JPOG December 2012 ID

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
CME ARTICLE
3 SK
P
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
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
221
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 Dr Tak-Yeung Leung Dr Raman Subramaniam

University of Indonesia Chinese University of Hong Kong Fetal Medicine and Gynaecology Centre, Malaysia
Board Director, Paediatrics Dr Karen Kar-Loen Chan Professor Tzou-Yien Lin Professor Walfrido W Sumpaico
Professor Pik-To Cheung The University of Hong Kong Chang Gung University, Taiwan MCU-DFT Medical Foundation, Philippines
Associate Professor Associate Professor Oh Moh Chay Professor Somsak Lolekha Professor Cheng Lim Tan
Department of Paediatrics KK Women’s and Children’s Hospital, Ramathibodi Hospital, Thailand KK Women’s and Children’s Hospital, Singapore
and Adolescent Medicine Singapore Professor Lucy Chai-See Lum Associate Professor Kok Hian Tan
The University of Hong Kong
Associate Professor Anette Jacobsen University of Malaya, Malaysia KK Women’s and Children’s Hospital, Singapore
Board Director, Obstetrics and Gynaecology KK Women’s and Children’s Hospital, Singapore Professor SC Ng Dr Surasak Taneepanichskul
Professor Pak-Chung Ho Professor Rahman Jamal National University of Singapore Chulalongkorn University, Thailand
Head, Department of Universiti Kebangsaan Malaysia Professor Hextan Yuen-Sheung Ngan Professor Eng-Hseon Tay
Obstetrics and Gynaecology The University of Hong Kong Thomson Women’s Cancer Centre, Singapore
The University of Hong Kong Dato’ Dr Ravindran Jegasothy
Hospital Kuala Lumpur, Malaysia Professor Carmencita D Padilla Professor PC Wong
University of the Philippines Manila National University of Singapore
Associate Professor Kenneth Kwek
KK Women’s and Children’s Hospital, Singapore Professor Seng-Hock Quak Dr George SH Yeo
National University of Singapore KK Women’s and Children’s Hospital, Singapore
Dr Siu-Keung Lam
Dr Tatang Kustiman Samsi Professor Hui-Kim Yap
Kwong Wah Hospital, Hong Kong
University of Tarumanagara, Indonesia National University of Singapore
Professor Terence Lao Professor Perla D Santos Ocampo Professor Tsu-Fuh Yeh
Chinese University of Hong Kong University of the Philippines China Medical University, Taiwan
Dr Kwok-Yin Leung Associate Professor Alex Sia
The University of Hong Kong KK Women’s and Children’s Hospital, Singapore
JPOG NOV/DEC 2012 • i
JPOG_NovDec_2012_TOC.indd 1 12/11/12 3:54 PM

Protein Whey dan Casein Isolat Protein Kedelai berkualitas
terhidrolisat parsial dengan yang diperkaya L-Methionine,
alerginisitas rendah untuk Karnitin untuk mengatasi alergi
mengurangi risiko dermatitis atopi. susu sapi.
CM
MY
CY
CMY
K
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.
Jackelina Pando Kelly, Jonathan Hourihane
Review Article
225 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
Publisher
Ben Yeo
Enquiries and Correspondence PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is
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JPOG NOV/DEC 2012 • ii

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.
Jennifer Sze Man Mak, Juan Bolaños, Wing Cheong Leung, Richard Boyd, Robert Kien Howe Chin
P
Continuing Medical Education 3 SK
247
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
The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence from UBM Media LLC. The articles
appearing on pages 49–53, and pages 67–80 are reprinted with permission of Consultant for Pediatricians. Copyright © 2011
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Review Articles Case Studies

Comprehensive reviews Interesting cases seen in general
providing the latest clinical practice and their management.
information on all aspects The Cover:
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JPOG NOV/DEC 2012 • iii

Dengan locust bean gum sebagai thickening agent
Diperkaya dengan AA dan DHA
Dengan Nukleotida
Referensi:
Peer Reviewed Journal Watch
ethinyl oestradiol dose of 20 µg, the increase in risk There were significant increases in the sling group
GYNAECOLOGY 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
Hormonal contraception and mal patches were not associated with significantly emptying 6 weeks after surgery (3.7% vs 0%).
cardiovascular risk 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.
Wei JT et al. A midurethral sling to reduce incontinence after vaginal
Although hormonal contraception may in- prolapse repair. NEJM 2012; 366: 2358–2367; Iglesia CB. Vaginal prolapse
repair – place midurethral sling now or later: Ibid: 2422–2424 (editorial).
crease the risks of thrombotic stroke and myocar-
dial infarction, the absolute risks are low. An edito-
rialist concludes that they are ‘safe enough’.
Effect of contraception on
Lidegaard Ø et al. Thrombotic stroke and myocardial infarction with
hormonal contraception. NEJM 2012; 366: 2257–2266; Petitti DB. maternal mortality rates
Hormonal contraceptives and arterial thrombosis – not risk-free but safe
enough. Ibid: 2316–2318 (editorial).
The Safe Motherhood Initiative begun in 1987 has

four strategies to reduce maternal mortality: family
planning, antenatal care, safe delivery, and postna-
Midurethral sling during vaginal
tal care. Now, the effects of contraceptive use on
prolapse surgery to reduce post-
operative incontinence 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 15–49 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 Increased use of contraception could prevent
dose of 30–40 µg, the risk of thrombotic stroke was 43.0%. The number needed to treat to prevent one many maternal deaths in developing countries.
increased 1.5- to 2.2-fold according to progestin case of urinary incontinence at 12 months was 6.3.
Ahmed S et al. Maternal deaths averted by contraceptive use: an analysis
type, compared with non-users. The risk of myocar- Bladder perforation occurred in 6.7% of the ure- of 172 countries. Lancet 2012; 380: 111–125; Gilmore K, Gebreyesus TA.
What will it take to eliminate preventable maternal deaths? Ibid: 87–88
dial infarction was increased 1.3- to 2.3-fold. At an thral sling group but in none of the control group. (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). a sensitivity and a specificity both of 0.94. There is
OBSTETRICS Live-birth rates similar to natural fecundity insufficient evidence about the use of either test to
can be achieved with favourable maternal and predict adverse pregnancy outcome.
Cumulative birth rates with embryo characteristics. The use of donor oocytes Urinary protein-to-creatinine ratio may be
assisted reproduction 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-
to-creatinine ratio for this purpose or about the
Luke B et al. Cumulative birth rates with linked assisted reproductive
technology cycles. NEJM 2012; 366: 2483–2491. use of either test to predict adverse pregnancy
outcome.
Morris RK et al. Diagnostic accuracy of spot urinary protein and albumin

Urinary protein-to-creatinine or to creatinine ratios for detection of significant proteinuria or adverse
pregnancy outcome in patients with suspected pre-eclampsia: systematic
albumin-to-creatinine ratio to review and meta-analysis. BMJ 2012; 345: (July 21): 14 (e4342).
detect significant proteinuria in

pregnancy PAEDIATRICS
Reducing measles mortality
One global goal was to halve measles deaths be-

tween 1999 and 2005, and that was achieved. A
new goal was then set to reduce measles mortality
by 90% between 2000 and 2010. There has been no
endemic measles virus transmission in the Ameri-
Rates 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
Data were available for 246,740 women proteinuria in pregnancy in the diagnosis of pre- India, measles deaths fell by 25% from 88,000 to
(471,208 cycles, 140,859 live births). Live-birth eclampsia. 65,500. In 2010, almost half (47%) of all deaths
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 2000–2010 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-
Simons E et al. Assessment of the 2010 global measles mortality
and 42, and 6.6% and 11.3% at age 43 or older. Us- tein-to-creatinine ratio appeared to be 0.30–0.35. reduction goal: results from a model of surveillance data. Lancet 2012;
379: 2173–2178; Orenstein WA, Hinman AR. Measles: the burden of
preventable deaths. Ibid: 2130–2131 (comment).
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

Peer Reviewed Journal Watch
The Millennium Villages project in who have not received antiretroviral therapy in
Africa 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 10–17 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 maternal–child 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,
The multifaceted intervention was beneficial of participants overall. The group rates for this and maternal use of illegal substances. Neutrope-
in several ways including reduced child mortality. 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.
Pronyk PM et al. The effect of an integrated multisector model for
achieving the Millennium Development Goals and improving child survival was not significantly different from M or MR. The Z6 + Nev and Z6 + Nelf L regimens were
in rural sub-Saharan Africa: a non-randomised controlled assessment.
Lancet 2012; 379: 2179–2188; Malenga G, Molyneux M. The Millennium
MR was the best of the three options. Most more effective than the Z6 regimen, and the Z6 +
Villages project. Ibid: 2131–2133 (comment).
young people with type 2 diabetes will probably Nev was less toxic than Z6 + Nef L.
need combination drug therapy or insulin within a
Nielsen-Saines K et al. Three postpartum antiretroviral regimens to
few years of diagnosis. prevent intrapartum HIV infection. NEJM 2012; 366: 2368–2379.
Management of type 2 diabetes TODAY Study Group. A clinical trial to maintain glycemic control in youth
in children and adolescents with type 2 diabetes. NEJM 2012; 366: 2247–2256; Allen DB. TODAY – a
stark glimpse of tomorrow. Ibid: 2315–2316 (editorial).
The increased prevalence of obesity in children and Zidovudine, lamivudine, and

adolescents has led to an increased incidence of ritonavir-boosted lopinavir for
type 2 diabetes. The physical and emotional chal- Treatment for infants of mothers HIV-infected children
lenges of adolescence, together with the increased who present late in pregnancy
frequency of obesity and diabetes in underprivi- with an untreated HIV-1 infection For mothers and infants, who have previously been
leged communities, add to the difficulties of diabe- 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

treatment: the liquid formulation is unpleasant to
taste and deteriorates in hot temperatures, and the
cost is twice that of the nevirapine-based regimen.
New drug formulations are needed urgently.
Violari A et al. Nevirapine versus ritonavir-boosted lopinavir for HIV-

infected children. NEJM 2012; 366: 2380–2389.
Neonatal screening with pulse

oximetry for critical congenital
heart defects: Systematic review
and meta-analysis
Babies with congenital heart defects may be dis-

charged from hospital before a diagnosis is made
and may subsequently become suddenly and criti-
cally ill. A new systematic review and meta-anal- 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- The trial included 55 children aged 5–11
six countries in sub-Saharan Africa and India has cal congenital heart defects. 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
A total of 287 nevirapine-naive HIV-infected was 0.50% in the first 24 hours after birth and consisted of giving egg white powder in three
children aged 2–36 months were randomized to zi- 0.05% when done later. phases, in increasing doses up to 2 g per day. Chal-
dovudine and lamivudine with either nevirapine or It is concluded that pulse oximetry screening lenges with egg white were performed at 10 and
ritonavir-boosted lopinavir. The median proportion should be introduced widely. 22 months. After a 5-g challenge at 10 months,
of CD4 T-cells was 15% and median plasma HIV-1
+
no allergic symptoms (or mild symptoms) occurred
Thangaratinam S et al. Pulse oximetry screening for critical congenital
RNA level 5.7 log10 copies/mL. Virological failure or heart defects in asymptomatic newborn babies: a systematic review and in 55% (immunotherapy) vs none (placebo). At 22
meta-analysis. Lancet 2012; 379: 2459–2464; Kemper AR, Martin GR.
Screening of newborn babies: from blood spot to bedside. Ibid: 2407–
treatment discontinuation by week 24 occurred in months, 75% of children in the immunotherapy
2408 (comment); The Lancet. A new milestone in the history of congenital
heart disease. Ibid: 2401 (editorial).
significantly more children in the nevirapine group 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 Oral immunotherapy for egg were able to eat egg at 30 and 36 months.
drug toxicity was also greater. allergy in children Oral immunotherapy may be successful in
The results were better with the ritonavir- some children with egg allergy.
boosted lopinavir-based regimen, but these re- By the age of 2.5 years, around 2.5% of children
Burks AW et al. Oral immunotherapy for treatment of egg allergy in
searchers point to difficulties in introducing this have developed egg allergy. Complete dietary children. NEJM 2012; 367: 233–243.

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PAEDIATRICS
PAEDIATRICS II Peer
Peer Reviewed
Reviewed
Imaging Paediatric
Brain Tumours
Dietary Intervention
Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology
in Eczema
Jackelina Pando Kelly, MMSc, MRCPCH; Jonathan Hourihane, MB, DM, FRCPCH
INTRODUCTION
Eczema, also known as atopic dermatitis has been proposed as a cutaneous manifes-
tation of a systemic disorder that also gives rise to asthma, food allergy, and allergic
rhinitis. It is a common, chronic, pruritic, and relapsing inflammatory dermatosis that
typically manifests during early childhood.
The current prevalence of eczema in developed countries is about 20%, represent-
ing a twofold to threefold increase during the past decades. The reason for this increase
remains unclear.
PATHOGENESIS
The pathophysiology of eczema is not yet fully understood. An interaction between

genetic and environmental factors has been implicated in the predisposition and
development of the disease. Eczema is associated with abnormalities in genes encod-
ing skin barrier molecules (filaggrin), markers, and cells of the inflammatory response;
immunoregulatory abnormalities; increased serum immunoglobulin E (IgE); impaired
delayed hypersensitivity reaction; and infectious agents.
Research has demonstrated that a combination of food allergy, defects in the gut
mucosal barrier, and increased intestinal permeability may be complicit in the pathogen-
esis of eczema. Therefore, dietary manipulation could be of use in controlling or prevent-
ing the disease, but this still remains controversial.
It is important to remember that food allergy and eczema coexist due to their com-
mon origins as manifestations of an allergic diathesis, but that one may not automatically
be implicated as a cause of the others.

PAEDIATRICS I Peer Reviewed
There is no convincing evidence that delaying the introduction their child’s eczema, rather than using prescription
of solid foods, including those considered to be highly allergic,
medications that they have been told, also errone-
beyond 6 months of age has a significant protective effect on
the development of eczema. ously, have major toxic side effects.
Food-allergic sensitization. Allergic sensiti-
zation to food allergens is frequent in infants and
children with eczema. The highest rates of food-
allergic sensitization occur during the first 2 years
of life, and they closely parallel the onset of eczema.
There is a direct correlation between eczema
severity and food allergen sensitization. The dem-
onstration of food allergen-specific IgE in infancy
is predictive not only of eczema severity, as shown
by the fact that sensitization to food and inhalant
allergens is present in 70–80% of patients with
moderate-to-severe eczema, but also of eczema per-
sistence and of the onset of allergic airways disease
later in childhood.
Food-allergic disease in patients with
eczema. Ingested food allergens are able to acti-
vate cutaneous mast cells and skin-associated lym-
phoid tissue, and in the sensitized host, they can
produce intense pruritus, causing scratching and
rubbing that lead to typical eczematous lesions.
At a cellular level, positive oral food challenges
in patients with eczema result in a sharp increase in
plasma histamine concentrations, activation of eo-
sinophils, and clonal expansion of allergen-specific
We will briefly review the association between skin homing T-cells.
food allergy and eczema and some of the dietary It has been reported that approximately one-
strategies that have been proposed in eczema. third 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
cow’s milk, cause flare-ups of their child’s 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-

PAEDIATRICS
tion mutations in the epidermal structural protein 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 Allergic eosinophilic Food protein–induced
Phenotypes of food allergy in patients with food allergy/ gastritis enterocolitis
eczema. Food-allergic reactions have been broadly Anaphylaxis Allergic eosinophilic Food protein–induced
classified into allergic (IgE or non-IgE-mediated) Oral allergy gastroenteritis proctitis
and non-allergic hypersensitivity reactions. The al- syndrome Food protein–induced
lergic reactions may be immediate IgE-mediated or Eczema enteropathy
Coeliac disease
delayed non-IgE-mediated. Intolerance is defined as
Eczema
a non-allergic reaction to a food and includes food
Any time, peak
aversion, and toxic, enzymatic or pharmacological
in early life Infancy–adolescence Usually infancy
reactions to foods.
Cox H, Hourihane J. 2011.
There is considerable overlap between IgE-
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 under-
stand the natural history and clinical presentation of Food-allergic triggers Non-allergic food triggers
food allergy in order to make or refute a diagnosis of of eczema of eczema
such in patients with eczema. Milk Tomato
IgE-mediated reactions to specific foods cause Egg Citrus
Peanut Acidic fruits and kiwi
stereotyped symptoms typically within 0–2 hours
Soya Yeast extract
(but nearly always within 30 minutes) of ingestion,
Wheat Others
affecting the skin, gastrointestinal tract, and res-
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 The gold standard test for food allergy
shown in Table 2. 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

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. troduction of formula feeds.
The history. A detailed allergy-focused his- – The type of formula feed.
tory should focus on the following areas: • Gastrointestinal symptoms: The presence of
• Family history of atopy: The risk of atopy in gastrointestinal symptoms, such as colic, ab-
creases if a parent or sibling has atopic dis- dominal pain, vomiting, reflux, feeding aver-
ease ( 20–40% and 25–35%, respectively), and sion, diarrhoea, constipation, blood or mucus
is higher still if both parents are atopic (40– in stools, and failure to thrive, in a patient with
60%). eczema should raise the possibility of food
• Infant feeding: allergy.
– A history of breast vs formula feeding, • History of immediate reactions to specific foods:
detailing period of exclusive breastfeed- A history of immediate reactions to food is
ing, and taking into account that the onset important to ascertain. This should explore the
of severe eczema during a period of exclu- time of onset in relation to ingestion, the
sive breastfeeding may be secondary to quantity of food required to cause a reaction,

PAEDIATRICS
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 child’s 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.
• History of eczematous or gastrointestinal reac-
tions to specific foods: A history of food caus-
It is difficult to prove
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
because clinical cases
to milk- and egg-free diet, there was no corre-
lation between the parents’ suggestions that do not always
milk and/or eggs triggered their child’s eczema. correlate well
• Current diet and prior history of tolerance to
with skin prick
foods:
– Which of the main allergenic foods are in- testing and IgE levels
cluded within the current diet?
– Has there been any previous attempt to
eliminate foods from the patient’s 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
is greater in young children, infants, and those causal. The selection of allergens for testing should
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 Oral food challenges (OFCs). OFC testing
children, who will have food challenges, should first remains the gold standard for diagnosing food al-
have their asthma well controlled. lergy, and the aim is to accurately identify causative
Allergy-specific test. When the index of sus- allergens.

Oral food challenge should only be used when the child suspected dermatologist and an intensive treatment, including
of having food allergy has severe eczema. moisturizers, topical steroids, and in some cases an-
tibiotics. The aim is to gain control of their eczema-
tous inflammation so that the skin is relatively clear
at the time of challenge.
A clarification of the presence or absence of
food allergy is important, as a positive diagnosis
can empower the child and family to safely proceed
with an appropriate management plan and advice on
specific allergen avoidance. Conversely, a negative
diagnosis allows for removal of unnecessary dietary
restrictions.
DIETARY MANAGEMENT IN
CHILDREN WITH ECZEMA
Although there is a lack of robust studies on dietary

avoidance in well-defined populations of children
with eczema and food allergy, confirmed on double-
blind, placebo-controlled food challenge testing,
available studies support the concern that food al-
lergy may play an important role in severe eczema,
particularly when the onset is within the first few
months of life. Furthermore, dietary elimination of
specific food allergens proven by allergy tests and
oral provocation tests result in improvement in ec-
Only 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 allergen–specific, based on a
when needed and interpreted with care. proper diagnosis of food allergy which is reached by
Severe eczema is an indication for hospital- reviewing the allergy tests within the context of a
based OFC. comprehensive clinical allergy history.
It is imperative to achieve control of the ec- It is important to remember that the overall nu-
zema prior to challenge testing. tritional 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.

PAEDIATRICS
Current data do not support prolonged dietary Box 1. Consensus statements from the NICE guideline on atopic
eczema for children aged 0–12 years
elimination for most children with eczema. In situa-
tions where special diets are attempted, the recom-
mendation is to do so for 4–8 weeks and then return
to a normal diet to assess the efficacy of the dietary • A diagnosis of food allergy should be considered in children
intervention. A dietician should be involved during with atopic eczema who have reacted previously to a food
the process, as prolonged unsupervised dietary re- with immediate symptoms, or in infants and young children
with moderate or severe atopic eczema that has not been
strictions in children can have severe nutritional
controlled by optimum management, particularly if associated
consequences.
with gut dysmotility (colic, vomiting, altered bowel habit) or
failure to thrive.
PRACTICAL APPROACH TO SPECIFIC • A 6–8 week trial of an extensively hydrolyzed protein formula
DIETARY ALLERGEN EXCLUSION IN or amino acid formula in place of cow’s milk formula for
ECZEMA bottle-fed infants aged less than 6 months with moderate or
severe atopic eczema that has not been controlled by optimal
An approach to the dietary elimination of foods treatment with emollients and mild topical corticosteroids.
causing reactions was proposed by a European task • Children with atopic eczema who follow a cow’s milk–free
force in 2007 and a German guideline task force in diet for longer than 8 weeks should be referred for specialist
dietary advice.
2009. These parameters rely on initial treatment
• Diets based on unmodified proteins of other species’ milk (ie,
of eczema prior to dietary elimination and OFC. If
goat’s milk) or partially hydrolyzed formulas should not be
treatment of eczema leads to sustained periods of used in children with atopic eczema for the management of
eczema clearance with minimal need for topical suspected cow’s milk allergy. Diets including soya protein can
corticosteroids, no further dietary intervention is be offered to children aged 6 months or over with specialist
required unless there is a specific history of imme- 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 eczema in their children.

PROPOSED IN ECZEMA Breastfeeding. Breast milk has well docu-
mented immunologic activity, including antibod-
Maternal dietary restriction during pregnancy. ies that act to neutralize foreign proteins, protect
Dietary allergens, including peanuts, cow’s 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 cow’s milk protein formula decreases the cumulative
recommended that pregnant women pursue elimi- incidence of atopic dermatitis and cow’s milk allergy
nation diets with the aim to prevent or alleviate in the first 2 years of life. Some studies have con-

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. cow’s milk allergy may have a role in the pathogen-
• A defective skin barrier may be implicated in the development esis of eczema has led to the investigations of the
of food allergy.
use of partially and extensively hydrolyzed formulas.
• Appropriate early intervention can impact significantly on
Although there is some evidence that hydro-
eczema severity, infant growth, and quality of life.
lyzed infant formulas have a positive effect on the
• Maternal dietary restrictions during pregnancy or lactation do
not appear to have any prophylactic effect on the incidence prevention of eczema, there is no evidence that
or severity of eczema, but breastfeeding itself may reduce the these formulas offer advantages over breast milk.
incidence of eczema, especially in high-risk infants. Delayed introduction of solid foods. The
• Breastfed babies, who develop eczema and gastrointestinal World Health Organization and the Department of
disturbances, may respond to a trial of maternal dietary Public Health (UK) recommend that introduction of
exclusion of usually milk, wheat, egg and soya; but this solid foods should be delayed until 6 months of age.
should be done with the guidance of a dietician.
There is no current convincing evidence that
• Hydrolyzed formulas, although not superior to breast milk,
delaying the introduction of solid foods beyond 6
may be superior to cow’s milk formulas in preventing eczema.
months of age has a significant protective effect
• Food allergy is frequently present in a subset of patients with
severe eczema who present with symptoms in early infancy. on the development of atopic disease, including
• In those patients, avoidance of the dietary allergen is eczema. This includes delaying the introduction of
recommended provided an accurate diagnosis has been made. foods that are considered to be highly allergic, such
• Some nutritional interventions might have an effect on eczema, as fish, eggs and food containing peanut protein.
and ongoing studies provide hope for future developments. Studies of the timing of introduction of solid
foods into the infant’s diet have yielded results that
are difficult to interpret.
Essential fatty acids. In recent years, the
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 women may be important populations to target for
decreased incidence of eczema in breastfed infants supplementation with essential fatty acids.
of mothers who followed a diet that restricted milk, Probiotics. Probiotics are living microorgan-
egg or fish. isms 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

PAEDIATRICS
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. 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 FURTHER READING
antigen degradation is necessary to develop toler-
Cox H, Hourihane J. Food allergy and eczema. In: Irvine A,
ance to dietary antigens. Hoeger P, Yan A, eds. Textbook of Pediatric Dermatology.
3rd ed. Blackwell Publishing Ltd; 2011:chap 31.
Finch J, Munhutu MN, Whitaker-Worth D. Atopic dermatitis and
nutrition. Clin Dermatol 2010;28:605–614.
Guidelines for the diagnosis and management of food allergy in
the United States: report of the NIAID-Sponsored Expert
Panel. Allergy Clin Immunol 2010;6:S1–S58.
Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions
for improving established atopic eczema in adults and
The results of several children: systematic review. Allergy 2009;64:258–264.
Greer F, Sicherer S, Burks W, the Committee on Nutrition and
studies suggest that Section on Allergy and Immunology. Effects of early
nutritional interventions on the development of atopic
exclusive breastfeeding
disease in infants and children: the role of maternal
for a minimum of 4 months dietary restriction, breastfeeding, timing of introduction
of complementary foods, and hydrolyzed formulas. Pediat-
could be recommended rics 2008;121:183–191.
Muraro A, Dreborg S, Halken S, et al. Dietary prevention of aller-
as a potential method of gic diseases in infants and small children, part III: criti-
cal review of published peer-reviewed observational and
eczema prophylaxis interventional studies and final recommendations. Pediatr
Allergy Immunol 2004;15:291–307.
von Berg A, Koletzko S, Grübl A, et al. The effect of hydrolyzed
cow’s milk formula for allergy prevention in the first year
of life: the German Infant Nutritional Intervention Study,
a randomized double-blind trial. J Allergy Clin Immunol
2003;111:533–540.
The hygiene hypothesis may explain the ben-

efits of probiotic therapy at the same time that © 2011 Elsevier Ltd. Initially published in Paediatrics and Child
Health 2011;21(9):406–410.
explains the increased burden of atopic disease in
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 Houri-
creased microbial exposure, as a result of extensive hane is Professor of Paediatrics and Child Health in the Depart-
use of antiseptics and vaccinations in the developed ment of Paediatrics, Cork University Hospital, Cork, Ireland.

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
Infectious Disease in Pregnancy
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 man-
agement of any infection in pregnant women and then discuss some of the diseases in
more detail.
PHYSIOLOGICAL CHANGES
Physiological and immune changes occur in pregnancy, making women more susceptible
to infections, and these are still not fully understood. A shift from cell-mediated to
humoral immunity occurs, which may affect susceptibility to and severity of some infec-
tious diseases, including an increased incidence of certain intracellular pathogens, such
as toxoplasmosis, listeriosis, influenza, and varicella.
Urinary tract infections are more common, related to progesterone effects and me-
chanical compression by the gravid uterus, as well as higher urinary glucose and pH
facilitating bacterial growth.
Respiratory infections may be more severe for several reasons. Diaphragmatic el-
evation reduces secretion clearance and functional residual capacity, and with the in-
creased oxygen demand, reduces tolerance to hypoxia, particularly in the third trimester.
Gastric acid aspiration is more common, and increased interstitial lung water is seen,
increasing the risk of acute lung injury.

OBSTETRICS I Peer Reviewed
ANTENATAL SCREENING AND Pregnant women should take precaution to prevent toxoplasmosis
infection.
PREVENTION
Screening
Since 2003, the UK Department of Health has rec-
ommended screening for hepatitis B, human immu-
nodeficiency virus (HIV), rubella and syphilis early
in pregnancy with a single blood sample, as well as
asymptomatic bacteriuria (ASB) with a urine sam-
ple. There is currently no clear evidence of benefit
from screening for other infections, although wom-
en may request additional screening, particularly if
they have experience of health care systems over-
seas. Whilst the current guidance in the UK is not
to screen women for group B Streptococcus (GBS),
cytomegalovirus (CMV) and toxoplasmosis, each
case should be considered on an individual basis,
and consultation with local infectious diseases/
virology services may be required. For women at
high-risk for HIV, it is important to repeat the HIV
test in the third trimester. A negative test at book-
ing can be falsely reassuring, and seroconversion
during pregnancy carries a higher risk of mother-to-
child transmission.
Primary Prevention
Mothers are advised about primary prevention childhood should protect during childbearing years.
measures to avoid toxoplasmosis infection such as The single vaccine has been in place since 1970,
thorough hand washing, cooking raw meats, and and the measles-mumps-rubella (MMR) since 1988.
avoiding contact with cat litter and soil. Listeria Until recently, the UK childhood immunization rates
avoidance includes not eating unpasteurized dairy were 92%. Following the 2003 negative press cov-
products or pate and washing salads thoroughly. erage, rates dropped to 80%, although they have
started to increase again. Women planning a family
Immunization should ensure immunity.
Ideally, women should be immunized prior to con- Live varicella vaccines are available pre-preg-
ception, but there are a few situations where im- nancy, and zoster immune globulin (IG) should be
munization of a pregnant woman is indicated. Live given to pregnant women non-immune to varicella
vaccines are usually avoided though, owing to the and up to 10 days following exposure. Varicella se-
risk of fetal infection. rology is also available, although immunity is usu-
UK immunization programmes for rubella in ally assumed from the history of typical rash.

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 contraindicat-
ed in pregnancy, but their use may be appropriate
INVESTIGATION AND depending on the clinical situation. Nitrofurantoin
MANAGEMENT is generally considered safe but should be avoided
at term because of the risk of haemolytic anaemia
Principles in the neonate. There are reports of ciprofloxacin
A good history is essential, considering the preg- causing an arthropathy in animal studies, but no ad-
nancy, gestational age, prior ASB, sexually trans- verse human effects have been reported. Trimetho-
mitted infections (STIs), travel, occupation, HIV risk prim has also caused adverse effects in animals,
factors, contacts with infectious diseases, and prior so should be used with caution in pregnancy, espe-
tuberculosis (TB) infection. There may only be non- cially as it may interfere with folic acid metabolism.
specific symptoms and signs, but these are impor- It should be avoided near term when used as co-
tant to consider, as obstetric sepsis can present this trimoxazole in combination with a sulfonamide, as
way before rapid deterioration. the later can cause fetal kernicterus. Tetracyclines
Involvement of the feto-maternal multidisci- increase the risk of fulminant maternal hepatitis in
plinary team is essential, including clinical micro- the third trimester and may stain fetal teeth after
biologists/virologists/infectious diseases, local TB 20 weeks’ gestation. Chloramphenicol should be
services, and the critical care team when appropri- used with caution because of the association with
ate. With evidence of STIs, genitourinary physi- the ‘grey baby syndrome’ (characterized by cyano-
cians should be involved, and screening for other sis, flaccidity and cardiovascular collapse) when
STIs should be undertaken. used in newborn infants. Aminoglycoside use (eg,
gentamicin) risks fetal ototoxicity and should only
Antibiotic Use in Pregnancy be used if there is evidence of serious gram-neg-
In general, penicillins, cephalosporins, and mac- ative infection. Similarly, vancomycin has been as-
rolides such as erythromycin (although less data on sociated with fetal nephrotoxicity and ototoxicity.
clarithromycin) are safe. Clindamycin is also prob-
ably safe although clinical experience is limited. MATERNAL INFECTION SYNDROMES
Penicillins are only 50% protein-bound and can
cross the placenta to achieve fetal concentrations Sepsis
that are therefore 50% of maternal levels. Amoxi- Obstetric sepsis is the most important cause of UK
cillin has increased renal clearance in pregnancy, maternal mortality; in the most recent confidential
therefore theoretically higher doses are needed, enquiry, the mortality related to sepsis increased
although in clinical practice, doses are used as out- from 0.85 deaths per 100,000 mortalities in 2003–
side pregnancy. Augmentin was shown to increase 2005 to 1.13 deaths in 2006–2008, making sepsis

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 chorioamnio- uncomplicated CS, given as a single dose after cord
nitis which may follow prolonged PROM (pPROM) 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 2006–2008 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-hour- Urinary Tract Infections
ly for signs of clinical chorioamnionitis. First-line Urinary tract infections (UTIs) are divided accord-
prophylaxis for pPROM is erythromycin. Diagnosis ing to the site of bacterial proliferation into ASB,
of chorioamnionitis is suggested by fever late in cystitis, and pyelonephritis.
pregnancy, uterine tenderness, offensive vaginal ASB is defined as urine colonization greater
discharge, and fetal tachycardia. Consequences in- than 105 colony-forming units per mL on two con-
clude PROM and premature labour, increased risk of secutive clean-catch urine samples (without ni-
neonatal pneumonia, bacteraemia, meningitis, and trites or leucocytes on dipstick). It occurs in 4–7%
death. Treatment is with broad-spectrum antibiotics of pregnant women and is important to recognize,
(ampicillin and gentamicin) and delivery. as symptomatic UTIs develop in 20–40% of cases,
Endometritis is a spectrum of endometrial, and there is an increased incidence of preterm de-
myometrial and parametrial infections, all of which livery and low-birth-weight infants. This has lead to

Studies showing the prevention of urinary tract infections in ten with symptoms of cystitis. Pyelonephritis is the
pregnancy with cranberry juice ingestion are lacking.
most common cause of septic shock in pregnancy,
and adult respiratory distress syndrome (ARDS) oc-
curs in 1–8% of cases, so patients should be closely
monitored. Diagnosis is based on the presence of
significant bacteriuria following mid-stream urine
culture, and the history and clinical signs. A renal
tract ultrasound scan should be performed to ex-
clude hydronephrosis and structural abnormalities.
Organisms are similar to those in lower tract UTIs,
with E coli in 70–80%, and Klebsiella pneumonia
and Proteus species less commonly, but important
in recurrent cases. Antibiotic choice reflects local
guidelines, usually with a first-generation cephalo-
sporin or combination ampicillin with gentamicin.
Most will be afebrile and asymptomatic following
48 hours of appropriate antibiotic treatment, and
intravenous therapy is then continued until the
patient has been afebrile for 48 hours. Failure to
respond after the initial 72 hours usually indicates
a resistant organism, renal tract stone, or anatomi-
cal obstruction. When discharged home, the mother
should be more closely watched for recurrence with
UK screening being recommended (see NICE guide- monthly urine cultures. Fetal effects of untreated
lines). ASB is due to Escherichia coli in 75–90% 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 1–4% 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. Respiratory Tract Infections
The right kidney is most often affected owing to Bacterial pneumonia has a similar incidence and
dextro-rotation of the uterus. The common present- outcome in pregnancy, although viral pneumonias
ing features are fever, loin pain, rigors, and less of- are more common and run a more severe course

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–
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 – Strepto-
coccus pneumoniae. This is usually fully sensitive
to amoxicillin (with some decreased susceptibility
Primary varicella
in strains from abroad).
Influenza pneumonia – influenza infection infections are more
presents with similar self-limiting symptoms, but if severe in pregnancy,
they last more than 5 days, complications are not
and progression to
unusual. Pneumonia has a greater mortality rate (up
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, previ-

ously only associated with immunodeficiency. One At least 6% of hepatitis C–positive 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 fulmi-
nant hepatic failure where the mortality is 5%. The
Hepatitis mechanism may relate to immunologic imbalance
Viruses causing hepatitis include the hepatitis associated with a predominant T helper subtype
viruses A–E, as well as Epstein-Barr virus, CMV, 2 cell response and suppression of cell-mediated
toxoplasmosis, and herpes simplex virus. immunity seen in pregnancy. There is no specific
Overall, the clinical course of hepatitis A, B, treatment.
C and D viruses is unchanged in pregnancy, but Herpes simplex virus (usually herpes simplex
prevention of vertical transmission is important. virus type 2) can also lead to fulminant hepatic
Vertical transmission with maternal hepatitis A failure in pregnancy, often with associated pneu-
virus infection is rare, and the neonate should be monitis or encephalitis. Diagnosis is made on liver
given IG at birth. Hepatitis B virus is screened for biopsy and serology, and specific treatment for the
antenatally as the risk of vertical transmission from mother and infant with acyclovir is available.
asymptomatic mothers is high; rates are up to 95%
if mothers are hepatitis B surface antigen- and e- Rash
antigen-positive. Vertical transmission usually oc- There are comprehensive guidelines on the man-
curs at delivery and is more likely if the hepatitis B agement of rashes in pregnancy from the Health
virus infection is associated with a high viral load. Protection Agency (www.hpa.org.uk).
Several strategies including vaccination and use of The important infections to consider in the dif-
hepatitis B virus specific IG are in place to decrease ferential diagnosis include rubella, parvovirus B19,
the chance of transmission. There is sometimes a varicella, measles, enteroviruses, and infectious
need to treat newly diagnosed pregnant women mononucleosis. The first three are discussed in a
with oral anti-viral agents for her own health. All later section.
new diagnoses should be referred urgently to the Measles infection in pregnancy can lead to in-
local hepatitis service. There is clear guidance on trauterine death and preterm delivery, although not
management available through the Department of congenital infection or damage. Indigenous measles
Health Green Book (see Further Reading). is rare in the UK following introduction of the MMR

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.
vaccines are available except for poliovirus, and IG
is advised for prophylaxis in exposed neonates. Malaria
Infectious mononucleosis is caused by primary Malaria contributes significantly to maternal
Epstein-Barr virus infection with no specific risk to mortality and morbidity in the developing world. In
the fetus. the UK, 2,000 cases are reported annually, mostly
in travellers from endemic areas. Untreated falci-
SPECIFIC PATHOGENS parum malaria is life-threatening in any population,
and pregnant women are more susceptible; anaemia
Tuberculosis can be severe, and there is an increase in maternal
The UK and worldwide TB infection rates are rising. mortality, preterm birth, miscarriage, and stillbirth.
Incidence peaks in the childbearing years (25–34 Immunity to malaria is altered by pregnancy,
years). In the UK, infection is most common in especially in primiparous women with high parasite
Asian and West-African populations. Pregnancy is loads, although the risk is reduced with successive
thought not to change the course of TB, although it pregnancies. Drugs are used for prevention in en-
does increase preterm births, especially in the de- demic areas, with effective reduction in maternal
veloping world. As in the non-pregnant population, anaemia, birth weight and possibly perinatal death.
transmission of Mycobacterium tuberculosis is via In the UK, women with malaria in pregnancy should
respiratory droplets. Overall 10% of those infected be admitted as there is an increased risk of severe
(initial infection is usually asymptomatic) will de- disease and hypoglycaemia. Suitable regimes de-
velop active TB, usually 1–2 years after infection. pend on the type of malaria and local resistance
More extra-pulmonary TB is being seen with HIV patterns, and chloroquine is the choice for Plasmo-
co-infection, and 5–10% of pregnant women have dium vivax, P malariae, P ovale, and quinine for P
extra-pulmonary disease (similar to the non-preg- falciparum. All regimes should be supplemented
nant population). Pregnancy and the peri-partum with folic acid.
period is a common time for latent TB to reactivate. Malaria prophylaxis: travel to a malarial
Diagnosis is by usual methods, and tuberculin skin area in pregnancy should be avoided; getting malar-
testing is safe in pregnancy. ia whilst pregnant increases the risk of miscarriage
Management is similar to in non-pregnant pa- as well as being life-threatening to the mother. No
tients. All four first-line drugs are thought safe and antimalarial is 100% effective, and women should
have been used for many years, including etham- seek advice from a local travel clinic. There are
butol and isoniazid. Pyridoxine should be added to guidelines available on the choice of agent to use

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 in preterm labour, temperature greater than 38°C in
HIV worldwide infection is increasing. UK sero- labour, preterm PROM, ROM for more than 18 hours
prevalence in pregnant women is 0.21%, with over prior to delivery, or a previously affected child.
300 HIV-infected women giving birth annually.
There is an increased risk of preterm delivery, low-
birth-weight infants and miscarriage with maternal
HIV infection, worse in mothers with advanced
The common vaginal
disease and poor nutrition. Antenatal screening is
done routinely in the UK. commensal, group B
The mother-to-child transmission rate in the Streptococcus, can lead
UK is now less than 1%. This has been achieved
to life-threatening
through a variety of interventions, notably the use
of antiretroviral combination therapy, a multidisci- neonatal effects
plinary approach to both the timing and method of
delivery, post-exposure prophylaxis for the infant,
and an avoidance of breastfeeding. Management
of each case is highly individualized and should Chlamydia trachomatis
be done in conjunction with a team of health care Genital tract infection with Chlamydia trachomatis
professionals including a midwife, obstetrician, is common in the UK and may lead to ectopic preg-
HIV specialist, and a neonatologist and paediatric nancy, preterm labour, puerperal infection, and oph-
nurse. Some antiretroviral drugs are safe in preg- thalmia neonatorum. Erythromycin is the advised
nancy although currently very few are licensed. treatment.
Guidelines are available (see Further Reading).
Bacterial Vaginosis
Group B Streptococcus This STI, caused by Gardnerella vaginalis, may
This common vaginal commensal can lead to cause chorioamnionitis, preterm delivery, and post-
life-threatening neonatal effects. Of the 20% partum fevers. Treatment is with erythromycin or
of mothers that carry it, 40–70% of infants be- metronidazole.
come colonized in the first week of life. Neonatal
infection can be early or late, presenting with pneu- Herpes Simplex Virus
monia, sepsis, meningitis, and death in up to 10% Maternal genital herpes is more virulent in preg-
(higher in preterm infants). As the overall UK infec- nancy. Early miscarriage (but not fetal abnormali-
tion rate in infants is 1%, routine screening is not ties) may occur, and late maternal primary infec-
currently offered. Neonatal disease is reduced by tion can lead to severe neonatal infection. Genital
administration of intra-partum intravenous penicil- lesions, especially in primary infection, contain

high viral concentrations, and transmission at de- are common, seen in 80–90% 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 200–300 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
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 Varicella is also
maternal infections that can lead to congenital ab-
important to recognize
normalities. These are discussed below, and sum-
marized in Table 1. and treat in pregnancy
as maternal complications
Rubella
are more severe
Symptoms of primary maternal rubella infection fol-
low viraemia are mild and include fever, headache,
joint pains, sore throat, and a maculopapular rash
usually appearing shortly after glandular enlarge-
ment. These non-specific symptoms make clinical
diagnosis unreliable. The fetus is at high-risk of Varicella
congenital rubella syndrome from infection during Varicella is highly infectious from 2 days prior un-
maternal viraemia, and significant malformations til 5 days following the typical vesicular rash. Fe-

Table 1. Fetal risks associated with certain maternal infections
Infection Rubella Varicella Cytomegalovirus Parvovirus B19 Toxoplasmosis

Congenital Ocular defects, Fetal varicella IUGR, HSM, micro- Fetal hydrops, Hydrocephalus,
defects heart (PDA), SNHL, syndrome: skin cephaly, jaundice, IUD (1st mental retardation,
mental retardation scars, eye defects, chorioretinitis, trimester). chorioretinitis
limb hypoplasia, intracranial Rarely persistent
developmental calcification, 20% neonatal infection
delay, mortality. Late and anaemia
microcephaly microcephaly,
SNHL, and
developmental
delay (15%)
Trimester most First – abnormali- All trimesters, espe- All trimesters First trimester Malformations high-
at risk (% risk ties in 80–90% cially 13–20 weeks est in first trimester.
of defects) survivors; risk (2%) More infections near
13–16 weeks of term (2% at 8 weeks
SNHL vs 75% at term)
Maternal Arthritis Pneumonia; Asymptomatic Febrile illness, Mostly
effects increased or IM syndrome erythema asymptomatic
mortality infectiosum, or flu-like;
aplastic lymphadenopathy
anaemia
Available TOP offered ZIG to mother None Intrauterine Spiramycin (cycled
treatment and neonate. transfusion. pyrimethamine,
Acyclovir within No vaccine sulfadiazine, and
24 h of rash onset folinic acid)
for mother and for
infected neonates
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 13–20 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 5–7 days Cytomegalovirus
for passive transfer of maternal IG if possible. If Fetal CMV infection is the second most prevalent
not, the neonate should be given zoster IG, as there cause of mental retardation after Down syndrome.
is a 20% neonatal infection risk if the mother devel- Childhood infection is common in developing coun-

tries, hence leads to herd immunity, however only Practice points

50–60% of women in developed counties have
positive serology. Primary maternal infection in
adults may be asymptomatic or lead to infectious • Most maternal infections do not harm the fetus
• All rash illnesses should be referred for specialist assessment
mononucleosis-like syndrome. Primary infection,
• Maternal obstetric sepsis may present with non-specific symp-
reactivation, or reinfection with a different strain toms and signs, and run a fulminant course
of CMV may lead to intrauterine infection, although • Obstetric sepsis remains a significant cause of maternal mortal-
the fetus is rarely affected in cases of reactivation. ity and should be identified early and managed aggressively
• The investigation of infections that can affect the fetus should
Primary infection leads to transplacental fetal be appropriate for both mother and fetus, usually in or in
infection in 40% of cases, and fetal sequelae may consultation with a feto-maternal medicine unit
occur over a wide timescale. Up to 7% will present • Screening is important for HIV as interventions exist to reduce
vertical transmission
at birth with defects (see Table 1). The mortality
is 20% in this group, and a further 15% will have
abnormalities found later at follow-up.
In cases of suspected maternal infection, Toxoplasmosis
blood serology is helpful, ideally with a paired sam- Maternal infection is rare (2 per 1,000 in the UK;
ple from booking to compare rising antibody titre, more common in France), and flu-like symptoms
noting that circulating IgM may persist for months. and lymphadenopathy occur in up to 15% of in-
When confirmed, fetal infection should be proven fected women. Fetal infection probably depends on
by culture and polymerase chain reaction of amni- the gestational age at maternal seroconversion. A
otic fluid at amniocentesis. Serial fetal ultrasound French study showed that there were more congeni-
is available to identify suggestive features such as tal abnormalities (see Table 1) with early maternal
ventriculomegaly and intracranial calcification, al- infections, and more fetal infections with serocon-
though no findings are specific. It must be remem- version at term.
bered that most infected neonates will in fact be Diagnosis is confirmed by amniocentesis, cho-
unaffected. There is no specific treatment, although rionic villus sampling or fetal blood sampling, and
a vaccine is in development, and screening for ma- ultrasound findings of intracranial calcification, he-
ternal immunity is therefore not routine in the UK. patomegaly and placental thickening are late and
non-specific. Treatment with spiramycin from time
Parvovirus B19 of maternal infection may reduce fetal infection
Parvovirus B19 infection is common, with 50–60% and, therefore, congenital abnormalities. In late
of adults having been infected. Infection in the first (after 32 weeks) high-risk fetal infections, 3-week
20 weeks of pregnancy can lead to intrauterine cycled courses of pyrimethamine, sulfadiazine and
death and fetal hydrops. These consequences usu- folinic acid may be added.
ally occur 3–5 weeks after the onset of maternal
infection, but can be later. There is no evidence to Syphilis
suggest that reinfection is a risk to the fetus. No Maternal infection with the spirochaete Treponema
vaccine or preventive measures are available, and pallidum has increased in recent years. Fetal infec-
an increased incidence occurs every 3–4 years, of- tion can occur at any stage, but most often in pri-
ten in schoolchildren. mary (90%), secondary and early latent infections.

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
National Institute for Clinical Excellence. Antenatal care: routine
of amniotic fluid or fetal blood, although these have
care for the healthy pregnant woman, Clinical Guideline 6.
a poor negative predictive value. London: National Institute for Clinical Excellence; October
2003.
Hepatitis guidelines: http://www.dh.gov.uk/prod_consum_dh
Listeria monocytogenes /groups/dh_digitalassets/@dh/@en/documents/digital
Listeriosis is caused by Listeria monocytogenes, asset/dh_108820.pdf.
HIV guidelines: www.bhiva.org.
a gram-positive bacillus, and although an unusual
Mackenzie I, Lever A. Management of sepsis. BMJ
infection, may have serious adverse outcome in 2007;335:929–932.
pregnancy. There are about 20 cases of Listeria as- Malaria prophylaxis: http://www.nathnac.org/pro/misc/pdfs
/RCOGPreventionMalariaPregnancy0410.pdf.
sociated with pregnancy in the UK per year. It is Maternal mortality. Saving Mothers Lives: Reviewing maternal
food-borne, from unpasteurized dairy products, and deaths to make motherhood safer: 2006–2008. The eighth
report of the Confidential Enquiries into Maternal Deaths
pregnant women should avoid such high-risk foods.
in the UK, 118. London: BJOG; 2011:1–203.
It can survive at low temperatures (such as the Nelson-Piercy C. Handbook of Obstetric Medicine. 4th ed. Obstet
fridge) on raw vegetables, hence the importance of Med 2011;4:87. doi:10.1258/om.2011.110023.
Royal College of Obstetricians and Gynecologists. Chickenpox
washing food in pregnancy. Maternal symptoms can in pregnancy: Guideline No 17. London: RCOG; September
be asymptomatic or with flu-like symptoms, and can 2007.
Royal College of Obstetricians and Gynecologists. Genital herpes in
range from mild to severe with ARDS. The diagnosis pregnancy: Guideline No 30. London: RCOG; September 2007.
is based on a high index of clinical suspicion, and Royal College of Obstetricians and Gynecologists. HIV in preg-
nancy: Guideline No 39. London: RCOG; April 2004.
on positive Gram stain from maternal blood, liquor
Royal College of Obstetricians and Gynecologists. Preterm prela-
or neonatal samples. bour rupture of membranes: Guideline No 44. London:
Maternal infection can lead to miscarriage, RCOG; November 2006.
Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria
premature labour, and if the infant survives, to pregnancy. Cochrane Database Syst Rev 2007;(2):CD000490.
perinatal listeriosis. Congenital listeriosis has also Tookey P. Rubella in England, Scotland and Wales. Euro Surveill
2004;9:21–23.
been reported following transplacental passage
WHO guidelines for treatment of severe H1N1 influenza A:
and can lead to fetal hydrops. Treatment is with http://www.who.int/csr/resources/publications/swine
high-dose ampicillin and gentamicin. flu/h1n1_guidelines_pharmaceutical_mngt.pdf.
© 2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology

and Reproductive Medicine 2011;21(12):331–338.
CONCLUSION
About the Authors
Infections during pregnancy are usually self- Sarah Logan is a Specialist Registrar in Infectious Diseases
at Royal Free Hospital, London, UK. Laura Price is a Specialist
limiting; however, awareness is needed to iden- Registrar in Respiratory and Intensive Care Medicine at Royal
tify those leading to significant maternal and fetal Brompton Hospital, London, UK.

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:

Perinatal Types, Functions and
Case Management—
Caring forBasics for Obstetricians
Mothers as They Care
Jennifer Sze Man Mak, MBChB; Juan Bolaños, BSc (Biotechnology); Wing Cheong Leung, MBBS, MD, FRCOG, FHKCOG, FHKAM (O&G);
for Babies
Richard Boyd, BSc (Hons), PhD; Robert Kien Howe Chin, MBBS, FRCOG, FHKCOG, FHKAM (O&G)
Ch’ng Ying Chia, MA (Applied Social Studies); Jemie Biwen Wang, Bachelor of Psychology (Hons);
Helen Chen, MBBS, M Med (Psych), Dip. Psychotherapy
INTRODUCTION
There is a major unmet clinical need of millions of patients globally suffering many ma-
jor diseases, which, in all cases, severely compromise the quality of life and frequently
lead to death. While advances are being made with more traditional drug-based thera-
pies, it is now clear that a major new impetus is required. The potential revolution in sci-
ence and medicine that stem cells represent is rapidly emerging as the new frontier in
clinical therapies. Given that stem cells are ‘regenerative medicine factories’, they may
be delivered as ‘stand-alone treatments’; but more likely, they will be potent adjuvants
and be combined with current strategies. Clearly, a great deal of preclinical and clinical
research on stem cells is required not only to capitalize on their treatment potential
but also to ensure that safety and ethical requirements are met. It is also imperative to
select the most appropriate source of stem cells for the variety of treatments. Ideally,
these stem cells should be derived from the patients themselves to overcome any issues
of immune rejection. It is now evident that the time of birth is a remarkable once-in-a-
lifetime opportunity to collect and cryopreserve a panel of stem cells, which effectively
represent nature’s ‘body repair kit’ for the duration of the newborn’s life. There are also
stem cells available for maternal utility.
Once regarded as medical waste, the umbilical cord, based on extensive ground-
breaking research, has now been revealed as an invaluable source of haematopoietic
stem cells (HSCs) and pluripotent mesenchymal cells (MSCs) both of which now have
increasing application in regenerative medicine. In addition, the amnion membrane is a
very rich source of pluripotential MSCs which, being equivalent to embryonic stem cells
(ESCs), are able to differentiate into many different types of tissues.
Accordingly, these advances in stem cell research, coupled with the ever-increas-
ing clinical efficacy, have led to the fast-growing establishment of cord blood banks

Figure 1. Stages of development of human embryos. BACKGROUND (HISTORY)

OF STEM CELLS
Zygote Stem cells are one of nature’s most powerful ‘build-

ing blocks’. They have the unique ability to both
self-renew to replenish their availability and differ-
Single-cell embryo
entiate into a variety of different cell types. Hence,
they not only create the organs and tissues in the
3-day embryo
body but also maintain them and assist in the repair
following damage or disease.
Embryonic stem cells
(pluripotent) There are two broad types of stem cells: ESCs
and adult stem cells.
5- to 7-day embryo
Human ESCs
Human ESCs are isolated from 4- to 5-day-old post-
fertilized blastocysts (Figure 1). Human ESCs are
4-week embryo
capable of indefinite ex vivo proliferation and can
• Embryonic germ cells differentiate into any specialized cell in the hu-
(pluripotent) man body. Adult stem cells are located in tissues
• Fetal tissue stem cells
6-week embryo throughout the body and function as a reservoir to
(pluripotent or multipotent)
replace damaged or ageing cells;3,4 they differenti-
ate only into the cell lineage of the organ system in
worldwide, which store umbilical cord blood (UCB) which they are located (Figure 2). UCB is a source
for future use and are of either a public or private of adult stem cells, in particular MSCs (or stromal
nature. This affluence of stem cell banks started in cells), which not only have the normal capacity to
the mid to late 1990’s in response to the potential differentiate into structural tissue (bone, muscle,
use of cord blood transplants for the treatment of cartilage, fat) but also have the important property
various disorders. However, the knowledge of stem of being anti-inflammatory.5
cells and cord blood banking are scarce among ESCs have great potential in generating tis-
pregnant women as shown by many studies, while sues and organs, yet there are several major prob-
most of them would like to be informed by health lems with them. The generation of ESCs requires
care professionals specifically and especially in destruction of discarded embryos from in vitro ferti-
early pregnancy so that they would have time to lization, which is ethically challenging if it involves
contemplate the virtues or otherwise of cryopreser- destruction of life. Furthermore, by virtue of the way
vation of their babies stem cells. 1,2 This article will ESCs are produced by long-term replicative culture
therefore review the background on stems cells and in vitro, there is a major safety issue: because of
UCB banking (UCBB) as well as patients’ knowledge their rapid proliferation, ESCs form teratomas upon
on this issue, and the role of obstetricians in con- transplantation.6 Most importantly, we do not have
veying adequate information to patients. Present our own ESCs, and therefore any ESC transplant
development on stem cells will also be discussed. will be allogeneic. An accessible and ethically

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
Organ/tissue
without assistance by doctors
or hospitals • Tissue/organ-specific stem
• Non-invasive method for collection cells
• Eg, eyes, heart, lung
Bone marrow (mesenchymal

cells and haematopoietic
Fat (mesenchymal cells) 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/new-
born stem cells. This was followed by experiments
Newborn Stem Cells in irradiated mice revealing that murine blood from
Given the difficulty in settling the dilemmas as- near-term and neonatal mice contained adequate
sociated with the use of human ESCs legally, with numbers of HSCs to effect bone marrow recovery.7

Obstetricians can educate pregnant women about umbilical cord blood banking.
The first pioneering haematopoietic cord blood 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, 8
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. 9
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-
12
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

cell transplants by its residual T lymphocytes in the and 90% expected their obstetrician to answer
haematopoietic progenitor cell product. 15
their questions on UCBB.18 Similar results were also
UCB as a source of HSC for transplant is more reported by Fernandez et al1 and Dinç 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 child’s 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 PATIENT’S KNOWLEDGE OF 93.3% completed the questionnaire. The majority
STEM CELLS AND UCBB (78.2%) had no idea about the chance of using self-
stored stem cells. Most were unclear about which
In 2003, Fernandez et al examined pregnant wom-
1
diseases other than leukaemia are amenable to
en’s 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 birthday—the 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
17
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. 1
providers, especially their obstetricians, and be
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.
Among patients familiar with UCBB, only 2.6% felt THE OBSTETRICIAN’S 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
pense and insufficient knowledge. Only 14% were
educated about UCBB by the nurse or obstetrician, Given this background, it is imperative that the ob-

stetrician be well educated of the pros and cons of Indication

stem cells so that appropriate advice to expecting HSC use is recommended especially in at-risk fami-
parents can be given. lies for which there is a known genetic or haema-
tological disease amenable to HSC transplantation
Advantages and Disadvantages of Cord for the affected child if HLA-compatible.25
Haematopoietic Progenitor Cells
Being an alternative to bone marrow as a source of Collection
HSCs for allergenic transplantation, cord blood has There are two techniques of cord blood collection:
both advantages and disadvantages.21,22 in vivo with placenta in utero, and in vitro with pla-
The advantages are as follows: centa ex utero.
• Faster availability: patients on average receive A comparison of the two techniques has
cord blood transplantation earlier than those shown larger unit volumes and higher total nucleat-
receiving conventional bone marrow grafts 23 ed cells counts with in vivo collection.26 It is recom-
• Ethnic diversity allows extension of donor pool: mended that collection should be done by a trained
with a greater tolerability of HLA mismatch, third party (ie, not by the attending obstetrician or
this allows a higher availability of specimen midwife) using methods and facilities appropriate
for transplantation to meet the European Tissues and Cells Directive.
• As a result of greater tolerability of HLA mis- The collection procedure must be undertaken ei-
match, there is lower incidence and severity of ther during the third stage or shortly after, a time
acute graft-versus-host disease with a relative when there is a risk of postpartum haemorrhage. 21
risk of 0.66 24 It is not guaranteed that sufficient volume can be
• Lower incidence of viral transmission, ie, cyto- collected; successful transplantation of cord blood
megalovirus and Epstein-Barr virus HSCs is related to the volume and cell dose col-
• No donor attrition compared with bone marrow lected. Stringent antiseptic technique is needed to
registry avoid bacterial contamination.27
• High proliferative capacity
• Painless collection of stem cells Ethical Issues
The disadvantages are as follows: The use of stem cells has generated lots of debate
• Low numbers of haematopoietic progenitor on bioethics, focusing on the principle of autonomy.
cells and stem cells (approximately 10% of a It is suggested that the cord blood belongs to the
marrow transplant12) in each cord blood unit, property of the child, as the placenta or cord blood
which may delay engraftment; this is hereby stem cells is biologically and genetically developed
addressed by experimental procedures like ex by the child. 28,29 On the other hand, one would sug-
vivo expansion of the cells and use of multiple gest that it is the mother’s property once the cord
UCB units in the same recipient to expand the is cut. However, legal rights of property are not
progenitor pool generally founded on genetic identity. Although
• Inability to obtain addition stem cells and/ based on the ontological status of the fetus, once
or lymphocytes from the graft donor for second it is outside the mother’s body, it is recognized as
transplantation in case of graft failure or dis- a legal individual by law but is unable to have full
ease relapse understanding and thus unable to give consent.

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 child’s 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
21
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
individual’s 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-
dicated. Details of the hospital’s policy should be
made available to all patients.
Cost and Choice of Banking

A report by the Broxmeyer et al, in a study, suggested that UCB can
Institute of Medicine be frozen and stored for at least 15 years with high-
ly efficient recovery of viable and highly functional
has recommended that
human stem cells.33 Data suggested that longer-
cord blood centres term storage is feasible and does not compromise
the quality of the engraftment ability of UCB unit. 34
establish clear policies as
The great therapeutic potential of UCB and the
to who must provide demonstration of the feasibility of cryopreserving
consent for donation with collected units and their utility for up to 15 or more
years led to the development of cord blood banks. A
consideration of paternal
cord blood bank is an establishment for collection,
objection to donation processing, and storage of cord blood. There has
and for public cord been an emergence of public and private banking in
the past two decades.
blood banking.
Public banks, being community-based, pro-
mote allogeneic donation of both related and unre-
lated cord blood, which is subsequently accessible
by the general population. Patients should be in-
Consent formed that they relinquish property rights to the
Obstetricians should not be obligated to obtain con- cord blood units after donation.
sent for private UCBB.31 Private banks, which are commercially based,
A report by the Institute of Medicine has rec- store cord blood for autologous use with cost as-
ommended that cord blood centres establish clear sociated with specimen processing and storage for
policies as to who must provide consent for dona- the harvested cord blood as a family biological in-

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 Immu-
nology 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 • Richest source of newborn stem cells
of burns since many years ago • High requirement for extraction technology
• It can form soft tissue, such as skin and
cornea, and have the potential to differenti-
ate into hepatic, pancreatic and neural cells
• High requirement for extraction technology
surance, which can also be used for other family cipient could have developed these disorders.
members. 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. 32
mately 1 in 20,000 28 to 37 in 100,000 (1 in 2,700).20
In public banks, the donated cord blood is not
assured of being banked or being made available Regulatory Issues
to donors if required in the future. Safety is a con- To establish a uniform standard for collection and
cern as the donated cord blood may carry genetic quality assurance, it is important that establish-
defects for disorders, such as congenital anaemia ments provide standardization of procurement, test-
or immunodeficiency, that are not apparent in the ing, processing, storage, distribution, documenta-
donor for months or years, by which time all iden- tion, labelling, equipment control, and cord blood
tifying information has been removed while the re- bank operations.

In the United Kingdom, cord blood collection 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
Lung fibrosis, chronic obstructive pulmonary disease37,38
agreement is required. The HTA stresses on four
Heart and vascular damage39
aspects of cord blood collection: safety, quality, Spinal disc injury40
consent, and lawfulness. The HTA does not regu- Suppress graft-versus-host disease in allogeneic bone marrow
late or provide advice about the effectiveness of transplant
Inhibit autoimmunity, eg, multiple sclerosis, diabetes, arthritis41
treatments using cord blood.36 Ageing tissues: tendon, muscle, cartilage, bone (hips, joints)42
In the United States, many cord blood banks 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-inflamma-
tory 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 (Wharton’s 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

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 informa-
tion to the public.
About the Authors
Dr Mak is Resident Trainee in the Department of Obstetrics and
CONCLUSION
Gynaecology, Kwong Wah Hospital, Hospital Authority, Hong
Kong. Mr Juan Bolaños is Research Fellow at ProStemCell Ltd,
This article reviews the current trends in UCB stor- Hong Kong. Dr Leung is Chief of Service in the Department of
Obstetrics and Gynaecology, Kwong Wah Hospital, Hospital
age, as well as recent consensus in the ethical and Authority, Hong Kong. Dr Boyd is Professor and Director in
commercial activities related to private and public the Monash Immunology and Stem Cell Laboratories, Monash
University, Australia. Dr Chin is Honorary Consultant in the
UCBB. Adult stem cells offer a new and realistic Department of Obstetrics and Gynaecology, Kwong Wah Hospi-
approach for the treatment of diseases, without the tal, Hospital Authority, Hong Kong.
References
1. Fernandez CV, Gordon K, Van den Hof M, of umbilical-cord blood or bone marrow from un- Outcomes after transplantation of cord blood or preservation and storage on transplant outcome.
Taweel S, Baylis F. Knowledge and attitudes of related donors in adults with acute leukemia. N bone marrow from unrelated donors in adults American Society of Hematology 49th Annual
pregnant women with regard to collection, test- Engl J Med 2004;351:2276–2285. with leukemia. N Engl J Med 2004;351:2265– Meeting and Exposition; December 8–11, 2007;
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2003;168:695–698. Nat Med 1998;4:150–151. 25. Hows JM. Status of umbilical cord blood 35. Fisk NM, Roberts IA, Markwald R, Mironov
2. Dinç H, Sahin NH. Pregnant women’s knowl- 14. Greaves MF, Wiemels J. Origins of chromo- transplantation in the year 2001. J Clin Pathol V. Can routine commercial cord blood banking be
edge and attitudes about stem cells and cord some translocations in childhood leukaemia. Nat 2001;54:428–434. scientifically and ethically justified? PLoS Med
blood banking. Int Nurs Rev 2009;56:250–256. Rev Cancer 2003;3:639–649. 26. Solves P, Moraga R, Saucedo E, et al. Com- 2005;2:e44.
3. van der Kooy D, Weiss S. Why stem cells? Sci- 15. Johnson FL. Placental blood transplantation parison between two strategies for umbilical 36. Stem cells and cord blood. Human Tissue Au-
ence 2000;287:1439–1441. and autologous banking—caveat emptor. J Pedi- cord blood collection. Bone Marrow Transplant thority Web site. http://www.hta.gov.uk/licensin
4. Pittenger MF, Mackay AM, Beck SC, et al. Mul- atr Hematol Oncol 1997;19:183–186. 2003;31:269–273. gandinspections/sectorspecificinformation/stem
tilineage potential of adult human mesenchymal 16. Rainaut M, Pagniez M, Hercend T, Daffos F, 27. Armitage S, Warwick R, Fehily D, Navarrete C, cellsandcordblood.cfm. Updated November 2010.
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siderations. J Islam Med Assoc N Am North Hum Immunol 1987:18:331–337. 1999;24:139–145. rogates lung fibrosis and augments repair. Am J
America 2010;42. http://jima.imana.org/article 17. Kline RM. Whose blood is it, anyway? Sci Am 28. Annas GJ. Waste and longing—the legal Respir Crit Care Med 2010;182:643–651.
/view/5197. 2001:284:42–49. status of placental-blood banking. N Engl J Med 38. Murphy S, Lim R, Dickinson H, et al. Human
6. Sell S. Stem Cells Handbook. New Jersey: Hu- 18. Perlow JH. Patients’ knowledge of umbilical 1999;340:1521–1524. amnion epithelial cells prevent bleomycin-in-
mana Press; 2004. cord blood banking. J Reprod Med 2006;51:642– 29. Munzer SR. The special case of property duced lung injury and preserve lung function. Cell
7. Broxmeyer HE, Kurtzberg J, Gluckman E, et 648. rights in umbilical cord blood for transplantation. Transplant 2011;20:909–923.
al. Umbilical cord blood hematopoietic stem and 19. Sugarman J, Kurtzberg J, Box TL, Horner Rutgers Law Rev 1999;51:493–568. 39. Minguell JJ, Erices A. Mesenchymal stem
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tion. Blood Cells 1991;17:313–329. bilical cord blood banking. Am J Obstet Gynecol storage and use: ethical issues. Blood Transfus Biol Med (Maywood) 2006;231:39–49.
8. Gluckman E, Broxmeyer HA, Auerbach AD, et 2002;187:1642–1646. 2010;8:139–148. 40. Goldschlager T, Jenkin G, Ghosh P, Zannettino
al. Hematopoietic reconstitution in a patient with 20. Work Group on Cord Blood Banking. Cord 31. Committee on Obstetric Practice; Committee A, Rosenfeld JV. Potential applications for using
Fanconi’s anemia by means of umbilical-cord blood banking for potential future transplanta- on Genetics. ACOG Committee Opinion No. 399: stem cells in spine surgery. Curr Stem Cell Res
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9. Kurtzberg J, Graham M, Casey J, Olson J, Ste- 21. Royal College of Obstetricians and Gynae- 32. Institute of Medicine. Cord blood: establish- toimmune disease by stem-cell transplantation.
vens CE, Rubinstein P. The use of umbilical cord cologists. Umbilical cord blood banking. Scien- ing a national hematopoietic stem cell bank Nature 2005;435:620–627.
blood in mismatched related and unrelated he- tific Advisory Committee Opinion Paper 2, revised program. Institute of Medicine Web site. http:// 42. Bruder SP, Fink DJ, Caplan AI. Mesenchymal
mopoietic stem cell transplantation. Blood Cells June 2006. Available at: http://www.rcog.org.uk www.iom.edu/Reports/2005/Cord-Blood-Estab stem cells in bone development, bone repair,
1994;20:275–283. /files/rcog-corp/uploaded-files/SAC2Umbilical lishing-a-National-Hematopoietic-Stem-Cell- and skeletal regeneration therapy. J Cell Bio-
10. Lansdorp PM, Dragowska W, Mayani H. CordBanking2006.pdf. Bank-Program.aspx. chem 1994;56:283–294.
Ontogeny-related changes in proliferative po- 22. Moise KJ Jr. Umbilical cord stem cells. Obstet 33. Broxmeyer HE, Srour EF, Hangoc G, et al. High- 43. Quintero AJ, Wright VJ, Fu FH, Huard J. Stem
tential of human hematopoietic cells. J Exp Med Gynecol 2005;106:1393–1407. efficiency recovery of functional hematopoietic cells for the treatment of skeletal muscle injury.
1993:178:787–791. 23. Barker JN, Krepski TP, DeFor TE, Davies SM, progenitor and stem cells from human cord blood Clin Sports Med 2009;28:1–11.
11. Hao QL, Shah AJ, Thiemann FT, Smogorze- Wagner JE, Weisdorf DJ. Searching for unrelated cryopreserved for 15 years. Proc Natl Acad Sci 44. Zhang Y, Li C, Jiang X, et al. Human placenta-
wska EM, Crooks GM. A functional comparison of donor hematopoietic stem cells: availability and USA 2003;100:645–650. derived mesenchymal progenitor cells support
CD34+CD38– cells in cord blood and bone marrow. speed of umbilical cord blood versus bone marrow. 34. Scaradavou A, Stevens CE, Dobrila L, Sung D, culture expansion of long-term culture-initiating
Blood 1995;86:3745–3753. Biol Blood Marrow Transplant 2002;8:257–260. Rubinstein P. National Cord Blood Program. “Age” cells from cord blood CD34+ cells. Exp Hematol
12. Rocha V, Labopin M, Sanz G, et al. Transplants 24. Laughlin MJ, Eapen M, Rubinstein P, et al. of cord blood (CB) unit: impact of long-term cryo- 2004;32:657–664.

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 :
1 Mengejar pertumbuhan bayi normal.
Bayi BBLR memiliki Kejar Tumbuh Rekomendasi SGM BBLR

Energi ESPGHAN1 110-135 kkal/kg/hari 120 kkal/kg/hari
kesempatan untuk Protein ESPGHAN1 3-3,6 g/100 kkal 3,1 g/100 kkal
Rasio Whey : Kasein 60 : 40
tumbuh kembang Asam Amino Esensial Codex Alimentarius2 11 jenis AAE 12 jenis AAE
optimal di periode
Mendukung perkembangan otak yang
emasnya 2 sesuai dengan tahapan usianya.
Perkembangan Otak Rekomendasi SGM BBLR

Rasio AA : DHA ESPGHAN1 1-2 : 1 1 : 1, 0,2% TFA
Kolin ESPGHAN1 7-50 mg/100 kkal 20 mg/100 kkal
LA : ALA ESPGHAN1 10-15 : 1 15 : 1
3 Mempermudah pencernaan dalam absorbsi.
Mudah Diserap Rekomendasi SGM BBLR

MCT ESPGHAN1 < 40% TFA 34% TFA
Maltodekstrin 100%
4 Pembentukan sel darah.
Pembentukan Sel Darah Rekomendasi SGM BBLR

Level Zat Besi 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.
1. ESPGHAN 2010
2. Codex Alimentarius 2007
Continuing Medical Education
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 op-
timally suited to pregnancy. Therefore,
it seems logical that care should begin
before conception. Most women do not
visit the obstetricians before pregnancy
has been confirmed. Family doctors or Family planning is an important part of preconception care.
other primary health care providers are
in a better position to provide precon-
ception care. Some of the preconcep- OBJECTIVES OF tries, maternal deaths are associated
tion care can even be introduced in the PRECONCEPTION CARE with high multiparity and closely spaced
community and in schools, in the form pregnancies.1 In developed countries, es-
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.
the effectiveness of commonly practised
preconception care will be examined PLANNED PARENTHOOD DIETARY AND VITAMIN
in this article. A practical checklist for SUPPLEMENTATION
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 concep-
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
also offspring of women with previous af- GOOD PRACTICE IN DRUG in recurrence of epileptic attacks, which
fected babies, and women on antiepileptic PRESCRIBING is even more detrimental than antiepi-
drugs (high-risk).3 For low-risk women, 400 leptic drugs to the mother and the baby.
µg 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 pregnant.
dence of neural tube defect has been found not to prescribe unless necessary and Category X drugs are those that have
in thalassaemia trait carriers. It is logical
4
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 µg 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
5
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. 3
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. 7
efits from use in pregnant women may be are safe for pregnancy, even if they do not

suspect that they are pregnant. PREVENTION OF INFECTIONS HAART (highly active antiretroviral ther-
apy with multiple agents) together with
AVOIDANCE OF IRRADIATION 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,
Diagnostic X-ray should be avoided during 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-
9
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 TREATMENT FOR OBESITY
ADVICE AGAINST LIFESTYLE proportion of cases. Vaccination against
SUBSTANCE USE chickenpox in susceptible women before It has increasingly been shown that obe-
pregnancy can be an option. 13
sity has adverse effects on pregnancy.
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
10
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.
Cigarette smoking is not teratogenic Screening for HIV and syphilis are Therefore, weight reduction should ideally
but doubles the risk of intrauterine growth part of routine antenatal care. However, be achieved before pregnancy.17
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- ATTENTION TO DENTAL
Women should be encouraged and be nancy. This also allows time for contact HYGIENE
helped to stop smoking before pregnancy. tracing and for more effective prevention
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 reduc-

ing premature deliveries. Effectiveness of WOMEN AND MEN WITH
post transplantation, should be referred
treatment before pregnancy in improving to a maternal medicine specialist for pre- MALIGNANT DISEASES
pregnancy outcome has not been stud- conception care. Preconception care for
ied. Provision of dental care as part of
19
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
CERVICAL SCREENING control. Therefore, achieving good gly-
21
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 SCREENING FOR GENETIC
of heavy bleeding and are generally not expectation. 22 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-
20
tension. any genetic disease before pregnancy is
vasive disease is detected, full treatment only advisable if (1) the particular genetic
cannot be given without terminating the WOMEN WITH MAJOR disease is common in the population, (2)
pregnancy. Therefore, screening before PSYCHIATRIC DISEASES reliable screening methods are avail-
pregnancy is more ideal than screening able, and (3) the affected individual has
during pregnancy. Women with major depression, bipolar poor quality of life or a major handicap.
disorders and schizophrenia should be An example is α- and β-thalassaemia in
WOMEN WITH MEDICAL under the care of a psychiatrist to ensure Southeast Asia. In Hong Kong, the prev-
DISEASES that the disease is well controlled before alence of α-thalassaemia carriers and
pregnancy. Many psychotropic drugs are β-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 α- and β-thalassaemia
es, renal diseases, cardiac diseases and mother and the baby. trait. 24 (However, it does not exclude car-

riers of haemoglobin E, which is preva- Preconception care checklist for primary care physicians
lent in Thailand, and haemoglobin E–β-
thalassaemia heterozygous may have History
transfusion-dependent anaemia.) Further • Family history, including genetic diseases
investigations, such as haemoglobin pat- • Past health
tern analysis and DNA studies may be • Past obstetric history, including all pregnancy losses
needed after excluding iron deficiency. • Use of alcohol, cigarette, and recreational drugs
• Psychological readiness for pregnancy and child rearing
Iron deficiency can be excluded by iron
profile studies, but a simple and practi-
Physical examination
cal way to exclude iron deficiency is a • Weight and height
therapeutic trial of iron supplement for 4 • Blood pressure
weeks. If red cell microcytosis is due to • Urine (for glucose and albumin)
iron deficiency alone, it should be cor- • Examination of the cardiovascular system
rected by supplement. Which genetic dis-
Investigations
eases to screen for and how they should
• Rubella immune status
be screened for should be determined to • Varicella immune status (if no known history of chickenpox or varicella zoster)
suit the local population. In general, it • Hepatitis B surface antigen (HBsAg)
is important that a screening test should • HIV screening
have a high sensitivity with a low false- • Syphilis screening
positive rate. There is some controversy • Complete blood count (to screen for anaemia and thalassaemia)
as to whether screening should be done • Cervical smear (if not already in a screening programme)
before or during pregnancy. If prenatal

Advice and treatment
diagnosis is readily available and accept- • Contraception advice if needed
able to the couple and early antenatal care • Provide necessary vaccinations
is accessible, antenatal screening may be • Body weight control if needed
more cost-effective than preconception • Folic acid supplementation if planning to get pregnant
screening. Preconception screening has • Appropriate use of drugs, avoid unnecessary drugs
the advantage of allowing more time for • Avoid unnecessary irradiation
• Cessation of smoking, drinking, or recreational drugs
couples to understand and consider the
options of prenatal diagnosis before the Referrals
pregnancy. Screening for genetic diseas- • Most couples do not need referrals to specialists
es, whether before pregnancy or during • Refer to obstetricians or fetomaternal medicine specialists
pregnancy, should only be done with in- ~ Women with significant medical illnesses or poor obstetric history
formed consent. Individuals should not be • Refer to medical geneticist
coerced into undergoing genetic testing or ~ 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 woman’s broth- potential parent has a genetic disease), Many tests to confirm the diagnosis and

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-
26
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-
nosis, if available, can be an option if they fully taken history. The box on page 174 is
are known to carry mutations which may SUMMARY a summary of this review and can be used
affect the baby. 25
as a checklist for primary care physicians
Preconception care can be provided in in providing preconception care.
WOMEN WITH BAD primary health care. Doctors should also
OBSTETRIC HISTORY be aware that whenever they are treating
About the Author
women in the reproductive age group, they
Dr Lee is Consultant in the Department of Obstetrics
Women with recurrent miscarriages (three are treating someone who may be preg- and Gynaecology, University of Hong Kong, Queen Mary
or more) in the first trimester, one or more nant or may become pregnant in the near Hospital, Hong Kong.
References
1. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van 8. Rayburn WF, Amanze AC. Prescribing medica- 15. European Collaborative Study. Mother-to- Ratner RE. Preconception care of diabetes, congeni-
Look PF. WHO analysis of causes of maternal death: tions safely during pregnancy. Med Clin North Am child transmission of HIV Infection in the era of tal malformations, and spontaneous abortions.
a systematic review. Lancet 2006;367:1066–1074. 2008;92:1227–1237. highly active antiretroviral therapy. Clin Infect Dis Diabetes Care 1996;19:514–541.
2. Nybo Anderson AM, Wohlfahrt J, Christens P, 9. Valentin J. ICRP Publication 84: Pregnancy and 2005;40:458–465. 22. Tieu J, Middleton P, Crowther CA. Preconcep-
Olsen J, Melbye M. Maternal age and fetal loss: Medical Radiation. Annals of the ICRP Volume 30/1. 16. Nuthalapaty FS, Rouse DJ. The impact of tion care for diabetic women for improving mater-
population based register linkage study. BMJ Elsevier 2000;1–39. obesity on obstetrical practice and outcome. Clin nal and infant health. Cochrane Database Syst Rev
2000;320:1708–1712. 10. Royal College of Obstetricians and Gynaecolo- Obstet Gynecol 2004;47:898–913. 2010;(12):CD007776.
3. De-Regil LM, Fernandez-Gaxiolo AC, Dowsell gists. Alcohol consumption and outcomes of preg- 17. Davies GA, Maxwell C, McLeod L, et al; Society 23. Schmidt KT, Rosendahl M, Ernst E, et al. Auto-
T, Pena-Rosas JP. Effects and safety of pericon- nancy. RCOG Statement No. 5; 2006. of Obstetricians and Gynaecologists of Canada. transplantation of cryopreserved ovarian tissue in
ceptional folate supplementation for prevent- 11. Walsh RA. Effects of maternal smoking on SOGC clinical practice guidelines: obesity in preg- 12 women with chemotherapy-induced premature
ing birth defects. Cochrane Database Syst Rev adverse pregnancy outcomes: examination of the nancy. No. 239, February 2010. Int J Gynecol Obstet
ovarian failure: the Danish experience. Fertil Steril
2010;(10):CD007950. criteria of causation. Hum Biol 1994;66:1059–1092. 2010;110:167–173.
2011;95:695–701.
4. Lam YH, Tang MH. Risk of neural tube defects in 12. Draper ES, Rankin J, Tonks AM, et al. Recre- 18. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP,
24. Lau YL, Chan LC, Chan YY, et al. Prevalence and
the offspring of thalassaemia carriers in Hong Kong ational drug use: a major risk factor for gastroschi- Goldenberg RL, Hauth JC. Periodontal infection and
genotypes of alpha- and beta-thalassemia carriers
Chinese. Prenat Diagn 1999;19:1135–1137. sis? Am J Epidemiol 2008;167:485–491. preterm birth: results of a prospective study. J Am
13. Royal College of Obstetricians and Gynaeco- Dent Assoc 2001;132:875–880. in Hong Kong—implications for population screen-
5. Blencowe H, Cousens S, Modell B, Lawn J. Folic
acid to reduce neonatal mortality from neural tube logists. Chickenpox in pregnancy. RCOG Green-top 19. Polyzos NP, Polyzos IP, Zavos A, et al. Obstetric ing. N Engl J Med 1997;336:1298–1301.
disorders. Int J Epidemiol 2010;39(Suppl 1):i110– Guideline No. 13; 2007. outcomes after treatment of periodontal disease 25. Geraedts JP, De Wert GM. Preimplantation
i121. 14. Wong VC, Ip HM, Reesink HW, et al. Preven- during pregnancy: systematic review and meta- genetic diagnosis. Clin Genet 2009;76:315–325.
6. Finglas PM, de Meer K, Molloy A, et al. Research tion of the HBsAg carrier state in newborn infants analysis. BMJ 2010;341:c7017. 26. Cowchock FS, Reece EA, Balaban D, Branch
goals for folate and related B vitamin in Europe. Eur of mothers who are chronic carriers of HBsAg and 20. Fader AN, Alward EK, Neiderhauser A, et DW, Plouffe L. Repeated fetal losses associated
J Clin Nutr 2006;60:287–294. HBeAg by administration of hepatitis-B vaccine al. Cervical dysplasia in pregnancy: a multi- with antiphospholipid antibodies: a collabora-
7. Rothman KJ, Moore LL, Singer MR, Nguyen US, and hepatitis-B immunoglobulin. Double-blind institutional evaluation. Am J Obstet Gynecol tive randomized trial comparing prednisone with
Mannino S, Milunsky A. Teratogenicity of high vita- randomised placebo-controlled study. Lancet 2010;203:113.e1–e6. low-dose heparin treatment. Am J Obstet Gynecol
min A intake. N Engl J Med 1995;333:1369–1373. 1984;323:921–926. 21. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, 1992;166:1318–1323.

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.
P
Artikel CME: 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 JPOG NOV/DEC 2012 • 263

JPOG 2012 Annual Index
Section First Author Issue Page
Gynaecology
Analgesia, analgesics, combined oral contraceptives, diagnosis, dysmenorrhoea, physiopathology Clinical Review Kolhe S Jul/Aug 147
Anovulation, ovulation induction Clinical Review Yeung WYT Jan/Feb 5
Atopobium, bacterial vaginosis, biofilms, Gardnerella, metronidazole Clinical Review Hay P Mar/Apr 60
Chronic pain, dysmenorrhoea, endometriosis, pelvic pain Clinical Review Raffi F May/Jun 93
Contraceptive agents, contraceptive failure, intrauterine devices, postcoital contraception,

CME Li HWR Jul/Aug 169
unplanned pregnancy
Early detection of cancer, ovarian neoplasms, randomized controlled trial CME Chan KKL Mar/Apr 81
Hormone replacement therapy, risks and benefits Clinical Review Farrell E Jul/Aug 157
Obstetrics
Abruptio placentae, antepartum haemorrhage, caesarean section, Doppler ultrasonography,
Clinical Review Athanasias PK Sep/Oct 193
placenta praevia, resuscitation
Acute fatty liver of pregnancy, HELLP syndrome, hepatitis, hyperemesis gravidarum, inflammatory
Clinical Review Cuckson C May/Jun 105
bowel diseases, obstetric cholestasis, pancreatitis, pregnancy
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,
CME Lee CP Nov/Dec 257
vaccination
Four-dimensional ultrasonography, three-dimensional ultrasonography, obstetrics CME Lau B Sep/Oct 213
Paediatrics
Adolescent, child, diabetic ketoacidosis, haemoglobin A1c, hypoglycaemia, type 1 diabetes mellitus Clinical Review Shulman RM Mar/Apr 49
Analgesics, child, diagnosis, headache, migraine disorders, prevention and control Clinical Review McShane MA Jul/Aug 164
Anaphylaxis, child, food hypersensitivity, immediate hypersensitivity Clinical Review Joshi P Jan/Feb 26
Atopic dermatitis, emollients, food allergy, topical calcineurin inhibitors, topical corticosteroids Clinical Review Shekariah T Mar/Apr 68
Biological therapy, child, Psoriasis Area and Severity Index, plaque, paediatric psoriasis Clinical Review Sharma V Jul/Aug 137
Child, differential diagnosis, limping, primary health care Clinical Review Cox A May/Jun 117
Child, genetic testing, hydroxymethylglutaryl-CoA reductase inhibitors, hyperlipidaemias,

Clinical Review Datta BN Sep/Oct 202
hyperlipoproteinaemia type II
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
JPOG Nov/Dec 2012 • 264
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JAN/FEB 2012

Infectious Disease in Pregnancy

Newborn Stem Cells: Types,

221 • Hormonal contraception and cardiovascular risk

Editorial Board Professor Biran Affandi Dr Tak-Yeung Leung Dr Raman Subramaniam

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225 Dietary Intervention in Eczema

234 Infectious Disease in Pregnancy

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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

264 2012 Annual Index

Review Articles Case Studies

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Diperkaya dengan AA dan DHA

The Safe Motherhood Initiative begun in 1987 has

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Morris RK et al. Diagnostic accuracy of spot urinary protein and albumin

detect significant proteinuria in

Reducing measles mortality

One global goal was to halve measles deaths be-

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The increased prevalence of obesity in children and Zidovudine, lamivudine, and

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Violari A et al. Nevirapine versus ritonavir-boosted lopinavir for HIV-

Neonatal screening with pulse

Babies with congenital heart defects may be dis-

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Your FREE gift* with any

Subscription to MIMS Contact Details

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Type of Practice*: ❏ GP ❏ Dentist ❏ Pharmacist ❏ Nurse

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

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Although there is a lack of robust studies on dietary

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allergy (Box 1).

OTHER DIETARY STRATEGIES eczema in their children.

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Practice points method of eczema prophylaxis, at least for mothers

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The hygiene hypothesis may explain the ben-

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