative treatment for HIV, but carriers
has been found to be associated with in-
abnormalities, in particular, gastroschi-
can remain healthy with monitoring and
creased risk of preterm delivery. 18 However,
sis.12 Cocaine use is associated with in-
early antiretroviral treatment. Prevention
treatment of the disease during pregnancy
creased incidence of placental abruption.
of perinatal transmission with antepartum
has been shown to be ineffective in reducJPOG NOV/DEC 2012 259
12/11/12 2:56 PM
WOMEN AND MEN WITH

treatment before pregnancy in improving to a maternal medicine specialist for pre- MALIGNANT DISEASES
ing premature deliveries. Effectiveness of
post transplantation, should be referred
pregnancy outcome has not been stud-
conception care. Preconception care for
ied. Provision of dental care as part of
women with diabetes is the best known
Many malignant diseases can be suc-
general health care is a good practice, but
model for preconception care in women
cessfully treated with modern medicine.
its role in preconception care has yet to
with significant chronic medical illness.
Women and men may want to start a fam-
be determined. However, for women with
It is well known that the incidence of
ily after treatment of malignant diseases.
medical diseases such as valvular heart
congenital abnormalities in fetuses of
Some treatment may affect the future fer-
disease, good dental hygiene is a very im-
diabetic women is directly proportional
tility of men and women. Storage of se-
portant part of preconception care.
to periconception glycosylated haemo-
men or even cryopreservation of ovarian
globin A 1C, which reflects the glycaemic
tissues before these treatments may be
control. Therefore, achieving good gly-
an option. 23 After treatment, some women
caemic control before pregnancy is im-
may be concerned about the risk of recur-
Cervical smears should be taken before
portant. Women with diabetes should
rence of the malignancy during pregnancy
pregnancy in women planning to get preg-
also be screened for diabetic retinopa-
because of altered hormonal and immune
nant, if they are not already in a regular
thy, nephropathy and ischaemic heart
status. Pregnancy does not affect the re-
screening programme. Hormonal changes
disease before pregnancy, as these com-
currence risk of most malignant diseases
in pregnancy may lead to problems in in-
plications greatly increase the maternal
if the woman is disease-free before em-
terpretation of cervical cytology. Cervical
risks and perinatal mortality and morbid-
barking on a pregnancy. It is best to con-
biopsy and treatment of cervical intraepi-
ity. However, good glycaemic control is
sult an oncologist on this.
thelial neoplasia during pregnancy are
difficult to achieve and intervention pro-
also associated with a higher incidence
grammes have, so far, fallen short of the
of heavy bleeding and are generally not
expectation. 22
19
CERVICAL SCREENING
21
SCREENING FOR GENETIC

DISEASES
advisable unless there is a suspicion of
Hypertension is often asymptomatic,
invasive disease. With experience, colpo-
and blood pressure should be checked
For families with no history of genetic
scopic examination during pregnancy to
even in women without a history of hyper-
diseases, screening for carrier status of
detect invasive lesions is effective. If in-
tension.
any genetic disease before pregnancy is
20
vasive disease is detected, full treatment

cannot be given without terminating the
pregnancy. Therefore, screening before
only advisable if (1) the particular genetic
WOMEN WITH MAJOR

PSYCHIATRIC DISEASES
pregnancy is more ideal than screening
disease is common in the population, (2)

reliable screening methods are available, and (3) the affected individual has
Women with major depression, bipolar
poor quality of life or a major handicap.
disorders and schizophrenia should be
An example is - and -thalassaemia in
under the care of a psychiatrist to ensure
Southeast Asia. In Hong Kong, the prev-
that the disease is well controlled before
alence of -thalassaemia carriers and
pregnancy. Many psychotropic drugs are
-thalassaemia is 5.0% and 3.4%, respec-
Women with significant medical dis-
FDA category C or D. However, their use
tively. 24 A simple complete blood picture
eases, such as diabetes, active thyroid
may be unavoidable, as relapse during
with mean corpuscular volume above 80 fL
diseases, epilepsy, autoimmune diseas-
pregnancy may be more detrimental to the
effectively exclude - and -thalassaemia
es, renal diseases, cardiac diseases and
mother and the baby.
trait. 24 (However, it does not exclude car-
during pregnancy.
WOMEN WITH MEDICAL

DISEASES
12/11/12 2:56 PM
riers of haemoglobin E, which is preva-
Preconception care checklist for primary care physicians
lent in Thailand, and haemoglobin Ethalassaemia heterozygous may have

transfusion-dependent anaemia.) Further
investigations, such as haemoglobin pattern analysis and DNA studies may be
needed after excluding iron deficiency.
Iron deficiency can be excluded by iron
profile studies, but a simple and practical 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 corrected by supplement. Which genetic diseases 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 falsepositive rate. There is some controversy
as to whether screening should be done
before or during pregnancy. If prenatal
diagnosis is readily available and acceptable 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 diseases, whether before pregnancy or during
pregnancy, should only be done with informed consent. Individuals should not be
coerced into undergoing genetic testing or
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
screening.
It is also a good practice to obtain a
genetic history from couples planning to
er has haemophilia, if the couple already
referral to a geneticist for preconception
get pregnant. If there are any genetic dis-
have a child with genetic disease, or one
counselling and testing is recommended.
eases in the family (eg, the womans broth-
potential parent has a genetic disease),
Many tests to confirm the diagnosis and

12/11/12 2:56 PM
then to determine the mutation of rarer
pregnancy loss after the first trimester,
future. Preconception care can be in the
genetic diseases are lengthy. Therefore, it
history of severe early onset pre-eclamp-
form of careful prescription and careful
is better if these can be confirmed before
sia, or history of severe early onset in-
ordering of investigations which are po-
the pregnancy rather than during pregnan-
trauterine fetal growth restriction should
tentially teratogenic. Preconception care
cy, as the window for prenatal diagnosis
be referred to an obstetrician or maternal
can be provided on specific request from
is short. In some cases, prenatal diagnosis
fetal medicine specialist for preconcep-
patients or actively promoted to all women
may not be possible and couples may need
tion care. Investigations for treatable or
and men of the reproductive age group.
to change their reproductive plans.
preventable causes (eg, antiphospholipid
History taking and advice giving are very
For couples who cannot accept ter-
syndrome) can be undertaken, and appro-
important components of preconception
mination of pregnancy following prenatal
priate management may optimize the out-
care. Some standard investigations are
diagnosis, preimplantation genetic diag-
come of future pregnancies in some cases.
useful, but these cannot replace a care-
26
nosis, if available, can be an option if they

are known to carry mutations which may
affect the baby.
fully taken history. The box on page 174 is
SUMMARY
a summary of this review and can be used

as a checklist for primary care physicians
25
Preconception care can be provided in
WOMEN WITH BAD

OBSTETRIC HISTORY
in providing preconception care.
primary health care. Doctors should also

be aware that whenever they are treating
women in the reproductive age group, they
Women with recurrent miscarriages (three
are treating someone who may be preg-
or more) in the first trimester, one or more
nant or may become pregnant in the near
About the Author

Dr Lee is Consultant in the Department of Obstetrics
and Gynaecology, University of Hong Kong, Queen Mary
Hospital, Hong Kong.
References
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Look PF. WHO analysis of causes of maternal death:
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2. Nybo Anderson AM, Wohlfahrt J, Christens P,
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population based register linkage study. BMJ
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3. De-Regil LM, Fernandez-Gaxiolo AC, Dowsell
T, Pena-Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev
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4. Lam YH, Tang MH. Risk of neural tube defects in
the offspring of thalassaemia carriers in Hong Kong
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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;60:287294.
7. Rothman KJ, Moore LL, Singer MR, Nguyen US,
Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med 1995;333:13691373.
8. Rayburn WF, Amanze AC. Prescribing medications safely during pregnancy. Med Clin North Am
2008;92:12271237.
9. Valentin J. ICRP Publication 84: Pregnancy and
Medical Radiation. Annals of the ICRP Volume 30/1.
Elsevier 2000;139.
10. Royal College of Obstetricians and Gynaecologists. Alcohol consumption and outcomes of pregnancy. 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;66:10591092.
12. Draper ES, Rankin J, Tonks AM, et al. Recreational drug use: a major risk factor for gastroschisis? Am J Epidemiol 2008;167:485491.
13. Royal College of Obstetricians and Gynaecologists. Chickenpox in pregnancy. RCOG Green-top
Guideline No. 13; 2007.
14. Wong VC,Ip HM,Reesink HW, et al.Prevention 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
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15. European Collaborative Study. Mother-tochild transmission of HIV Infection in the era of
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2005;40:458465.
16. Nuthalapaty FS, Rouse DJ. The impact of
obesity on obstetrical practice and outcome. Clin
Obstet Gynecol 2004;47:898913.
17. Davies GA, Maxwell C, McLeod L, et al; Society
of Obstetricians and Gynaecologists of Canada.
SOGC clinical practice guidelines: obesity in pregnancy. No. 239, February 2010. Int J Gynecol Obstet
2010;110:167173.
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;132:875880.
19. Polyzos NP, Polyzos IP, Zavos A, et al. Obstetric
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20. Fader AN, Alward EK, Neiderhauser A, et
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Ratner RE. Preconception care of diabetes, congenital malformations, and spontaneous abortions.
Diabetes Care 1996;19:514541.
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12 women with chemotherapy-induced premature
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25. Geraedts JP, De Wert GM. Preimplantation
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12/11/12 2:56 PM
CME Questions
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:
P
3 SK
Preconception Care
Jawab pertanyaan di bawah ini dengan Benar atau Salah
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.

T F F T F T F F F T

1 2 3 4 5 6 7 8 9 10
Answers
JPOG advanced online publication; 1 July 2012 263
12/11/12 2:56 PM
JPOG 2012 Annual Index

Section
First Author
Issue
Page
Analgesia, analgesics, combined oral contraceptives, diagnosis, dysmenorrhoea, physiopathology
Clinical Review
Kolhe S
Jul/Aug
147
Anovulation, ovulation induction
Clinical Review
Yeung WYT
Jan/Feb
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
Abruptio placentae, antepartum haemorrhage, caesarean section, Doppler ultrasonography,

placenta praevia, resuscitation
Clinical Review
Athanasias 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
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
Gynaecology
Obstetrics
Paediatrics
JPOG Nov/Dec 2012 264
JPOG_NovDec_2012_Annual Index_P264_ID_FINAL.indd 264
12/11/12 3:10 PM

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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Infectious Disease in Pregnancy

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

221 Hormonal contraception and cardiovascular risk

222 Cumulative birth rates with assisted reproduction

Management of type 2 diabetes in children and adolescents

Treatment for infants of mothers who present late in pregnancy with

Professor Biran Affandi

Board Director, Paediatrics

Dr Karen Kar-Loen Chan

Professor Tzou-Yien Lin

Professor Walfrido W Sumpaico

Associate Professor Oh Moh Chay

Professor Somsak Lolekha

Professor Cheng Lim Tan

Professor Lucy Chai-See Lum

Associate Professor Kok Hian Tan

Professor Hextan Yuen-Sheung Ngan

Professor Eng-Hseon Tay

Professor Carmencita D Padilla

Professor Seng-Hock Quak

Dr Tatang Kustiman Samsi

Professor Terence Lao

Professor Hui-Kim Yap

Professor Perla D Santos Ocampo

Professor Tsu-Fuh Yeh

Associate Professor Alex Sia

Professor Pik-To Cheung

Associate Professor Anette Jacobsen

JPOG NOV/DEC 2012 i

Protein Whey dan Casein

Isolat Protein Kedelai berkualitas

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

225 Dietary Intervention in Eczema

Jackelina Pando Kelly, Jonathan Hourihane

234 Infectious Disease in Pregnancy

Sarah Logan, Laura Price

Agnes Chieng, Sam Shum

Edwin Yu, Ho Wai Hung,

UBM Medica Pacific Limited

Enquiries and Correspondence

PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is

JPOG NOV/DEC 2012 ii

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Continuing Medical Education

257 Preconception Care

264 2012 Annual Index

Interesting cases seen in general

Lisa Low, Illustrator

JPOG NOV/DEC 2012 iii

Dengan locust bean gum sebagai thickening agent

Diperkaya dengan AA dan DHA

ethinyl oestradiol dose of 20 g, the increase in risk

There were significant increases in the sling group

was less in general, and there was no increased

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

risk with drospirenone as the progestin. Transder-

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

mal patches were not associated with significantly

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

increased risk for either thrombotic stroke or myo-

The insertion of a midurethral sling was ef-