JPOG December 2013 ID

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JAN/FEB 2012 Vol. 38 No. 1

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Your partner in paediatric and O&G practice

NOV/DEC 2013 Vol. 39 No. 6 Your partner in paediatric and O&G practice

CME ARTICLE

5 SKP Gestational Diabetes

IN PRACTICE

JOURNAL WATCH

GYNAECOLOGY

Painful Bladder Syndrome

PAEDIATRICS

Asthma in Children

Chronic Fatigue Syndrome in Children and

Young People

NOV/DEC 2013

Vol. 39 No. 6


Journal Watch

221 • 3IQ safe and effective for diagnosing urgency urinary incontinence

• Effects of infant feeding practices on childhood cognition at age 3 and 7 years

• Consumption of sugar-sweetened beverages linked to weight gain in young children

222 • Breastfeeding has a protective effect against obesity in Japanese schoolchildren

• Late preterm infants not at higher risk of ADHD, learning disabilities

223 • Obesity rates among US adolescents may be stabilizing

• Early-term infants have higher rates of neonatal morbidity, NICU admission

224 • Standard practices for obtaining consent for caesarean delivery suboptimal

• Early-term labour induction linked to higher rates of specific maternal morbidity

Board Director, Paediatrics

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

Board Director, Obstetrics and Gynaecology

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

Editorial Board Professor Biran AffandiUniversity of Indonesia

Dr Karen Kar-Loen ChanThe University of Hong Kong

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

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

Professor Rahman JamalUniversiti Kebangsaan Malaysia

Dato’ Dr Ravindran JegasothyHospital Kuala Lumpur, Malaysia

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

Dr Siu-Keung LamPrestige Medical Centre, Hong Kong

Professor Terence LaoChinese University of Hong Kong

Dr Kwok-Yin LeungThe University of Hong Kong

Dr Tak-Yeung LeungChinese University of Hong Kong

Professor Tzou-Yien LinChang Gung University, Taiwan

Professor Somsak LolekhaRamathibodi Hospital, Thailand

Professor Lucy Chai-See LumUniversity of Malaya, Malaysia

Professor SC NgNational University of Singapore

Professor Hextan Yuen-Sheung NganThe University of Hong Kong

Professor Carmencita D PadillaUniversity of the Philippines Manila

Professor Seng-Hock QuakNational University of Singapore

Dr Tatang Kustiman SamsiUniversity of Tarumanagara, Indonesia

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

Dr Raman SubramaniamFetal Medicine and Gynaecology Centre, Malaysia

Professor Walfrido W Sumpaico MCU-FDT Medical Foundation, Philippines

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

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

Professor Surasak TaneepanichskulChulalongkorn University, Thailand

Professor Eng-Hseon TayThomson Women Cancer Centre, Singapore

Professor PC WongNational University of Singapore

Adjunct Professor George SH YeoKK Women’s and Children’s Hospital, Singapore

Professor Hui-Kim YapNational University of Singapore

Professor Tsu-Fuh YehChina Medical University, Taiwan

JPOG NOV/DEC 2013 • i

221

224

JPOG_NovDec_2013_SG_MY_ID_PH_TOC.indd 1 12/4/13 7:29 PM

• Mendukung perkembangan otak sejak awal

• Mendukung perkembangan sistem daya tahan tubuh sejak awal

• Mendukung pertumbuhan sejak awal

• Kemampuan belajar dan kognitif yang optimal

• Perkembangan sistem daya tahan tubuh untuk mengurangi alergi dan infeksi

• Komposisi tubuh yang optimal untuk mengurangi resiko terkena penyakit tidak menular (non-communicable diseases)

Tahun pertama di awal kehidupan adalah tahapan yang penting dimana nutrisi yang optimal dapat mendukung kesehatan dan pertumbuhan yang pesat sehingga memberikan awal yang baik untuk masa depannya.

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 pasokan 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.

Referensi:

2. Arslanoglu Set al. j, Nutr. 2008;13B:1091-10951. Gibson R.A, et al. Maternal and Child Nutrition 2011. pp17-26

3. Dupont C. Protein requirements during the first year of life. Am J Clin Nutr 2003;77(suppl):1544S-9S.4. Flynn A. The role of dietary calcium in bone health. Proceeding of the Nutrition Society (2003), 62: 851 – 858.5. Brown KH, Peerson JM, Rivera J, and Allen LH, Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials.

Iklan Pronutra Ukuran: 215x280 mm

Nutribaby Royal dengan Pronutra+

Gizi Sejak Awal Kehidupan (Early Life Nutrition)

Early LifeNutrition

SHORT TERM IMPACT LONG TERM BENEFIT

dengan prebiotik lc FOS-sc GOS 1:9Membantu memperkuat daya tahan tubuh bayi 2

dengan AA DHA 1:1 dan zat besiDukung pertumbuhan dan perkembangan otak 1

dengan protein, kalsium, dan zincMendukung tumbuh kembang optimal 3,4,5

NOV/DEC 2013

Vol. 39 No. 6


Enquiries and Correspondence

JPOG NOV/DEC 2013 • iii

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

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

PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is published 6 times a year by MIMS Pte Ltd. CIRCULATION: JPOG is a controlled circulation for medical practitioners in South East Asia. It is also available on subscription to members of allied professions. SUBSCRIPTION: The price per annum is US$42 (surface mail, students US$21) and US$48 (overseas airmail, students US$24); back issues US$8 per copy. EDITORIAL MATTER published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of MIMS Pte Ltd. Although great care has been taken in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. COPYRIGHT: © 2013 MIMS Pte Ltd. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, in any language, without written consent of copyright owner. Permission to reprint must be obtained from the publisher. ADVERTISEMENTS are subject to editorial acceptance and have no influence on editorial content or presentation. MIMS Pte Ltd does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Philippine edition: Entered as second-class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.

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

Hong KongKristina Lo-Kurtz, Jacqueline Cheung, Marisa Lam, Miranda WongTel: (852) 2559 5888Email: [email protected]

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Review ArticlePaediatrics

225 Asthma in Children

Childhood asthma has a very high disease burden measured in financial and social terms. Wheezing in the preschool age has increased but prediction of long-term symptoms is difficult. The mechanisms causing inflammation are now better understood. Guidelines for management are well established, but the use of measures for inflammation are less clinically helpful than expected.

Warren Lenney

Review ArticleGynaecology

232 Painful Bladder Syndrome

Painful bladder syndrome is a chronic debilitating condition, which is difficult to diagnose and treat. Its aetiology and pathogenesis are very poorly understood. A diagnosis is generally made after all other potential causes of pain and lower urinary tract symptoms are excluded. Treatment options are very limited but are generally targeted to providing symptomatic relief.

Maria Vella, Dudley Robinson, Linda Cardozo

In Practice

244 Dermatology Clinic: An Enlarging Lesion on the Neck

Gayle Fischer

244 Clinical Case: Rectal Bleeding in Pregnancy—Don’t Assume It’s Benign

Christopher S Pokorny

225

232


Persembahan SGM Presinutri untuk Bayi dengan Kebutuhan Medis Khusus

ASI adalah nutrisi terbaik bagi Ananda. Namun jika terdapat indikasi medis, rangkaianSGM Presinutri menyediakan dukungan nutrisi agar Ananda dapat tumbuh dan berkembang dengan optimal.

Bayi intoleransi lakto

sa/d

iare

Bayi prematur/berat la

hir r

end

ah

Ba

yi intoleransi/alergi protein susu

sap

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NOV/DEC 2013

Vol. 39 No. 6


JPOG NOV/DEC 2013 • iv

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

Case StudiesInteresting cases seen in general practice and their management.

Pictorial MedicineVignettes of illustrated cases with clinical photographs.

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

Review ArticlePaediatrics

245 Chronic Fatigue Syndrome in Children and Young People

Chronic fatigue syndrome is a relatively common and serious condition in children and young people, having a significant impact on their physical, emotional, and cognitive well being. This review explores the best practice approach to assessment, diagnosis, and management of chronic fatigue syndrome in children and young people.

Carrie Mackenzie, Alison Wray

254 In Practice (Answers)

Continuing Medical Education

257 Gestational Diabetes

Historically, there has been a lot of controversy over most aspects of gestational diabetes mellitus (GDM) as well as the relationship between GDM and type II diabetes mellitus. Recently, several major studies have substantially resolved these areas of controversy.

LL Chan, WL Lau, WC Leung

5 SKP

Lisa Low, Illustrator

The Cover:Chronic Fatigue Syndrome

© 2013 MIMS Pte Ltd

245

257

Indonesia


Journal Watch

JPOG NOV/DEC 2013 • 221

Peer reviewed

GYNAECOLOGY

3IQ safe and effective for diagnosing urgency urinary incontinence

Urinary incontinence affects up to a third of women

in the US, but many fail to receive appropriate

treatment. Diagnostic measures such as the 3 In-

continence Questions (3IQ) have been developed

to aid primary care providers in diagnosing and

initiating treatment, and a recent study has shown

that long-term fesoterodine therapy initiated on the

basis of the 3IQ is both safe and effective.

Researchers invited 567 women who had

completed a 12-week randomized controlled trial

of fesoterodine therapy for urgency urinary incon-

tinence diagnosed by the 3IQ to participate in a

9-month open-label continuation study. They col-

lected data on incontinence and voiding episodes

using voiding diaries. Patient satisfaction was de-

termined by questionnaire, and safety was evalu-

ated by monitoring post-void residual volumes and

adverse events.

In total, 498 (87.8%) of the women received

at least one dose of medication during the open-

label study. Compared with baseline in the ran-

domized trial, at the end of the open-label study

fesoterodine was linked to a reduction in the mean

total number of incontinence (4.64 vs 1.16) and ur-

gency incontinence (3.95 vs 0.90) episodes per day

(P < 0.0001 for both). Patient satisfaction increased

from 89% at 3 months to 92% and 93% at 6 and

9 months, respectively. Twenty-six women expe-

rienced one or more serious adverse events, but

only one was considered to be treatment-related.

Specialist evaluation of 22 women found that the

3IQ had misclassified five but without any adverse

outcomes.

Hess R et al. Long-term efficacy and safety of questionnaire-based initiation of urgency urinary incontinence treatment. Am J Obstet Gynecol 2013; doi:10.1016/j.ajog.2013.05.008.

Effects of infant feeding practices on childhood cognition at age 3 and 7 years

Nutrients in breast milk may benefit the developing

brain, but no exact relationship between maternal

diet during lactation and childhood cognition has

been determined to date. Now, a study has found

that longer duration and greater exclusivity of

breastfeeding is associated with better receptive

language at age 3 and higher verbal and non-verbal

IQ at age 7.

The prospective, longitudinal, Project Viva

study evaluated feeding practices among a US

prebirth cohort of 1,312 mothers and assessed the

cognitive capabilities of their children at ages 3

and 7 years (1,224 at age 3; 1,037 at age 7) using

the Peabody Picture Vocabulary Test at age 3 years,

the Wide Range Assessment of Visual Motor Abili-

ties at ages 3 and 7 years, and the Kaufman Brief

Intelligence Test and Wide Range Assessment of

Memory and Learning at age 7 years. Adjustments

were made for sociodemographic background, ma-

ternal intelligence, and home environment.

Longer breastfeeding duration was associ-

ated with a higher Peabody Picture Vocabulary Test

score at age 3 (0.21; 95% CI, 0.03–0.38 points per

month breastfed) and higher intelligence on the

Kaufman Brief Intelligence Test at age 7 (0.35; 95%

CI, 0.16–0.53). Beneficial effects of breastfeeding

on Wide Range Assessment of Visual Motor Abili-

ties at age 3 appeared to be greater for women

who consumed ≥ 2 servings of fish per week com-

pared with < 2 servings per week (0.24; 95% CI,

0.00–0.47 points per month breastfed vs -0.01;

95% CI, -0.22 to 0.20 points per month breastfed),

but the difference was not statistically significant.

Breastfeeding duration was not associated with

Wide Range Assessment of Memory and Learning

scores.

An accompanying editorial notes that the pu-

tative connection between breastfeeding and cog-

nition has widespread and lifelong implications,

but that the current problem is not the initiation

of breastfeeding. Rather, it is the continuation of

breastfeeding through to age 6 months. The sug-

gestion is made that large-scale structural changes

are required to support mothers in this endeavour.

Belfort MB et al. Infant feeding and childhood cognition at ages 3 and 7 years: effects of breastfeeding duration and exclusivity. JAMA Pediatr 2013; doi:10.1001/jamapediatrics.2013.455; Christakis DA. Breastfeeding and cognition: can IQ tip the scale? Ibid: doi:10.1001/jamapediatrics.2013.470 (editorial).

Consumption of sugar-sweetened beverages linked to weight gain in young children

Although consumption of sugar-sweetened bev-

erages (SSBs) has been linked to weight gain in

PAEDIATRICS

JPOG_NovDec_2013__SG MY PH ID_Combine.indd 221 12/4/13 5:16 PM


school-aged children and adolescents, results for

younger children have been mixed. Now, a US study

has shown that consumption of SSBs is also linked

to weight gain in 2- to 5-year-old children.

The researchers compared the consumption

of SSBs (soda pop, sports drinks, and fruit drinks

that are not 100% fruit juice) and body mass index

(BMI) z scores among 9,600 children followed up as

part of the US-based Early Childhood Longitudinal

Survey–Birth Cohort study (a representative survey

of the US population of children born in 2001). Ad-

justments were made for race/ethnicity, socioeco-

nomic status, mother’s BMI, and TV viewing.

Increased consumption of SSBs compared

with infrequent/no consumption of such beverages

was associated with higher BMI z scores among

children aged 4 (0.756 ± 0.048 vs 0.644 ± 0.024; P

< 0.05) and 5 (0.849 ± 0.051 vs 0.662 ± 0.018; P <

0.01), but not among those aged 2 (0.362 ± 0.087 vs

0.461 ± 0.039; P > 0.05). Moreover, children aged 5

who regularly consumed SSBs (ie, ≥ 1 serving/day)

had a higher odds ratio (OR) for being obese than

infrequent/non-drinkers (< 1 serving/day) (OR, 1.43;

95% CI, 1.10–1.85; P < 0.01). A prospective analy-

sis also showed that children who were already

exposed to such beverages at age 2 had a greater

subsequent increase in BMI z score over the follow-

ing 2 years than infrequent/non-drinkers (P < 0.05).

The researchers suggest that paediatricians

and parents should discourage the consumption of

SSBs to avoid potential unhealthy weight gain in

children.

DeBoer MD et al. Sugar-sweetened beverages and weight gain in 2- to 5-year-old children. Pediatrics 2013;132:1–8.

Breastfeeding has a protective effect against obesity in Japanese schoolchildren

Breastfeeding has been suggested to protect

against obesity in children, but the evidence re-

mains inconclusive and most studies have been

performed among children in Western countries.

Recently, however, researchers in Japan have con-

firmed a protective effect of breastfeeding against

obesity.

Secondary analyses of data collected from

2001 through 2009 during the ongoing nationwide

Longitudinal Survey of Babies in the 21st century

were undertaken. All 43,367 singleton children

born after 37 gestational weeks with available in-

formation on feeding during infancy were eligible,

but some were excluded because of missing data

or were lost to follow-up. In total, 29,907 were in-

cluded in the analysis at age 7 and 30,780 at age

8. Data were adjusted for the children’s sex and

screen time as well as for maternal educational at-

tainment, and smoking and working status.

At age 7, 7.3% of the children were classi-

fied as overweight and 2.1% as obese, according

to the International Obesity Task Force body mass

index cut-off points based on sex and age. The cor-

responding values at age 8 were 7.8% and 1.9%. In

addition, compared with formula feeding, exclusive

breastfeeding at age 6–7 months was associated

with a decreased risk of being overweight (odds

ratio [OR], 0.85; 95% CI, 0.69–1.05) or obese (OR,

0.55; 95% CI, 0.39–0.78) at ages 7 and 8 (under-

weight: OR, 0.84; 95% CI, 0.68–1.03; obese: OR,

0.44; 95% CI, 0.31–0.63).

An accompanying editorial notes the impor-

tance of the provision of further data from an Asian

population but questions the need for further such

studies because a causal relationship can never be

proven for ethical reasons, and because a number

of other factors have a greater impact on obesity,

such as low levels of physical activity. The question

is raised as to whether a focus on preventive care

of postpartum mothers as well as babies may be

more appropriate.

Yamakawa M et al. Breastfeeding and obesity among schoolchildren: a nationwide longitudinal survey in Japan. JAMA Pediatr 2013; doi:10.1001/jamapediatrics2013.2230; Bovbjerg ML et al. Breastfeeding and childhood obesity: where do we go from here? Ibid: doi:10.1001/jamapediatrics.2013.2854 (editorial).

Late preterm infants not at higher risk of ADHD, learning disabilities

Late preterm infants have previously been suggest-

ed to be at greater risk of learning and behavioural

problems than term infants, but most studies have

evaluated clinic-referred children at early school

age, and findings have been mixed. Now, a pop-

ulation-based study suggests that late preterm in-

fants are not at greater risk of developing attention

deficit/hyperactivity disorder (ADHD) and learning

disabilities compared with term infants.

The study included 5,699 children born in

Rochester, Minnesota, US, between 1976 and 1982,

who were still resident in the community after 5

years and who did not have a severe intellectual

disability. The cumulative incidence of ADHD and

learning disabilities in reading, written language,

and math by age 19 was determined by comparing


Journal Watch


Peer reviewedPeer reviewed

medical and school records for former late preterm

(34 to < 37 weeks) and term (37 to < 42 weeks)

infants. Adjustments were made for maternal edu-

cation and perinatal complications.

No statistically significant differences were

observed between former late preterm (n = 256)

and term (n = 4,419) infants at age 19 in terms of

the cumulative incidence of ADHD (7.7% vs 7.2%;

P = 0.84) or of learning disabilities relating to read-

ing (14.2% vs 13.1%; P = 0.57), written language

(13.5% vs 15.7%; P = 0.36), and math (16.1% vs

15.5%; P = 0.89).

The researchers conclude that former late

preterm infants have similar rates of ADHD and

learning disabilities as term infants.

Harris MN et al. ADHD and learning disabilities in former late preterm infants: a population-based birth cohort. Pediatrics 2013;132:e630–e636.

Obesity rates among US adoles-cents may be stabilizing

Obesity rates among US adolescents have been of

concern for some time given that obesity is a risk

factor for many leading causes of mortality. How-

ever, a recent study has indicated that obesity rates

among US adolescents may be stabilizing and that

this may be due to changes in obesogenic behav-

iours.

Nationally representative US students in

grades 6–10 anonymously completed the Health

Behavior in School-aged Children (HBSC) survey,

which assesses body mass index (BMI), physical

activity, and sedentary and dietary behaviours, in

2001–2002, 2005–2006, and 2009–2010. African-

American and Hispanic students were oversampled

to obtain better estimates for these populations.

Obesogenic behaviours remained common

over the study period, but the amount of time spent

engaging in physical activity increased over time,

as did the consumption of fruit and vegetables and

Early-term infants have higher rates of neonatal morbidity, NICU admission

Full-term neonates born between 37 and 41 weeks’

gestational age have traditionally been considered

a homogenous, low-risk group. However, a recent

study has provided further evidence that early-

term births (370/7–386/7 weeks) are associated with

higher rates of neonatal morbidity and neonatal

intensive care unit (NICU) or neonatology service

admission than term births (390/7–416/7 weeks).

The retrospective, population-based birth

cohort study evaluated 33,488 live births at major

birthing hospitals in Erie County, New York, be-

tween January 1, 2006, and December 31, 2008.

Data on NICU or neonatology service admission

were extracted from medical records.

Of the 33,488 live births, 29,741 were at a

gestational age between 37 and 416/7 weeks and

9,031 (27%) were early-term. Compared with term

neonates, early-term neonates were at significantly

higher risk for NICU or neonatology service admis-

sion (8.8% vs 5.3%; adjusted odds ratio [OR], 1.64),

duration of hospital stay ≥ 5 days (1.9% vs 1.2%;

adjusted OR, 1.37), respiratory morbidity (5.4% vs

3.3%; adjusted OR, 1.58), respiratory support (2.0%

vs 1.1%; adjusted OR, 1.93), mechanical ventilation

or intubation (0.6% vs 0.1%; adjusted OR, 4.57),

surfactant use (0.3% vs 0.05%; adjusted OR, 6.29),

hypoglycaemia (4.9% vs 2.5%; adjusted OR, 1.92),

administration of intravenous fluids (7.5% vs 4.4%;

adjusted OR, 1.68), and treatment with intravenous

antibiotics (2.6% vs 1.6%; adjusted OR, 1.62). In

addition, significantly more early-term neonates

were delivered by caesarean section than term ne-

onates (38.4% vs 29.3%). Caesarean delivery was

found to increase the risk for NICU or neonatology

service admission and morbidity, but even early-

term infants delivered vaginally had a significantly

higher rate of NICU or neonatology service admis-

the frequency of eating breakfast. Moreover, the

amount of time spent viewing TV decreased and

the consumption of sweets and sweetened bever-

ages declined. Although a trend towards weight

gain remained—the average BMI increased from

2001–2002 to 2005–2006—there was no increase

in average BMI between 2005–2006 and 2009–

2010, which may indicate that obesity rates are

beginning to stabilize.

The researchers comment that these find-

ings indicate that public health initiatives may be

beginning to have an effect. However, they note

that paediatricians should be aware of age-, sex-,

and ethnicity-based differences in behaviour when

interpreting these findings. A number of these dif-

ferences are noted in the study. For example, older

adolescents were more frequent users of comput-

ers, consumed fewer fruits and vegetables and

more sweets and soft drinks, and ate breakfast less

frequently than younger adolescents.

Iannotti RJ et al. Trends in physical activity, sedentary behaviour, diet, and BMI among US adolescents, 2001–2009. Pediatrics 2013;132:606-614.



sion than term infants.

An accompanying editorial notes that these

findings reinforce the conception of maturation as

a continuum and highlight the difficulties associat-

ed with using a preset gestational age as an index

of separation between immaturity and maturity.

Sengupta S et al. Adverse neonatal outcomes associated with early-term birth. JAMA Pediatr. 2013; doi:10.1001/jamapediatrics.2013.2581. Oh W et al. Not all “term” infants are created equal. JAMA Pediatr. 2013; doi:10.1001/jamapediatrics.2013.2593 (editorial).

Standard practices for obtaining consent for caesarean delivery suboptimal

Currently, the standard practice for obtaining in-

formed consent to caesarean delivery in the US

is to obtain the patient’s consent at the time the

decision to perform a caesarean is made. However,

a novel study has shown that this approach does

not allow sufficient time for patients to evaluate

potential risks, particularly among women who are

at greatest risk.

The retrospective chart review of 90 patients

who underwent caesarean delivery during labour

compared the time from consent to incision to ac-

tual delivery among women with and without fetal

heart rate indications.

The median consent time among all women

was 48 minutes (interquartile range, 25–72 min-

utes), but it was < 30 minutes in 28.9% of women

and < 15 minutes in 10%. Moreover, after adjusting

for potential confounders, the odds of delivery < 30

minutes after consent were 4.7 times higher (95%

CI, 1.4–15.2; P = 0.01) among women with fetal

heart rate indications. In addition, the consent time

was not higher among obese women or those who

had previously experienced a caesarean delivery,

to 1,601,253 women without pregnancy complica-

tions who delivered singletons at 37–42 completed

weeks’ gestation.

The rate of postpartum haemorrhage requir-

ing blood transfusion was increased by labour

induction at 38 weeks’ (adjusted rate ratio [aRR],

1.28; 95% CI, 1.11–1.49), 39 weeks’ (aRR, 1.21;

95% CI, 1.06–1.38), and 40 weeks’ (aRR, 1.12; 95%

CI, 1.00–1.26) gestation. Similarly, induction at

38 and 39 weeks’ gestation was associated with

higher rates of puerperal sepsis (aRR, 1.27; 95%

CI, 1.13–1.99; and aRR, 1.24; 95% CI, 1.09–1.82,

respectively) and induction at 38 weeks’ gesta-

tion with higher rates of venous thromboembolism

(aRR, 2.94; 95% CI, 1.59–5.46). However, the ab-

solute increase in morbidity rates was small, and

the number needed to harm was substantial for all

three conditions.

Liu S et al. Gestational age-specific severe maternal morbidity associated with labor induction. Am J Obstet Gynecol 2013; 209:209.e1-8.

and these women may face the greatest risks.

The researchers comment that although

a short consent time does not necessarily imply

a poor-quality conversation regarding potential

risks, it is unlikely that a high-quality informed

consent process can occur in under 50 minutes.

They suggest that an alternative approach should

be adopted, such as the inclusion of informed con-

sent discussions during routine prenatal care. An

accompanying editorial and roundtable discussion

support this suggestion.

Salmeen K et al. Time from consent to cesarean delivery during labor. Am J Obstet Gynecol 2013;209:212.e1-6; Chervenak FA et al. Preventive ethics for cesarean delivery: the time has come. Ibid: dx.doi.org/10.1016/j.ajog.2013.05.040 (editorial); Macones GA. Time from consent to cesarean delivery: Salmeen K et al. Ibid: dx.doi.org/10.1016/j.ajog.2013.07.018 (roundtable discussion).

Early-term labour induction linked to higher rates of specific maternal morbidity

Labour induction is widely used to prevent adverse

maternal, fetal, and infant outcomes. Although

generally considered safe, problems such as pro-

longed labour, chorioamnionitis, fetal death, and

uterine rupture can occur. In a recent study, re-

searchers in Canada compared the gestational

age-specific effects of labour induction on severe

obstetric morbidity and found that women who

were induced at an earlier term had higher rates

of specific severe maternal morbidity than similar

women who were treated expectantly, although the

absolute risks were low.

The researchers compared data from hos-

pital records collated in the Discharge Abstract

Database of the Canadian Institute for Health In-

formation for 2003–2011 (excluding Quebec). The

database includes all maternal hospital admissions

for delivery as well as links to newborn infant

admissions. The analysis was performed using a

pregnancies-at-risk approach and was restricted

OBSTETRICS


Abdominal discomfort sering timbul pada beberapa bulan pertama usia bayi dan salah satu penyebabnya adalah gangguan saluran cerna. Pada literatur, gangguan saluran cerna ini dilaporkan berkaitan dengan pemberian makan, terutama pada bayi yang mendapat susu formula. Prevalensi abdominal discomfort yang didapat dari laporan dokter sekitar 18-27%. Data dari beberapa negara di Asia, Eropa, Amerika Latin, Amerika, Rusia dan China melaporkan 40-60% bayi mengalami gangguan saluran cerna sebelum usia 6 bulan. Dalam suatu kajian pada 2.879 bayi sejak lahir hingga usia 6 bulan, 150 dokter anak melaporkan ada 54,9% bayi yang mengalami gangguan saluran cerna dengan gejala: regurgitasi 23,1%; kolik 20,5%; konstipasi 17,6%; gagal tumbuh 15,2%; muntah 6% dan diare 4,1%. Sebanyak 60% dari bayi-bayi tersebut diganti minuman atau makanannya. Bahkan tidak jarang, ibu menghentikan pemberian ASI.

Berdasarkan kriteria ROME III, gejala regurgitasi tergolong gangguan fungsional yang penyebabnya bukan karena kelainan organik dan merupakan proses yang normal. Regurgitasi normal terjadi sampai 4 kali sehari dan tidak disertai gejala lain maupun komplikasi. Frekuensi regurgitasi akan berkurang dengan bertambahnya usia bayi.

Kolik pada bayi (Infantile colic) Empat puluh persen bayi dapat mengalami infantile colic, baik pada bayi yang mendapatkan ASI maupun susu formula, yang terjadi sejak lahir hingga usia 4 bulan. Dari 1000 bayi dengan gejala infantile colic, umumnya menangis berkepanjangan setiap malam pada waktu yang hampir sama, sehingga mengganggu pola tidurnya. Punggung bayi akan tampak melengkung, lutut ditarik ke dada, kaki dan tangan mengepal serta memperlihatkan ekspresi kesakitan. Umumnya infantile colic disertai gejala sekunder, seperti: regurgitasi atau gumoh yang sering, kram abdominal, konstipasi, distensi abdomen, flatus, episode borborygmi/bising usus karena pergerakan gas, yang dimulai setelah pemberian makan. Gejala-gejala ini akan berkurang atau menghilang dengan adanya gerakan peristaltik usus yang

dr. Badriul Hegar Syarif, PhD, Sp.A(K) Divisi GastroenterologiDepartmen Ilmu Kesehatan Anak Fakultas Kedokteran Universitas Indonesia RS. Dr. Cipto Mangunkusumo, Jakarta.

Hanya untuk Kalangan Medis

Abdominal Discomfort in infantJust Functional or Something More Serious?

mendorong gas keluar dari saluran cerna.

Etiologi infantile colic tidak jelas dan faktor penyebabnya berbeda antar satu bayi dengan yang lainnya. Penyebab organik hanya sebesar <5%, mencakup kelainan gastrointestinal, psikososial, atau tahapan neurodevelopment yang dengan pertambahan usia akan menghilang. Berbagai keadaan berperan terhadap patofisiologi infantile colic, antara lain gastroesofageal refluks (GER), intoleransi laktosa, hormon pada usus, mikroflora atau trauma, dismotilitas, gangguan pemberian makan, infeksi, psikologikal dan hipersensitivitas terhadap lingkungan. Dokter perlu memastikan lebih dulu tidak ada penyebab organik pada kolik dan menyakinkan orang tua bahwa kolik yang terjadi pada bayi yang sehat dapat sembuh dengan sendirinya tanpa efek samping jangka panjang. Tidak ada kriteria khusus mengenai terapi dan umumnya penggantian susu formula tidak bermanfaat, medikasi juga tidak efektif. Terlalu cepat perubahan pemberian makan tidak dianjurkan. Intervensi perilaku kebanyakan tidak terbukti dan tidak lebih efektif dari pemberian plasebo.

Ditemukan bahwa 44% bayi yang mengalami kolik ternyata menderita alergi susu sapi (ASS). Hal ini terbukti dengan pemberian formula hipoalergenik yang hasilnya lebih efektif dibandingkan susu formula rendah laktosa. Bila kolik pada bayi ASS yang mendapatkan ASI, pemberian ASI sebaiknya tetap dilanjutkan dan Ibu menghindari konsumsi makanan yang mengandung produk susu sapi. Sedangkan untuk bayi yang mendapat susu formula, lakukan rekomendasi tata laksana ASS dengan memberikan formula protein terhidrolisa ekstensif dan eliminasi susu sapi. Pada beberapa uji acak terkontrol, susu berbahan dasar kedelai tidak memberikan hasil yang adekuat. Sedangkan pada pemberian laktosa pada bayi kolik pada suatu studi terkontrol, dengan memberikan susu formula enzim laktase tidak memberikan hasil yang berbeda bermakna dengan plasebo.

Ketidaknyamanan pada abdomen (abdominal discomfort) pada bayi sering dikeluhkan oleh orang tua yang datang ke tempat praktik dan tak jarang menyebabkan kekhawatiran. Apa penyebab abdominal discomfort pada umumnya, apakah perlu penanganan lebih lanjut dan apa yang perlu dilakukan dokter pada kasus ini, dibahas oleh dr. Badriul Hegar Syarif, PhD, Sp.A(K) pada PIT IKA ke-6 di Solo pada bulan Oktober 2013 lalu dengan moderator dr. Lucia Endang Dewi Lestari, Sp.A(K).

SHL-JPOG PIT IKA_MJ.indd 1 11/27/2013 4:38:36 PM

Tata laksana Infantile colic harus dicari faktor organik atau red flag-nya terlebih dulu. Bila tidak ada red flag, cari penyebab lain bayi rewel seperti apakah ia lapar? Bosan? Atau pemberian teknik makan yang salah. Bila ada red flag maka perlu dipikirkan adanya GERD, ASS, intoleransi laktosa dan penyakit gastrointestinal lainnya. Bila tidak ada red flag dan pada evaluasi tidak ditemukan teknik pemberian makan yang salah, namun bayi tetap rewel, lihat faktor kecemasan atau stres pada Ibu. Bila memang ada faktor ibu yang mempengaruhi, rujuk ke psikolog atau psikiater. Bila tidak ada faktor kecemasan pada Ibu, tetapi tidak ada perbaikan maka perlu dievaluasi kembali diagnosis awal apakah terdapat ASS atau intolerasi laktosa? Bila telah diterapi sesuai gejala dan tetap tidak ada perbaikan rujuk ke dokter anak konsultan gastroenterologi. (lihat gambar 1).

diperlihatkan, antara lain pemberian susu formula hidrolisat, susu formula rendah atau bebas laktosa atau terapi antirefluks. Bila dalam 2 minggu hingga maksimum 1 bulan tidak ada respons, maka perlu dipikirkan diagnosis lain.

Medikasi dengan simethicone yang memiliki efek menurunkan gas dalam lambung dibuktikan pada 2 studi tidak menunjukkan manfaat, sedangkan obat golongan antikolinergik (dicylomine, pipenazolate bromide) pada review didapatkan sedikit lebih efektif dari plasebo hanya selama beberapa hari pertama saja dan selanjutnya tidak berbeda bermakna dengan plasebo. Efek samping terapi yang dilaporkan, bayi menjadi letargi, apnea pada pemberian dicycloine dan tidak dapat digunakan pada bayi berusia < 6 bulan serta menyebabkan kantuk. Golongan Proton pump inhibitors/PPI pada kolik bayi dilaporkan beberapa studi tidak menunjukkan manfaat. Sedangkan pada studi perbandingan probiotik L reuteri protectis vs. plasebo pada kolik bayi dilaporkan probiotik dapat menurunkan kejadian bayi rewel (75% vs. 38%) terutama pada 7 hari pertama. Hormon melatonin dalam ASI memiliki efek hipotonik dan relaksasi otot polos gastrointestinal yang diekskresikan oleh ibu pada malam hari, sehingga memperbaiki waktu tidur bayi dan mengurangi kolik.

Gas berlebih dalam saluran cerna (Fussiness and gassiness)Sejumlah udara dalam saluran cerna adalah keadaan normal, namun bila berlebihan akan menyebabkan distensi abdominal dan rasa nyeri. Riwayat klinis dan pemeriksaan fisik dapat diidentifikasi etiologinya pada 66,3% kasus. Pemeriksaan tes tambahan dilakukan berdasarkan temuan klinis. Telusuri adanya red flag sebagai skrining pada kasus ini, dan buktikan lebih dulu penyebabnya apakah ada kecurigaan terhadap faktor organik. Bila tidak ada red flag tetapi terdapat ruam popok dan tanda intoleransi laktosa, maka bila bayi mendapat ASI, pemberian ASI tetap diteruskan. Bila bayi mendapat susu formula, sebaiknya diberikan yang kadar laktosanya diturunkan. Bila gejala tidak membaik rujuk ke dokter anak konsultan gastroenterologi. (lihat gambar 2).

Kesimpulan :

1. Abdominal discomfort sangat sering pada bayi.

2. Abdominal discomfort tidak hanya sekedar gangguan fungsional, tetapi merupakan keadaan yang perlu mendapat perhatian.

3. Studi tersamar ganda dan intervensi prospektif masih sangat terbatas dilakukan pada bayi dengan abdominal discomfort.

4. Diperlukan pedoman pendekatan tata laksana bayi dengan abdominal discomfort.

Gambar 1. Tata laksana infantile colic

Gambar 2. Tata laksana fussiness & gassiness Gambar 3. Suasana Lunch Symposium “Abdominal Discomfort in infant” di PIT IKA Solo 8 Oktober 2013

Infantile Colic

Evaluate and treat:• Anxiety in parents• Maternal depression• Absence of mother child reciprocity

Maintain support

Improvement?Consider modification of

infant diet and try an eHF/CM-free diet in BF

Refer to pediatric gastroenterologist

Refer to Psychology/psychiatry

• ≤ 3 month of age• Fussiness, irritability, or crying >>• ≥ 3 hours/day• ≥ 3 days/week• At least one week

Organic cause Red Flag

Consider GERD, CMA, low lactase activity, or other

GI disease

No Yes

NoYes

Evaluate and establish correct

feeding technique and baby comfort

Improvement?

Consider diagnosis of CMA

No Yes

NoYes

Fussiness, Gassiness: Accompanied by Crying

Breastfed infant Formula fed infant

Y. Vandenplas et al. / Nutrition xxx (2012) 1-11

Yes

No

No

Excessive Crying/Gas/Fussiness

RED FLAGS?• Failure to thrive• Frequent regurgitation, vomiting, and “cough episodes”• Sandifer’s position• Family history of atopy• Respiratory/dermatological symptoms of atopy• GI bleeding

Organic cause? Refer to pediatric GI specialist

Education Reassurances

Refer to pediatric GI specialist

Problem solved??

Discharge

• BF: no change• Formula-fed: lactose may be withdrawn from the diet temporarily

No

Yes

The patient has:• Diaper rash, or• Diarrhea post-gastroenteritis, or• Reducing substances in feces

Yes

Bayi dengan kolik berat dan persisten perlu dipertimbangkan adanya ASS, GER, dan transient low lactase activity sesuai dengan temuan dan pemeriksaan klinisnya. Terapi empirical dapat diberikan selama 2 minggu sesuai gejala-gejala klinis yang

SHL-JPOG PIT IKA_MJ.indd 2 11/27/2013 4:38:38 PM

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Imaging Paediatric Brain Tumours

Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology

PAEDIATRICS i Peer reviewed


INTRODUCTION

Childhood asthma has been described for centuries, but its prevalence, aetiology, man-

agement, and outcome have changed beyond recognition in the last 40 years. No dis-

ease is static. Updates are needed to keep pace with those changes.

In the early 1970s, references were made to infants identified as ‘fat, happy wheez-

ers’, but their numbers were few and most children with doctor-diagnosed asthma were

of school age. Over the next 20 years, there was an explosion of recurrent wheezing in

the preschool age. These young children have now been carefully studied, resulting in

the recognition of differing asthma phenotypes. Can we truly identify different asthma

symptoms in certain age groups, treat them effectively and thereby alter the long-term

outcome? What have we learned about the pathological basis of asthma? Can epide-

miological studies be extrapolated to clinical disease progression in individual children?

What can we tell parents and children today that we could not tell them 20 years ago?

THE BURDEN OF PAEDIATRIC ASTHMA

The high prevalence of childhood asthma was demonstrated in the phase III report from

the International Study of Asthma and Allergies in Childhood (ISAAC) in 2007.1 The study

took place in 40 countries involving 66 centres, which reported asthma prevalence in

children aged 6–7 and 13–14 years. Its aim was to discover if prevalence had changed

from the first ISAAC survey published in 1998. ISAAC III showed significant increases in

‘asthma ever’, smaller increases in ‘wheeze in the last 12 months’ but less variation in

prevalence between countries, mainly due to increases in non-English speaking/develop-

ing countries with some reduction in Western Europe, North America, and Australasia.


Asthma in ChildrenWarren Lenney, MD, FRCP, FRCPCH, DCH




PAEDIATRICSPAEDIATRICS I Peer revIewed

The financial burden is traditionally divided

into direct and indirect costs. Direct costs relate to

costs of hospital admission, emergency room, out-

patient and community practitioner visits, medicinal

costs, family costs for travel to hospital or to medi-

cal appointments, as well as the cost of altering the

home such as purchase of non-allergenic bedding.

Indirect costs are calculated as days missed from

school, days missed from work for the parent to look

after the child when ill, and, although uncommon, if

a child dies from asthma, it is possible to calculate

the loss of potential earnings the child would have

accrued had they lived a full and healthy life.

The cost of childhood asthma is far (up to

10-fold) greater when asthma is uncontrolled. A

prevalence study in 25 European Union Member

States in 2004 estimated the highest annual cost

at €1529, the average at €613, and the lowest at

€142 per child/individual.2 These differences often

reflected the variation in healthcare services in dif-

ferent countries. Given the prevalence of asthma in

the UK – it affects 1 in 7 children – its financial

burden is huge. All effort is needed to ensure that

control of symptoms and exacerbations is achieved

wherever possible.

There is also the social burden of asthma

affecting both the child and family. This relates

to missed sleep because of nocturnal symptoms,

problems with developing friendships at school,

less participation in sporting and leisure activities,

and higher levels of depression. Parents also worry

about adverse effects of medicines taken over many

years.

SYMPTOMS IN THE FIRST 3 YEARS OF LIFE

Up to one in three children have had at least one

episode of wheezing by their third birthday. Debate

has raged for 40 years about whether this consti-

tutes part of the spectrum of asthma and whether

symptoms early in life can predict progression of

disease through childhood and into adult life. In

the 1970s, it was believed that ‘wheezy bronchitis’

was part of the asthma spectrum, but in the 21st

century the main thrust has been to separate phe-

notypes into episodic (viral) wheeze or multi-trigger

wheeze. Other terms such as persistent wheeze

and intermittent recurrent wheeze only confuse

the picture. The triggers that may instigate non-

viral wheeze are tobacco smoke, exercise, emotion,

and various aeroallergens. An excellent review of

The financial burden associated with childhood asthma is far greater when the asthma is uncontrolled.




What’s new?

• Prevalence and hospital admissions are beginning to fall in Eng-lish-speaking countries

• Good asthma control means a much lower financial burden• Very severe asthma management requires a tertiary care, multidis-

ciplinary team• Recent smoking legislation may benefit children with asthma

preschool wheezing can be found in the European

Respiratory Society (ERS) Task Force paper in the

European Respiratory Journal 2008.3 It discusses

the overlap in phenotypes and the finding that a

child’s phenotype may change from one to the other

when followed prospectively for 1 year or more. It

is very difficult, therefore, at any single time point

to give clear advice to parents about the likelihood

of symptoms continuing or disappearing. What

is agreed is that the more severe and persistent

the symptoms, the more likely they are to persist.

Although epidemiological studies try to separate epi-

sodic viral wheeze and multiple-trigger wheeze, be-

cause of the overlap, it is much more difficult when

dealing with an individual child. The relationship

between atopy and disease progression has been

closely studied and the single most useful indicator

of persistence of symptoms is the presence of al-

lergen sensitization on skin-prick testing at 2 years

of age.4 However, this is not an investigation under-

taken by most UK clinicians in very young children.

MECHANISMS OF SYMPTOM DEVELOPMENT AND PROGRESSION

Children sensitized at an early age to the common

aeroallergens (house-dust mite and cat being the

two most common sources) react differently to res-

piratory viruses than those not sensitized. Although

respiratory syncytial virus (RSV) results in repeated

wheezing and coughing episodes in childhood, rhi-

novirus is thought to be more important in causing

asthma exacerbations in children.5

In normal bronchial epithelial cells, the pres-

ence of virus leads to rapid induction of interferon-β

(IFN-β). This then induces more of itself as well as

interferon-α (IFN-α). Other compounds such as ri-

bonuclease and protein kinase R join in to kill and

phagocytose the virus, thereby limiting the infec-

tive process. In sensitized asthmatic bronchial epi-

thelial cells, IFN-β is greatly reduced so anti-viral

processes are not induced; this leads to very high

viral load and the development of inflammation.

A Swedish cohort study has consistently sug-

gested a relationship between early RSV infection,

early sensitization and asthma patterns throughout

childhood,6 whereas most others have not. This

study managed to follow up 46 of the original 47

infants with RSV infection and 92 of the 93 control

subjects for 18 years.

GENERAL MANAGEMENT OF ASTHMA

There are multiple local, national and international

guidelines on asthma management. The Scottish

Intercollegiate Guidelines Network (SIGN)/British

Thoracic Society guidelines are regularly updated;

their outline can be found in the British National

Formulary for Children. A step-wise approach is

recommended, but the step most often forgotten

is to step down when control has been achieved

following a reasonable period of stability. Parents

understand this and often reduce or stop treatment

if there are no symptoms. There is no evidence that

this is inappropriate and, indeed, we know that the

long-term use of inhaled corticosteroids (ICS) has no




Table 1. Passive smoke exposure and incidence of wheeze

Smoking exposure

Age at outcome (y)

Number of studies

Pooled odds ratio

Prenatal maternal Maternal Paternal

≤ 2 1120

1.441.72


3–4 740

1.251.77


5–18 522

1.381.651.31

Passive smoke exposure and incidence of wheeze (adapted from Royal College of Physicians

report ‘Passive smoking and children’ 2010; page 85).

effect on the natural history of the disease. When

ICS are stopped after many years usage, those with

persisting active disease eventually show falls in

lung function and increases in symptoms.

ARE THERE NEW WAYS OF MONITORING CLINICAL PROGRESS?

Asthma is an inflammatory condition. Studies have

assessed enhanced control by measuring inflamma-

tory markers in the blood and sputum and measur-

ing fractional exhaled nitric oxide (FeNO). As small,

portable FeNO monitors became available, there

was hope that FeNO would be clinically helpful.

After a decade of usage, the general belief is that

FeNO is a marker of atopy but is probably not help-

ful as an adjunct to good clinical history-taking and

careful clinical examination. The clinical assess-

ment should include lung function testing (spirom-

etry) in all children old enough to produce reliable

values for forced vital capacity and forced expira-

tory volume in 1 second (FEV1). The child with low

FEV1 (eg, below 80% expected) values should be

given 6–10 puffs of salbutamol and have spirometry

re-checked 20 minutes later. Repeated increases

clearly indicate non-adherence with prescribed

treatment and need addressing. This can be more

difficult than it may seem. The reasons for non-

adherence are complex and multiple.

VERY SEVERE ASTHMA IN CHILDREN

In the majority of children, asthma is relatively

easy to diagnose and manage by following guide-

line recommendations. However, approximately 5%

have very severe symptoms despite high doses of

medication including ICS, long-acting β2-agonists

(LABAs), multiple doses of short-acting β2-agonists

and other treatments, such as theophyllines or leu-

kotriene-receptor antagonists (LTRAs). These need

specialist assessment by tertiary respiratory teams.

It is imperative to assess the family background. Is

there a lack of adherence to treatments? Is the home

environment contributing to poor control? Are there

contributory psychosocial factors? Discussions with

primary care personnel, checking with the pharma-

cist that prescriptions are collected regularly, and

visits to the family are often necessary to establish

the cause for poor control. The gathering of all the

relevant information needs a multidisciplinary team

that includes specialist paediatricians, respiratory

nurses, psychologists, and social workers. The role

of nurse-led home visits is now well established.7

Invasive procedures such as bronchoscopy may be

needed.

In keeping with the recognition that more se-

vere disease continues into adult life, one of the

longest followed-up asthma cohorts has recently

been published from Melbourne, Australia.8 Pa-

tients were recruited from a 1957 birth cohort at the

age of 7 years and reviewed regularly to 50 years of

age. At 10 years, a cohort of very severe asthmatic

children was included. Of the total cohort, 346 (76%)




participated in the follow-up at 50 years and 197 of

these completed questionnaires and lung function

testing. Chronic obstructive pulmonary disease was

diagnosed in 28 adults (14%) and 24 of these were

from the very severe cohort introduced at 10 years

of age. The authors comment that early aggressive

therapy for very severe asthma in childhood may, in

the future, prevent airway remodelling and reduce

both the symptoms of asthma throughout life and

the development of chronic obstructive pulmonary

disease as a long-term complication.

THE ENVIRONMENT AND WHEEZE/ASTHMA

The Royal College of Physicians published ‘Pas-

sive smoking and children’ in 2010.9 The single

most useful measure that may reduce the preva-

lence and influence the symptoms of wheeze and

asthma in children is to encourage the birth and

rearing of children in an environment free from

tobacco smoke. The developing fetus in a mother

who smokes receives as much nicotine and other

tobacco constituents as an adult who smokes 20

cigarettes per day. The odds ratio for wheeze in re-

lation to passive smoke exposure was significantly

increased in all ages from birth to 18 years of age.

This is illustrated in Table 1.

The British Lung Foundation launched its Chil-

dren’s Charter early in 2011. Having undertaken a

confirmatory survey amongst UK children, the Char-

ter’s first point is ‘Children should be able to en-

joy a smoke-free environment both inside and out-

side the home’. The British Lung Foundation went

on to recommend a change in UK law prohibiting

parents from smoking in cars when children were

present. Scotland banned smoking in public places

and workplaces in March 2006. Over the next 3.6

years, there was a significant fall in daily hospital

admissions for asthma in children. This can be seen

in Figure 1, including 95% confidence intervals and

smoothed admissions for children with asthma.

Figure 1. Daily hospital admissions for asthma among children between January 2000 and October 2009.

Ast

hma

adm

issi

ons

(num

ber/

day)

8

7

6

4

5

0

3

2

1

Upper 95% CI

Smoothed hospitalizations

Lower 95% CI

1-Jan-00 1-Jan-02 1-Jan-04 1-Jan-06 1-Jan-08 33-Oct-09

Adapted from NEJM 2010;363: page 1141

It was believed that

‘wheezy bronchitis’ was

part of the asthma spectrum,

but in the 21st century the

main thrust has been to

separate phenotypes

into episodic (viral) wheeze

or multi-trigger wheeze




INCIDENCE AND CONTROL OF WHEEZING THROUGHOUT CHILDHOOD

The profile of asthma incidence seen in the 2008 Ger-

man asthma cohort study10 can be replicated through-

out all Western European countries. The numbers are

greatest in the first few years of life, falling to low

levels by 12 years of age. A UK study, the Health Tech-

nology Assessment–funded MASCOT study, opened

in 2009 with the intention of enrolling 900 children

with asthma poorly controlled at step 3 (low-dose ICS

alone) of the SIGN national asthma guidelines. It had

difficulty recruiting children and closed early in Janu-

ary 2011.11 A positive inference may be that there are

fewer poorly controlled asthmatic children in the UK

than there were 10 years ago.

NEWER PHARMACEUTICAL TREATMENTS

The early YearsIn the preschool age group, children with episodic

viral wheeze respond to short-acting β2-agonists

when given through a spacer (with facemask at-

tached in those under 3 years old). Those with

repeated symptoms affecting activity, sleep, and

nursery attendance require preventative treatment

but respond less well to ICS than children with mul-

tiple trigger wheeze. LTRAs in the form of montelu-

kast granules or chewable tablets (4 mg) have been

used increasingly in this age group. Studies from

UK, Europe, and Australasia have reported varying

outcomes, but the SIGN national guidelines (up-

dated in June 2009) recommend LTRAs in this age

About 5% of children have very severe asthma symptoms despite high doses of medications.




REFERENCES

1. Pearce N, Aït-Khaled N, Beasley R, et al. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2007;62:758–766.2. van den Akker-van Marle ME, Bruil J, Detmar SB. Evaluation of cost of disease: assessing the burden to society of asthma in children in the European Union. Allergy 2005;60:315–335.3. Brand PLP, Baraldi H, Bisgaard AL, et al; ERS Task Force. Definition, assessment and treat-ment of wheezing disorders in preschool chil-dren: an evidence-based approach. Eur Respir J 2008;32:1096–1110.

4. Schultz A, Brand PLP. Episodic viral wheeze and multiple trigger wheeze in preschool chil-dren: a useful distinction for clinicians? Paediatr Respir Rev 2011;12:160–164.5. Friedlander SL, Busse WW. The role of rhino-virus in asthma exacerbations. J All Clin Immu-nol 2005;116:267–273.6. Sigurs N, Alijassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010;65:1045–1052.7. Bracken M, Fleming L, Hall P, et al. Results of nurse-led home visits for children with difficult asthma. Thorax 2007;62(suppl 111):A21– A22.8. Tai ASN, Tran H, Roberts M, Clarke N, Wilson

JW, Robertson CF. Pediatric origins of adult chronic obstructive pulmonary disease (COPD): childhood asthma. Am J Respir Crit Care Med 2010;181:A2275.9. Passive smoking and children. A report by the Tobacco Advisory Group of the Royal College of Physicians. Royal College of Physicians, March 2010.10. Matricardi PM, Illi S, Grüber C, et al. Wheez-ing in childhood: incidence, longitudinal pat-terns and factors predicting persistence. Eur Respir J 2008;32:585–592.11. Lenney W, Perry S, Price D. Clinical trials and tribulations: The MASCOT Study. Thorax 2011;66:457–458.

12. Lemanske RF Jr, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corti-costeroids. New Engl J Med 2010;362:975–985.13. Salpeter SR, Buckley NS, Ormiston TM, Sal-peter EE. Meta-analysis: effect of long-acting β-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med 2006;144:904–912.14. Carroll WD, Jones PW, Boit P, Clayton S, Cliff I, Lenney W. Childhood evaluation of salmeterol tolerance – a double-blind rand-omized controlled trial. Pediatr Allergy Immunol 2010;21:336–344.

Practice points

• Encourage families to ensure their child has a smoke-free environ-ment

• Episodic viral wheeze is extremely common in the first 3 years• Multi-trigger wheeze persists longer, but there is overlap with epi-

sodic viral wheeze in many young children• Strive for good asthma control• Know where your nearest tertiary care asthma centre is for refer-

ral of children with very severe asthma symptoms despite conven-tional treatment

group. Their administration to very young children

is often easier for parents than the use of spacer

devices for ICS delivery.

The School Age YearsLittle has changed over the past 5 years in rela-

tion to therapeutic management in this age group.

There is still a relative paucity of data on the use

of combination therapy (ICS and LABA) when low-

dose ICS are insufficient to maintain good clinical

control, but a North American study12 confirmed

that the first step-up therapy should be combination

therapy rather than the addition of LTRA. Because

of safety issues of LABA usage, raised by the Food

and Drug Administration, meta-analyses have been

undertaken in all age groups.13 A UK safety study

examined whether tolerance to LABAs was a clini-

cal concern.14 The general consensus is that, when

used in addition to ICS, LABAs are effective and

safe in children, but there is still a need for further

studies as children are underrepresented in clinical

trials compared with adults with asthma.

An exciting development has been the licens-

ing of omalizumab, an anti-IgE monoclonal an-

tibody, for use in children aged 6 years and over

with very severe asthma. This will be used only

in a very small number of children but can have a

dramatic impact on symptoms and has revolution-

ized the lives of a few patients with very severe

symptoms. At present, the National Institute for

Health and Clinical Excellence has not approved its

use in children under 12 years of age. It is given by

subcutaneous injection either fortnightly or monthly

depending on body weight and the absolute concen-

tration of serum IgE.

© 2012 Elsevier Ltd. Initially published in Medicine 2012;40(5):238–242.

About the AuthorWarren Lenney is Professor of Respiratory Child Health at Keele University and Consultant Respiratory Paediatrician at University Hospital of North Staffordshire with research interests in cystic fibrosis, asthma and bronchiolitis. Conflict of Interest: WL has lectured, participated in advisory panels and has been involved in research studies with Abbott Laboratories, Astra Zeneca, Altana Pharma, GSK, MSD, Novartis and Pfizer.


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Di dunia, insidens dan mortalitas Kanker Serviks cukup besar, namun di Eropa dan Australia penanganan kanker ini sudah sangat baik, dibandingkan dengan negara berkembang. Angka mortalitas di Eropa dan Australia separuh dari angka insidensnya, tetapi di wilayah lain seperti Asia, Amerika Selatan dan Afrika didapatkan angka mortalitas yang lebih besar. Di Asia Oceania sendiri, mortalitas terti nggi dijumpai di India, Philippines, dan Thailand. Di Indonesia, data dari Departemen Kesehatan (2012) menunjukan kasus baru kanker serviks mencapai 40-45 pasien per hari dengan angka kemati an mencapai 20-25 pasien per hari. Lebih dari 70% kasus berada di stadium lanjut (di atas stadium IIIb). Dapat dikatakan seti ap satu jam, seorang perempuan meninggal karena kanker serviks di Indonesia. Sayangnya, cakupan skrining juga masih rendah yaitu < 5% (idealnya 80%).

Penyebab kanker serviks ini adalah Human Papillomavirus (HPV). Kanker serviks 100% berkaitan dengan Human Papillomavirus (HPV). HPV terbagi dalam 2 kelompok, yaitu onkogenik (penyebab kanker) dan non-onkogenik (ti dak menyebabkan kanker seperti HPV ti pe 6 & 11). Di dunia, diketahui ada 15 HPV ti pe onkogenik, dan HPV ti pe 16 & 18 menyebabkan 70% kasus kanker serviks. Sekitar 30% penyebab lainnya adalah HPV onkogenik ti pe 31, 33, 45, 51, dll. Dari data peneliti an yang dilakukan oleh Martel C dkk (dimuat di jurnal Lancet Oncology pada tahun 2012), kasus kanker yang disebabkan HPV pada wanita mencapai 568.400/tahun, sedangkan pada pria mencapai 39.000/tahun.

Uniknya, infeksi HPV ini ti dak seperti infeksi lainnya, karena HPV adalah virus yang “cerdas” . Virus Human Papilloma ini ti dak dapat menembus membran basalis dan ti dak menyebabkan viremia sehingga tubuh kita ti dak dapat mengenali virus yang masuk ke dalam tubuh. Respon anti bodi terhadap infeksi alamiah pun hanya dijumpai pada 50% wanita yang pernah terinfeksi oleh HPV. Dari peneliti an, diketahui bahwa perempuan yang terinfeksi alamiah memiliki serum anti bodi yang rendah sehingga anti bodi dari infeksi alamiah ti dak dapat memberikan perlindungan terhadap re-infeksi. Di sisi lain infeksi HPV pada epitel serviks mudah terjadi dan hanya memerlukan waktu

Kanker Serviks dan Tindakan Pencegahannya dr. Sarah Dina, SpOG(K)Departemen Obstetri Ginekologi-Divisi Onkologi GinekologiRS. H. Adam Malik, Medan - Fakultas Kedokteran Universitas Sumatera Utara

The Journey of Cervical Cancer Preventi on

sekitar 6-12 minggu untuk menginfeksi sel ‘tetangganya’ dan merusak sel serviks itu sendiri. Untuk menjadi kanker, dibutuhkan waktu 10-15 tahun.

Tahapan lesi pra-kanker dimulai dari displasia ringan hingga berat, walaupun pada sebagian perempuan dengan displasia dapat mengalami regresi spontan. Dari peneliti an yang dilakukan oleh Prof. Andrijono, infeksi yang dijumpai pada LSIL (low grade squamous epithelial lesion) umumnya HPV ti pe 6 atau 11, yang merupakan ti pe HPV yang ti dak menyebabkan progresivitas ke derajat yang lebih ti nggi. 57% LSIL dapat mengalami regresi sedangkan hanya 1% berlanjut ke karsinoma. Pada HSIL (High-grade squamous intraepithelial lesion), terdapat hubungan yang kuat dengan infeksi yang disebabkan oleh HPV ti pe 16 & 18 (lihat tabel 1 dibawah ini)

Pencegahan kanker serviks mencakup pencegahan primer dan pencegahan sekunder. Pencegahan primer meliputi edukasi dan vaksinasi, sedangkan pencegahan sekunder meliputi pap smear atau IVA. Pencegahan sekunder bisa mendeteksi sel-sel abnormal, lesi pra-kanker dan kanker serviks, tetapi ti dak dapat mencegah terjadinya infeksi HPV yang dapat menyebabkan kanker serviks. Sedangkan pencegahan primer dengan vaksinasi dapat menginduksi anti bodi sehingga mencegah infeksi HPV ti pe onkogenik menjadi kanker serviks yang invasif. Pencegahan primer dengan edukasi pun ti dak kalah penti ngnya untuk meningkatkan kesadaran akan kanker serviks dan pencegahannya. Vaksinasi yang diikuti dengan skrining memberikan perlindungan terbaik dalam mencegah kanker serviks.

Penti ngnya perhati an dan peran tenaga medis dalam pencegahan kanker serviks untuk melindungi perempuan Indonesia menjadi fokus utama salah satu lunch symposium pada PIT POGI ke-20 yang berlangsung tanggal 17 September 2013 dengan tema besar “Perjalanan dalam Pencegahan Kanker Serviks”. Kanker Serviks dan Tindakan Pencegahannya dibahas oleh dr. Sarah Dina, SpOG(K), Vaksin HPV 16/18 dengan Sistem Adjuvant AS04: Data Pendukung Pencegahan Kanker Serviks Terkini dibahas oleh dr. Sigit Purbadi, SpOG(K), dengan moderator simposium Prof. dr. Budi R Hadibroto, SpOG(K).

Kanker Serviks dan Tindakan Pencegahannya dr. Sarah Dina, SpOG(K)Departemen Obstetri Ginekologi-Divisi Onkologi GinekologiRS. H. Adam Malik, Medan - Fakultas Kedokteran Universitas Sumatera Utara

LSIL (NIS I) 57% 32% 11% 1%HSIL (NIS II) 43% 35% 22% 5%HSIL (NIS III) 32% 56% - >12%

Regresi PersistentProgres ke

NIS IIIProgres keKarsinoma

Tabel 1. Perjalanan Kanker Serviks

SHL-JPOG PIT IKA_GSK.indd 1 12/2/2013 4:34:18 PM

Komposisi vaksin HPV 16/18 mengandung anti gen HPV 16 dan 18 dengan suatu sistem adjuvant AS04 (garam aluminium + Monophosphoryl lipid A/ MPL - untuk memperkuat respon imun). Anti gen vaksin berupa VLP (Virus-like Parti cles) tanpa materi geneti k DNA yang bersifat non-infeksius dan non-onkogenik.

Dari studi yang dilakukan oleh Rotelli-Marti ns dkk (dimuat di jurnal Human Vaccine & Immunotherapeuti c pada tahun 2012), didapatkan bahwa kadar anti bodi terhadap HPV ti pe 16 & 18 tetap ti nggi dan bertahan hingga 8,4 tahun. Pada lanjutan studi yang sama, vaksin HPV 16/18 dengan adjuvant AS04 ini masih konsisten menunjukkan kadar anti bodi HPV 16 dan 18 yang ti nggi dan bertahan lama hingga 9,4 tahun.

Suatu studi fase III PATRICIA (Pappiloma Trial Against Cancer in Young Adults) dengan design studi yang acak tersamar ganda (double-blind, randomized 1 : 1), membandingkan kelompok yang diberikan vaksin HPV 16/18 dan kelompok kontrol dengan analisis akhir dilakukan sampai 48 bulan. Studi ini melibatkan 18.644 wanita dengan kisaran usia 15-25 tahun. Kelompok studi TVC-naïve pada studi PATRICIA ini adalah kelompok subjek yang telah menerima minimal 1 dosis vaksin HPV 16/18 dengan sitologi yang normal, HPV DNA negati ve untuk 14 ti pe HPV onkogenik dan seronegati f untuk HPV ti pe 16 & 18. Sebagaimana telah diketahui bahwa HPV ti pe 16 & 18 berkaitan dengan 70% dari kanker serviks, dan ada 30% HPV onkogenik lainnya yang juga menyebabkan kanker serviks. Untuk kelompok studi ini, hasil efi kasi terhadap lesi derajat ti nggi (CIN3+) yang berkaitan dengan HPV 16/18 mencapai 100%. Hasil efi kasi terhadap lesi derajat ti nggi (CIN3+) tanpa melihat ti pe HPV Onkogenik, hasilnya mencapai 93,2% pada kelompok studi TVC-naïve. (lihat tabel 1 dan tabel 2)

Efi kasi menyeluruh vaksin HPV 16/18 terhadap CIN 3+ sebesar 93.2% terlepas dari ti pe HPV onkogenik pada kelompok TVC-naïve. Oleh karena itu, bila pencegahan primer dikombinasikan dengan pencegahan sekunder, perlindungan dapat mendekati 100%.

Beberapa rekomendasi pemberian vaksin HPV di Indonesia, telah dibuat oleh Himpunan Onkologi Ginekologi Indonesia (HOGI), Satgas Imunisasi Dewasa (PAPDI) dan Satgas Imunisasi Anak (IDAI).

Vaksin HPV 16/18 diindikasikan untuk perempuan berusia 10-25 tahun untuk pencegahan infeksi persisten, lesi serviks premalignan, dan kanker serviks yang disebabkan oleh HPV ti pe 16 & 18. Pemberian vaksinasi lengkap terdiri dari 3 dosis dengan jadwal yang direkomendasikan adalah bulan 0, 1, dan 6 secara intramuskular di bagian deltoid (ti dak secara intravaskular atau intradermal). Hingga saat ini pemberian booster masih belum diperlukan.

Pada uji klinis dengan 45.000 dosis vaksin HPV 16/18, efek samping yang paling sering ditemukan adalah nyeri dan kemerahan di tempat sunti kan. Yang perlu diingat pada pemberian vaksin ini adalah bahwa vaksinasi merupakan ti ndakan memasukkan anti gen ke dalam tubuh yang mungkin menyebabkan reaksi anafi laksis (kontraindikasi), walaupun kejadiannya sangat kecil. Oleh karena itu hal ini perlu diinformasikan kepada pasien saat memberikan vaksinasi.

Kesimpulan:• Kanker serviks merupakan beban penyakit di negara maju dan

negara berkembang. Penyebab kanker serviks adalah HPV (Human Papillomavirus) ti pe onkogenik. HPV ti pe onkogenik ti pe 16 & 18 menyebabkan 70% kasus kanker serviks dan HPV ti pe onkogenik lainya seperti HPV ti pe 31, 33, 45, 51, dll menyebabkan sekitar 30% kejadian kanker serviks. Beban kanker yang disebabkan HPV pada wanita, jauh lebih besar daripada pria. Di Indonesia, seti ap satu jam satu perempuan meninggal karena kanker serviks.

• Pencegahan terhadap kanker serviks terbagi atas pencegahan primer dan pencegahan sekunder. Vaksinasi yang diikuti dengan skrining memberikan perlindungan terbaik dalam mencegah kanker serviks.

• Studi peneliti an yang sudah dimuat di jurnal internasional menunjukkan kadar anti bodi terhadap HPV ti pe 16 & 18 tetap ti nggi dan bertahan lama sampai 9,4 tahun.

• Studi peneliti an terbaru dari vaksin HPV 16/18 (studi PATRICIA), yang juga sudah dimuat di jurnal internasional, menunjukkan bahwa untuk kelompok studi TVC-naïve, vaksin ini memberikan hasil efi kasi terhadap CIN3+ sebesar 93,2% tanpa melihat ti pe HPV.

• Pemberian vaksinasi lengkap terdiri dari 3 dosis dengan jadwal yang direkomendasikan adalah bulan 0,1 dan 6 secara intramuskular di bagian deltoid. Hingga saat ini pemberian booster belum diperlukan.

Vaksin HPV 16/18 dengan Sistem Adjuvant AS04: Data Pendukung Pencegahan Kanker Serviks Terkini dr. Sigit Purbadi, SpOG(K)Departemen Obstetri Ginekologi - Divisi Onkologi Ginekologi RS. Dr. Cipto Mangunkusumo, Jakarta - Fakultas Kedokteran Universitas Indonesia

Vaksin HPV 16/18 dengan Sistem Adjuvant AS04: Data Pendukung Pencegahan Kanker Serviks Terkini dr. Sigit Purbadi, SpOG(K)Departemen Obstetri Ginekologi - Divisi Onkologi Ginekologi RS. Dr. Cipto Mangunkusumo, Jakarta - Fakultas Kedokteran Universitas Indonesia

Vaccine 5,466 3 Control 5,452 44

GroupEndpoint N n Vaccine e�cacy, %(95% CI)

93,2 (78.9-98.7)CIN3+

Tabel 1. PATRICIA: Hasil efi kasi terhadap lesi derajat ti nggi tanpa melihat ti pe HPV

GroupEndpoint N n Vaccine e�cacy, %(95% CI)

Vaccine 5,466 0 Control 5,452 27

100,0 (85.5-100.0)CIN3+

Tabel 2. PATRICIA: Hasil efi kasi terhadap lesi derajat ti nggi yang berasosiasi dengan HPV 16/18

SHL-JPOG PIT IKA_GSK.indd 2 12/2/2013 4:34:19 PM

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Ovarian Cancer: Current Management and Future Directions

Siân E Taylor, BSc, MB ChB, MRCOG, MD; John M Kirwan, MB ChB, MRCOG

INTRODUCTION

Painful bladder syndrome (PBS) or interstitial cystitis (IC) is a chronic condition which

causes a significant debilitating effect on quality of life. It was first described by Skene

as ‘an inflammation that has destroyed the mucous membrane partly or wholly and ex-

tended to the muscular parietes’ in 1887.

Since then, multiple different attempts at defining the condition have been made.

The general consensus now is that it is a clinical diagnosis characterized by vague

bladder pain and non-specific urinary symptoms. The International Continence Society

defines PBS as ‘the complaint of suprapubic pain related to bladder filling, accompanied

by other symptoms such as increased daytime and night-time frequency, in the absence

of proven urinary infection or other obvious pathology’. The International Continence So-

ciety reserved the diagnosis of IC for patients with ‘typical cystoscopic and histological

features’. The classic cystoscopic changes generally are glomerulations, haemorrhages

and occasionally a Hunner’s ulcer. Typical histological changes include an abundance of

mast cells. The European Society for the Study of PBS/IC renamed PBS as the bladder

pain syndrome (BPS). Bladder pain syndrome is defined as ‘chronic (> 6 months) pelvic

pain, pressure or discomfort perceived to be related to the urinary bladder accompanied

by at least one other urinary symptom such as persistent urge to void or frequency’.

Confusable diseases such as the overactive bladder syndrome and other conditions like

endometriosis should be excluded. Further classification could be performed, depending

on cystoscopic findings following hydrodistension and morphological changes on blad-

der biopsy.

Painful Bladder Syndrome Maria Vella, MRCOG; Dudley Robinson, MD, FRCOG;

Linda Cardozo, MD, FRCOG

GYNAECOLOGY i Peer reviewed



GYNAECOLOGYGYNAECOLOGY I Peer revIewed

PREVALENCE

Large population-based studies are thought to be

the most accurate way of identifying the preva-

lence of the disease. However, accurate epidemio-

logic studies have been hampered by a variety of

factors, namely the lack of an accepted definition,

the absence of a validated diagnostic marker, and

the overlapping symptoms between the overactive

bladder syndrome and bladder pain. Prevalence

rates are therefore highly variable. The older stud-

ies quote a prevalence rate of 18.1/100,000 wom-

en, whereas, more recently, a rate of 197/100,000

women has been quoted. It typically affects pre-

menopausal women.

Most of the epidemiologic studies performed

are based on symptom questionnaires. The nature

of the disease spans a large spectrum of symptoms.

Hence, because different questionnaires address

different symptoms, prevalence rates vary depend-

ing on the questionnaire used. This was highlighted

when the two main symptom-based questionnaires

used to assess women with BPS, the O’Leary-Sant

questionnaire and the Pelvic Pain and Urgency/Fre-

quency, were compared in the same population. The

prevalence rate using the former was 0.57%. This

was in marked contrast to the 12.6% prevalence

rate obtained using the Pelvic Pain and Urgency/

Frequency questionnaire, hence highlighting the

need for a more standardized questionnaire to be

used for epidemiologic studies. In a recent large

telephone survey in the United States, a prevalence

rate of 3–7% was identified (only soft markers or

associated diseases like fibromyalgia).

AETIOLOGY AND PATHOGENESIS

The aetiology and pathogenesis of PBS is very poor-

ly understood. Over the years, a number of theo-

ries have been put forward. Inflammation and mast

cell activation are thought to have a role. Both are

thought to be implicated and are generally found in

histological samples of most ulcerative and some

non-ulcerative BPS.

Other theories include the possible implication

of infection as an initial trigger, although document-

ed evidence of a urinary tract infection at the onset

of symptoms has only been found in a limited num-

ber of patients. Furthermore, no particular organism

or class of organisms has ever been demonstrated.

Autoantibodies, namely antinuclear antibod-

ies, have been found in some patients with BPS.

This, together with similar clinical and histological

features found in some patients with autoimmune

disorders, has prompted the possibility of an un-

derlying autoimmune theory in the pathogenesis of

some patients with BPS.

Epidemiologic studies on painful bladder syndrome are hindered by various factors, resulting in widely varying prevalence rates.




More recently, there is some evidence to sug-

gest that PBS may be part of a generalized somatic

disorder, thus explaining the possible co-existence

with other chronic conditions such as fibromyalgia

and irritable bowel syndrome. They share features

like symptoms of fatigue and pain and also show an

association with ‘stress’ and psychosocial factors.

Both fibromyalgia and BPS/IC patients display sub-

stantial clinical overlap, and studies have shown

that the latter display diffusely increased periph-

eral nociception as seen in patients with fibromy-

algia. It may therefore be speculated that the same

types of central mechanisms that contribute to the

pathogenesis of fibromyalgia may be operative in

the pathogenesis of BPS/IC.

The general consensus is that the pathogen-

esis involves damage occurring to the bladder epi-

thelium by a primary insult. This may be in the form

of bacterial cystitis, bladder trauma, an autoim-

mune disorder, toxins, etc. The triggering factor will

then set off the cascade of events seen in Figure 1.

This figure also highlights the importance of mast

cells and their interaction with other inflammatory

cells and the nervous system. All of these factors

are implicated in the pathogenesis.

Genetics may also play a role in the aetiology.

A study using a combined mail-in and telephone

survey concluded that adult female first-degree rel-

atives have a prevalence rate of BPS 17 times that

of the normal population, suggesting a possible ge-

netic susceptibility to the condition. A potential ge-

netic role was also shown in a twin study that dem-

onstrated a higher concordance of BPS amongst

monozygotic compared with dizygotic twins.

CLINICAL PRESENTATION

The clinical presentation of these patients may be

very variable. Symptoms are generally vague and

may develop over a number of years. They gener-

ally start off having mild episodic symptoms last-

ing for several days, which tend to become more

severe and consistent with time. The episodic and

non-specific nature of the disease is generally re-

sponsible for a delay in making a diagnosis.

Patients generally present with pain and lower

urinary tract symptoms (these are the two essential

diagnostic criteria). Pain is commonly suprapubic,

although it may also be experienced in the lower

abdominal region, vulva or vagina, urethra, or even

rectum. It may be described as a burning pain, as a

lower abdominal pressure sensation or urethral pain

experienced when passing urine. Urinary symptoms

typically include frequency and, less commonly, ur-

gency. Nocturia is less common in these patients.

A variety of factors may exacerbate symptoms,

including certain acidic foods like tomatoes and al-

Figure 1. Possible mechanisms involved in pathogenesis of Painful bladder syndrome (Moutzouris D et al and Hanno et al).

Insult to urothelium by, e.g,bacterial cystitis, bladder trauma, etc

Damage to bladder epithelium which fails to repair the damage

Leakage of urine constituentsinto urothelitum

Mast cell activationand

release of histamine

C-fibreactivation

Immunogenicresponse

Bladder injury±

chronic neuropathic pain




cohol, spicy foods, caffeine, and chocolate. Some

patients claim that their symptoms are exacerbated

by sexual intercourse. This may cause a significant

negative impact on their relationships. In some

women, symptoms are significantly worse in their

premenstrual week. A higher prevalence of system-

ic and autoimmune disorders like rheumatoid arthri-

tis and Sjogren’s syndrome is found in patients with

BPS. Symptoms of these conditions may therefore

coexist with the more typical symptoms of bladder

pain and lower urinary tract symptoms which these

patients usually present with.

MANAGEMENT

History and Physical examinationInvestigation of these patients aims to exclude any

other pathology prior to making a diagnosis of BPS.

Their initial management should include a thorough

history and physical examination. History should fo-

cus on eliciting the individual symptoms and any of

their specific characteristics. A diagnosis of BPS is

generally made when there is ‘a combination of an

unpleasant sensation (pain, pressure or discomfort)

perceived to be related to the urinary bladder, as-

sociated with lower urinary tract symptoms of more

than 6 weeks duration, in the absence of infection

or any other identifiable cause’ (Hanno et al).

During history taking, emphasis should be

made on the site of the pain and its character. The

relationship of the pain to bladder filling and emp-

tying should be noted. Any associated lower urinary

tract symptoms, any bladder or urological previous

diseases, and any past history of pelvic surgery,

pelvic irradiation, or autoimmune diseases should

all be enquired about. Any exacerbating or reliev-

ing factors or any specific pattern of the symptoms

should also be identified.

A thorough physical examination should also

be carried out, including a general assessment and

examination of the lower abdomen. This helps iden-

tify scars from previous surgery, any obvious organ

enlargement as well as any areas of tenderness.

Hernial orifices should also be examined.

In addition, a pelvic examination should be

performed in order to be able to map pain over

the vulval area. A bimanual examination aims to

identify any enlarged organs as well as eliciting

any tender points over the urethra, bladder, levator

muscles, or adnexae. This helps in diagnosing BPS

and also to exclude any other diseases that may be

part of the differential diagnosis.

investigationsA number of investigations are available in order

to make an accurate diagnosis, exclude any confus-

able diseases, and define the severity of the illness.

Patients with painful bladder syndrome usually present with pain (commonly suprapubic) and lower urinary tract symptoms.




There is however no single investigation or test

that will identify PBS.

Initial Investigations

Laboratory testing – a urinary dipstick and uri-

nalysis for culture, and sensitivity and cytology are

essential initial investigations. Specific testing for

Ureaplasma urelyticum, Mycoplasma hominis, and

Chlamydia may be helpful in some patients. These

initial investigations may help exclude patients

with lower urinary tract symptoms secondary to

infection and may help to identify the necessary

diagnostic and treatment pathway that needs to be

followed.

Frequency volume chart – a 3-day voiding

diary is recommended in the first instance. This

simple investigation helps identify patients with

true frequency as opposed to patients who void

very often, for example, due to excessive drinking.

A functional bladder capacity can also be obtained.

Assessment of pain scores – it is recom-

mended that the severity of pain should be record-

ed using a visual analogue score for pain over 24

hours. A visual analogue score may also be used

in conjunction with a frequency volume chart and

quality of life scores in order to monitor disease

progression or response to treatment.

Assessment of impact on quality of life

– it is considered good clinical practice to evalu-

ate quality of life in anybody presenting with lower

urinary tract symptoms. The O’Leary-Sant symptom

score should be used for this purpose in patients

with BPS. It may also be used in order to monitor

the response to any treatment.

Further Investigations

These may be necessary. The levels of evidence and

their grades of recommendation are summarized in

Table 1.

Potassium testing – this test works on the

principle that these patients have increased epi-

thelial permeability. A volume of normal saline is

initially instilled into the bladder via a urinary cath-

eter. It is held for 5 minutes during which the pa-

tient is asked to rank their urgency and pain on a

6-point analogue scale. The bladder is then drained

and a 0.4-M potassium chloride solution is instilled.

Once again, patients are asked to rank their sense

of urgency and pain on the same 6-point scale. A

positive test is one that elicits pain and provocation

of symptoms. Whilst this test has not been shown

to be of any clinical value and is not really used in

the diagnostic algorithm of these patients, it may

have some prognostic value in being able to predict

Table 1. Levels of evidence and grades of recommendations for invasive tests

Investigation Level of evidence Grade of recommendation

Urodynamics 4 C

Cystoscopy 2 B

The general consensus

is that the pathogenesis

involves damage occurring

to the bladder epithelium

by a primary insult




response to treatment. Further studies are needed

to fully evaluate the potential use of this test.

Urodynamics – urodynamic studies are not

mandatory and are not recommended on a routine

basis. However, they may be very useful in order to

exclude other conditions like detrusor overactivity,

particularly in patients presenting with confusing

symptoms.

Cystoscopy – cystoscopy with or without hy-

drodistension is considered an optional investiga-

tion, although it is mandatory in all patients pre-

senting with haematuria. Classical features include

glomerulations (described as punctuate petechial

haemorrhages occurring after hydrodistension) and

Hunner’s ulcers (patches of red mucosa exhibiting

small vessels radiating to a central pale scar). How-

ever, cystoscopic findings do not generally correlate

with the degree of symptoms exhibited, although

the presence of a Hunner’s lesion is usually asso-

ciated with generalized body pain and urinary ur-

gency.

There has been a great variation in the degree

of hydrodistension. The European Society for the

Study of PBS/IC has therefore suggested a stand-

ardized procedure for cystoscopy and hydrodisten-

sion. ‘A rigid cystoscope is preferred to facilitate

taking of adequate biopsies. Glycine or correspond-

ing filling fluid should be used to allow for coagula-

tion after biopsies. Infusion height should be ap-

proximately 80 cm above the symphysis pubis. A

dripping chamber is used and the bladder is filled

until fluid dribbling stops. If necessary a digital

block is applied around the urethra to prevent leak-

age. Pre-distension inspection includes observation

for radiating vessels, coagulum or fibrin deposits,

white spots, hyperaemia, oedema, cracks, scars or

any other mucosal changes. Continuous inspection

while filling the bladder is advised. When maximum

capacity is reached, the distension is maintained

for 3 minutes. The bladder is emptied and the col-

our of the fluid checked for the degree of bleeding.

The total volume drained is the measured maximum

bladder capacity. During a second filling, the blad-

der is filled to approximately one-third to two-thirds

of the bladder capacity to achieve optimal vision for

inspection and biopsies. The bladder should not be

filled to maximum capacity or distended again to

avoid further provocation of changes with doubtful

reproducibility.’

Other Investigations

Biomarkers – in a quest to develop a non-invasive

diagnostic test for these patients, a number of bio-

markers have been studied. These include tryptase,

urinary histamine, IL-6 and, more recently, antipro-

liferative factor. Antiproliferative factor has been

extensively studied and is shown to be increased in

patients with documented BPS and may therefore be

used as a potential biomarker. However, whilst it has

both a high specificity (90.6%) and a high sensitivity

(91.4%) for BPS in order to be an effective biomarker,

it also needs to be reproducible in other laboratories.

It has as yet not been replicated and the biological

assay has not been proven for commercial use. The

search for an adequate biomarker continues.

Table 2. Levels of evidence and grades of recommendation for conservative therapy

Treatment Level of evidence Grade of recommendation

Behavioural modification

3 C

Physical therapy

3 C

Stress reduction

4 C

Dietary modification

4 C




TreatmentA combination of the lack of definitive diagnostic

tests and standardized clinical criteria make BPS a

difficult condition to treat. The mainstay of treat-

ment is targeted at trying to obtain symptomatic re-

lief, and over the years a variety of different forms

of treatment have been tried. These can be broadly

divided into conservative measures, oral medica-

tion, intravesical therapies, neuromodulation, and

surgery.

Conservative Measures

These, in combination with analgesia, form the ini-

tial management of patients presenting with BPS.

Table 2 summarizes their levels of evidence and

grades of recommendation.

Behavioural modification – this is the cor-

nerstone of treatment for these patients. Patient

motivation is essential. It includes timed voiding,

controlled fluid intake (generally limited to about

1.5 L per day), bladder retraining (gradually ex-

tended voiding interval), and pelvic floor muscle

training. There are no associated side effects. It

is thought to be particularly useful in patients who

complain of frequency and urgency in addition to

bladder pain, and there have been reports of up to

50% of patients showing improvement.

Physical therapy – pelvic floor biofeedback

and soft tissue massage may stimulate relaxation

of pelvic floor muscles and can therefore reduce

pelvic pain. This therapy tends to work better in

patients who are highly motivated and who also

have associated symptoms of urinary frequency and

urgency. In addition, it does not carry any side ef-

fects.

Stress reduction – it has previously been

shown that mental stress aggravates the symptoms

of BPS. Consequently, it is thought that stress-

relieving mechanisms may help improve these

patients’ quality of life. Different strategies ad-

vised have included taking regular exercise, trying

to work shorter hours, and trying to create a less

stressful home environment. Furthermore, a number

of patient education and support groups are avail-

able, and patients are encouraged to take part in

these.

Dietary manipulation – some foods are

thought to exacerbate symptoms. These gener-

ally include caffeine-based products (tea, coffee,

chocolate), fizzy drinks, citrus fruits and juices,

alcohol, spicy foods, and acidic foods like, for ex-

ample, tomatoes. The influence of these foods is

very variable, and the general consensus is not

to put patients on a strict diet but to advise them

to experiment with different foods and try to find

out which foods tend to aggravate their symptoms

themselves.

Medical Management

The main categories of medication used in bladder

pain syndrome include analgesics, antidepressants,

immunosuppressants, antihistamines, and glycosa-

Table 3. Levels of evidence and grades of recommendation for medical therapy

Treatment Level of evidence Recommendation

Analgesics (see text)

4 C

Amitriptyline 2 B

Cimetidine3 C

Gabapentin 4 C

Sodium pentosan-polysulfate

1 D

Hydroxyzine 1 D

Antibiotics 4 D




minoglycans. Table 3 summarizes their levels of evi-

dence and grades of recommendation.

Analgesics – pain is one of the main symp-

toms these patients present with. Its evaluation

and adequate analgesia are therefore fundamental

to their management. Pain evaluation should in-

clude categorical scales (rating as mild, moderate,

and severe), visual analogue scales, and pain ques-

tionnaires like the McGill questionnaire. It is some-

times very difficult to be able to find the correct

combination of analgesics. It is therefore advisable

that these patients should be managed together

with a pain consultant.

Three main classes of drugs are used for pain

management. These include antipyretic analgesics,

opioids, and neuropathic analgesics.

Antipyretic analgesics. The main drugs

used from this group are paracetamol and non-ste-

roidal anti-inflammatory drugs, such as ibuprofen

and diclofenac. Whilst paracetamol is widely avail-

able and is generally used for mild pain, there is

very little evidence for its use in chronic pelvic pain.

Non-steroidal anti-inflammatory drugs have been

shown to be superior to placebo and to paraceta-

mol when treating chronic pelvic pain. They are also

thought to act synergistically with opioids, and it

is recommended to use the two in combination for

patients with refractory pain. They should however

be used with caution as they are associated with

a number of side effects including gastrointesti-

nal bleeds. It is recommended that they should be

avoided in patients who are asthmatic and those

with cardiovascular disease.

Opioid analgesia. It is now accepted that

opioid analgesics may be used for the management

of chronic pelvic pain. They should however only be

used within the following guidelines issued by the

European Association of Urology.

European guidelines for use of opioids in

chronic/non-acute urogenital pain state:

• ‘All other reasonable treatments must have been

tried and failed.

• The decision to instigate long-term opioid ther-

apy should be made by an appropriately trained

specialist in consultation with another physi-

cian (preferably the patient’s family doctor).

• Where there is a history or suspicion of drug

abuse, a psychiatrist or psychologist with an

interest in pain management and drug addiction

should be involved.

Pain evaluation and adequate analgesia are fundamental to the management of painful bladder syndrome.




• The patient should undergo a trial of opioids.

• The dose required needs to be calculated by

careful titration.

• The patient should be made aware (and possibly

give written consent):

– that opioids are strong drugs and associated

with addiction and dependency

– the opioids will normally only be prescribed

from one source

– the drugs will be prescribed for fixed periods

of time, and a new prescription will not be

available until the end of that period

– the patient will be subjected to spot urine and

possibly blood checks to ensure that the drug

is being taken as prescribed and that non-pre-

scribed drugs are not being taken

– inappropriate aggressive behaviour associated

with demanding the drug will not be accepted

– hospital specialist review will normally occur

at least once a year

– the patient may be requested to attend a spe-

cialist psychiatric/psychology review

– failure to comply with the above may result in

the patient being referred to a drug depend-

ency agency and the use of therapeutic, anal-

gesic opioids being stopped

• Morphine is the first-line drug, unless there are

contraindications to morphine or special indi-

cations for another drug. The drug should be

prescribed in a slow-release/modified slow-re-

lease form. Short-acting preparations are unde-

sirable and should be avoided where possible.

Parenteral dosing is undesirable and should be

avoided where possible.”

Neuropathic analgesics. These include tri-

cyclic antidepressants, serotonin reuptake inhibi-

tors, and anticonvulsants.

There is good evidence for the use of tricy-

clic antidepressants in the management of pelvic

pain. The most widely used is amitriptyline. They

are used in much lower doses than they would be

used for mood problems. They are thought to work

by increasing the levels of norepinephrine and/or

serotonin.

Similarly, serotonin reuptake inhibitors also

act by inhibiting reuptake of serotonin. However,

they appear to be less effective than tricyclic an-

tidepressants.

Anticonvulsants have been used in the man-

agement of pain for many years. Although there is

little evidence to show their effectiveness in man-

aging acute pain, they are useful in managing neu-

ropathic pain and may therefore be used to manage

Evidence for the use of intravesical therapies in patients with painful bladder syndrome is limited.




Table 4. Levels of evidence and grades of recommendation for intravesical therapy


Dimethyl sulfoxide

2 B

Hyaluronic acid 1 D

Chondroitin sulfate

4 D

Oxybutynin 4 D

Botulinum toxin

4 D

some of these patients.

Antihistamines – the rationale behind using

antihistamines for the treatment of bladder pain

syndrome is the theory that mast cells releasing an

increased level of histamine may be involved in the

pathogenesis leading to interstitial cystitis. Both

hydroxyzine and cimetidine have been used, the

former being the more widely used of the two. Hy-

droxyzine works as an H1-receptor antagonist and

has anxiolytic and anticholinergic properties along

with its ability to decrease inflammation. Whilst an

open-label study has shown 40% of patients had

some improvement after 3 months of therapy, a ran-

domized controlled trial (RCT) has failed to show

its efficacy. It is still used as one of the first-line

treatments.

Cimetidine, an H2-receptor antagonist, has

also been shown to be beneficial in a small RCT

and is sometimes used.

Immunosuppressants – cyclosporin, an im-

munosuppressant routinely used in organ trans-

plantation, has shown some promising results. It is

thought to act by inhibiting the activation of mast

cells and T cells. Its beneficial effects only last for

the duration of time patients are taking the drug.

Furthermore, it is associated with multiple side

effects like impairment of renal function and in-

creased susceptibility to infection. Hence, caution

must be exerted when taken long-term.

Glycosaminoglycans – sodium pentosan-

polysulfate is a synthetic sulfated polysaccharide

which theoretically works by replenishing the dam-

aged glycosaminoglycan layer overlying the transi-

tional epithelium in patients with BPS. In addition,

it is also thought to inhibit histamine release from

mast cells. It is an oral preparation and is the only

drug approved by the Food and Drug Administration

for symptoms associated with BPS. It is generally

well tolerated with few side effects (gastrointes-

tinal upset, abdominal pain, and headache are the

more common ones). Its safety and clinical efficacy

have been reported in several short-term RCTs.

More recently, its long-term efficacy and safety

were also demonstrated in a study where patients

were followed up for a mean time of 2 years.

Antibiotics – there are conflicting reports of

antibiotic use for patients with BPS. Some studies

suggest that empirical treatment with doxycycline

may be beneficial, while others report no long-

term improvement following antibiotic treatment.

At present, there is no evidence to suggest rec-

ommending antibiotics in the routine treatment of

patients with BPS.

Intravesical Therapies

Intravesical treatments are widely used in the treat-

ment of these patients. Evidence for their use is

limited. Table 4 summarizes the levels of evidence

and recommendations for the different intravesical

therapies in use.

Dimethyl sulfoxide – Dimethyl sulfoxide

has been used for the treatment of BPS patients

for a long time. It is the only intravesical therapy

approved for use in these patients by the Food and

Drug Administration. Its mechanism of action is




not fully understood, although it is thought to act

by inhibition of mast cell activation, hence reduc-

ing inflammation. Some small studies have shown

its beneficial effect. It is instilled weekly for 6–8

weeks. Treatment is then suspended until symp-

toms recur. It is thought to have limited side ef-

fects, although its long-term effects are unknown.

Hyaluronic acid – this is a mucopolysac-

charide which is thought to work by repairing the

GAG layer of the bladder mucosa. Studies have not

shown it to be superior to placebo, and it is there-

fore not recommended in clinical practice.

Chondroitin sulfate – this is another muco-

polysaccharide. Some reports have shown it to be

effective when used in combination with hyaluronic

acid.

Oxybutynin – intravesical oxybutynin when

used in combination with bladder retraining has

been reported to be beneficial in some patients. Its

long-term effects are however unknown.

Botulinum toxin – intravesical injection of

botulinum toxin A may be used in cases of refrac-

tory BPS. A systematic review involving three RCTs

and seven prospective studies showed that some

improvement in eight of the studies. A meta-analy-

sis could not be performed due to the heterogeneity

of reported outcomes. There was a trend towards

short-term benefit, but the systematic review con-

cluded that more robust evidence from further well-

designed trials is needed.

Neuromodulation

Sacral neuromodulation may be recommended in

patients with persistent symptoms which are re-

fractory to oral and intravesical therapies. It in-

volves the implantation of a permanent electrode

to stimulate S3 or S4 nerve roots. Several studies

have shown promising results with success rates

after implantation ranging from 60% to 77% with

follow-up ranging between 19 and 36 months.

Whilst initial results appear promising, there is

however currently insufficient evidence to deter-

mine its role in the treatment of BPS. Further larger

prospective trials are needed.

Surgery

This should be reserved for those patients with

severely debilitating symptoms who have failed

all other forms of treatment. Surgical options are

listed in Table 5.

Hydrodistension – this technique is used

Table 5. Levels of evidence and grades of recommendation for intravesical therapy


Hydrodistension 3 C

Ulcer resection 3 C

Cystoplasty 3 C

Urinary diversion ± cystectomy

3 C

[Dimethyl sulfoxide]

is the only intravesical

therapy approved for

use in... patients by

the Food and Drug

Administration




both for diagnostic purposes and for treatment of

BPS. Most studies reported are retrospective and

uncontrolled. Poor results are reported in the more

recent studies with symptomatic relief obtained in

only a small proportion of patients for a short pe-

riod of time.

Ulcer resection – this was initially de-

scribed as an open procedure by Hunner for treat-

ment of patients with IC. It was later abandoned

owing to the associated morbidity and recurrence

of symptoms. More recently, transurethral resec-

tion has been reported. A large clinical series has

reported significant improvement in most of their

patients, with symptomatic relief lasting for about

23 months. Transurethral resection, coagulation, or

laser ablation of Hunner’s lesions is a recommend-

ed treatment for patients with BPS type 3X.

Cystoplasty/urinary diversion/cystectomy

– these major surgical procedures should only be

considered when all other treatment forms have

failed. They aim to increase the bladder’s func-

tional capacity or divert urine. Patients need to be

carefully selected and very thoroughly counselled

beforehand. They are rarely used in clinical practice

but may be the ultimate option for patients with re-

fractory BPS.

CONCLUSION

Bladder pain syndrome is a chronic debilitating

clinical condition that is still poorly understood.

It is thought to have variable aetiology and a di-

verse clinical presentation. It is therefore a difficult

condition to treat, with limited effective treatment

options.

FURTHER READING

Abrams PH, Cardozo L, Fall M, et al. The standardisation of terminol-ogy of lower urinary tract function: report from the standardisation sub-committee of the international continence society. Neurourol

Urodyn 2002;21:167.Van de Merwe J, Nordling J, Bouchelouche K, et al. Diagnostic crite-

ria, classification, and nomenclature of painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 2008;53:60.

Moutzouris D, Falagas M. Interstitial cystitis: an unsolved enigma. Clin J Am Soc Nephrol 2009;4:1844–1857.

Hanno P, Lin A, Nordling J, et al. Bladder pain syndrome international consultation on incontinence. Neurourol Urodyn 2010;29:191–198.

Hanno P, Dmochowski R. Status of international consensus on inter-stitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn 2008.

Fall M, Baranowski A, Fowler CJ, et al. EAU guidelines on chronic pelvic pain. Eur Urol 2004;46:681.

Sairanen J, Forsell T, Ruutu M. Long term outcome of patients with interstitial cystitis treated with low dose cyclosporine A. J Urol 2004;171:2138–2141.

Parsons CL. Bladder surface glycosaminoglycan: efficient mechanism of environmental adaptation. Urology 1986;27:9.

Al-Zahrani AA, Gajewski JB. Long term efficacy and tolerability of pentosan polysulfate sodium in the treatment of painful bladder syndrome. Can Urol Assoc J Apr 2011;5:113–118.

© 2012 Elsevier Ltd. Initially published in Obstetrics, Gynaecol-ogy and Reproductive Medicine 2012;22(2):44–49.

About the AuthorsMaria Vella is a Subspecialty Trainee in Urogynaecology at King’s

College Hospital, London, UK. Dudley Robinson is a Consultant

Urogynaecologist at King’s College Hospital, London, UK. Linda

Cardozo is Professor of Urogynaecology at King’s College Hospi-

tal, London, UK.

Practice points

• Painful bladder syndrome is a chronic debilitating condition that is difficult to treat.

• Its aetiology and pathogenesis are largely unknown, although mast cells and destruction of the glycosaminoglycan layer in the bladder are thought to play an essential role.

• It is generally a diagnosis of exclusion.• Cystoscopy may show glomerulations and a Hunner’s ulcer. The

degree of these changes may be used to classify the disease.• Treatment is generally aimed at providing symptomatic relief.• The only drug approved by the Food and Drug Administration for

painful bladder syndrome is sodium pentosanpolysulfate.



IN PRACTICEIN PRACTICE I Peer revIewed


Dermatology CinicAn Enlarging Lesion on the Neck Gayle Fischer, MB BS, MD, FRCP

What is the diagnosis of this enlarging lesion occurring on a 13-year-old boy’s neck?

(Answers on p. 254)

(Answers on p. 255)

CASE HISTORYA 13-year-old boy presented with a raised,

hyperkeratotic, warty lesion on his neck

(Figure 1). His parents said it had been

there since his first year of life but had

recently enlarged and become more prom-

inent. The patient’s voice broke recently.

The lesion is not symptomatic but it often

gets caught on his collar.

Figure 1. The lesion occurring on the patient’s neck, which has recently enlarged and become more prominent.

Does Angela require investigation at this stage or can this be deferred until after her baby is born?

Angela, a 28-year-old woman who is 14

weeks pregnant, presents to her GP with

a 2-month history of intermittent rectal

bleeding. Over this period, she has been

passing bright blood on to her toilet paper,

and at times into the toilet bowl. In addi-

tion, her stools are looser than in the past,

and she reports occasional urgency. There

has been no abdominal pain or weight

loss. Her general health is good, and she is

not taking any regular medications. There

is no relevant family history.

Clinical CaseRectal Bleeding in Pregnancy: Don’t Assume It’s BenignChristopher S Pokorny, MB BS, FRACP, FRCP, FACG

IN PRACTICE i Peer reviewed


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Dr. Sumadiono, Sp.A(K)FK Universitas Gajah MadaRSU. Sardjito - Yogyakarta

The 6th Child Health Annual Scienti�ic Meeting Indonesian Pediatric Society

Long term Outcome Growth and Development Snapshot of Allergic Children

Insiden alergi pada anak saat ini makin meningkat dengan cepat dan menjadi permasalahan kesehatan utama di beberapa negara, terlebih onset alergi umumnya timbul sebagai march allergy sejak awal kehidupan anak. Bagaimana kaitan alergi dengan tumbuh kembang anak dan outcome-nya dalam jangka panjang, serta dampak manajemen alergi dibahas dalam suatu snapshot presentasi duet pakar tumbuh kembang dan alergi anak DR. Dr. Ahmad Suryawan, Sp.A(K) dan Dr. Sumadiono, Sp.A(K) serta moderator Dr. Endang Dewi Lestari, Sp.A(K), MPH pada kesempatan Dinner Symposium PIT IKA ke-6 di Solo Oktober 2013 lalu.

Manajemen alergi melibatkan hampir semua disiplin ilmu kesehatan anak, diantaranya aspek preventif sebelum bayi lahir dan deteksi dini setelah bayi lahir yang termasuk dalam perinatologi; respirologi terkait rinitis alergi, asma dan angioedema laring; nutrisi dan gastrohepatologi terkait alergi protein susu sapi; pediatrik sosial tumbuh kembang dan endokrinologi; kegawatdaruratan pediatrik seperti anafi laksis, angioedema; kardiologi terkait efusi perikardial, syok distributif; hematologi terkait reaksi alergi pada kemoterapi dan reaksi alergi transfusi; nefrologi terkait alergi terhadap material dialisis dan pada penelitian terbaru ditemukan nocturnal enuresis terkait IgE dan alergi makanan; radiologi terkait alergi terhadap kontras, endoskopi dan MRI; neurologi terkait gejala ataksia, neuropati dan kasus Sindrom Steven Johnson akibat pemberian antiepilesi; kasus infeksi dan tropical medicine terkait alergi obat. Anamnesis, riwayat penyakit dan pemeriksaan fi sik pada pasien alergi merupakan pendekatan lini pertama. Sedangkan untuk memastikan diagnosis, dilakukan pemeriksaan IgE mediated (skin prick test/SPT, dan IgE spesifi k serta uji eliminasi provokasi) atau pada yang non IgE mediated dilakukan atopy patch test dan eliminasi provokasi. Tes alergi hendaknya dilakukan dengan tes yang telah valid, misalnya tes alergen berbasis IgE spesifi k in vitro atau SPT sebagai pendekatan alergi lini kedua. Pemeriksaan molecular based allergy/ MA sebagai lini ketiga dilakukan apabila

hasil tes lini pertama dan kedua belum dapat mendukung diagnosis alergi. Kendala manajemen alergi yang umum ditemui: penghindaran yang sulit dilakukan, biaya dan SDM terbatas, ketersediaan susu formula, distribusi dokter anak di Indonesia tidak merata serta pemeriksaan SPT yang tidak dimiliki di semua senter kesehatan. Disamping itu, penanganan alergi perlu evaluasi jangka panjang. Penanganan alergi pada anak berbeda dengan penanganan orang dewasa karena perlu dicermati dampaknya pada kualitas hidup dan tumbuh kembang di masa mendatang. Dampak alergi terhadap tumbuh kembang jangka panjang, dapat disebabkan oleh beberapa hal antara lain: (1) perjalanan alami penyakit alergi (2) efek samping obat (3) kondisi kronis dan (4) presipitasi lingkungan, misalnya dampak diet/eliminasi alergi. Evaluasi tumbuh kembang pada anak alergi meliputi pengukuran parameter pertumbuhan antropometri berat badan, tinggi badan, indeks masa tubuh (IMT) dan lingkar kepala. Disamping itu, perlu dipantau pengaruhnya terhadap perkembangan motorik, berbicara dan bahasa, sosialisasi, perilaku, emosi dan kognitif.

Manajemen alergi dan evaluasi tumbuh kembang Salah satu studi dampak alergi pada anak terhadap pertumbuhan jangka panjang, dilakukan secara longitudinal oleh Mukaida K, dkk di Jepang tahun 2010 yang melibatkan 11.473 anak-anak usia

DR. Dr. Ahmad Suryawan, Sp.A(K)FK Universitas AirlanggaRSUD Dr. Soetomo - Surabaya

sekolah dengan asma bronkial, dermatitis atopik, rinitis alergi, konjungtivitis alergi dan alergi makanan. Eliminasi telur, susu dan gandum dilakukan pada usia awal (0-1 tahun) dan diikuti hingga usia 7-15 tahun. Kemudian dilakukan pengukuran antropometri, dan didapatkan hal unik sbb: Bila diet eliminasi pada bayi (Food avoidance infant /FAI) dapat dilakukan terminasi secara bertahap antara uisa 1-3 tahun, maka tidak didapatkan perbedaan yang bermakna dalam hal berat badan, tinggi badan dan lingkar kepala saat berusia 7-15 tahun dibandingkan kelompok anak yang tidak dilakukan eliminasi diet (Non-FAI). Namun bila terminasi diet eliminasi dilakukan antara usia 3-6 tahun atau diteruskan hingga berusia diatas 6 tahun, pada anak FAI didapatkan simpang baku berat badan yang lebih rendah secara bermakna (p=0.01) dibandingkan anak non-FAI. Sedangkan untuk tinggi badan dan lingkar kepala, tidak didapatkan perbedaan bermakna. Pada anak yang mengalami eliminasi diet 1 jenis, mempunyai simpang baku tinggi badan yang lebih tinggi (p=0.02) dibanding yang mengalami eliminasi diet 2-3 jenis. Eliminasi diet susu, lebih berdampak terhadap rendahnya tinggi badan dibandingkan eliminasi diet telur atau gandum (P=0.04). Studi lain mencatat anak-anak usia 3-10 tahun yang sepanjang periode hidupnya dieliminasi susu sapi selama 4 bulan akan memiliki IMT yang tinggi, namun penyebabnya bukan karena kegemukan melainkan tinggi badan dan tulang kepala lebih kecil dibanding anak-anak yang tidak alergi. Selain itu karena bone mineral content dan none density-nya lebih rendah, maka sekira 24% anak-anak tersebut memiliki risiko mengalami patah tulang. Aspek pengobatan jangka panjang alergi juga dapat mempengaruhi tumbuh kembang seorang anak. Studi meta-analisis Sharek PL dkk pada jurnal Pediatrics (2000) membandingkan inhalasi steroid dan inhalasi nonsteroid, menunjukkan hasil bahwa dosis moderat beclomethasone dan fl utikason sebagai terapi asma ringan sampai sedang pada anak, menyebabkan penurunan kecepatan pertumbuhan linier masing-masing sebesar 1,51 cm / tahun dan 0,43 cm / tahun. Sedangkan studi meta-analisis lain, oleh Allen DB dkk, membandingkan kortikosteroid inhalasi beclomethasone dipropionate dan oral dan hasilnya menunjukkan inhalasi beclomethasone dipropionate tidak berkaitan dengan penurunan tinggi badan liner. Baik beclomethasone dosis tinggi maupun rendah pada anak dengan alergi tingkat rendah maupun tinggi. Studi Allen ini akhirnya menyimpulkan bahwa secara statistik tidak terbukti adanya keterkaitan antara beclomethasone dipropionate dosis tinggi dan terapi jangka panjang yang diberikan pada pasien asma berat. (lihat grafi k 1). Anak-anak asma perlu dipantau tinggi akhirnya saat dewasa. Walau penggunaan obat asma tidak berkaitan dengan risiko keterlambatan atau kegagalan pencapaian tinggi badan (TB), namun mungkin akan ada keterlambatan onset of puberty, baik laki-laki maupun perempuan. Deselarasi TB pada delayed puberty bersifat fi siologis dan

selanjutnya saat masuk masa puberty akan terjadi aselerasi, sehingga anak-anak akan mencapai tinggi badan akhir dengan aman. Studi survey cross section Forrest CB, dkk mengobservasi dampak asma pada status kesehatan setelah usia dewasa. Studi ini melibatkan 3.109 remaja dan membandingkan kelompok anak-anak sehat dengan anak-anak dengan asma. Keluaran jangka panjang dinilai dengan CHIP-AE (Child Health and Illness Profi le, Adolescent Edition) dan hasilnya anak-anak dengan asma akan mengalami persepsi kesejahteraan yang lebih rendah, lebih banyak pembatasan fi sik, namun tidak mempengaruhi prestasi akademik maupun prestasi dalam pekerjaan. Skor perubahan perilaku dapat digunakan sebagai prediktor yang baik untuk memprediksi apakah anak yang mengalami dermatitis atopi akan berkembang menjadi asma (OR adjusted 1.15 ; 95% CI 1.02-1.29). Dimasa mendatang perlu dibangun suatu pondasi status kesehatan bagi anak-anak dengan alergi dan merangkul berbagai disiplin ilmu dalam suatu kerangka kerja. Dengan demikian, kualitas hidup anak akan meningkat. Selain itu, perlu diterapkan upaya preventif dan intervensi alergi jangka panjang maupun jangka pendek, dan pentingnya diadakan suatu registrasi/registry. Penelitian lanjut diperlukan untuk mengurangi miss-diagnosis dan terapan manajemen yang tepat berdasarkan rekomendasi IDAI. Salah satu langkah wawasan kedepan yang kini telah dilakukan adalah diluncurkannya revisi rekomendasi diagnosis, tata laksana alergi susu sapi 2013.

Kesimpulan o Alergi pada anak berpengaruh pada tumbuh kembang dan

untuk penanganan yang komprehensif perlu melibatkan disiplin ilmu kesehatan anak lainnya.

o Untuk meningkatkan kualitas hidup anak dengan alergi perlu dibuat suatu pondasi dari berbagai disiplin ilmu dan kerangka kerja yang kuat.

- . 30

- . 20

- . 10

- . 00

+. 10

+. 20

+. 30

+. 40

+. 50

+. 60

+. 70no growthimpairment

growthimpairment

LowDosage

LowDosage

HighDosage

High SeverityLow Severity

Grafik 1: efek keparahan asma dan dosis inhalasi BDP pada pertumbuhan linier.

HighDosage

EFFECTSIZE

SHL-JPOG PIT IKA_Shanghiang.indd 1 12/5/2013 11:31:59 AM

Dr. Sumadiono, Sp.A(K)FK Universitas Gajah MadaRSU. Sardjito - Yogyakarta

The 6th Child Health Annual Scienti�ic Meeting Indonesian Pediatric Society

Long term Outcome Growth and Development Snapshot of Allergic Children

Insiden alergi pada anak saat ini makin meningkat dengan cepat dan menjadi permasalahan kesehatan utama di beberapa negara, terlebih onset alergi umumnya timbul sebagai march allergy sejak awal kehidupan anak. Bagaimana kaitan alergi dengan tumbuh kembang anak dan outcome-nya dalam jangka panjang, serta dampak manajemen alergi dibahas dalam suatu snapshot presentasi duet pakar tumbuh kembang dan alergi anak DR. Dr. Ahmad Suryawan, Sp.A(K) dan Dr. Sumadiono, Sp.A(K) serta moderator Dr. Endang Dewi Lestari, Sp.A(K), MPH pada kesempatan Dinner Symposium PIT IKA ke-6 di Solo Oktober 2013 lalu.

Manajemen alergi melibatkan hampir semua disiplin ilmu kesehatan anak, diantaranya aspek preventif sebelum bayi lahir dan deteksi dini setelah bayi lahir yang termasuk dalam perinatologi; respirologi terkait rinitis alergi, asma dan angioedema laring; nutrisi dan gastrohepatologi terkait alergi protein susu sapi; pediatrik sosial tumbuh kembang dan endokrinologi; kegawatdaruratan pediatrik seperti anafi laksis, angioedema; kardiologi terkait efusi perikardial, syok distributif; hematologi terkait reaksi alergi pada kemoterapi dan reaksi alergi transfusi; nefrologi terkait alergi terhadap material dialisis dan pada penelitian terbaru ditemukan nocturnal enuresis terkait IgE dan alergi makanan; radiologi terkait alergi terhadap kontras, endoskopi dan MRI; neurologi terkait gejala ataksia, neuropati dan kasus Sindrom Steven Johnson akibat pemberian antiepilesi; kasus infeksi dan tropical medicine terkait alergi obat. Anamnesis, riwayat penyakit dan pemeriksaan fi sik pada pasien alergi merupakan pendekatan lini pertama. Sedangkan untuk memastikan diagnosis, dilakukan pemeriksaan IgE mediated (skin prick test/SPT, dan IgE spesifi k serta uji eliminasi provokasi) atau pada yang non IgE mediated dilakukan atopy patch test dan eliminasi provokasi. Tes alergi hendaknya dilakukan dengan tes yang telah valid, misalnya tes alergen berbasis IgE spesifi k in vitro atau SPT sebagai pendekatan alergi lini kedua. Pemeriksaan molecular based allergy/ MA sebagai lini ketiga dilakukan apabila

hasil tes lini pertama dan kedua belum dapat mendukung diagnosis alergi. Kendala manajemen alergi yang umum ditemui: penghindaran yang sulit dilakukan, biaya dan SDM terbatas, ketersediaan susu formula, distribusi dokter anak di Indonesia tidak merata serta pemeriksaan SPT yang tidak dimiliki di semua senter kesehatan. Disamping itu, penanganan alergi perlu evaluasi jangka panjang. Penanganan alergi pada anak berbeda dengan penanganan orang dewasa karena perlu dicermati dampaknya pada kualitas hidup dan tumbuh kembang di masa mendatang. Dampak alergi terhadap tumbuh kembang jangka panjang, dapat disebabkan oleh beberapa hal antara lain: (1) perjalanan alami penyakit alergi (2) efek samping obat (3) kondisi kronis dan (4) presipitasi lingkungan, misalnya dampak diet/eliminasi alergi. Evaluasi tumbuh kembang pada anak alergi meliputi pengukuran parameter pertumbuhan antropometri berat badan, tinggi badan, indeks masa tubuh (IMT) dan lingkar kepala. Disamping itu, perlu dipantau pengaruhnya terhadap perkembangan motorik, berbicara dan bahasa, sosialisasi, perilaku, emosi dan kognitif.

Manajemen alergi dan evaluasi tumbuh kembang Salah satu studi dampak alergi pada anak terhadap pertumbuhan jangka panjang, dilakukan secara longitudinal oleh Mukaida K, dkk di Jepang tahun 2010 yang melibatkan 11.473 anak-anak usia

DR. Dr. Ahmad Suryawan, Sp.A(K)FK Universitas AirlanggaRSUD Dr. Soetomo - Surabaya

sekolah dengan asma bronkial, dermatitis atopik, rinitis alergi, konjungtivitis alergi dan alergi makanan. Eliminasi telur, susu dan gandum dilakukan pada usia awal (0-1 tahun) dan diikuti hingga usia 7-15 tahun. Kemudian dilakukan pengukuran antropometri, dan didapatkan hal unik sbb: Bila diet eliminasi pada bayi (Food avoidance infant /FAI) dapat dilakukan terminasi secara bertahap antara uisa 1-3 tahun, maka tidak didapatkan perbedaan yang bermakna dalam hal berat badan, tinggi badan dan lingkar kepala saat berusia 7-15 tahun dibandingkan kelompok anak yang tidak dilakukan eliminasi diet (Non-FAI). Namun bila terminasi diet eliminasi dilakukan antara usia 3-6 tahun atau diteruskan hingga berusia diatas 6 tahun, pada anak FAI didapatkan simpang baku berat badan yang lebih rendah secara bermakna (p=0.01) dibandingkan anak non-FAI. Sedangkan untuk tinggi badan dan lingkar kepala, tidak didapatkan perbedaan bermakna. Pada anak yang mengalami eliminasi diet 1 jenis, mempunyai simpang baku tinggi badan yang lebih tinggi (p=0.02) dibanding yang mengalami eliminasi diet 2-3 jenis. Eliminasi diet susu, lebih berdampak terhadap rendahnya tinggi badan dibandingkan eliminasi diet telur atau gandum (P=0.04). Studi lain mencatat anak-anak usia 3-10 tahun yang sepanjang periode hidupnya dieliminasi susu sapi selama 4 bulan akan memiliki IMT yang tinggi, namun penyebabnya bukan karena kegemukan melainkan tinggi badan dan tulang kepala lebih kecil dibanding anak-anak yang tidak alergi. Selain itu karena bone mineral content dan none density-nya lebih rendah, maka sekira 24% anak-anak tersebut memiliki risiko mengalami patah tulang. Aspek pengobatan jangka panjang alergi juga dapat mempengaruhi tumbuh kembang seorang anak. Studi meta-analisis Sharek PL dkk pada jurnal Pediatrics (2000) membandingkan inhalasi steroid dan inhalasi nonsteroid, menunjukkan hasil bahwa dosis moderat beclomethasone dan fl utikason sebagai terapi asma ringan sampai sedang pada anak, menyebabkan penurunan kecepatan pertumbuhan linier masing-masing sebesar 1,51 cm / tahun dan 0,43 cm / tahun. Sedangkan studi meta-analisis lain, oleh Allen DB dkk, membandingkan kortikosteroid inhalasi beclomethasone dipropionate dan oral dan hasilnya menunjukkan inhalasi beclomethasone dipropionate tidak berkaitan dengan penurunan tinggi badan liner. Baik beclomethasone dosis tinggi maupun rendah pada anak dengan alergi tingkat rendah maupun tinggi. Studi Allen ini akhirnya menyimpulkan bahwa secara statistik tidak terbukti adanya keterkaitan antara beclomethasone dipropionate dosis tinggi dan terapi jangka panjang yang diberikan pada pasien asma berat. (lihat grafi k 1). Anak-anak asma perlu dipantau tinggi akhirnya saat dewasa. Walau penggunaan obat asma tidak berkaitan dengan risiko keterlambatan atau kegagalan pencapaian tinggi badan (TB), namun mungkin akan ada keterlambatan onset of puberty, baik laki-laki maupun perempuan. Deselarasi TB pada delayed puberty bersifat fi siologis dan

selanjutnya saat masuk masa puberty akan terjadi aselerasi, sehingga anak-anak akan mencapai tinggi badan akhir dengan aman. Studi survey cross section Forrest CB, dkk mengobservasi dampak asma pada status kesehatan setelah usia dewasa. Studi ini melibatkan 3.109 remaja dan membandingkan kelompok anak-anak sehat dengan anak-anak dengan asma. Keluaran jangka panjang dinilai dengan CHIP-AE (Child Health and Illness Profi le, Adolescent Edition) dan hasilnya anak-anak dengan asma akan mengalami persepsi kesejahteraan yang lebih rendah, lebih banyak pembatasan fi sik, namun tidak mempengaruhi prestasi akademik maupun prestasi dalam pekerjaan. Skor perubahan perilaku dapat digunakan sebagai prediktor yang baik untuk memprediksi apakah anak yang mengalami dermatitis atopi akan berkembang menjadi asma (OR adjusted 1.15 ; 95% CI 1.02-1.29). Dimasa mendatang perlu dibangun suatu pondasi status kesehatan bagi anak-anak dengan alergi dan merangkul berbagai disiplin ilmu dalam suatu kerangka kerja. Dengan demikian, kualitas hidup anak akan meningkat. Selain itu, perlu diterapkan upaya preventif dan intervensi alergi jangka panjang maupun jangka pendek, dan pentingnya diadakan suatu registrasi/registry. Penelitian lanjut diperlukan untuk mengurangi miss-diagnosis dan terapan manajemen yang tepat berdasarkan rekomendasi IDAI. Salah satu langkah wawasan kedepan yang kini telah dilakukan adalah diluncurkannya revisi rekomendasi diagnosis, tata laksana alergi susu sapi 2013.

Kesimpulan o Alergi pada anak berpengaruh pada tumbuh kembang dan

untuk penanganan yang komprehensif perlu melibatkan disiplin ilmu kesehatan anak lainnya.

o Untuk meningkatkan kualitas hidup anak dengan alergi perlu dibuat suatu pondasi dari berbagai disiplin ilmu dan kerangka kerja yang kuat.

- . 30

- . 20

- . 10

- . 00

+. 10

+. 20

+. 30

+. 40

+. 50

+. 60

+. 70no growthimpairment

growthimpairment

LowDosage

LowDosage

HighDosage

High SeverityLow Severity

Grafik 1: efek keparahan asma dan dosis inhalasi BDP pada pertumbuhan linier.

HighDosage

EFFECTSIZE

SHL-JPOG PIT IKA_Shanghiang.indd 1 12/5/2013 11:31:59 AM

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FA Cover SHL 20.5x27.5cm oke.pdf 2 11/8/13 6:50 PM

Journal of Paediatrics, Obstetrics & Gynaecology (JPOG) is a peer-reviewed journal of

clinical reviews that covers all aspects of paediatrics, obstetrics and gynaecology, with a

focus on patient and disease management. The Journal is published every 2 months in

Hong Kong, Singapore, Malaysia, Indonesia and the Philippines.

EDITORIAL AND PEER REVIEW

All review articles and case studies submitted will undergo a prompt evaluation by the Editor for appropriateness of publication in JPOG. Once accepted, all clinical review papers will be sent to expert consultants for peer review. We adopt a blinded peer review approach, which means the identities of authors and that of the reviewer are kept confidential.

Accepted manuscripts are copyedited according to journal style and returned to the authors for final approval. Authors are responsible for all statements made in their work and should ensure the accuracy of the content.

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Clinical ReviewsSystematic critical assessments of literature and data sources pertaining to clinical topics. Reviews should emphasize factors such as cause, diagnosis, prognosis, treatment and prevention. A list of up to five key points of the article should be provided.

Reviews are, in general, invited papers from recognized experts in a specific field, however unsolicited papers of good quality are also welcome. The paper should not exceed 3,000 words, and the number of references cited should be limited to 40.

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Letters to the EditorLetters may be sent to the Editorial Office bye-mail to [email protected] or posted on the JPOG website at www.jpog.com. Lettersshould not exceed 300 words, have no more than five references and contain no more than one illustration.Lettersmaybeeditedprior topublication.

Book ReviewsBook reviews are prepared by invited reviewers commenting on newly published books with interesting clinical topics. Book reviews should be limited to 200 words.

Reviews with substantial educational value will be included as continuing medical education articles. Authors of selected articles are requested to include10true/falsequestionsforreaderstorespond.Pleaseprovideanswersseparately with explanations. The quiz questions should be in the form of declarative statements with an objective to test not only recall of a specific fact, but also comprehension and application of information presented in the article. Authors should be careful to:

• Testsignificantcontentandavoidtrivialstatements;

• Writestatementsthatcanbeclassifiedunequivocallyaseithertrueorfalseandavoidambiguity;

• Avoid takingstatementsverbatim fromthe text,whichacandidatecouldeasilycheckback.Paraphrasestatementswhereverpossible;

• Notdeliberatelytryto“trick”candidateswithquestions;

• Constructstatementsthathaveonlyonemajorpoint;

• Avoidusingnegativestatements,astheseareunnecessarilyconfusing;and

• Avoidreferringtoinformationthatcannotbefoundinthearticleorisnotinferred by the article’s content.

Instructions FOR AUTHORS

Instructions FOR AUTHORS

MANUSCRIPT SUBMISSION

All material is assumed to be submitted exclusively unless otherwise stated, and must not have been published previously in print or electronic format, and is not under consideration by another publication or electronic medium.

CriteriaOnly papers written in English will be considered for publication. For clinical reviews, statements are best supported by data and references. The topic should be of interest and relevance to the practice of paediatrics, obstetrics and gynaecology in Asia.

ProcedureSubmission by e-mail: The manuscript should be prepared in Microsoft Word format and submitted as an e-mail attachment to [email protected]. Tables can

Journal article:1. McCaffery K, Forrest S, Waller J, et al. Attitudes towardsHPVtesting:aqualitativestudyofbeliefsamongIndian, Pakistani, African-Caribbean and white BritishwomenintheUK.BrJCancer2003;88:42-46.

Book:2. Lask B, Bryant-Waugh R. Anorexia Nervosa andRelatedEatingDisordersinChildhoodandAdolescence.2nded.Hove:PsychologyPress;2000.

3. Wolf A. Analgesia in the neonate. In: Textbook of Neonatology. 3rd ed. Edinburgh: Churchill Livingstone;1999.

Website:4. Lepine LA, Hillis SD, Marchbanks PA, et al.Hysterectomy surveillance-United States, 1980 1993. Available at www.cdc.gov/mmwr/preview/mmwrhtml/ 00048898.htm.AccessedDecember10,2001.

Thesis:5. King L. Modern Literary Apparitions and TheirMind-Altering Effects [master’s thesis]. Evanston, Ill: NorthwesternUniversity;1994.

Title PageA title page should contain the following information:• Titleofthepaper• Fullnamesofallauthors• Academicqualificationsofallauthors• Titlesandaffiliationsofallauthors• E-mail,mailingaddress,telephoneandfaxnumbersofthecorresponding

author

Abstract/Introduction(Clinical Reviews only) The abstract should be a concise outline of the main purpose of the paper containing approximately 50 words.

Illustrations/FiguresIllustrationsincludephotographs,pho-tomicrographs,chartsanddiagrams;theymust be of professional quality and of a size permitting some reduction in the finalcopy.Patientidentificationshouldbeobscured,andtransferarrowsshouldbe used to indicate subtle but salient points.

TablesEach column should have a short or abbre-viated heading. Place explanatorymatterinfootnotes,notintheheading.Non-standardabbreviationsusedineachtable should be defined in the footnotes.

Language and StyleBritish spelling is used. Système Inter-national (SI) units are used except for bloodpressurevalueswhicharetobereportedinmmHg.Fortheexpressionof length, area, mass and volume, metric system is used. Temperatures are to be given indegreeCelsius.Non-proprietarynamesofmedical substances shouldbeusedunless the specific brand/trade name of a drug is directly relevant to the discussion.

be submitted in either Microsoft Word or Excel format, and illustrations in .tif or .jpg format with high quality resolution (at least 300 dpi).

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ReferencesReferences must be numbered consecutively in order of appearance in the text. When listing references,followtheVancouverstyle.Journalnames should be abbreviated according to IndexMedicus.Listallauthorsand/oreditorsuptosix;ifmorethansix,listthefirstthreeandetal. Examples for referencing style:

MANUSCRIPT PREPARATION

Imaging Paediatric Brain Tumours

Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology


INTRODUCTION

Chronic fatigue syndrome (CFS) or myalgic encephalomyopathy (ME) is a relatively com-

mon and serious condition affecting between 0.1% and 2% of children and young people

aged under 18. It received public recognition as a specific clinical condition in 2002,

and understanding of the condition is slowly improving. However, it is a heterogeneous

condition with no diagnostic tests, so diagnosis can be a complex task, particularly as

the child or adolescent can present with a range of signs and symptoms. The presenta-

tion and course of the condition are often seen to ebb and flow, further exacerbating the

difficulty in predicting, understanding, and managing symptoms.

Although the National Institute for Health and Care Excellence (NICE) guidance

recommends referral to a paediatrician after 6 weeks of symptoms, the time from onset

of symptoms to initial consultation with an appropriate professional is extremely vari-

able and, for some children and young people, never takes place. Inevitably, the lack of

positive investigative findings coupled with the ongoing debate about the pathophysi-

ological basis of the condition leads to considerable and confusing debate amongst pro-

fessionals and lay groups alike. This, in turn, frequently contributes to a poor patient/

carer experience with delay in diagnosis and, not infrequent, hostility.

This is unfortunate as CFS is a serious illness causing significant school absence

and has long-term consequences for the educational, social. and psychological develop-

ment of the child or young person if there is no appropriate intervention. It also has an

impact on family function and, in some instances, may result in financial hardship. As

specialist provision is patchy, it is important that any professional working with children

and young people with CFS has a thorough understanding of the condition and its man-

agement.

Chronic Fatigue Syndrome in Children and Young People

Carrie Mackenzie, MBChB, FRCPCH, DCCH, MD; Alison Wray, BA, MPhil CPsychol





DEFINITION

The fact that the terminology associated with this

condition has created such controversy over a num-

ber of years indicates the difficulties inherent in

labelling such a heterogeneous group of individu-

als who present with a wide range of physical and

emotional symptoms. However, the persisting and

disabling fatigue universal in this group of children

and young people has lead to our team favouring

the use of the term chronic fatigue syndrome. We

believe this reduces confusion and assists in ac-

ceptance of the diagnosis when used in conjunction

with a sympathetic explanation of the very variable

nature of the condition, which includes both physi-

cal and psychological symptoms. The term favoured

and adopted by the Royal College of Paediatrics

and Child Health is CFS/ME, but in our experience

the term ME carries with it a much more physical

or medical basis which patients and carers often

confuse with conditions such as multiple sclerosis.

Moreover, there are still those who believe that

CFS and ME are two separate and distinct entities,

which share features with other conditions such as

‘medically unexplained symptoms’ or other func-

tional somatic disorders and overlap with chronic

pain syndromes. In making the diagnosis, it is cru-

cial to also ‘demedicalize’ the condition, drawing

a line under all that has gone before in terms of

investigating the constellation of presenting symp-

toms and reaching agreement with the affected

child or young person and their carers that the way

forward is by means of rehabilitation from the point

they now find themselves at. Indeed if this does not

happen, it may prove difficult to engage the child

and family fully in a treatment programme (Table 1).

EPIDEMIOLOGY

Prevalence data for CFS are heterogeneous and

confusing as a result of different study methodolo-

gies (eg, settings and diagnostic criteria) and dif-

ferent age limits. A number of studies report preva-

lence rates from 0.1% to 2% of children under 18.

Most studies focus on the condition in adolescents;

those reporting prevalence rates in younger chil-

dren show it to be markedly lower. There remains

Table 1. Definition of chronic fatigue syndrome in children and young people

• NICE guidance – Chronic fatigue syndrome/myalgic encephalo-myopathy involves a complex range of symptoms that includes fatigue, malaise, headaches, sleep disturbance, difficulties with concentration, and muscle pain. The pattern and intensity of symptoms vary between people and during the course of each person’s illness.

• Royal College of Paediatrics and Child Health – generalized fa-tigue persisting after routine tests and investigations have failed to identify an obvious underlying ‘cause’. The fatigue is likely to be associated with other ‘classical’ symptoms, such as difficulty in concentrating and disturbed sleep patterns, and is classically exacerbated by effort (both mental and physical).

In making

the diagnosis,

it is crucial to also

‘demedicalize’

the condition




a distinct need for further research to truly under-

stand the prevalence of CFS in the child and adoles-

cent population.

The evidence on gender remains inconclusive.

Some studies report no significant gender differ-

ence, whereas others report a female excess of 2:1.

Our own figures based on 176 children and young

people under 16 show a ratio of two boys to every

three girls.

PATHOLOGY AND PATHOGENESIS

There has been a plethora of research into CFS, but

the very wide and varied nature of the hypotheses

being pursued indicates the clear lack of under-

standing of the pathophysiological basis for this

condition. Many of our children and young people

can describe an intercurrent illness immediately

prior to the onset of their fatigue, but the exact na-

ture of this usually relatively minor illness is often

unclear and it is by no means a universal precursor.

It may well be that some external ‘trigger’ provokes

an autoimmune process in genetically predisposed

individuals, but the evidence for this does not yet

exist and it seems likely that the causation is multi-

factorial. Various aetiological factors, such as level

of exercise taken, personal and maternal psycho-

logical well being, gender, socioeconomic status,

birth weight, birth order, coexistence of atopic con-

ditions, exposure to certain viruses, school attend-

ance, and achievement, have all been considered,

but as yet their contribution, if any, remains un-

clear. Any hope of intervention to prevent CFS in fu-

ture generations will demand a better understand-

ing of the aetiological factors at play. However, the

once popular stereotypical picture of the affected

individual being female, highly intelligent, and high

achieving is not borne out by our experience.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

The diagnosis of CFS relies not only on the exclu-

sion of other pathology by means of appropriately

As the symptoms of chronic fatigue syndrome overlap with other diagnoses, necessary investigations are needed to exclude any other disease.




Table 2. Investigations

These tests should usually be done:• Urinalysis for protein, blood and glucose• Full blood count• Urea and electrolytes• Liver function• Thyroid function• Erythrocyte sedimentation rate or plasma viscosity• C-reactive protein• Random blood glucose• Serum creatinine• Screening blood tests for gluten sensitivity• Serum calcium• Creatine kinase• Serum ferritin

directed investigations but also on the presenta-

tion of symptom clusters shared by other children

and young people with the condition in addition to

persistent and disabling fatigue. These symptoms

may classically include malaise, sleep disorder,

headache, dizziness, poor temperature control, ab-

dominal pain, nausea, anorexia, sore throat, tender

lymphadenopathy, arthralgia, myalgia, and cognitive

difficulties such as poor short-term memory, im-

paired concentration, anxiety, and low mood. Since

many of these symptoms overlap with diagnoses rel-

evant to many disciplines such as gastroenterology,

rheumatology, endocrinology, neurology, infectious

diseases and immunology, oncology, and haematol-

ogy, as well as childhood and adolescent mental

health, it is beholden upon us to ensure that appro-

priate paediatric subspecialists have been consulted

and the necessary investigations undertaken. How-

ever, in the absence of any other disease, the history

and, often, normal examination findings are key in

making the diagnosis (see Table 2).

INVESTIGATIONS

As a minimum, we require that the child or young

person will have undergone the screening investi-

gations set out in the NICE guidance and that the

results of these tests are normal when seen for ini-

tial assessment by the specialist CFS team.

Diagnosis marks the start of a long and chal-

lenging journey for the child or young person and

their carers. It is important to demedicalize and

demystify the condition and positively and confi-

dently recognize the symptom clusters shared by

CFS sufferers. A further key feature of the initial

consultation is to explain the nature of the con-

dition, acknowledge the difficulties they have en-

countered on their journey thus far, and reassure

the patients and their carers that the expectation

is that their condition will improve and that, in our

experience, the vast majority of children and young

people with CFS recover and go on to achieve

academic qualifications. Ninety-nine percent of

young people aged 16 seen by our specialist team

achieved some academic qualifications and were

able to progress to the next stage of their educa-

tion or training. The vast majority of children and

young people will not require transition to adult

CFS services. About 5% continue to have a persist-

ing and disabling illness.

“I visited the clinic and was diagnosed with

CFS. It was a relief to know that my debilitat-

ing symptoms had a name. After more than 9

months of feeling so terrible, someone could

finally tell me what was wrong.”

“It helped when I knew I had CFS. It was far

better knowing than being left worrying or try-

ing to guess.”

The fact that CFS is a heterogeneous group is




now generally agreed and evidence is growing to

support this. One study has identified three pheno-

types in CFS in children that are differentially asso-

ciated with severity; the musculoskeletal phenotype

is associated with muscle and joint pain and these

children have worse fatigue. The migraine pheno-

type which is associated with headache, abdomi-

nal pain, nausea, dizziness and noise sensitivity is

associated with a lower level of physical function,

worse pain, and lower school attendance. The sore

throat phenotype is associated with sore throat and

tender lymph nodes and is the least severe.

IMPACT OF THE CONDITION

“It is one of the loneliest illnesses in the world

because we don’t have anything to show for it.”

Everyone involved with CFS agree that the condi-

tion has a profound impact, not only on the child

or young person, but also on their families. It is as-

sociated with considerable school absence, social

isolation, loss, changes in family relationships, and

parental time off work.

“My symptoms meant that I started to miss a

lot of school – I just didn’t have the energy to

make it through the day.”

“My daughter lost all her spark.”

MANAGEMENT

Once children and young people and their families

have gained an understanding of the condition, the

basis of treatment and an optimistically realistic

expectation of what the future might hold, a coordi-

nated multidisciplinary approach to management is

required in the majority of cases. Commonly, occu-

pational therapist, physiotherapist, nurse special-

One aspect in the management of chronic fatigue syndrome involves establishing a good sleep hygiene.

ist, and clinical psychologist may need to be involved.

Evidence-based guidelines recommend the follow-

ing:

Activity management: this is a person-centred,

goal-directed approach to managing a child or young

person’s symptoms. It uses analysis of activity and

graded activity through learning the skills of pacing to

improve physical and cognitive function.




Figure 1. Vicious cycle.

Sleep disorder/muscle weakness

Furtherrest

Increased rest/reduced activity

Worseningof symptomson exercise

CFS

Sleep disorder/muscle weakness

Moreinactivity

Fatigue/achesand pains

Loss ofcontrol

Reducedactivity

Cognitive behaviour therapy: this is an in-

dividualized psychological therapy which incorpo-

rates two major components: the cognitive element

which focuses on the identification and modifica-

tion of thoughts, beliefs, and assumptions which

may shape the child or young person’s understand-

ing of their condition, and the behavioural element

which aims to gradually and consistently introduce

a change in behaviour, eg, an increase in activity

or return to school. A cognitive behaviour therapy

model can include treatment of accompanying anxi-

ety or depression and can be tailored to include in-

volvement of the family.

Graded exercise therapy: this is a struc-

tured and supervised programme of exercise agreed

between doctor, therapist (usually a physiothera-

pist), and the child or young person. It is based on

their current level of ability. Intensity and duration

of exercise begin at a very low level and are in-

creased very slowly depending on progress. The

aim of graded exercise therapy is to increase fit-

ness and stamina.

The primary aim of management is to re-

establish the child or young person in a sustain-

able routine and then to help them learn to self

manage the condition. At the outset of treat-

ment, this commonly involves three aspects:

sleep hygiene, activity/energy management, and

school liaison.

In the absence of a clear understanding of the

cause of CFS, we make use of a number of analo-

gies which ‘fit’ well with patients’ experience of

the condition. We ‘explain’ to the child that their

body is like a battery that has lost its charge and

now requires recharging. The ways to do this are

good sleep hygiene and activity management or

graded exercise therapy. We also find that the idea

of vicious cycles arising as a consequence of the

condition is a useful concept with which families

can identify (Figure 1).

SLEEP HYGIENE

Disordered sleep patterns are commonly found in

CFS including day/night reversal, interrupted sleep,

insomnia, or hypersomnia. It is therefore important

to establish effective and positive sleep routines

which include

• Establishing a regular waking time

• Avoiding prolonged sleep and day time sleeps

• Always sleep at night in own bedroom and avoid

use of computer/TV prior to bed

• Relaxation to aid falling asleep and consistent

bedtime routine

Melatonin and/or amitriptyline are used in

some cases to support good sleep hygiene and im-




prove the quality of sleep.

ACTIVITY/ENERGY MANAGEMENT

The young person needs to keep a diary to establish

their baseline of activity. Activity meaning every-

thing that they do from having a shower being on

the computer to going to school. Realistic goals

then need to be agreed with the young person so

that they avoid the boom and bust pattern of activ-

ity which hinders recovery. It can be useful to think

in terms of the different energy demands of situa-

tions, eg, high or low.

Increase in activity levels needs to take place

gradually and be carefully monitored. We would

recommend a 15% increase in activity, eg, if able

to read for 30 minutes a day increase to 35 minutes.

SCHOOL LIAISON

Chronic fatigue syndrome has a negative impact on

education, and many children and young people are

unable to attend full-time school. A crucial element

of any successful management plan, therefore, is

the establishment of a sustainable educational

routine. This may involve the home tuition services

initially, followed by a carefully managed plan for

school re-integration. It is very likely to involve

part-time school attendance. A recent study sug-

gests that the factor most strongly associated with

reduced school attendance is poor physical func-

tion. It is therefore important to ensure that the

child or young person is fully engaged with treat-

ment to improve physical function. However, it is

also necessary to be aware of the cognitive impact

of CFS and to ensure teachers are informed of the

effects of CFS on memory, information processing,

and concentration. Children with CFS are entitled

to exam concessions when taking public exams if

requested by a doctor.

The key professional needs to be prepared

to put considerable time into liaising with educa-

tional services. In our experience, this patient group

needs more time for liaison than other children with

a chronic illness.

MANAGEMENT OF SPECIFIC PHYSICAL SYMPTOMS

We find that as the child or young person learns

to manage their fatigue effectively and their well

being begins to improve so other troubling symp-

toms such as nausea, abdominal pain, myalgia,

and joint pain all decrease. We therefore tend to

avoid specific pharmacological agents. Gastrointes-

tinal symptoms can be managed through diet and

ensuring healthy eating and adequate fluid intake,

avoiding caffeine and sugary drinks. Small frequent

meals are often better than three heavy meals. Pain

is managed with simple analgesics like paraceta-

mol and/or ibuprofen. In addition, relaxation and

cognitive behaviour techniques may be considered

in parallel to improve pain.

ROLE OF THE FAMILY

The role of the family is crucial in helping a child

or young person learn to manage this condition.

Table 3. Top tips for management from our team

These patients take time• in clinic, so it is useful to book appointments at the end of clinic• to recoverStay confident when the inevitable relapse occursRemember progress is always slower than you expectThere is no quick fixInvolve parents




Family life is affected and families have to adjust

their expectations of what they can do together.

Some parents have to stop work in order to care for

their child. Support and encouragement from family

members is valued by children and young people; it

is therefore important that parents understand the

condition fully and are involved in treatment.

The package of care we have developed in-

volves an initial period of treatment of six sessions

every 3–4 weeks. At the end of this, we hold a multi-

disciplinary team review, and a further six sessions

can be offered to consolidate activity management

and continue with school liaison. Other contributing

factors may have emerged by this stage, such as

anxiety, low mood, or family factors. It is then ap-

propriate to arrange cognitive behaviour therapy or

family therapy (Table 3).

PROVISION OF SERVICES

The provision of services for children and young

people with CFS remains patchy. Despite NICE

guidance which recommends referral to specialist

services immediately if severely affected, within 3

months if moderately affected, and within 6 months

if mildly affected, there are still only 13 specialist

teams in Britain and these are often small with lim-

ited capacity. The burden of treating this condition

for the majority therefore lies with paediatricians

and local therapy services. However, the special-

ist teams now have considerable experience of this

perplexing, enigmatic condition. We would encour-

age professionals working with CFS to consult with

a specialist team. In recognition of the scarcity of

Practice points

• Children and young people with chronic fatigue syndrome (CFS) do recover with good outcomes

• CFS is a clinically heterogeneous syndrome characterized by persisting and disabling fatigue. It is usually associated with a cluster of other troubling symptoms

• Diagnosis is made by a paediatrician once other potential disor-ders have been excluded

• CFS is a genuine physical illness and this needs to be communi-cated to child and family

• CFS is increasingly being recognized as a cause of significant school absence/poor school attendance in children and young people

• Demedicalization of symptomatology is essential and beneficial and in particular the need to draw a line under previous investi-gations and management in order to move forward is crucial

• The absence of a ‘magic wand/pharmacological cure’ requires to be explained from the outset

• Management requires a multidisciplinary team approach, and both cognitive behaviour therapy, graded exercise therapy, and activity management are recommended treatments

• Commitment to the acceptance of the need for rehabilitation by means of energy management and the adoption of good routines on the part of patients and carers are very important

• Professionals need patience and confidence and to be prepared for relapses

• It is important to engage family members as well as the child or young person

Family life

is affected

and families have

to adjust their

expectations of

what they can

do together.




resources, we have been instrumental in setting up

a clinical network in North and Central England for

those working with CFS in order to improve knowl-

edge and services.

PREVENTION OF THE PRIMARY DISEASE AND DISEASE COMPLICATIONS AND DISABILITIES

In the absence of a recognized aetiology, the search

for a method of primary prevention of the condition

seems futile. However, prompt recognition of the

condition and onward referral to a specialist ser-

vice where available, with expertise in managing

the condition seems likely to be in the best inter-

est of the affected individuals and their families.

Since CFS affects not only the child or young person

but also those around them, the sooner appropri-

ate education and support is put in place the more

effective rehabilitation can be and the less likely

physical and psychological co-morbidities are to

become entrenched. The absence from school and

lack of socialization with peers leave these children

and young people at very real risk of long-term psy-

chological and emotional difficulties which early

recognition and intervention might go a long way to

ameliorate or even prevent.

CONCLUSION

Chronic fatigue syndrome is a disabling and serious

condition affecting physical and mental function

and compounded by the uncertain and unpredict-

able course of the illness. There is still much to

understand about this enigmatic condition and both

clinicians and researchers have a duty to develop

understanding of the causes and course of the con-

dition. However, it is clear that early diagnosis and

appropriate management greatly facilitate recov-

ery, and the majority of children and young people

make good recoveries.

“To me keeping positive and determination I

think were really important in my recovery. I

think it was really important to keep trying –

you go through such bad times and good times

with this condition it is important to know you

will get there eventually.”

FURTHER READING

Chalder T, Goodman R, Wessely S, Meltzer R. The epidemiology of fatigue in children. Br Med J 2003;327:654–655.

Chalder T, Hussain K. Self-help for chronic fatigue syndrome. Blue Stallion Publications, 2002.

Collingridge E. Severe ME/CFS: a guide to living association of young people with ME 2010.

Crawley E, Sterne JAC. Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy. Arch Dis Child 2009;94:752–756.

Davies S, Crawley E. Chronic fatigue syndrome in children aged 11 years old and younger. Arch Dis Child 2008;93:419–421.

Garralda M, Chalder T. Practitioner review: chronic fatigue syndrome in childhood. J Child Psychol Psychiatry 2005;46:1143–1151.

Haig-Ferguson A, Tucker P, Eaton N, Hunt L, Crawley E. Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy. Arch Dis Child 2009;94:757–762.

Jelbert R, Stedmon J, Stephens A. A qualitative exploration of adolescents’ experience of chronic fatigue syndrome. Clin Child Psychol Psychiatry 2010;15:267–283.

National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. Clinical guide-line no 53. London: NICE, 2007.

Royal College of Paediatrics and Child Health. Evidence based guide-lines for the management of CFS/ME in children and young people. London: RCPCH, 2004.

Van de Putte EM, Engelbert R, Kuis W, Sinnema G, Kimpen J, Uiter-waal C. Chronic fatigue and health control in adolescents and parents. Arch Dis Child 2005;90:1020–1024.

Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome in adults: national birth cohort study. Br Med J 2004;329:941–943.

© 2013 Elsevier Ltd. Initially published in Paediatrics and Child Health 2013;23(1):35–39.

About the AuthorsCarrie Mackenzie is Consultant Paediatrician in the Children’s Hospital, Sheffield, UK. Alison Wray is Principal Clinical Psychologist in the Dept of Clinical Psychology at the Children’s Hospital, Sheffield, UK.


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ASI adalah yang Terbaik

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mendukung perkembangan kognitif bayi1-2

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membantu mencegah anemia5 danvitamin c membantu penyerapannya

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Formula Presinutri, nutrisi presisi untuk mendukung tumbuh kembang optimal Ananda yang diperkaya dengan:

Referensi:1. Koletzko, Berthold, et al. The roles of LC-PUFA in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J. Perinat. Med 36 2008.2. Georgieff, Michael K. Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr 2007;85(suppl):614S-20S.3. Niness, Kathy R. 1999. Nutritional and Health Benefits of Inulin and Oligofrucose. J. Nutr. 129: 1402S-1406S.4. Salgueiro et al. The Role of Zinc in the Growth and Development of Children. Nutrition 18:510-519, 2002.5. Untoro, Juliawati, et al. 2005. Multiple Micronutrient Supplements Improve Micronutrient Status and Anemia But Not Growth and Morbidity of Indonesian Infants. J. Nutr. 135: 639s-645s.6. Vlaardingerbroek, H, et al. Amino Acids for the Neonate: Search for the Ideal Dietary Composition. NeoReviews 2011;12;e506-e516.

Karena Anda mengerti yang terbaik untuk Ananda

Draft Revisi Diagnosis dan Tata Laksana Alergi Susu SapiAngka kejadian alergi susu sapi sebesar 2-7,5%, dimana 15%-nya terjadi akibat konsumsi protein susu sapi dan produknya. Alergi susu sapi ini dapat menimbulkan gejala ringan, sedang hingga berat. Manifestasi yang berat dapat bermanifestasi sebagai gejala kolik, gangguan pertumbuhan, anemia defi siensi besi, perdarahan dan dermatitis atopi yang luas. Sosialisasi untuk meningkatkan awareness para dokter pun telah dilakukan, namun masih didapatkan banyak permasalahan diantaranya keterbatasan ketersediaan skin prick test (SPT)/uji tusuk kulit, IgE spesifi k, APT (Atopy Patch Test), formula asam amino, formula terhidrolisat ekstensif, hingga persoalan harga, rasa susu formula, dan rasa takut akan efek samping.

Untuk menegakkan diagnosis alergi susu sapi, Vandenplas dkk 2007 merujuk pada riwayat penyakit, manifestasi klinis, SPT, IgE RAST, dan uji provokasi dan eliminasi, sedangkan pendekatan menurut Canonica dkk 2013, menerapkan lini pertama pada riwayat penyakit, dan lini kedua dilakukan SPT atau in vitro dengan specifi c IgE dan Molecular based allergy (MA) sebagai lini ketiga yang dapat dilakukan bila hasil lini pertama dan kedua meragukan. Pada rekomendasi tahun 2009/2010, bayi yang mendapatkan ASI eksklusif, ASI tetap dilanjutkan pemberiannya dan ibu dianjurkan untuk pantang protein susu sapi dan apapun yang mengandung protein susu sapi selama 6 bulan. Sedangkan pada bayi yang mendapatkan formula susu sapi, dianjurkan untuk menghindari susu sapi. Pada bayi yang memiliki

dr. Sumadiono, Sp.A(K)Bagian Ilmu Kesehatan Anak Fakultas Kedokteran - Universitas Gajah MadaRSUP Dr. Sardjito - Yogyakarta

SIMPOSIUM HIGHLIGHT

Diagnosis dan Tata Laksana Alergi Susu Sapi

gejala alergi susu sapi ringan hingga sedang diberikan susu formula terhidrolisat ekstensif minimal 6 bulan. Formula susu terhidrolisat parsial (dengan berat molekul 3000-10000 kD) diberikan sebagai pencegahan, sedangkan formula susu terhidrolisat ekstensif (< 1500kD) diberikan sebagai pencegahan sekaligus sebagai terapi. Pada bayi yang memiliki gejala alergi susu sapi berat diberikan formula asam amino minimal 6 bulan. Susu kedelai dapat dipertimbangkan bila ada masalah dengan biaya, rasa dan ketersediaan pada bayi usia > 6 bulan. Baik formula susu asam amino maupun susu kedelai diberikan hanya sebagai terapi, bukan sebagai pencegahan. Selain ketersediaan beberapa jenis formula, perlu dipikirkan harga dan kebutuhan bayi, mengingat upah per kapita di Indonesia masih rendah. Demikian pula dengan rasa formula susu yang akan diberikan, sebaiknya dokter mencoba terlebih dahulu sebelum memberikannya kepada pasien dan melakukan edukasi orang tua mengenai hal ini, karena seringkali orang tua mengeluh bayinya menolak diberikan formula susu terhidrolisat atau asam amino yang terasa pahit.

Sekitar 30% pasien dengan dermatitis atopi yang diberikan formula kedelai, didapatkan hanya sedikit yang mengalami reaksi klinis (Jarmila dkk, 2013). Pada pasien dengan asma, konsumsi genistein dalam susu kedelai dikaitkan dengan kontrol fungsi paru yang lebih baik (Bime dkk, 2012). Studi lain yang meneliti pemberian formula kedelai pada bayi dengan alergi susu sapi hanya 10% (studi James J 2003) atau 14% (studi Zeiger dkk, 1990) yang mengalami reaksi simpang. Studi di Jakarta (Munasir dkk) menunjukkan hanya 17,5%

Kejadian penyakit alergi antara lain asma, rinitis alergi, eksema, dan alergi makanan meningkat di seluruh dunia dan sebagai pedoman diantara klinisi untuk keseragaman diagnosis dan tata laksana alergi susu sapi, maka Ikatan Dokter Anak Indonesia (IDAI) membuat revisi rekomendasi

tata laksana alergi susu sapi 2009/2010 yang telah dievaluasi selama 3 tahun. Hal ini menjadi salah satu bahasan pada ‘The 6th Child Health Annual Scientifi c Meeting of Indonesian Pediatric Society’ pada tanggal 5-9 Oktober 2013 lalu di Solo yang bertemakan ‘Acceleration of MDGs 2015 Achievement with Comprehensive Management of Pediatric Problems’, dengan pembicara dr. Sumadiono, Sp.A(K) dan sebagai moderator adalah Prof. Dr. dr. Agus Firmansyah, Sp.A(K).

SHL-JPOG PIT IKA_Sari Husada.indd 1 12/2/2013 4:33:28 PM

yang tersensitisasi namun yang menderita alergi kedelai hanya sebesar 4%. Sedangkan penelitian lain oleh Juffrie dkk (2012), tidak ditemukan sensitisasi terhadap protein kedelai pada anak dengan alergi susu sapi.

Sebuah studi follow-up pada asupan nutrien, status nutrisi dan pertumbuhan pada bayi dengan alergi susu sapi yang diberikan formula kedelai dan formula terhidrolisat ekstensif (Seppo dkk, 2005) menunjukkan kedua hasil status nutrisi yang sama baiknya pada pertumbuhan dan perkembangan bayi. Menurut Australasian Society of Clinical Immunology and Allergy (2004), manajemen alergi susu sapi dapat diberikan alternatif formula kedelai, karena sekitar 50-80% anak dengan alergi susu sapi dapat toleran dengan formula kedelai. Namun pemberian formula kedelai juga perlu hati-hati pada bayi prematur dan hipotiroid kongenital (Paediatr Child Health Vol. 14 No 2, Februari 2009). Penelitian yang dilakukan oleh EPSGHAN Committee on Nutrition (2006) menunjukkan hasil, belum ada bukti yang mendukung pemberian formula kedelai sebagai pencegahan pada kolik dan regurgitasi. Formula kedelai mengandung fitat, aluminium, dan fitoestrogen. Walau kandungan aluminium susu kedelai lebih tinggi (500-2500 ug/l) bila dibandingkan susu sapi dan ASI namun kini telah diformulasikan cukup aman dengan asupan per hari sampai dengan 200mL/kg/hari berarti hanya <0,5mg/kg/hari dimana jumlah ini jauh lebih rendah dari tolerable intake untuk aluminium yaitu 1 mg/kg/hari, kecuali untuk bayi prematur dan bayi dengan insufisiensi ginjal harus hati-hati, karena belum memiliki data keamanan jangka panjang.

Kandungan fitat (1-2%) dalam isolat protein kedelai diduga dapat mengurangi penyerapan mineral telah dilakukan reduksi pada semua produk kedelai sehingga dapat meningkatkan absorpsi dan availabilitas zink, tembaga dan mineral lain (Bhatia J, 2008).

Pada pemberian kedelai dengan kandungan fitoestrogen telah dibuktikan oleh Gilchrist dkk (2010) melalui penelitian pada 120 bayi usia 4 bulan dan hal ini tidak terbukti dapat menimbulkan gangguan pada perkembangan reproduktif. Pada penelitian lainnya, yang dilakukan Merrit dan Jenks 2004, Lasekan dkk 1999, Fommon dkk 1993, dan Strom dkk 2001 menunjukkan pola pertumbuhan pada kelompok bayi yang serupa antara bayi yang diberikan susu sapi dan kedelai.

Pada draft revisi tahun 2013 untuk bayi alergi susu sapi dengan ASI eksklusif dengan gejala ringan sampai sedang, ASI dapat diteruskan (dengan eliminasi susu sapi dan apapun yang mengandung protein susu sapi pada diet ibu). Bila ASI tidak mencukupi, maka dapat diberikan formula terhidrolisat ekstensif. Bila ada masalah dengan dana dan ketersediaan susu terhidrolisat ekstensif bisa diganti dengan susu formula kedelai sejak awal kehidupan namun harus ada edukasi dan persetujuan (informed consent) dari orang tua untuk kemungkinan timbulnya efek samping dan perlu dimonitor selama 6 bulan.

Pada kelompok bayi yang mendapat formula susu, dapat diberikan formula terhidrolisat ekstensif pada gejala ringan-sedang, bila tidak bisa, dapat diberikan formula susu kedelai sejak awal kehidupan. Pada gejala yang berat, harus dirujuk dan berikan formula asam amino dan bila tidak ada, dapat diberikan formula terhidrolisat ekstensif.

Untuk lebih jelas tata laksana alergi susu sapi dilihat pada tabel di bawah ini.

Kesimpulan:

• Kejadian alergi, asma, rinitis alergi, dan eksema termasuk alergi makanan meningkat di seluruh dunia.

• Sebagai revisi tata laksana alergi susu sapi adalah:

- untuk kelompok bayi yang mendapatkan ASI eksklusif, ASI dilanjutkan, bila memerlukan tambahan dapat diberikan formula terhidrolisat ekstensif dan bila ada masalah dana dan ketersediaan susu terhidrolisat ekstensif sebagai alternatif dapat diberikan formula kedelai sejak awal kehidupan dengan edukasi dan persetujuan orang tua (informed concent).

- untuk kelompok bayi yang mendapatkan susu formula, bayi langsung pantang dan diganti dengan formula terhidrolisat ekstensif (pada gejala ringan dan sedang). Pada gejala berat, dapat diberikan formula asam amino. Bila ada masalah dana dan ketersediaan susu terhidrolisat ekstensif sebagai alternatif dapat diberikan formula kedelai sejak awal kehidupan disertai dengan edukasi dan persetujuan orang tua (informed concent).

TATA LAKSANA ALERGI SUSU SAPI PADA BAYI DENGAN SUSU FORMULACuriga alergi susu sapi (ASS)

Pemeriksaan klinis:-Temuan klinis-Riwayat keluarga (faktor risiko)

ASS ringan/sedang Satu/lebih gejala dibawah ini:-Regurgitasi berulang, muntah, diare, konstipasi (dengan atau tanpa ruam perianal), darah pada tinja-Anemia de�siensi besi-Demam atopik (DA), angiedema, urtikaria-Pilek, batuk kronik, mengi-Kolik persisten (> 3 jam perhari/minggu) selama lebih dari 3 minggu

ASS beratSatu/lebih gejala dibawah ini:-Gagal tumbuh karena diare dan atau regurgitasi, muntah dan atau anak tidak mau makan-Anemia de�seinsi besi karena kehilangan darah di tinja, ensefalopati karena kehilangan protein, enteropati atau kolitis ulseratif kronik yang sudah terbukti melalui endoskopi atau histologi-DA berat dengan anemia-hipoalbuminemia atau gagal tumbuh atau anemia de�siensi besi-Laringoedema akut atau obstruksi bronkus dengan kesulitan bernapas-Syok ana�laksis

Bila ragu-raguKonsultasikan/

periksakan: Uji tusuk kulit IgE spesi�k

Diet eliminasi dengan formula susu terhidrolisat ekstensif minimal 2-4 minggu *

Perbaikan Tidak ada perbaikan Rujuk ke dokter spesialis anak konsultanDiet eliminasi susu sapi

Formula asam amino minimal 2-4 minggu #- Uji provokasi terbuka- Berikan susu formula susu sapi dibawah pengawasan

- Diet eliminasi susu sapi Formula asam amino minimal 2-4 minggu * atau-Pertimbangkan diagnosis alergi makanan lain (telur, seafood, kacang, dll) atau alergi susu sapi bersamaan dengan alergi makanan lain-Pertimbangkan diagnosis lain

Gejala (-)Diberikan protein

susu sapi dan dimonitor

Gejala (+)Eliminasi protein susu sapi

dari makanan selama 9-12 bulan dan minimal selama 6 bulan

Ulangi uji provokasi

Tidak ada perbaikan Perbaikan

Evaluasi diagnosis Uji provokasi

Tidak ada perbaikan Perbaikan

Evaluasi diagnosis Uji provokasi

# Bila ada masalah dana dan ketersediaan susu formula asam amino dapat dicoba susu terhidrolisat ekstensif*Bila ada masalah dana dan ketersediaan susu terhidrolisat ekstensif sebagai alternatif dapat diberikan formula kedelai sejak awal kehidupan dengan edukasi dan informed consent kemungkinan alergi/efek samping formula kedelai

Modi�kasi dari:Vandenplas Y, dkk. Arch Dis Child. 2007;92:902-8Brill H. Can Fam Physician 2008;54:1258-64Kemp AS, dkk. MJA 2008;188:109-12

SHL-JPOG PIT IKA_Sari Husada.indd 2 12/2/2013 4:33:29 PM

SGM Soya Presinutriformula isolat protein1

kedelai untuk mendukung pertumbuhan optimal Ananda yang alergi protein susu sapi

Mendukung pertumbuhan fisik yang optimal.

Stimulasi pertumbuhan bakteri baik untuk saluran cerna sehat.

Mencegah anemia defisiensi besi.

Mendukung perkembangan otak yang optimal.

ASI adalah nutrisi terbaik bagi Ananda untuk mencegah timbulnya alergi. Namun, jika pemberian ASI tidak memungkinkan karena terdapat indikasi medis, SGM Soya menyediakan nutrisi bagi Ananda yang alergi protein susu sapi untuk mendukung pertumbuhan dan perkembangan optimal di periode emasnya.

Referensi : 1. Russel J Merritt and Belinda H Jenks. American Society for Nutritional Sciences 2004, The Journal of Nutrition. Safety of Soy-Based Infant Formula Containing Isoflavones : The Clinical Evidence



Dermatology ClinicAn Enlarging Lesion on the NeckGayle Fischer, MB BS, MD, FACD

Answer:

verrucous) and seborrhoeic keratoses, they

have little in common with these lesions.

• Viral warts are very unlikely to have

their onset in a patient’s first year of life

or to persist unchanged for more than 2

or 3 years. It is also unusual for many

viral warts to be grouped on the shoul-

der or neck (as in this patient’s case),

although this presentation is not uncom-

mon on the hands (Figure 2) and feet.

• Seborrhoeic keratoses generally oc-

cur from middle age, and they present as

discrete lesions (Figure 3). The back is a

typical location, but they can be found on

any part of the skin.

CAUSE

The cause of verrucous epidermal naevi

is unknown, but they are believed to arise

from a post-zygotic mutation resulting in

epidermal mosaicism.

The lesions are harmless and have

no potential for malignant transformation

and, particularly when localized, are rarely

associated with any other abnormali-

ties. They can easily be differentiated

from a viral wart on histopathology, but

they may be confused with a seborrhoeic

keratosis unless the pathologist is aware

of the age of the patient.

TREATMENT

Treatment is often requested for verrucous

epidermal naevi for cosmetic or functional

reasons. Although there are superficial abla-

tive procedures such as laser ablation that

are effective, these lesions will often recur

afterwards. Naevi that have any protruding

areas or are interfering with function need

complete excision to avoid recurrence.

© 2013 Medicine Today Pty Ltd. Initially published in

Medicine Today August 2013;14(8):58–59. Reprinted with

permission.

About the AuthorAssociate Professor Fischer is Associate Professor of Dermatology at Sydney Medical School – Northern, University of Sydney, Royal North Shore Hospital, Sydney, NSW, Australia.

VERRUCOUS EPIDERMAL NAEVUS

DIAGNOSIS

The correct diagnosis in this case is a verru-

cous epidermal naevus, a birthmark that occurs

mainly on the trunk and limbs. These lesions

may be congenital, but in over half of cases

the onset is in the first year after birth. They

may spread beyond their original size with age,

usually over a few months but sometimes sev-

eral years. It is not unusual for them to become

more raised and ‘warty’ at puberty.

The colour of verrucous epidermal

naevi ranges from flesh-coloured to brown

and black. They may occur as single or mul-

tiple grouped lesions and can have a linear

or whorled distribution. On the chest, there

is often a dramatic cut-off at the midline.

DIFFERENTIAL DIAGNOSIS

Although verrucous epidermal naevi resem-

ble common viral warts (hence the name

Figure 3. A typical seborrhoeic keratosis in a woman aged in her 60s.Figure 2. True viral warts.




IN PRACTICE


IN PractIce I Peer revIewed



Clinical CaseRectal Bleeding in Pregnancy: Don’t Assume It’s BenignChristopher S Pokorny, MB BS, FRACP, FRCP, FACG

COMMENTARY

Possible CausesRectal bleeding at anytime requires con-

sideration of the underlying cause (see the

box on this page listing the possible caus-

es). The passage of bright blood suggests

a source in the rectum or sigmoid. Minor

rectal bleeding as a result of small tears,

fissures, or haemorrhoids is not uncommon

during pregnancy as constipation devel-

ops at some stage in up to 40% of preg-

nant women.1 In most cases, constipation

responds to an increase in dietary fibre and

fluid intake. Iron supplements may also

contribute to constipation and may need to

be ceased if the constipation is severe.

Anal fissures tend to be accom-

panied by marked pain (as opposed to

haemorrhoids that are usually painless)

and generally result from straining. When

haemorrhoids are painful, a degree of

prolapse, thrombosis, or strangulation

may be present. A number of factors

are associated with the development of

haemorrhoids during pregnancy. These

include mechanical compression of veins

because of the enlarging uterus, straining

as a result of worsening constipation, and

hormone-related vascular changes.2 In

Angela’s case, her stools have been softer

and her urgency raises the question of

rectal pathology.

Although infectious forms of gastro-

enteritis can cause bloody diarrhoea, this

is unlikely in Angela’s case, particularly

given the duration of her symptoms and the

intermittent nature of her rectal bleeding.

A rapid onset of symptoms, particularly in

the presence of nausea, vomiting, abdomi-

nal pain, and fever does, however, raise

the possibility of an infectious cause. In

such instances, stool microscopy and cul-

ture should be requested. It is important to

remember that parasitic infections such as

Giardia do not cause rectal bleeding.

Inflammatory bowel disease (eg, ul-

cerative proctitis) can occur for the first

time during pregnancy, especially in the

first trimester, and Angela’s symptoms are

in keeping with this.3 Apart from urgency,

mucus may be passed as well as blood,

and the stool volume is generally small in

such cases. Specific questioning about ex-

traintestinal manifestations is sometimes

of help – for example, peripheral arthritis,

low back pain, red eyes (episcleritis, uvei-

tis), erythema nodosum, and aphthous

ulcers. There may also be a family his-

tory of inflammatory bowel disease.4

Given Angela’s age, a rectal or distal

Answer:

Causes of rectal bleeding in pregnancy

Common• Haemorrhoids• Tears and fissures

Uncommon• Infectious colitis• Inflammatory bowel disease• Diverticular disease• Colorectal malignancy/

polyps• Ischaemic colitis




Figure. An example of rectal cancer viewed at sigmoidoscopy.

colonic malignancy or polyp, diverticular

disease, or ischaemic colitis are much

less likely. In addition, ischaemic colitis

generally occurs in the context of signifi-

cant vascular disease or atrial fibrilla-

tion. However, these conditions need to

be considered in the differential diagno-

ses, although rectal bleeding from more

proximal malignant lesions tends to be

dark in colour and diverticular bleeding

usually is profuse.

investigationsGentle digital examination of the rectum

with careful inspection of the perianal

area should be performed at the time of

consultation. Initial investigation should

include a full blood count, but anaemia is

not unusual in pregnancy. There is abso-

lutely no point in faecal occult blood test-

ing as this is only of potential benefit in

1. Anderson AS. Dietary factors in the aetiology and treatment of constipation during pregnancy. Br J Obstet Gynaecol 1986;93:2452.

2. Avsar AF, Keskin HL. Haemorrhoids during pregnancy. J Obstet Gynaecol 2010;30:231–237.3. Korelitz BI. Pregnancy, fertility and inflam-

matory bowel disease in pregnancy. Am J Gastroenterol 1985;80:365.4. Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996;334:841–848.

5. Cappell MS. Sedation and analgesia for gastrointestinal endoscopy during preg-nancy. Gastrointest Endosc Clin N Am 2006;16:131.

REFERENCES

IN PRACTICE i Peer reviewedIN PRACTICE i Peer reviewed


asymptomatic individuals.

The next investigation should be di-

rect visualization by flexible sigmoidos-

copy after an enema to evacuate the rec-

tum and sigmoid. In the first trimester, it is

best to avoid sedation with midazolam and

propofol. Flexible sigmoidoscopy without

sedation is generally well tolerated and

allows the mucosa to be inspected and bi-

opsies to be taken.5

If these tests fail to provide the an-

swer as to the cause of Angela’s rectal

bleeding, she should be monitored. If her

bleeding persists, full colonoscopy will

need to be considered, although if possi-

ble this should be deferred until after her

baby is born. However, if necessary before

then, it can be safely performed especially

in the later stages of pregnancy.

OUTCOME

In Angela’s case, flexible sigmoidoscopy

was performed and sadly revealed a rectal

cancer (see Figure). Although rectal bleed-

ing is not uncommon in pregnancy, this

case highlights the need to investigate ap-

propriately. However, in the vast majority of

cases the cause will be benign.

© 2012 Medicine Today Pty Ltd. Initially published in

Medicine Today June 2012;13(6):73–74. Reprinted with

permission.

About the AuthorAssociate Professor Pokorny is Conjoint Associate Professor of Medicine, University of New South Wales; and Visiting Gastroenterologist, Sydney and Liverpool Hospitals, Sydney, NSW, Australia.

Although rectal

bleeding is not

uncommon

in pregnancy,

this case highlights

the need to

investigate

appropriately


Formula Act of 1980, dan telah direkomendasikan sebagai susu pengganti untuk anak dengan alergi susu sapi (ESPA / ESPGHAN, 1999 ).2

Peran susu formula soya

Alergi susu sapi merupakan suatu penyakit alergi yang disebabkan oleh reaksi yang tidak diinginkan, yang diperantarai secara imunologis terhadap protein susu sapi. Mekanisme ini dapat terjadi melalui reaksi hiper sensitifitas tipe 1 yang diperantarai oleh IgE, namun demikian alergi susu sapi dapat juga terjadi tanpa diperantarai oleh IgE.1

Insidens alergi susu sapi sekitar 2-7,5%, dan reaksi alergi terhadap susu sapi masih mungkin terjadi pada 0,5% bayi yang mendapatkan ASI eksklusif. Gejala yang timbul sebagian besar adalah gejala klinis yang ringan sampai sedang, hanya sekitar 0,1-1% yang bermanifestasi berat. Prinsip utama terapi untuk alergi susu sapi adalah menghindari (complete avoidance) semua bentuk produk susu sapi, tetapi dengan tetap harus memberikan nutrisi yang seimbang dan sesuai untuk tumbuh kembang bayi dan anak. Saat ini semakin banyak produk susu formula yang ditawarkan untuk bayi dengan alergi susu sapi, salah satunya adalah susu formula soya.1,2

Susu formula soya adalah isolat protein kedelai berkualitas yang telah di hidrolisa, dan diperkaya dengan AA, DHA, Omega 3 dan Omega 6, dan Prebiotik. Susu formula soya sudah memenuhi semua kebutuhan nutrisi dan standard keamanan, sesuai dengan safety standards of the Infant

Susu formula soya pada tata-laksana alergi susu sapi Pilihan utama susu formula pada bayi dengan alergi susu sapi adalah susu terhidrolisat ekstensif atau susu asam amino. Apabila susu terhidrolisat ekstensif atau susu asam amino tidak tersedia atau terdapat kendala biaya atau rasa, maka sebagai alternatif dapat diberikan susu formula soya. Tetapi dengan penjelasan dan informed consent kepada orang tua mengenai kemungkinan reaksi silang terhadap protein soya. Proporsi alergi terhadap susu formula soya pada pasien alergi susu sapi pada usia dibawah 6 bulan lebih tinggi dibandingkan dengan yang usia diatas 6 bulan (25 % versus 5 %).1

tidak berbeda, dan keduanya memenuhi nilai standard. Sehingga untuk bayi dengan alergi susu sapi, dapat dipilih susu formula soya atau susu terhidrolisa sempurna, sebagai susu penggantinya.3

Penelitian lain, 170 anak dengan alergi susu sapi, secara acak diberikan susu formula soya atau susu sapi terhidrolisa sempurna. Setelah diikuti sampai usia 2 tahun, ternyata susu formula soya dapat diterima dengan baik pada sebagian besar anak dengan alergi susu sapi yang Ig E mediated. Dengan demikian susu formula soya dapat direkomendasikan sebagai pilihan pertama pada anak dengan alergi susu sapi yang berusia diatas 6 bulan.4

Keamanan susu formula soya pada alergi susu sapi Suatu penelitian retrospective diadakan pada tahun 1999 dengan subyek orang dewasa berusia 20-34 tahun. Saat bayi, subyek penelitian ini ikut dalam penelitian yang diadakan pada tahun 1965-1975 di Universitas A. Pada penelitian ini 248 anak mendapat susu formula soya dan 563 anak mendapat susu sapi pada masa bayinya.

Peran dan Keamanan Susu Formula Soya pada Alergi Susu Sapi

Dr. E.M. Dadi Suyoko, SpA(K)

Peran susu formula soya untuk bayi dan anak dengan alergi susu sapi telah dibuktikan dalam beberapa penelitian. Hasil dari penelitian-penelitian tersebut, dapat menjelaskan manfaat dan keamanan susu formula soya dalam tata-laksana alergi susu sapi.

Penelitian yang membandingkan kecukupan nutrisi dan pertumbuhan pada bayi dengan alergi susu sapi, yang mendapat susu formula soya dibandingkan dengan yang mendapat susu sapi terhidrolisa sempurna (extensively hydrolyzed formula). Dari 168 bayi, 84 bayi mendapat susu formula soya, dengan umur rata-rata waktu mulai mendapat susu formula soya 7,8 bulan, dan sisanya 84 bayi mendapatkan susu sapi terhidrolisa sempurna (extensively hydrolyzed formula), dengan umur rata-rata waktu mulai diberikan 7,5 bulan. Pada penelitian ini diperoleh kesimpulan bahwa status nutrisi dan pertumbuhan untuk kedua kelompok

Kesimpulan dari penelitian ini adalah bahwa konsumsi susu formula soya tidak mempengaruhi kesehatan secara umum maupun pada organ-organ reproduksi. Penelitian ini lebih memperkuat rekomendasi mengenai keamanan penggunaan susu formula soya.5

Daftar Pustaka: 1. Rekomendasi diagnosis dan tata laksana alergi susu sapi.

IDAI 2010. 2. Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen I,

Puntis J, dkk. Soy protein infant formulae and follow-on formulae: a commentary by ESPGHAN committee on nutrition. J ped gastroenetrol and nutrition 2006;42:352-61

3. Seppo L, Korpela R, Lonnerdal B, Metsaniitty L, Juntunen BK, Klemola T, dkk. A follow-up study of nutrient intake, nutritional status, and growth in infants with cows milk allergy fed either a soy foemula or an extensively hydrolized whey formula. Am J Clin Nutr 2005;82:140-5

4. Klemola T, Vanto T, Juntunen BK, Kalimo K, Korpela R, Varjonen E. Allergy to soy formula and to extensively hydrolized whey formula in infants with cow’s milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J pediatr 2002;140:219-24.

5. Strom L.B. et al. Exposure to Soy-Based Formula in Infancy and Endocrinological and Reproductive Outcomes in Young Adulthood. JAMA, 2001 :286; 807 – 814.

Formula Act of 1980, dan telah direkomendasikan sebagai susu pengganti untuk anak dengan alergi susu sapi (ESPA / ESPGHAN, 1999 ).2

Peran susu formula soya

Alergi susu sapi merupakan suatu penyakit alergi yang disebabkan oleh reaksi yang tidak diinginkan, yang diperantarai secara imunologis terhadap protein susu sapi. Mekanisme ini dapat terjadi melalui reaksi hiper sensitifitas tipe 1 yang diperantarai oleh IgE, namun demikian alergi susu sapi dapat juga terjadi tanpa diperantarai oleh IgE.1

Insidens alergi susu sapi sekitar 2-7,5%, dan reaksi alergi terhadap susu sapi masih mungkin terjadi pada 0,5% bayi yang mendapatkan ASI eksklusif. Gejala yang timbul sebagian besar adalah gejala klinis yang ringan sampai sedang, hanya sekitar 0,1-1% yang bermanifestasi berat. Prinsip utama terapi untuk alergi susu sapi adalah menghindari (complete avoidance) semua bentuk produk susu sapi, tetapi dengan tetap harus memberikan nutrisi yang seimbang dan sesuai untuk tumbuh kembang bayi dan anak. Saat ini semakin banyak produk susu formula yang ditawarkan untuk bayi dengan alergi susu sapi, salah satunya adalah susu formula soya.1,2

Susu formula soya adalah isolat protein kedelai berkualitas yang telah di hidrolisa, dan diperkaya dengan AA, DHA, Omega 3 dan Omega 6, dan Prebiotik. Susu formula soya sudah memenuhi semua kebutuhan nutrisi dan standard keamanan, sesuai dengan safety standards of the Infant

Susu formula soya pada tata-laksana alergi susu sapi Pilihan utama susu formula pada bayi dengan alergi susu sapi adalah susu terhidrolisat ekstensif atau susu asam amino. Apabila susu terhidrolisat ekstensif atau susu asam amino tidak tersedia atau terdapat kendala biaya atau rasa, maka sebagai alternatif dapat diberikan susu formula soya. Tetapi dengan penjelasan dan informed consent kepada orang tua mengenai kemungkinan reaksi silang terhadap protein soya. Proporsi alergi terhadap susu formula soya pada pasien alergi susu sapi pada usia dibawah 6 bulan lebih tinggi dibandingkan dengan yang usia diatas 6 bulan (25 % versus 5 %).1

tidak berbeda, dan keduanya memenuhi nilai standard. Sehingga untuk bayi dengan alergi susu sapi, dapat dipilih susu formula soya atau susu terhidrolisa sempurna, sebagai susu penggantinya.3

Penelitian lain, 170 anak dengan alergi susu sapi, secara acak diberikan susu formula soya atau susu sapi terhidrolisa sempurna. Setelah diikuti sampai usia 2 tahun, ternyata susu formula soya dapat diterima dengan baik pada sebagian besar anak dengan alergi susu sapi yang Ig E mediated. Dengan demikian susu formula soya dapat direkomendasikan sebagai pilihan pertama pada anak dengan alergi susu sapi yang berusia diatas 6 bulan.4

Keamanan susu formula soya pada alergi susu sapi Suatu penelitian retrospective diadakan pada tahun 1999 dengan subyek orang dewasa berusia 20-34 tahun. Saat bayi, subyek penelitian ini ikut dalam penelitian yang diadakan pada tahun 1965-1975 di Universitas A. Pada penelitian ini 248 anak mendapat susu formula soya dan 563 anak mendapat susu sapi pada masa bayinya.

Peran susu formula soya untuk bayi dan anak dengan alergi susu sapi telah dibuktikan dalam beberapa penelitian. Hasil dari penelitian-penelitian tersebut, dapat menjelaskan manfaat dan keamanan susu formula soya dalam tata-laksana alergi susu sapi.

Penelitian yang membandingkan kecukupan nutrisi dan pertumbuhan pada bayi dengan alergi susu sapi, yang mendapat susu formula soya dibandingkan dengan yang mendapat susu sapi terhidrolisa sempurna (extensively hydrolyzed formula). Dari 168 bayi, 84 bayi mendapat susu formula soya, dengan umur rata-rata waktu mulai mendapat susu formula soya 7,8 bulan, dan sisanya 84 bayi mendapatkan susu sapi terhidrolisa sempurna (extensively hydrolyzed formula), dengan umur rata-rata waktu mulai diberikan 7,5 bulan. Pada penelitian ini diperoleh kesimpulan bahwa status nutrisi dan pertumbuhan untuk kedua kelompok

Kesimpulan dari penelitian ini adalah bahwa konsumsi susu formula soya tidak mempengaruhi kesehatan secara umum maupun pada organ-organ reproduksi. Penelitian ini lebih memperkuat rekomendasi mengenai keamanan penggunaan susu formula soya.5



INTRODUCTION

Gestational diabetes mellitus (GDM) is a

controversial subject in obstetrics. It is

defined by the National Diabetes Data

Group in 1985 as carbohydrate intolerance

of variable severity with onset or first rec-

ognition during pregnancy.1 The first case

report of GDM appeared in 1824, which

described a mother with thirst, polyuria

and glycosuria and the death of a mac-

rosomic infant from shoulder impaction.

Historically, there has been a lot of contro-

versy over most aspects of GDM, includ-

ing screening, diagnosis, risks, treatment,

and the relationship between GDM and

type II diabetes mellitus. Recently, several

major studies have substantially resolved

these areas of controversy, eg, the Hyper-

glycaemia and Adverse Pregnancy Out-

comes (HAPO) study,2 the Australian Car-

bohydrate Intolerance Study in Pregnant

Women (ACHOIS),3 and the Maternal-Fetal

Medicine Units Network treatment of mild

gestational diabetes (MFMUN-GDM)4 clin-

ical trials, which will be discussed further

in this article.

INCIDENCE

The reported incidence of GDM

varies with diagnostic criteria and

characteristics of the population being

studied (eg, age, body build, ethnic

origins). The United States reported an

incidence of 3–8%,5 with a rising trend

in more recent publications. The United

Kingdom reported an incidence of 2%6

and Canada described 3.8%.7 In Hong

Kong, a study8 performed in a university

teaching hospital, Queen Mary Hospital,

showed that of the 16,383 women

managed in the period 1998–2001, the

prevalence of GDM increased from 1.3%

(≤ 20 years), 2.5% (20–24 years), 6.2%

(25–29 years), 10.3% (30–34 years),

21.7% (35–39 years), and 31.9% (≥ 40

years), respectively, from the youngest

to the oldest cohort (P < 0.001). Another

study9 performed in a different university

teaching hospital in Hong Kong, Prince

of Wales Hospital, found that the

prevalence of GDM was 14.2%. In

our hospital, a regional hospital with

around 6,000 deliveries per year, the

incidences of GDM in 2008 and 2009

were 13.2% and 14.2%, respectively.

SCREENING AND DIAGNOSIS

The diagnostic criteria of GDM were ini-

tially established more than 40 years ago,

and these criteria were not designed to

identify pregnant women at increased risk

for adverse perinatal outcomes but rather

women at higher risk for the development

of diabetes after pregnancy. Following the

publication of the HAPO study, the Interna-

tional Association of Diabetes and Preg-

nancy Study Groups (IADPSG) established

a new set of diagnostic guidelines (Figure

1).10 As more and more women suffer from

diabetes before pregnancy, the IADPSG

recommends screening women with risk

factors at the booking visit by using ran-

dom plasma glucose, fasting plasma glu-

cose, or glycated haemoglobin A1c paired

with diagnostic thresholds, according to

the current guidelines for the diagnosis

of pre-existing diabetes. Moreover, GDM

can be diagnosed at the booking visit with

a fasting plasma glucose between 5.1

mmol/L and 7.0 mmol/L, hence lowering

the thresholds of GDM in most guidelines.

They also recommend that all women who

do not have diabetes should be screened

Gestational Diabetes LL Chan, MBBS, MRCOG; WL Lau, MBBS, FRCOG, FHKAM (O&G); WC Leung, MBBS, MD, FRCOG, FHKAM (O&G), Cert RCOG (Maternal & Fetal Medicine)

Diagnosis and treatment of gestational diabetes can help reduce the risk of many adverse pregnancy outcomes due to this condition.

5 SKP

JPOG_NovDec_2013_CME_Final_ID.indd 257 12/4/13 7:40 PM


at 24–28 weeks’ gestation with the 75-g

oral glucose tolerance test. In contrast

to the World Health Organization criteria

which use an abnormal fasting or 2-hour

plasma glucose for the diagnosis of diabe-

tes, the IADPSG suggests that an abnormal

1-hour plasma glucose is adequate for the

diagnosis. They also take into account the

continuous association between maternal

blood glucose concentrations and adverse

perinatal outcomes as seen in HAPO. The

agreed thresholds represent an odds ratio

of 1.75 for birth weight, cord C-peptide,

and fetal body weight being greater than

the 90th percentile, relative to the odds of

those outcomes at mean glucose values.

Applying this system of testing and diag-

nostic criteria will probably double the in-

cidence of GDM.11

RISKS

The HAPO study2 was a 10-year, prospec-

tive, blinded, multicentre study, which

enrolled 25,505 pregnant women. It aimed

at studying the associations between the

risks of adverse pregnancy outcomes and

the degrees of maternal glucose intoler-

ance less severe than overt diabetes.

Exclusion criteria include fasting plasma

glucose > 5.8 mmol/L, or the 2-hour plas-

ma glucose ≥ 11.2 mmol/L, or a random

plasma glucose ≥ 8.9 mmol/L. It showed

an unambiguous, linear, positive asso-

ciation between maternal glycaemia and

adverse pregnancy outcomes (eg, birth

weight > 90th percentile, caesarean sec-

tion, cord plasma C-peptide level reflec-

tive of fetal hyperinsulinemia, neonatal

hypoglycaemia, excess neonatal adiposity,

shoulder dystocia or birth injury, neonatal

hyperbilirubinaemia, pre-eclampsia).12,13

The risk factors and health risks of GDM

are summarized in Tables 1 and 2.

TREATMENT

The ACHOIS3 and the MFMUN-GDM4

Figure 1. Flow chart showing guidelines as suggested by IADPSG10

1hG = 1-hour plasma glucose in 75-g oral glucose tolerance test; 2hG = 2-hour plasma glucose in 75-g oral glucose tolerance test; DM = diabetes mellitus; FG = fasting glucose; GDM = gestational diabetes mellitus; HbA1c = glycated haemoglobin A1c; IADPSG = The International Association of Diabetes and Pregnancy Study Groups; OGTT = oral glucose tolerance test; RG = random glucose.

GDM ifFG ≥ 5.1 mmol/L, or

1hG ≥ 10.0 mmol/L, or2hG ≥ 8.5 mmol/L

DM ifFG ≥ 7.0 mmol/L

NormalGDM if

FG ≥ 5.1 mmol/L, but < 7.0 mmol/L

DM ifFG ≥ 7.0 mmol/L, or

HbA1c ≥ 6.5%, orRG ≥ 11.1 mmol/L

At booking visit, all or high-risk women should have FG, HbA1c, RG tested

75-g OGTT at 24–28 weeks




clinical trials demonstrated that diagnosis

and treatment of GDM were worthwhile

because these reduced the risk of many

adverse pregnancy outcomes of GDM. In

both studies which were double blind,

women diagnosed with GDM in the late

second and early third trimesters were

randomized to two groups, ie, routine care

or intervention. Intervention in both trials

included dietary modification, blood glu-

cose monitoring, and, if needed, insulin

treatment. In the ACHOIS trial,3 a compos-

ite measure of serious perinatal complica-

tions (defined as one or more of death,

shoulder dystocia, bone fracture, and

nerve palsy) was reduced by diagnosis and

intervention (adjusted odds ratio, 0.33;

95% confidence interval, CI, 0.14–0.75; P =

0.01). A similar composite measure in the

MFMUN-GDM trial4 was also decreased

but was not statistically significant (rela-

tive risk, 0.87; 97% CI, 0.72–1.07; P =

0.14). In both studies, rates of large-for-

gestational-age (LGA)/macrosomia, pre-

eclampsia and maternal pregnancy weight

gain were reduced by intervention. Rates

of shoulder dystocia and caesarean sec-

tion were significantly decreased by treat-

ment in the MFMUN-GDM trial only. Rates

of induction of labour and of admission to

the neonatal unit were increased by treat-

ment in the ACHOIS trial only. Generally,

these two trials showed that identification

and treatment of GDM with a standard ap-

proach improved pregnancy outcomes.

DIETARY MODIFICATION

The scientific evidence for making nutri-

tional recommendations for women with

Table 1. Risks factors of gestational diabetesa

Risk factors Odds ratio References

Overweight

Obesity

Severe obesity

Prior gestational diabetes

Prior macrosomic infant

Maternal age greater than 25 y

Maternal age greater than 35 y

Multiple gestation

South East Asian

Hispanic

African American

Polycystic ovarian syndrome

Parent with diabetes

Sibling with diabetes

Periodontal disease

Low maternal birth weight

2

3.7

7

23

3.3

1.4

2.3

2.2b

7.6b

2.4b

1.8b

2.9

3.2

7.1

2.6

1.9

Torloni et al, Chu et alTorloni et al, Chu et alTorloni et al, Chu et alMcGuire et alMcGuire et alCypryk et alXiong et alRauh-Hain et alDornhorst et alDooley et alDooley et alToulis et alKim et alKim et alXiong et alSeghieri et al

aReprinted from Obstetrics and Gynecology Clinics of North America, 37(2), Pridjian et al, Update on gestational diabetes, 255–267, 2010, with permission from Elsevier.bRelative risk compared with white race.

Table 2. Health risks of gestational diabetesa

Mother Fetus Newborn Child/Adult

Birth trauma

Increased caesarean deliveryPre-eclamp-sia/ Gestational hypertensionType 2 diabetes

Metabolic syndrome

Hyperinsulinaemia

Cardiomyopathy

Stillbirth

Large for gestational age/macrosomiaBirth trauma

Respiratory distress syndromeHypoglycaemia

Hypocalcaemia

Hypomagnesaemia

Hyperviscosity PolycythaemiaHyperbilirubinaemiaCardiomyopathy

Obesity

Type 2 diabetes

Metabolic syndrome

aReprinted from Obstetrics and Gynecology Clinics of North America, 37(2), Pridjian et al, Update on gestational diabetes, 255–267, 2010, with permission from Elsevier.



GDM is limited. Referral to nutritional

counselling should ideally occur within

48 hours of the diagnosis of GDM.15 The

first meeting with a professional dietitian

should be arranged within 1 week of the

referral, and a total of three visits are sug-

gested.16 Throughout the pregnancy, the

diet should be adjusted and individualized

to meet the patient’s food choice, financial

needs, culture, habits, weight gain, physi-

cal activity, and blood glucose goals.

The Dietary Reference Intakes rec-

ommends no increase in calories for the

first trimester but an additional 340 kcal/

day during the second trimester and 452

kcal/day during the third trimester.17 In

obese women with GDM, a 30% caloric

restriction help to avoid ketonuria or an

increase in free fatty acids,18 while im-

proving glycaemic control. A more severe

caloric restriction is not recommended.

The National Institute for Clinical Excel-

lence (NICE) guidelines19 in the UK recom-

mend that women with GDM whose pre-

pregnancy body mass index is above 27

kg/m2 should restrict caloric intake (to 25

kcal/kg/day or less) and engage in moder-

ate exercise (of at least 30 minutes daily).

The goal of fractionating food intake

into three meals and two to three snacks

in between meals is to distribute the glu-

cose intake throughout the day in order to

control the postprandial glucose, while

at the same time maintaining a satisfac-

tory nutritional intake. The evening snack

decreases the night-time ketogenesis re-

lated to fasting.

Generally, 40–45% of the calories in

the daily diet come from carbohydrates,

but this must be individualized.20 One

study showed that in women with GDM,

carbohydrate restriction to < 42% led

to fewer LGA infants, reduced rates of

caesarean sections for macrosomia and

cephalopelvic disproportion, and reduced

need for insulin treatment, compared with

a higher carbohydrate content (45–50%).21

Few studies have focused on the benefit

of carbohydrates with a low glycaemic in-

dex (GI), which is a measure of how much

each gram of available carbohydrate in

the food increasing a person’s blood glu-

cose level following consumption of the

food, relative to consumption of glucose.

Food with carbohydrates that break down

quickly during digestion and release glu-

cose rapidly into the bloodstream tend to

have a high GI, while food with carbohy-

drates that break down more slowly, re-

leasing glucose more gradually into the

bloodstream, tend to have a low GI. There

have been no randomized studies with

sufficient sample size to draw a conclu-

sion on the benefits of carbohydrates with

a low GI. Increased dietary fibre intake

is traditionally recommended for women

with GDM, as it may reduce the postpran-

dial blood glucose. But no proof exists that

extra dietary fibre intake is beneficial in

these women.

PHARMACOTHERAPY

Drug treatment is necessary in 7–20% of

women with GDM when, despite dietary

modification, there is insufficient glucose

control, high levels of fasting glucose, sub-

optimal weight gain (due to caloric restric-

tion), or persistent hunger sensation. The

Fifth International Workshop-Conference

on Gestational Diabetes recommends the

following blood glucose concentrations:

fasting plasma glucose, 5.0–5.5 mmol/L;

1-hour postprandial plasma glucose, < 7.8

mmol/L; and 2-hour postprandial plasma

glucose, < 6.7–7.1 mmol/L.22 The NICE

guidelines19 recommend drug treatment

if diet and exercise cannot control the

blood glucose for 1–2 weeks, or if ultra-

sound shows possible fetal macrosomia

(abdominal circumference above the 70th

percentile) at diagnosis.

Oral Hypoglycaemic Agents

Glyburide (or glibenclamide) is a sec-

ond-generation sulfonylurea. It binds to

receptors that are associated with the

adenosine triphosphate-dependent po-

tassium channels of pancreatic β cells to

increase insulin secretion and insulin sen-

sitivity of peripheral tissues. The onset of

action takes approximately 1 hour with the

peak level at 4 hours after intake. Stud-

ies on the placental transfer of glyburide

are contradictory. In vitro studies showed

minimal placental transfer, but the fetal

response to various dosages of glyburide

is not completely known.23 A meta-analy-

sis by Moretti et al24 reported no differ-

ences between the insulin and glyburide

groups with regard to birthweight, LGA/

macrosomia, gestation at delivery, admis-

sions to neonatal units, or neonatal hypo-

glycaemia.

Metformin belongs to the biguanide

group. It inhibits hepatic gluconeogenesis

and glucose absorption, and stimulates

glucose uptake in peripheral tissues. The

onset of action takes approximately 1 hour




with the peak level at 2–4 hours after in-

take. Metformin does cross the placenta.

Because it acts as an insulin sensitizer in

peripheral tissues rather than as an insu-

lin analogue, it is believed that fetal me-

tabolism is less likely to be affected.25 The

Metformin in Gestational Diabetes (MiG)

trial26 of 751 women showed similar peri-

natal complications in both the metformin

and insulin groups, with better acceptabil-

ity in the metformin group; but subsequent

insulin was indicated in 46.3% of women

taking metformin.

Long-term safety data on infants

whose mothers were treated with glybur-

ide or metformin are lacking. Early neona-

tal complications, such as hypoglycaemia,

are not common and do not differ very much

from those resulting from insulin therapy.

When counselling patients, health carers

can reassure them that the rates of con-

genital malformations with the use of oral

hypoglycaemic agents and insulin do not

differ. The maternal glucose control (fast-

ing blood glucose and 2-hour postprandial)

by oral hypoglycaemic agents and insulin

is also comparable.

Acarbose, an alpha glucosidase in-

hibitor, has been used less often. Prelimi-

nary studies showed that it was effective

in decreasing postprandial hyperglycae-

mia in GDM, but its use has been limited

by its side effects, like abdominal cramp-

ing.27 Further studies are needed to better

evaluate the potential placental transfer

of this drug, as small amounts of acarbose

can be absorbed into the bloodstream.

Insulin

Traditionally, insulin has been regarded as

the standard treatment for diabetes, espe-

cially when diet and exercise fail to con-

trol the maternal blood glucose and there

is no risk of placental transfer of insulin

to the fetus.

Insulin requirements are not constant

throughout the day: it is low at night with

a sharp rise at dawn, followed by a grad-

ual decrease during the rest of the day.

Women in the first trimester are at risk of

hypoglycaemic events because of emesis,

and blood glucose levels should be closely

monitored with appropriate adjustment of

insulin. After the second trimester, insulin

requirements rise. During labour, short-

acting insulin should be used to achieve

optimal glucose levels of between 4 and 8

mmol/L and to prevent neonatal hypogly-

caemia. After delivery, glycaemic control

must be relaxed to prevent maternal hy-

poglycaemia, especially in breastfeeding

women. Insulin therapy should be stopped

in women who have not taken insulin be-

fore pregnancy, while those women who

are taking insulin for pre-existing diabetes

should resume their pre-pregnant insulin

dosages.

There are two types of insulin: hu-

man insulin and insulin analogue. The

short-acting insulin analogue aspart has

been shown to be safe in pregnancy in a

randomized trial28 and has been registered

for this indication. The short-acting insu-

lin analogue lispro has also been shown

to be safe in observational studies. How-

ever, there is no safety data available on

the long-acting insulin analogues detemir

and glargine; both are prescribed off-

label. Therefore, long-acting human insu-

lin should be used instead.

ANTENATAL MANAGEMENT

Once GDM is diagnosed, visits to health

carers or dietitians by the pregnant women

should be made at least every 1–2 weeks

and more frequently if complications oc-

cur. There is no consensus on the frequen-

cy and timing of antenatal surveillance

tests in women with GDM. It is crucial to

manage women, who do not comply with

advice, require drugs, have macrosomic or

growth-restricted fetuses, or have other

obstetric complications, as though they

had pre-existing diabetes and to begin

close antenatal monitoring (eg, the NICE

guidelines19 suggest anomaly scan, echo-

cardiography, growth scan at 28, 32 and 36

weeks’ gestation, tests of fetal well-being

after 38 weeks’ gestation). History review,

blood pressure measurement, and urine

albumin testing to diagnose pre-eclampsia

are also essential at every visit. In an at-

tempt to prevent macrosomia and to guide

the treatment, a randomized trial29 com-

pared ultrasound performed at 32 weeks’

gestation with ultrasound at both 28 and

32 weeks’ gestation. The rate of macroso-

mia was significantly higher in the group

assessed only at 32 weeks (71.1% vs

33.3%; P < 0.005).

The mode and timing of delivery of

women with GDM is controversial because

sufficient data are lacking to make a rec-

ommendation.

Induction of labour in women with

insulin-treated diabetes at 38 weeks’

gestation is intended to reduce the risk

of stillbirth. One study30 failed to detect a

benefit to expectant management beyond

38 weeks’ gestation, as the rate of caesar-



ean delivery was not reduced but rather

the rates of LGA infants and shoulder

dystocia were increased. For uncompli-

cated GDM, no strong evidence exists to

support earlier induction of labour, which

was also confirmed by a Cochrane review

of randomized trials on elective delivery in

women with diabetes.31

Prophylactic pre-labour caesarean

section using estimated fetal weight by ul-

trasound has been proposed but is contro-

versial. Recommendations concerning the

lower estimated fetal weight thresholds

for prophylactic caesarean section vary

from 4,000 to 4,500 g. Both the American

College of Obstetricians and Gynecologists

and the Royal College of Obstetricians and

Gynaecologists recommend prophylactic

caesarean section if the estimated fetal

weight is > 4,500 g. Another issue is the

inaccuracy of ultrasound in estimating

fetal weight, which leads to an increase

in unnecessary caesarean deliveries and,

therefore, caesarean-associated mater-

nal and fetal morbidities, and additional

health-care costs.

POSTPARTUM MANAGEMENT

Approximately 50% of women with GDM

will develop type 2 diabetes within 5 to

10 years.32 An Italian study33 showed

that GDM is a stronger predictor of later

metabolic syndrome after adjustments for

pre-pregnancy body mass index and age.

In a large 4- to 23-year follow-up study

in Denmark, 68% of the 481 women with

previously diagnosed GDM had impaired

glucose regulation, 59% had elevated

fasting serum insulin, 54% had central

obesity, 28% had hypertension, and 35%

had dyslipidemia, presenting with higher

triglycerides levels and lower high-density

lipoprotein cholesterol levels compared

with the control group.34

Diagnostic testing for diabetes is

appropriate 6 weeks after delivery. It is

unclear whether a traditional 2-hour 75-g

oral glucose tolerance test or fasting

plasma glucose test may be more useful

at this time. The frequency of follow-up

blood glucose tests for early detection of

impaired glucose tolerance or diabetes

varies from annual to triennial. Advice on

postpartum weight loss, which may help

reduce the occurrence of type 2 diabetes

mellitus, includes breastfeeding, dietary

modification, and exercising for at least

150 minutes every week.35

CONCLUSION

Without further cost analyses and confir-

mation of results from randomized inter-

vention trials, the IADPSG guidelines are

unlikely to be widely adopted worldwide.

Without a uniform diagnosis, research on

risks and management is difficult. Women

with GDM should be treated with dietary

modification, appropriate exercise, and

drugs, if necessary. Oral hypoglycaemic

agents (eg, glyburide, metformin) are as

useful as but not better than insulin alone

in terms of early pregnancy outcomes.

About the AuthorsDr Chan is a resident trainee, and Dr Lau and Dr Leung are consultants, practicing in the Department of Obstet-rics and Gynaecology, Kwong Wah Hospital, Kowloon, Hong Kong SAR.

REFERENCES

1. National Diabetes Data Group. Classifica-tion and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039–1057.

2. Metzger BE, Lowe LP, Dyer AR, et al; HAPO Study Cooperative Research Group. Hyperglyce-mia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.

3. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbo-hydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy out-comes. N Engl J Med 2005;352:2477–2486.

4. Landon MB, Spong CY, Thom E, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medi-cine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339–1348.

5. Coustan DR. Gestational diabetes. In: Diabetes in America. 2nd ed. NIH Publication No. 95–1468. Bethesda, MD: National Diabetes Data Group, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases; 1995:703–717.

6. Scott DA, Loveman E, McIntyre L, Waugh N. Screening for gestational diabetes: a systematic review and economic evaluation. Health Technol Assess 2002;6:1–161.

7. Griffin ME, Coffey M, Johnson H, et al. Univer-sal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med 2000;17:26–32.

8. Lao TT, Ho LF, Chan BC, Leung WC. Maternal age and prevalence of gestational diabetes mel-litus. Diabetes Care 2006;29:948–949.

9. Ko GTC, Tam WH, Chan JCN, Rogers M. Preva-lence of gestational diabetes mellitus in Hong

Kong based on the 1998 WHO criteria. Diabet Med 2002;19:80.10. International Association of Diabetes and Pregnancy Study Groups. International Asso-ciation of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classifi-cation of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–682.11. Moses RG. New consensus criteria for GDM: problem solved or Pandora’s box? Diabetes Care 2010;33:690–691.12. HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthro-pometrics. Diabetes 2009;58:453–459.13. HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gy-necol 2010;202:255.e1–255.e7.14. Pridjian G, Benjamin TD. Update on gesta-tional diabetes. Obstet Gynecol Clin North Am

2010;37:255–267.15. American Diabetes Association. Nutrition recommendations and interventions for Diabetes. A position statement of the American Diabetes Association. Diabetes Care 2008;31(Supp1):S61–S78.16. Reader D, Splett P, Gunderson EP; Diabetes Care and Education Dietetic Practice Group. Im-pact of gestational diabetes mellitus nutrition practice guidelines implemented by registered dietitians on pregnancy outcomes. J Am Diet As-soc 2006;106:1426–1433.17. Food and Nutrition Board, Institute of Medi-cine. Dietary Reference Intakes for Energy, Carbo-hydrate, Fiber, Fat, Fatty Acids, Cholesterol, Pro-tein, and Amino Acids. Washington, DC: National Academies Press; 2002.

A complete list of references can be obtained upon request to the editor.


Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh MIMS, bekerjasama dengan Ikatan Dokter Indonesia.

Setelah membaca artikel ‘Gestational Diabetes’, jawab pertanyaan berikut kemudian kirimkan dengan menggunakan formulir jawaban yang sudah disediakan ke CME Journal of Paediatrics, Obstetrics & Gynaecology, untuk mendapatkan 5 SKP.

Artikel CME:

Gestational Diabetes

Jawab pertanyaan di bawah ini dengan Benar atau Salah

5 SKP

1. Gestational diabetes mellitus (GDM) can present in the first trimester.

2. The incidence of GDM in Hong Kong is 25%.

3. The selected thresholds in the International Association of Diabetes and Pregnancy Study Groups guidelines represent

an odds ratio of 1.75 for birth weight and cord C-peptide, relative to the odds of those outcomes at mean glucose values.

4. Rates of shoulder dystocia and caesarean section were significantly reduced by treatment in the ACHOIS and MFMUN-

GDM trials.

5. In obese women with GDM, there should be a 40% restriction of caloric intake.

6. Metformin is registered and approved for use in pregnancy.

7. Glyburide can cause fetal hyperinsulinaemia.

8. The National Institute for Clinical Excellence recommends fortnightly growth scans in women with GDM from 32 weeks’

gestation.

9. The Royal College of Obstetricians and Gynaecologists recommends prophylactic caesarean section

if the estimated fetal weight is greater than 4,000 g.

10. The 75-g oral glucose tolerance test is the recommended test in the postnatal period of women with GDM.

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JPOG NOv/Dec 2013 • 264

JPOG 2013 Annual Index

Section First Author Issue Page

DermAtOlOGyAdolescent, aetiology, differential diagnosis, verrucous epidermal naevus In Practice Fischer G Nov/Dec 244

Aetiology, anti-bacterial agents, antiviral agents, child, differential diagnosis, erythema multiforme

In Practice Fischer G Sep/Oct 206

GynAecOlOGyAdenomyosis, endometrial ablation techniques, endometrial hyperplasia, endometrial neoplasms, leiomyoma, metrorrhagia, perimenopause, polyps, progestins, tranexamic acid

Clinical Review Eden J Mar/Apr 74

Adjuvant chemotherapy, CA-125 antigen, gynaecological surgical procedures, ovarian neoplasms, palliative care

Clinical Review Taylor SE Jul/Aug 155

Aetiology, analgesics, cystoscopy, diagnosis, interstitial cystitis Clinical Review Vella M Nov/Dec 232

Bone density conservation agents, hormone replacement therapy, postmenopausal osteoporosis, primary prevention, secondary prevention, selective oestrogen receptor modulators

Clinical Review Daroszewska A Sep/Oct 181

Complementary therapies, drug therapy, hormone replacement therapy, hot flushes, menopause CME Ang SB Jan/Feb 37

Infertility, ovulation induction, polycystic ovary syndrome Clinical Review Kini S May/Jun 100

OBStetrIcSAetiology, diagnosis, haemorrhage, pregnancy, rectal neoplasms, rectum In Practice Pokorny CS Nov/Dec 244

Carbetocin, caesarean section, drug toxicity, oxytocics, pharmacology, postpartum haemorrhage Clinical Review Yussof SM Sep/Oct 207

Chronic renal insufficiency, kidney transplantation, pregnancy, renal dialysis Clinical Review Hall M Sep/Oct 195

Dietary modification, gestational diabetes, hypoglycemic agents, insulin, type 2 diabetes mellitus CME Chan LL Nov/Dec 257

Eclampsia, pre-eclampsia, pregnancy-induced hypertension Clinical Review McCarthy FP Mar/Apr 49

Ectopic pregnancy, first pregnancy trimester, habitual abortion, hydatidiform mole, hyperemesis gravidarum, pregnancy complications, spontaneous abortion

Clinical Review Pugsley H Jul/Aug 146

Ectopic pregnancy, imaging CME Lam SL Mar/Apr 81

Fever, postpartum period, puerperal infection, sepsis, Streptococcus pyogenes Clinical Review Glackin KG Jan/Feb 28

Inherited blood coagulation disorders, postpartum haemorrhage, prenatal diagnosis, thrombocytopenia, thrombotic microangiopathies

Clinical Review Lefkou E Jan/Feb 15

Krukenberg tumour, pregnancy, prognosis Case Study Mohd Azri MS May/Jun 122

Obstetric labour complications, placenta accreta, placenta praevia, postpartum haemorrhage, prenatal care

Clinical Review Jegasothy R May/Jun 93

Prenatal diagnosis, Streptococcus agalactiae CME Leung KY Sep/Oct 213

Repeat caesarean section, reproductive history, vaginal birth after caesarean CME Yung WK Jul/Aug 169

PAeDIAtrIcSAcute abdomen, appendicitis, children, familial intestinal malrotation, intussusception, peritonitis, vomiting

Clinical Review Makin E Mar/Apr 61

Adolescent, aetiology, child, chronic fatigue syndrome, cognitive therapy, diet therapy, differential diagnosis, intrinsic sleep disorders

Clinical Review Mackenzie C Nov/Dec 245

Adolescent, child, diagnosis, infant, sleep disorders, therapy Clinical Review Wong PPC Jan/Feb 5

Asthma, child, respiratory sounds, tobacco smoke pollution Clinical Review Lenney W Nov/Dec 225

Autistic disorder, diagnosis, pervasive child development disorders, symptom assessment Clinical Review Yates K May/Jun 112

Child, constipation, encopresis, infant, laxatives, toilet training Clinical Review Dowling T Jul/Aug 164

Cochlear implantation, deafness, hearing aids, hearing loss, otitis media with effusion Clinical Review Elloy MD Jul/Aug 137

rePrODuctIve meDIcIneAetiology, artificial insemination, fertilization in vitro, male infertility, semen analysis CME Lee VCY May/Jun 125

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Documents

JPOG December 2013 ID