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JOURNAL WATCH
PAEDIATRICS
Dietary Intervention
in Eczema
OBSTETRICS
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CME ARTICLE
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224 Neonatal screening with pulse oximetry for critical congenital heart
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Oral immunotherapy for egg allergy in children
224
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Chinese University of Hong Kong
Dr Raman Subramaniam
Fetal Medicine and Gynaecology Centre, Malaysia
Professor SC Ng
National University of Singapore
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Chulalongkorn University, Thailand
Professor PC Wong
National University of Singapore
Dr George SH Yeo
KK Womens and Childrens Hospital, Singapore
Dr Kwok-Yin Leung
The University of Hong Kong
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247 Newborn Stem Cells: Types, Functions and Basics for Obstetricians
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Infectious Disease in Pregnancy
2012 UBM Medica
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GYNAECOLOGY
Hormonal contraception and
cardiovascular risk
Journal Watch
of complications.
cardial infarction.
Although hormonal contraception may in-
crease the risks of thrombotic stroke and myocardial infarction, the absolute risks are low. An editorialist concludes that they are safe enough.
Lidegaard et al. Thrombotic stroke and myocardial infarction with
hormonal contraception. NEJM 2012; 366: 22572266; Petitti DB.
Hormonal contraceptives and arterial thrombosis not risk-free but safe
enough. Ibid: 23162318 (editorial).
Effect of contraception on
maternal mortality rates
The Safe Motherhood Initiative begun in 1987 has
four strategies to reduce maternal mortality: family
planning, antenatal care, safe delivery, and postnatal care. Now, the effects of contraceptive use on
maternal mortality worldwide have been estimated
from three international databases.
monal contraception.
JPOG_NovDec_2012_COMBINE.indd 221
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OBSTETRICS
Urinary protein-to-creatinine or
albumin-to-creatinine ratio to
detect significant proteinuria in
pregnancy
PAEDIATRICS
rates.
eclampsia.
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Journal Watch
was improved.
JPOG_NovDec_2012_COMBINE.indd 223
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results.
The results were better with the ritonavirboosted lopinavir-based regimen, but these re-
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PAEDIATRICS
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Imaging Paediatric
Brain Tumours
Dietary Intervention
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 manifestation of a systemic disorder that also gives rise to asthma, food allergy, and allergic
rhinitis. It is a common, chronic, pruritic, and relapsing inflammatory dermatosis that
typically manifests during early childhood.
The current prevalence of eczema in developed countries is about 20%, representing a twofold to threefold increase during the past decades. The reason for this increase
remains unclear.
PATHOGENESIS
The pathophysiology of eczema is not yet fully understood. An interaction between
genetic and environmental factors has been implicated in the predisposition and
development of the disease. Eczema is associated with abnormalities in genes encoding skin barrier molecules (filaggrin), markers, and cells of the inflammatory response;
immunoregulatory abnormalities; increased serum immunoglobulin E (IgE); impaired
delayed hypersensitivity reaction; and infectious agents.
Research has demonstrated that a combination of food allergy, defects in the gut
mucosal barrier, and increased intestinal permeability may be complicit in the pathogenesis of eczema. Therefore, dietary manipulation could be of use in controlling or preventing the disease, but this still remains controversial.
It is important to remember that food allergy and eczema coexist due to their common origins as manifestations of an allergic diathesis, but that one may not automatically
be implicated as a cause of the others.
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allergy.
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IgE-mediated
IgE/non-IgE-mediated
Non-IgE-mediated
Immediate
food allergy/
Anaphylaxis
Oral allergy
syndrome
Eczema
Allergic eosinophilic
gastritis
Allergic eosinophilic
gastroenteritis
Food proteininduced
enterocolitis
Food proteininduced
proctitis
Food proteininduced
enteropathy
Coeliac disease
Eczema
Infancyadolescence
Usually infancy
eczema (Table 1). Therefore, it is important to understand the natural history and clinical presentation of
food allergy in order to make or refute a diagnosis of
such in patients with eczema.
IgE-mediated reactions to specific foods cause
stereotyped symptoms typically within 02 hours
(but nearly always within 30 minutes) of ingestion,
affecting the skin, gastrointestinal tract, and res-
Food-allergic triggers
of eczema
Milk
Egg
Peanut
Soya
Wheat
Tomato
Citrus
Acidic fruits and kiwi
Yeast extract
Others
flare of eczema.
imposed on children.
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The diagnosis of food allergy in children with eczema includes taking a detailed allergy-focused history.
The history. A detailed allergy-focused history should focus on the following areas:
Family history of atopy: The risk of atopy in
creases if a parent or sibling has atopic dis ease ( 2040% and 2535%, respectively), and
is higher still if both parents are atopic (40
60%).
Infant feeding:
A history of breast vs formula feeding,
detailing period of exclusive breastfeed ing, and taking into account that the onset
of severe eczema during a period of exclu sive breastfeeding may be secondary to
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PAEDIATRICS
cient s everity to cause anaphylaxis. It is neces- low, the tests are useful for ruling out a diagnosis of
PAEDIATRICS
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It is difficult to prove
do not always
correlate well
years.
asthma.
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Oral food challenge should only be used when the child suspected
of having food allergy has severe eczema.
DIETARY MANAGEMENT IN
CHILDREN WITH ECZEMA
Although there is a lack of robust studies on dietary
avoidance in well-defined populations of children
with eczema and food allergy, confirmed on doubleblind, placebo-controlled food challenge testing,
available studies support the concern that food allergy may play an important role in severe eczema,
particularly when the onset is within the first few
months of life. Furthermore, dietary elimination of
specific food allergens proven by allergy tests and
oral provocation tests result in improvement in ecOnly children with severe eczema with a histo-
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tions where special diets are attempted, the recommendation is to do so for 48 weeks and then return
to a normal diet to assess the efficacy of the dietary
tolerance.
in the first 2 years of life. Some studies have conJPOG NOV/DEC 2012 231
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Practice points
cows milk allergy may have a role in the pathogenesis of eczema has led to the investigations of the
use of partially and extensively hydrolyzed formulas.
Although there is some evidence that hydrolyzed infant formulas have a positive effect on the
prevention of eczema, there is no evidence that
these formulas offer advantages over breast milk.
Delayed introduction of solid foods. The
World Health Organization and the Department of
Public Health (UK) recommend that introduction of
solid foods should be delayed until 6 months of age.
There is no current convincing evidence that
delaying the introduction of solid foods beyond 6
months of age has a significant protective effect
on the development of atopic disease, including
eczema. This includes delaying the introduction of
foods that are considered to be highly allergic, such
as fish, eggs and food containing peanut protein.
Studies of the timing of introduction of solid
foods into the infants diet have yielded results that
are difficult to interpret.
Essential fatty acids. In recent years, the
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FURTHER READING
Cox H, Hourihane J. Food allergy and eczema. In: Irvine A,
Hoeger P, Yan A, eds. Textbook of Pediatric Dermatology.
3rd ed. Blackwell Publishing Ltd; 2011:chap 31.
Finch J, Munhutu MN, Whitaker-Worth D. Atopic dermatitis and
nutrition. Clin Dermatol 2010;28:605614.
Guidelines for the diagnosis and management of food allergy in
the United States: report of the NIAID-Sponsored Expert
Panel. Allergy Clin Immunol 2010;6:S1S58.
Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions
for improving established atopic eczema in adults and
children: systematic review. Allergy 2009;64:258264.
Greer F, Sicherer S, Burks W, the Committee on Nutrition and
Section on Allergy and Immunology. Effects of early
nutritional interventions on the development of atopic
disease in infants and children: the role of maternal
dietary restriction, breastfeeding, timing of introduction
of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121:183191.
Muraro A, Dreborg S, Halken S, et al. Dietary prevention of allergic diseases in infants and small children, part III: critical review of published peer-reviewed observational and
interventional studies and final recommendations. Pediatr
Allergy Immunol 2004;15:291307.
von Berg A, Koletzko S, Grbl A, et al. The effect of hydrolyzed
cows milk formula for allergy prevention in the first year
of life: the German Infant Nutritional Intervention Study,
a randomized double-blind trial. J Allergy Clin Immunol
2003;111:533540.
The hygiene hypothesis may explain the benefits of probiotic therapy at the same time that
explains the increased burden of atopic disease in
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Langkah
selanjutnya
adalah
pemberian
nutrisi.
nyeri dada.
akan
sembuh
sendiri
(self-limiting),
Penanganan regurgitasi
Pemberian ASI tetap dilanjutkan, karena kejadian
regurgitasi pada bayi yang mendapat ASI lebih sedikit
dibandingkan dengan bayi yang mendapatkan susu
formula.
dipertimbangkan
untuk
memberikan
farmakoterapi.
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.
PAEDIATRICS
OBSTETRICS
OBSTETRICS
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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 management of any infection in pregnant women and then discuss some of the diseases in
more detail.
PHYSIOLOGICAL CHANGES
Physiological and immune changes occur in pregnancy, making women more susceptible
to infections, and these are still not fully understood. A shift from cell-mediated to
humoral immunity occurs, which may affect susceptibility to and severity of some infectious diseases, including an increased incidence of certain intracellular pathogens, such
as toxoplasmosis, listeriosis, influenza, and varicella.
Urinary tract infections are more common, related to progesterone effects and mechanical compression by the gravid uterus, as well as higher urinary glucose and pH
facilitating bacterial growth.
Respiratory infections may be more severe for several reasons. Diaphragmatic elevation reduces secretion clearance and functional residual capacity, and with the increased oxygen demand, reduces tolerance to hypoxia, particularly in the third trimester.
Gastric acid aspiration is more common, and increased interstitial lung water is seen,
increasing the risk of acute lung injury.
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Screening
Since 2003, the UK Department of Health has recommended screening for hepatitis B, human immunodeficiency virus (HIV), rubella and syphilis early
in pregnancy with a single blood sample, as well as
asymptomatic bacteriuria (ASB) with a urine sample. There is currently no clear evidence of benefit
from screening for other infections, although women may request additional screening, particularly if
they have experience of health care systems overseas. Whilst the current guidance in the UK is not
to screen women for group B Streptococcus (GBS),
cytomegalovirus (CMV) and toxoplasmosis, each
case should be considered on an individual basis,
and consultation with local infectious diseases/
virology services may be required. For women at
high-risk for HIV, it is important to repeat the HIV
test in the third trimester. A negative test at booking can be falsely reassuring, and seroconversion
during pregnancy carries a higher risk of mother-tochild transmission.
Primary Prevention
Mothers are advised about primary prevention
measures to avoid toxoplasmosis infection such as
thorough hand washing, cooking raw meats, and
avoiding contact with cat litter and soil. Listeria
avoidance includes not eating unpasteurized dairy
products or pate and washing salads thoroughly.
Immunization
Ideally, women should be immunized prior to conception, but there are a few situations where immunization of a pregnant woman is indicated. Live
vaccines are usually avoided though, owing to the
risk of fetal infection.
UK immunization programmes for rubella in
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culating strains.
Other antibiotics are relatively contraindicated in pregnancy, but their use may be appropriate
INVESTIGATION AND
MANAGEMENT
Principles
A good history is essential, considering the pregnancy, gestational age, prior ASB, sexually transmitted infections (STIs), travel, occupation, HIV risk
factors, contacts with infectious diseases, and prior
tuberculosis (TB) infection. There may only be nonspecific symptoms and signs, but these are important to consider, as obstetric sepsis can present this
way before rapid deterioration.
Involvement of the feto-maternal multidisciplinary team is essential, including clinical microbiologists/virologists/infectious diseases, local TB
services, and the critical care team when appropriate. With evidence of STIs, genitourinary physicians should be involved, and screening for other
STIs should be undertaken.
be used if there is evidence of serious gram-negative infection. Similarly, vancomycin has been associated with fetal nephrotoxicity and ototoxicity.
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or septic shock.
pneumonia.
Antepartum infections include chorioamnionitis which may follow prolonged PROM (pPROM)
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to pregnancy.
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partum.
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gation.
Primary varicella
infections are more
severe in pregnancy,
and progression to
varicella pneumonia
is more common
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perinatally.
final trimester.
third trimester, with 15% of cases leading to fulminant hepatic failure where the mortality is 5%. The
Hepatitis
Viruses causing hepatitis include the hepatitis
viruses AE, as well as Epstein-Barr virus, CMV,
toxoplasmosis, and herpes simplex virus.
Overall, the clinical course of hepatitis A, B,
C and D viruses is unchanged in pregnancy, but
prevention of vertical transmission is important.
Vertical transmission with maternal hepatitis A
virus infection is rare, and the neonate should be
given IG at birth. Hepatitis B virus is screened for
antenatally as the risk of vertical transmission from
asymptomatic mothers is high; rates are up to 95%
if mothers are hepatitis B surface antigen- and eantigen-positive. Vertical transmission usually occurs at delivery and is more likely if the hepatitis B
virus infection is associated with a high viral load.
Several strategies including vaccination and use of
hepatitis B virus specific IG are in place to decrease
the chance of transmission. There is sometimes a
need to treat newly diagnosed pregnant women
with oral anti-viral agents for her own health. All
new diagnoses should be referred urgently to the
local hepatitis service. There is clear guidance on
management available through the Department of
Health Green Book (see Further Reading).
Rash
There are comprehensive guidelines on the management of rashes in pregnancy from the Health
Protection Agency (www.hpa.org.uk).
The important infections to consider in the differential diagnosis include rubella, parvovirus B19,
varicella, measles, enteroviruses, and infectious
mononucleosis. The first three are discussed in a
later section.
Measles infection in pregnancy can lead to intrauterine death and preterm delivery, although not
congenital infection or damage. Indigenous measles
is rare in the UK following introduction of the MMR
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preterm delivery.
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SPECIFIC PATHOGENS
Tuberculosis
The UK and worldwide TB infection rates are rising.
Incidence peaks in the childbearing years (2534
years). In the UK, infection is most common in
Asian and West-African populations. Pregnancy is
thought not to change the course of TB, although it
does increase preterm births, especially in the developing world. As in the non-pregnant population,
transmission of Mycobacterium tuberculosis is via
respiratory droplets. Overall 10% of those infected
(initial infection is usually asymptomatic) will develop active TB, usually 12 years after infection.
More extra-pulmonary TB is being seen with HIV
co-infection, and 510% of pregnant women have
extra-pulmonary disease (similar to the non-pregnant population). Pregnancy and the peri-partum
period is a common time for latent TB to reactivate.
Diagnosis is by usual methods, and tuberculin skin
testing is safe in pregnancy.
Management is similar to in non-pregnant patients. All four first-line drugs are thought safe and
have been used for many years, including ethambutol and isoniazid. Pyridoxine should be added to
Malaria
Malaria contributes significantly to maternal
mortality and morbidity in the developing world. In
the UK, 2,000 cases are reported annually, mostly
in travellers from endemic areas. Untreated falciparum malaria is life-threatening in any population,
and pregnant women are more susceptible; anaemia
can be severe, and there is an increase in maternal
mortality, preterm birth, miscarriage, and stillbirth.
Immunity to malaria is altered by pregnancy,
especially in primiparous women with high parasite
loads, although the risk is reduced with successive
pregnancies. Drugs are used for prevention in endemic areas, with effective reduction in maternal
anaemia, birth weight and possibly perinatal death.
In the UK, women with malaria in pregnancy should
be admitted as there is an increased risk of severe
disease and hypoglycaemia. Suitable regimes depend on the type of malaria and local resistance
patterns, and chloroquine is the choice for Plasmodium vivax, P malariae, P ovale, and quinine for P
falciparum. All regimes should be supplemented
with folic acid.
Malaria prophylaxis: travel to a malarial
area in pregnancy should be avoided; getting malaria whilst pregnant increases the risk of miscarriage
as well as being life-threatening to the mother. No
antimalarial is 100% effective, and women should
seek advice from a local travel clinic. There are
guidelines available on the choice of agent to use
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first trimester.
Chlamydia trachomatis
Genital tract infection with Chlamydia trachomatis
is common in the UK and may lead to ectopic pregnancy, preterm labour, puerperal infection, and ophthalmia neonatorum. Erythromycin is the advised
treatment.
Bacterial Vaginosis
This STI, caused by Gardnerella vaginalis, may
cause chorioamnionitis, preterm delivery, and postpartum fevers. Treatment is with erythromycin or
metronidazole.
Herpes Simplex Virus
Maternal genital herpes is more virulent in pregnancy. Early miscarriage (but not fetal abnormalities) may occur, and late maternal primary infection can lead to severe neonatal infection. Genital
lesions, especially in primary infection, contain
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diagnosis is limited.
Peer Reviewed
Varicella is also
important to recognize
and treat in pregnancy
as maternal complications
Rubella
Symptoms of primary maternal rubella infection follow viraemia are mild and include fever, headache,
joint pains, sore throat, and a maculopapular rash
usually appearing shortly after glandular enlargement. These non-specific symptoms make clinical
diagnosis unreliable. The fetus is at high-risk of
congenital rubella syndrome from infection during
maternal viraemia, and significant malformations
Varicella
Varicella is highly infectious from 2 days prior until 5 days following the typical vesicular rash. FeJPOG NOV/DEC 2012 243
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Infection
Rubella
Varicella
Cytomegalovirus
Parvovirus B19
Toxoplasmosis
Congenital
defects
Ocular defects,
Fetal varicella
heart (PDA), SNHL, syndrome: skin
mental retardation scars, eye defects,
limb hypoplasia,
developmental
delay,
microcephaly
Fetal hydrops,
Hydrocephalus,
IUD (1st
mental retardation,
trimester).
chorioretinitis
Rarely persistent
neonatal infection
and anaemia
Trimester most
at risk (% risk
of defects)
First trimester
Maternal
effects
Arthritis
Pneumonia;
increased
mortality
Asymptomatic
or IM syndrome
Mostly
asymptomatic
or flu-like;
lymphadenopathy
Available
treatment
TOP offered
ZIG to mother
and neonate.
Acyclovir within
24 h of rash onset
for mother and for
infected neonates
None
Febrile illness,
erythema
infectiosum,
aplastic
anaemia
Intrauterine
transfusion.
No vaccine
Spiramycin (cycled
pyrimethamine,
sulfadiazine, and
folinic acid)
HSM = hepatosplenomegaly; IM = infectious mononucleosis; IUGR = intrauterine growth retardation; PDA = patent ductus arteriosus; SNHL = sensorineural hearing loss; TOP = termination of pregnancy; ZIG = zoster
immune globulin.
Cytomegalovirus
Fetal CMV infection is the second most prevalent
cause of mental retardation after Down syndrome.
Childhood infection is common in developing coun-
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Practice points
Parvovirus B19
Parvovirus B19 infection is common, with 5060%
of adults having been infected. Infection in the first
20 weeks of pregnancy can lead to intrauterine
death and fetal hydrops. These consequences usually occur 35 weeks after the onset of maternal
infection, but can be later. There is no evidence to
suggest that reinfection is a risk to the fetus. No
vaccine or preventive measures are available, and
an increased incidence occurs every 34 years, often in schoolchildren.
Toxoplasmosis
Maternal infection is rare (2 per 1,000 in the UK;
more common in France), and flu-like symptoms
and lymphadenopathy occur in up to 15% of infected women. Fetal infection probably depends on
the gestational age at maternal seroconversion. A
French study showed that there were more congenital abnormalities (see Table 1) with early maternal
infections, and more fetal infections with seroconversion at term.
Diagnosis is confirmed by amniocentesis, chorionic villus sampling or fetal blood sampling, and
ultrasound findings of intracranial calcification, hepatomegaly and placental thickening are late and
non-specific. Treatment with spiramycin from time
of maternal infection may reduce fetal infection
and, therefore, congenital abnormalities. In late
(after 32 weeks) high-risk fetal infections, 3-week
cycled courses of pyrimethamine, sulfadiazine and
folinic acid may be added.
Syphilis
Maternal infection with the spirochaete Treponema
pallidum has increased in recent years. Fetal infection can occur at any stage, but most often in primary (90%), secondary and early latent infections.
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FURTHER READING
Listeria monocytogenes
Listeriosis is caused by Listeria monocytogenes,
a gram-positive bacillus, and although an unusual
infection, may have serious adverse outcome in
pregnancy. There are about 20 cases of Listeria associated with pregnancy in the UK per year. It is
food-borne, from unpasteurized dairy products, and
pregnant women should avoid such high-risk foods.
It can survive at low temperatures (such as the
fridge) on raw vegetables, hence the importance of
washing food in pregnancy. Maternal symptoms can
be asymptomatic or with flu-like symptoms, and can
range from mild to severe with ARDS. The diagnosis
is based on a high index of clinical suspicion, and
on positive Gram stain from maternal blood, liquor
or neonatal samples.
Maternal infection can lead to miscarriage,
premature labour, and if the infant survives, to
perinatal listeriosis. Congenital listeriosis has also
been reported following transplacental passage
and can lead to fetal hydrops. Treatment is with
high-dose ampicillin and gentamicin.
CONCLUSION
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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
for Babies
Chng Ying Chia, MA (Applied Social Studies); Jemie Biwen Wang, Bachelor of Psychology (Hons);
Helen Chen, MBBS, M Med (Psych), Dip. Psychotherapy
INTRODUCTION
There is a major unmet clinical need of millions of patients globally suffering many major diseases, which, in all cases, severely compromise the quality of life and frequently
lead to death. While advances are being made with more traditional drug-based therapies, it is now clear that a major new impetus is required. The potential revolution in science and medicine that stem cells represent is rapidly emerging as the new frontier in
clinical therapies. Given that stem cells are regenerative medicine factories, they may
be delivered as stand-alone treatments; but more likely, they will be potent adjuvants
and be combined with current strategies. Clearly, a great deal of preclinical and clinical
research on stem cells is required not only to capitalize on their treatment potential
but also to ensure that safety and ethical requirements are met. It is also imperative to
select the most appropriate source of stem cells for the variety of treatments. Ideally,
these stem cells should be derived from the patients themselves to overcome any issues
of immune rejection. It is now evident that the time of birth is a remarkable once-in-alifetime opportunity to collect and cryopreserve a panel of stem cells, which effectively
represent natures body repair kit for the duration of the newborns life. There are also
stem cells available for maternal utility.
Once regarded as medical waste, the umbilical cord, based on extensive groundbreaking research, has now been revealed as an invaluable source of haematopoietic
stem cells (HSCs) and pluripotent mesenchymal cells (MSCs) both of which now have
increasing application in regenerative medicine. In addition, the amnion membrane is a
very rich source of pluripotential MSCs which, being equivalent to embryonic stem cells
(ESCs), are able to differentiate into many different types of tissues.
Accordingly, these advances in stem cell research, coupled with the ever-increasing clinical efficacy, have led to the fast-growing establishment of cord blood banks
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Zygote
BACKGROUND (HISTORY)
OF STEM CELLS
Stem cells are one of natures most powerful building blocks. They have the unique ability to both
self-renew to replenish their availability and differ-
Single-cell embryo
5- to 7-day embryo
4-week embryo
6-week embryo
Human ESCs
Human ESCs are isolated from 4- to 5-day-old postfertilized blastocysts (Figure 1). Human ESCs are
capable of indefinite ex vivo proliferation and can
differentiate into any specialized cell in the human body. Adult stem cells are located in tissues
throughout the body and function as a reservoir to
replace damaged or ageing cells;3,4 they differentiate only into the cell lineage of the organ system in
which they are located (Figure 2). UCB is a source
of adult stem cells, in particular MSCs (or stromal
cells), which not only have the normal capacity to
differentiate into structural tissue (bone, muscle,
cartilage, fat) but also have the important property
of being anti-inflammatory.5
ESCs have great potential in generating tissues and organs, yet there are several major problems with them. The generation of ESCs requires
destruction of discarded embryos from in vitro fertilization, which is ethically challenging if it involves
destruction of life. Furthermore, by virtue of the way
ESCs are produced by long-term replicative culture
in vitro, there is a major safety issue: because of
their rapid proliferation, ESCs form teratomas upon
transplantation.6 Most importantly, we do not have
our own ESCs, and therefore any ESC transplant
will be allogeneic. An accessible and ethically
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Figure 2. The cell lineage of each organ system in the human body.
Organ/tissue
Tissue/organ-specific stem
cells
Eg, eyes, heart, lung
thereby highlighting research on placental/newborn stem cells. This was followed by experiments
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Obstetricians can educate pregnant women about umbilical cord blood banking.
11
12
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15
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17
Given this background, it is imperative that the obJPOG NOV/DEC 2012 251
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Indication
HSC use is recommended especially in at-risk families for which there is a known genetic or haematological disease amenable to HSC transplantation
for the affected child if HLA-compatible.25
Collection
There are two techniques of cord blood collection:
in vivo with placenta in utero, and in vitro with placenta ex utero.
A comparison of the two techniques has
shown larger unit volumes and higher total nucleated cells counts with in vivo collection.26 It is recommended that collection should be done by a trained
third party (ie, not by the attending obstetrician or
midwife) using methods and facilities appropriate
to meet the European Tissues and Cells Directive.
The collection procedure must be undertaken either during the third stage or shortly after, a time
when there is a risk of postpartum haemorrhage. 21
It is not guaranteed that sufficient volume can be
collected; successful transplantation of cord blood
HSCs is related to the volume and cell dose collected. Stringent antiseptic technique is needed to
avoid bacterial contamination.27
Ethical Issues
The use of stem cells has generated lots of debate
on bioethics, focusing on the principle of autonomy.
It is suggested that the cord blood belongs to the
property of the child, as the placenta or cord blood
stem cells is biologically and genetically developed
by the child. 28,29 On the other hand, one would suggest that it is the mothers property once the cord
is cut. However, legal rights of property are not
generally founded on genetic identity. Although
based on the ontological status of the fetus, once
it is outside the mothers body, it is recognized as
a legal individual by law but is unable to have full
understanding and thus unable to give consent.
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OBSTETRICS
use, then the mother will hold in trust till the child
21
Peer Reviewed
A report by the
Institute of Medicine
has recommended that
cord blood centres
establish clear policies as
to who must provide
consent for donation with
consideration of paternal
objection to donation
and for public cord
blood banking.
Consent
Obstetricians should not be obligated to obtain consent for private UCBB.31
A report by the Institute of Medicine has recommended that cord blood centres establish clear
policies as to who must provide consent for dona-
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Figure 3. A variety of progenitor cells in umbilical cord, cord blood, amnion, and placenta/chorion.
period.
32
Regulatory Issues
To establish a uniform standard for collection and
quality assurance, it is important that establishments provide standardization of procurement, testing, processing, storage, distribution, documentation, labelling, equipment control, and cord blood
bank operations.
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CD34 + cells.44
FUTURE DEVELOPMENT
cells in the body and have strong anti-inflammatory properties, and can be considered for repair
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of ESCs.
CONCLUSION
This article reviews the current trends in UCB storage, as well as recent consensus in the ethical and
commercial activities related to private and public
UCBB. Adult stem cells offer a new and realistic
approach for the treatment of diseases, without the
References
1. Fernandez CV, Gordon K, Van den Hof M,
Taweel S, Baylis F. Knowledge and attitudes of
pregnant women with regard to collection, testing and banking of cord blood stem cells. CMAJ
2003;168:695698.
2. Din H, Sahin NH. Pregnant womens knowledge and attitudes about stem cells and cord
blood banking. Int Nurs Rev 2009;56:250256.
3. van der Kooy D, Weiss S. Why stem cells? Science 2000;287:14391441.
4. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal
stem cells. Science 1999;284:143147.
5. Fadel H. Cord blood banking: ethical considerations. J Islam Med Assoc N Am North
America 2010;42. http://jima.imana.org/article
/view/5197.
6. Sell S. Stem Cells Handbook. New Jersey: Humana Press; 2004.
7. Broxmeyer HE, Kurtzberg J, Gluckman E, et
al. Umbilical cord blood hematopoietic stem and
repopulating cells in human clinical transplantation. Blood Cells 1991;17:313329.
8. Gluckman E, Broxmeyer HA, Auerbach AD, et
al. Hematopoietic reconstitution in a patient with
Fanconis anemia by means of umbilical-cord
blood from an HLA-identical sibling. N Engl J Med
1989;321:11741178.
9. Kurtzberg J, Graham M, Casey J, Olson J, Stevens CE, Rubinstein P. The use of umbilical cord
blood in mismatched related and unrelated hemopoietic stem cell transplantation. Blood Cells
1994;20:275283.
10. Lansdorp PM, Dragowska W, Mayani H.
Ontogeny-related changes in proliferative potential of human hematopoietic cells. J Exp Med
1993:178:787791.
11. Hao QL, Shah AJ, Thiemann FT, Smogorzewska EM, Crooks GM. A functional comparison of
CD34+CD38 cells in cord blood and bone marrow.
Blood 1995;86:37453753.
12. Rocha V, Labopin M, Sanz G, et al. Transplants
of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N
Engl J Med 2004;351:22762285.
13. Rowley JD. Backtracking leukemia to birth.
Nat Med 1998;4:150151.
14. Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat
Rev Cancer 2003;3:639649.
15. Johnson FL. Placental blood transplantation
and autologous bankingcaveat emptor. J Pediatr Hematol Oncol 1997;19:183186.
16. Rainaut M, Pagniez M, Hercend T, Daffos F,
Forestier F. Characterization of mononuclear cell
subpopulations in normal fetal peripheral blood.
Hum Immunol 1987:18:331337.
17. Kline RM. Whose blood is it, anyway? Sci Am
2001:284:4249.
18. Perlow JH. Patients knowledge of umbilical
cord blood banking. J Reprod Med 2006;51:642
648.
19. Sugarman J, Kurtzberg J, Box TL, Horner
RD. Optimization of informed consent for umbilical cord blood banking. Am J Obstet Gynecol
2002;187:16421646.
20. Work Group on Cord Blood Banking. Cord
blood banking for potential future transplantation: subject review. American Academy of Pediatrics. Pediatrics 1999;104:116118.
21. Royal College of Obstetricians and Gynaecologists. Umbilical cord blood banking. Scientific Advisory Committee Opinion Paper 2, revised
June 2006. Available at: http://www.rcog.org.uk
/files/rcog-corp/uploaded-files/SAC2Umbilical
CordBanking2006.pdf.
22. Moise KJ Jr. Umbilical cord stem cells. Obstet
Gynecol 2005;106:13931407.
23. Barker JN, Krepski TP, DeFor TE, Davies SM,
Wagner JE, Weisdorf DJ. Searching for unrelated
donor hematopoietic stem cells: availability and
speed of umbilical cord blood versus bone marrow.
Biol Blood Marrow Transplant 2002;8:257260.
24. Laughlin MJ, Eapen M, Rubinstein P, et al.
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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
Kejar Tumbuh
Rekomendasi
Energi
ESPGHAN1
110-135 kkal/kg/hari 120 kkal/kg/hari
ESPGHAN1
3-3,6 g/100 kkal 3,1 g/100 kkal
Protein
60 : 40
Rasio Whey : Kasein
12 jenis AAE
Asam Amino Esensial Codex Alimentarius2 11 jenis AAE
Perkembangan Otak
Rasio AA : DHA
Kolin
LA : ALA
ESPGHAN1
ESPGHAN1
ESPGHAN1
MCT
Maltodekstrin
1-2 : 1
1 : 1, 0,2% TFA
7-50 mg/100 kkal 20 mg/100 kkal
10-15 : 1
15 : 1
Rekomendasi
ESPGHAN1
SGM BBLR
34% TFA
100%
SGM BBLR
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.
ESPGHAN 2010
Codex Alimentarius 2007
SGM BBLR
Mudah Diserap
1.
2.
SGM BBLR
Preconception Care
Lee Chin Peng, MBBS, FRCOG, FHKAM(O&G)
INTRODUCTION
Pregnancy is usually confirmed after
the missed menstrual period, a few
weeks after the conception. In early
pregnancy, the embryo is susceptible
to teratogens. Furthermore, the health
of the pregnant woman may not be optimally suited to pregnancy. Therefore,
it seems logical that care should begin
before conception. Most women do not
visit the obstetricians before pregnancy
has been confirmed. Family doctors or
OBJECTIVES OF
tion care can even be introduced in the PRECONCEPTION CARE
these.
PLANNED PARENTHOOD
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the anaemia.
usually prescribed.
pregnant.
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PREVENTION OF INFECTIONS
HAART (highly active antiretroviral therapy with multiple agents) together with
AVOIDANCE OF IRRADIATION
Diagnostic X-ray should be avoided during
the pregnancy.
13
from alcohol.
10
11
ATTENTION TO DENTAL
HYGIENE
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expectation. 22
19
CERVICAL SCREENING
21
tension.
20
during pregnancy.
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History
Physical examination
Investigations
Referrals
Most couples do not need referrals to specialists
Refer to obstetricians or fetomaternal medicine specialists
~ Women with significant medical illnesses or poor obstetric history
Refer to medical geneticist
~ Couple with suspected genetic diseases or are potential carriers
screening.
It is also a good practice to obtain a
genetic history from couples planning to
JPOG_NovDec_2012_CME_ID.indd 261
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26
SUMMARY
25
References
1. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van
Look PF. WHO analysis of causes of maternal death:
a systematic review. Lancet 2006;367:10661074.
2. Nybo Anderson AM, Wohlfahrt J, Christens P,
Olsen J, Melbye M. Maternal age and fetal loss:
population based register linkage study. BMJ
2000;320:17081712.
3. De-Regil LM, Fernandez-Gaxiolo AC, Dowsell
T, Pena-Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev
2010;(10):CD007950.
4. Lam YH, Tang MH. Risk of neural tube defects in
the offspring of thalassaemia carriers in Hong Kong
Chinese. Prenat Diagn 1999;19:11351137.
5. Blencowe H, Cousens S, Modell B, Lawn J. Folic
acid to reduce neonatal mortality from neural tube
disorders. Int J Epidemiol 2010;39(Suppl 1):i110
i121.
6. Finglas PM, de Meer K, Molloy A, et al. Research
goals for folate and related B vitamin in Europe. Eur
J Clin Nutr 2006;60:287294.
7. Rothman KJ, Moore LL, Singer MR, Nguyen US,
Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med 1995;333:13691373.
8. Rayburn WF, Amanze AC. Prescribing medications safely during pregnancy. Med Clin North Am
2008;92:12271237.
9. Valentin J. ICRP Publication 84: Pregnancy and
Medical Radiation. Annals of the ICRP Volume 30/1.
Elsevier 2000;139.
10. Royal College of Obstetricians and Gynaecologists. Alcohol consumption and outcomes of pregnancy. RCOG Statement No. 5; 2006.
11. Walsh RA. Effects of maternal smoking on
adverse pregnancy outcomes: examination of the
criteria of causation. Hum Biol 1994;66:10591092.
12. Draper ES, Rankin J, Tonks AM, et al. Recreational drug use: a major risk factor for gastroschisis? Am J Epidemiol 2008;167:485491.
13. Royal College of Obstetricians and Gynaecologists. Chickenpox in pregnancy. RCOG Green-top
Guideline No. 13; 2007.
14. Wong VC,Ip HM,Reesink HW, et al.Prevention of the HBsAg carrier state in newborn infants
of mothers who are chronic carriers of HBsAg and
HBeAg by administration of hepatitis-B vaccine
and hepatitis-B immunoglobulin. Double-blind
randomised placebo-controlled study. Lancet
1984;323:921926.
15. European Collaborative Study. Mother-tochild transmission of HIV Infection in the era of
highly active antiretroviral therapy. Clin Infect Dis
2005;40:458465.
16. Nuthalapaty FS, Rouse DJ. The impact of
obesity on obstetrical practice and outcome. Clin
Obstet Gynecol 2004;47:898913.
17. Davies GA, Maxwell C, McLeod L, et al; Society
of Obstetricians and Gynaecologists of Canada.
SOGC clinical practice guidelines: obesity in pregnancy. No. 239, February 2010. Int J Gynecol Obstet
2010;110:167173.
18. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP,
Goldenberg RL, Hauth JC. Periodontal infection and
preterm birth: results of a prospective study. J Am
Dent Assoc 2001;132:875880.
19. Polyzos NP, Polyzos IP, Zavos A, et al. Obstetric
outcomes after treatment of periodontal disease
during pregnancy: systematic review and metaanalysis. BMJ 2010;341:c7017.
20. Fader AN, Alward EK, Neiderhauser A, et
al. Cervical dysplasia in pregnancy: a multiinstitutional evaluation. Am J Obstet Gynecol
2010;203:113.e1e6.
21. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA,
Ratner RE. Preconception care of diabetes, congenital malformations, and spontaneous abortions.
Diabetes Care 1996;19:514541.
22. Tieu J, Middleton P, Crowther CA. Preconception care for diabetic women for improving maternal and infant health. Cochrane Database Syst Rev
2010;(12):CD007776.
23. Schmidt KT, Rosendahl M, Ernst E, et al. Autotransplantation of cryopreserved ovarian tissue in
12 women with chemotherapy-induced premature
ovarian failure: the Danish experience. Fertil Steril
2011;95:695701.
24. Lau YL, Chan LC, Chan YY, et al. Prevalence and
genotypes of alpha- and beta-thalassemia carriers
in Hong Kongimplications for population screening. N Engl J Med 1997;336:12981301.
25. Geraedts JP, De Wert GM. Preimplantation
genetic diagnosis. Clin Genet 2009;76:315325.
26. Cowchock FS, Reece EA, Balaban D, Branch
DW, Plouffe L. Repeated fetal losses associated
with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with
low-dose heparin treatment. Am J Obstet Gynecol
1992;166:13181323.
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CME Questions
Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh Medical Progress Institute,
sebuah institusi yang didedikasikan untuk pembelajaran CME, bekerjasama dengan Ikatan Dokter
Indonesia.
Setelah membaca artikel Preconception Care, jawab pertanyaan berikut kemudian kirimkan dengan
menggunakan formulir jawaban yang sudah disediakan ke CME Medical Progress/ Journal of Paediatrics,
Obstetrics & Gynaecology, untuk mendapatkan 3 SKP.
Artikel CME:
P
3 SK
Preconception Care
Jawab pertanyaan di bawah ini dengan Benar atau Salah
1. Preconception folic acid supplement use prevents neural tube defects.
2. Folic acid 5 mg daily should be prescribed to all women who are planning to get pregnant.
3. Antiepileptic drugs must be stopped in women who are planning to get pregnant.
4. Women planning to get pregnant should be advised to abstain from alcohol.
5. Women who are HIV carriers should be advised against pregnancy.
6. Obesity is associated with higher maternal mortality and morbidity.
7. Treatment of periodontal disease during pregnancy improves the pregnancy outcome.
8. Cervical screening cannot be done during pregnancy.
9. All women should be referred to obstetricians for preconception care.
10. Blood pressure should be checked during preconception care.
T F F T F T F F F T
1 2 3 4 5 6 7 8 9 10
Answers
JPOG advanced online publication; 1 July 2012 263
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First Author
Issue
Page
Clinical Review
Kolhe S
Jul/Aug
147
Clinical Review
Yeung WYT
Jan/Feb
Clinical Review
Hay P
Mar/Apr
60
Clinical Review
Raffi F
May/Jun
93
CME
Li HWR
Jul/Aug
169
CME
Chan KKL
Mar/Apr
81
Clinical Review
Farrell E
Jul/Aug
157
Clinical Review
Athanasias PK
Sep/Oct
193
Acute fatty liver of pregnancy, HELLP syndrome, hepatitis, hyperemesis gravidarum, inflammatory
bowel diseases, obstetric cholestasis, pancreatitis, pregnancy
Clinical Review
Cuckson C
May/Jun
105
CME
Yap TL
May/Jun
125
In Practice
Fischer G
Sep/Oct
201
CME
TK Lo
Jan/Feb
37
Clinical Review
Logan S
Nov/Dec
234
Clinical Review
Mak JSM
Nov/Dec
247
Folic acid, non-prescription drugs, preconception care, primary health care, reproductive history,
vaccination
CME
Lee CP
Nov/Dec
257
CME
Lau B
Sep/Oct
213
Adolescent, child, diabetic ketoacidosis, haemoglobin A1c, hypoglycaemia, type 1 diabetes mellitus
Clinical Review
Shulman RM
Mar/Apr
49
Clinical Review
McShane MA
Jul/Aug
164
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
Clinical Review
Cox A
May/Jun
117
Clinical Review
Datta BN
Sep/Oct
202
Clinical Review
Kelly JP
Nov/Dec
225
In Practice
Wooley S
Mar/Apr
59
Clinical Review
Bhavsar H
Sep/Oct
181
Gynaecology
Obstetrics
Paediatrics
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