Chronic Fatigue Syndrome in Children and Young People. Gestational Diabetes. Painful Bladder Syndrome. Asthma in Children

JAN/FEB 2012 Nov/Dec 2013Vol. Vol.38 39No. No.16

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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

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CME ARTICLE

P 5 SK

Gestational Diabetes

IN PRACTICE

JOURNAL WATCH

GYNAECOLOGY

Painful Bladder Syndrome

PAEDIATRICS

Asthma in Children

Chronic Fatigue Syndrome in Children and Young People www.jpog.com

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NO V/DEC Vol. 39

2013 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

221

222 • Breastfeeding has a protective effect against obesity in Japanese schoolchildren • Late preterm infants not at higher risk of ADHD, learning disabilities Obesity rates among US adolescents may be stabilizing 223 • • 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

224

Editorial Board

Professor Biran Affandi University of Indonesia

Dr Tak-Yeung Leung Chinese University of Hong Kong

Dr Raman Subramaniam Fetal Medicine and Gynaecology Centre, Malaysia

Board Director, Paediatrics

Dr Karen Kar-Loen Chan The University of Hong Kong

Professor Tzou-Yien Lin Chang Gung University, Taiwan

Professor Walfrido W Sumpaico MCU-FDT Medical Foundation, Philippines

Professor Oh Moh Chay KK Women’s and Children’s Hospital, Singapore

Professor Somsak Lolekha Ramathibodi Hospital, Thailand

Professor Cheng Lim Tan KK Women’s and Children’s Hospital, Singapore

Professor Lucy Chai-See Lum University of Malaya, Malaysia

Professor Kok Hian Tan KK Women’s and Children’s Hospital, Singapore

Professor SC Ng National University of Singapore

Professor Surasak Taneepanichskul Chulalongkorn University, Thailand

Professor Hextan Yuen-Sheung Ngan The University of Hong Kong

Professor Eng-Hseon Tay Thomson Women Cancer Centre, Singapore

Professor Carmencita D Padilla University of the Philippines Manila

Professor PC Wong National University of Singapore

Professor Seng-Hock Quak National University of Singapore

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

Dr Tatang Kustiman Samsi University of Tarumanagara, Indonesia

Professor Hui-Kim Yap National University of Singapore

Professor Alex Sia KK Women’s and Children’s Hospital, Singapore

Professor Tsu-Fuh Yeh China Medical University, Taiwan

Professor Pik-To Cheung Associate Professor Department of Paediatrics and Adolescent Medicine The University of Hong Kong Board Director, Obstetrics and Gynaecology Professor Pak-Chung Ho Head, Department of Obstetrics and Gynaecology The University of Hong Kong

Associate Professor Anette Jacobsen KK Women’s and Children’s Hospital, Singapore Professor Rahman Jamal Universiti Kebangsaan Malaysia Dato’ Dr Ravindran Jegasothy Hospital Kuala Lumpur, Malaysia Associate Professor Kenneth Kwek KK Women’s and Children’s Hospital, Singapore Dr Siu-Keung Lam Prestige Medical Centre, Hong Kong Professor Terence Lao Chinese University of Hong Kong Dr Kwok-Yin Leung The University of Hong Kong

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Gizi Sejak Awal Kehidupan (Early Life Nutrition) 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.

Early Life Nutrition

SHORT TERM IMPACT

LONG TERM BENEFIT

• Mendukung perkembangan sistem daya tahan tubuh sejak awal

• Perkembangan sistem daya tahan tubuh untuk mengurangi alergi dan infeksi

• Mendukung perkembangan otak sejak awal

• Mendukung pertumbuhan sejak awal

• Kemampuan belajar dan kognitif yang optimal

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

Nutribaby Royal dengan Pronutra+ dengan AA DHA 1:1 dan zat besi Dukung pertumbuhan dan perkembangan otak 1 dengan prebiotik lc FOS-sc GOS 1:9 Membantu memperkuat daya tahan tubuh bayi 2 dengan protein, kalsium, dan zinc Mendukung tumbuh kembang optimal 3,4,5

Referensi: 1.

Gibson R.A, et al. Maternal and Child Nutrition 2011. pp17-26

2.

Arslanoglu Set al. j, Nutr. 2008;13B:1091-1095

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.

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.


NO V/DEC Vol. 39

2013 No. 6

Review Article Paediatrics

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 Article Gynaecology

225

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

232 244 Clinical Case: Rectal Bleeding in Pregnancy—Don’t Assume It’s Benign

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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 secondclass 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.

JPOG NOV/DEC 2013 • iii


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Namun jika terdapat indikasi medis, rangkaian SGM Presinutri menyediakan dukungan nutrisi agar Ananda dapat tumbuh dan berkembang dengan optimal.

Indonesia


NO V/DEC Vol. 39

2013 No. 6

Review Article Paediatrics

245 Chronic Fatigue Syndrome in Children and Young People

245

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

P 5 SK

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

257

Review Articles

Case Studies

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

Interesting cases seen in general practice and their management.

Pictorial Medicine Vignettes 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 Editor MIMS Pte Ltd, 6 Shenton Way, OUE Downtown 2, #15-08, Singapore 068809 Tel: (65) 6290 7400 Fax: (65) 6290 7401 E-mail: [email protected]

The Cover: Chronic Fatigue Syndrome © 2013 MIMS Pte Ltd

Lisa Low, Illustrator

JPOG NOV/DEC 2013 • iv


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Peer Reviewed

GYNAECOLOGY

3IQ safe and effective for diagnosing urgency urinary incontinence

Journal Watch

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

the Wide Range Assessment of Visual Motor Abili-

at least one dose of medication during the open-

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

label study. Compared with baseline in the ran-

Intelligence Test and Wide Range Assessment of

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

Memory and Learning at age 7 years. Adjustments

fesoterodine was linked to a reduction in the mean

were made for sociodemographic background, ma-

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

ternal intelligence, and home environment.

gency incontinence (3.95 vs 0.90) episodes per day

Longer breastfeeding duration was associ-

(P < 0.0001 for both). Patient satisfaction increased

ated with a higher Peabody Picture Vocabulary Test

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

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

9 months, respectively. Twenty-six women expe-

month breastfed) and higher intelligence on the

rienced one or more serious adverse events, but

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

only one was considered to be treatment-related.

CI, 0.16–0.53). Beneficial effects of breastfeeding

Specialist evaluation of 22 women found that the

on Wide Range Assessment of Visual Motor Abili-

3IQ had misclassified five but without any adverse

ties at age 3 appeared to be greater for women

outcomes.

who consumed ≥ 2 servings of fish per week com-

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.

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

PAEDIATRICS

Wide Range Assessment of Memory and Learning scores. An accompanying editorial notes that the pu-

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-

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

tative connection between breastfeeding and cognition has widespread and lifelong implications, but that the current problem is not the initiation of breastfeeding. Rather, it is the continuation of

continence Questions (3IQ) have been developed to aid primary care providers in diagnosing and

Nutrients in breast milk may benefit the developing

breastfeeding through to age 6 months. The sug-

initiating treatment, and a recent study has shown

brain, but no exact relationship between maternal

gestion is made that large-scale structural changes

that long-term fesoterodine therapy initiated on the

diet during lactation and childhood cognition has

are required to support mothers in this endeavour.

basis of the 3IQ is both safe and effective.

been determined to date. Now, a study has found

Researchers invited 567 women who had

that longer duration and greater exclusivity of

completed a 12-week randomized controlled trial

breastfeeding is associated with better receptive

of fesoterodine therapy for urgency urinary incon-

language at age 3 and higher verbal and non-verbal

tinence diagnosed by the 3IQ to participate in a

IQ at age 7.

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).

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

The prospective, longitudinal, Project Viva

lected data on incontinence and voiding episodes

study evaluated feeding practices among a US

using voiding diaries. Patient satisfaction was de-

prebirth cohort of 1,312 mothers and assessed the

termined by questionnaire, and safety was evalu-

cognitive capabilities of their children at ages 3

ated by monitoring post-void residual volumes and

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

Although consumption of sugar-sweetened bev-

adverse events.

the Peabody Picture Vocabulary Test at age 3 years,

erages (SSBs) has been linked to weight gain in

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

JPOG NOV/DEC 2013 • 221

JPOG_NovDec_2013__SG MY PH ID_Combine.indd 221

12/4/13 5:16 PM

school-aged children and adolescents, results for

sis also showed that children who were already

breastfeeding at age 6–7 months was associated

younger children have been mixed. Now, a US study

exposed to such beverages at age 2 had a greater

with a decreased risk of being overweight (odds

has shown that consumption of SSBs is also linked

subsequent increase in BMI z score over the follow-

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

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

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

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

The researchers compared the consumption

The researchers suggest that paediatricians

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

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

and parents should discourage the consumption of

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

SSBs to avoid potential unhealthy weight gain in

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

children.

part of the US-based Early Childhood Longitudinal Survey–Birth Cohort study (a representative survey

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

An accompanying editorial notes the importance 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 the US population of children born in 2001). Ad-

of other factors have a greater impact on obesity,

justments were made for race/ethnicity, socioeconomic status, mother’s BMI, and TV viewing.

0.44; 95% CI, 0.31–0.63).

Breastfeeding has a protective effect against obesity in Japanese schoolchildren

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.

Breastfeeding has been suggested to protect against obesity in children, but the evidence remains inconclusive and most studies have been

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).

performed among children in Western countries. Recently, however, researchers in Japan have confirmed a protective effect of breastfeeding against obesity. Secondary analyses of data collected from

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

2001 through 2009 during the ongoing nationwide Longitudinal Survey of Babies in the 21st century

Late preterm infants have previously been suggest-

were undertaken. All 43,367 singleton children

ed to be at greater risk of learning and behavioural

born after 37 gestational weeks with available in-

problems than term infants, but most studies have

formation on feeding during infancy were eligible,

evaluated clinic-referred children at early school

but some were excluded because of missing data

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

Increased consumption of SSBs compared

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

ulation-based study suggests that late preterm in-

with infrequent/no consumption of such beverages

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

fants are not at greater risk of developing attention

was associated with higher BMI z scores among

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

deficit/hyperactivity disorder (ADHD) and learning

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

screen time as well as for maternal educational at-

disabilities compared with term infants.

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

tainment, and smoking and working status.

The study included 5,699 children born in

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

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

Rochester, Minnesota, US, between 1976 and 1982,

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

fied as overweight and 2.1% as obese, according

who were still resident in the community after 5

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

to the International Obesity Task Force body mass

years and who did not have a severe intellectual

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

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

disability. The cumulative incidence of ADHD and

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

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

learning disabilities in reading, written language,

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

addition, compared with formula feeding, exclusive

and math by age 19 was determined by comparing



12/4/13 5:16 PM

Peer Reviewed

medical and school records for former late preterm

the frequency of eating breakfast. Moreover, the

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

amount of time spent viewing TV decreased and

infants. Adjustments were made for maternal edu-

the consumption of sweets and sweetened bever-

cation and perinatal complications.

ages declined. Although a trend towards weight

Journal Watch

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

No statistically significant differences were

gain remained—the average BMI increased from

Full-term neonates born between 37 and 41 weeks’

observed between former late preterm (n = 256)

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

gestational age have traditionally been considered

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

in average BMI between 2005–2006 and 2009–

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

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

2010, which may indicate that obesity rates are

study has provided further evidence that early-

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

beginning to stabilize.

term births (37 0/7–386/7 weeks) are associated with

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

The researchers comment that these find-

higher rates of neonatal morbidity and neonatal

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

ings indicate that public health initiatives may be

intensive care unit (NICU) or neonatology service

15.5%; P = 0.89).

beginning to have an effect. However, they note

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

The researchers conclude that former late

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

The retrospective, population-based birth

preterm infants have similar rates of ADHD and

and ethnicity-based differences in behaviour when

cohort study evaluated 33,488 live births at major

learning disabilities as term infants.

interpreting these findings. A number of these dif-

birthing hospitals in Erie County, New York, be-

ferences are noted in the study. For example, older

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

adolescents were more frequent users of comput-

Data on NICU or neonatology service admission

ers, consumed fewer fruits and vegetables and

were extracted from medical records.

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 adolescents may be stabilizing

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.

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

Obesity rates among US adolescents have been of

higher risk for NICU or neonatology service admis-

concern for some time given that obesity is a risk

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

factor for many leading causes of mortality. How-

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

ever, a recent study has indicated that obesity rates

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

among US adolescents may be stabilizing and that

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

this may be due to changes in obesogenic behav-

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

iours.

or intubation (0.6% vs 0.1%; adjusted OR, 4.57), Nationally representative US students in

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

grades 6–10 anonymously completed the Health

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

Behavior in School-aged Children (HBSC) survey,

administration of intravenous fluids (7.5% vs 4.4%;

which assesses body mass index (BMI), physical

adjusted OR, 1.68), and treatment with intravenous

activity, and sedentary and dietary behaviours, in

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

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

addition, significantly more early-term neonates

American and Hispanic students were oversampled

were delivered by caesarean section than term ne-

to obtain better estimates for these populations.

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

Obesogenic behaviours remained common

found to increase the risk for NICU or neonatology

over the study period, but the amount of time spent

service admission and morbidity, but even early-

engaging in physical activity increased over time,

term infants delivered vaginally had a significantly

as did the consumption of fruit and vegetables and

higher rate of NICU or neonatology service admis-



12/4/13 5:16 PM

sion than term infants.

and these women may face the greatest risks.

to 1,601,253 women without pregnancy complications who delivered singletons at 37–42 completed

An accompanying editorial notes that these

The researchers comment that although

findings reinforce the conception of maturation as

a short consent time does not necessarily imply

a continuum and highlight the difficulties associat-

a poor-quality conversation regarding potential

The rate of postpartum haemorrhage requir-

ed with using a preset gestational age as an index

risks, it is unlikely that a high-quality informed

ing blood transfusion was increased by labour

of separation between immaturity and maturity.

consent process can occur in under 50 minutes.

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

They suggest that an alternative approach should

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

be adopted, such as the inclusion of informed con-

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

sent discussions during routine prenatal care. An

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

accompanying editorial and roundtable discussion

38 and 39 weeks’ gestation was associated with

support this suggestion.

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

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).

OBSTETRICS Standard practices for obtaining consent for caesarean delivery suboptimal

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).

weeks’ gestation.

CI, 1.13–1.99; and aRR, 1.24; 95% CI, 1.09–1.82, respectively) and induction at 38 weeks’ gestation with higher rates of venous thromboembolism (aRR, 2.94; 95% CI, 1.59–5.46). However, the absolute increase in morbidity rates was small, and the number needed to harm was substantial for all

Currently, the standard practice for obtaining informed consent to caesarean delivery in the US

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

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.

is to obtain the patient’s consent at the time the decision to perform a caesarean is made. However,

Labour induction is widely used to prevent adverse

a novel study has shown that this approach does

maternal, fetal, and infant outcomes. Although

not allow sufficient time for patients to evaluate

generally considered safe, problems such as pro-

potential risks, particularly among women who are

longed labour, chorioamnionitis, fetal death, and

at greatest risk.

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

The retrospective chart review of 90 patients

searchers in Canada compared the gestational

who underwent caesarean delivery during labour

age-specific effects of labour induction on severe

compared the time from consent to incision to ac-

obstetric morbidity and found that women who

tual delivery among women with and without fetal

were induced at an earlier term had higher rates

heart rate indications.

of specific severe maternal morbidity than similar

The median consent time among all women was 48 minutes (interquartile range, 25–72 min-

women who were treated expectantly, although the absolute risks were low.

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

The researchers compared data from hos-

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

pital records collated in the Discharge Abstract

for potential confounders, the odds of delivery < 30

Database of the Canadian Institute for Health In-

minutes after consent were 4.7 times higher (95%

formation for 2003–2011 (excluding Quebec). The

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

database includes all maternal hospital admissions

heart rate indications. In addition, the consent time

for delivery as well as links to newborn infant

was not higher among obese women or those who

admissions. The analysis was performed using a

had previously experienced a caesarean delivery,

pregnancies-at-risk approach and was restricted



12/4/13 5:16 PM

Hanya untuk Kalangan Medis

Abdominal Discomfort in infant

Just Functional or Something More Serious? 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).

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

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.

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).

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

Consider GERD, CMA, low lactase activity, or other GI disease

Organic cause Red Flag

Yes

No Improvement?

Evaluate and establish correct feeding technique and baby comfort

Yes

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

No

Maintain support Consider modification of infant diet and try an eHF/CM-free diet in BF

Improvement?

Yes

No

No

Refer to Psychology/psychiatry

Refer to pediatric gastroenterologist

Consider diagnosis of CMA

Yes

Gambar 1. Tata laksana infantile colic

Fussiness, Gassiness: Accompanied by Crying Excessive Crying/Gas/Fussiness Breastfed infant

No

No

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

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

Yes Organic cause? Refer to pediatric GI specialist

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.

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

Education Reassurances

No

Formula fed infant

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.

Problem solved??

Yes Discharge

Refer to pediatric GI specialist Y. Vandenplas et al. / Nutrition xxx (2012) 1-11

Gambar 2. Tata laksana fussiness & gassiness

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

Gambar 3. Suasana Lunch Symposium “Abdominal Discomfort in infant” di PIT IKA Solo 8 Oktober 2013


Tidak ada untuk mengatasi alergi susu sapi pada bayi

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PAEDIATRICS PAEDIATRICS

II

Peer Peer Reviewed Reviewed

Imaging Paediatric Asthma in Children Brain Tumours Warren Lenney, MD, FRCP, FRCPCH, DCH

Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology

INTRODUCTION Childhood asthma has been described for centuries, but its prevalence, aetiology, management, and outcome have changed beyond recognition in the last 40 years. No disease is static. Updates are needed to keep pace with those changes. In the early 1970s, references were made to infants identified as ‘fat, happy wheezers’, 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 epidemiological 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/developing countries with some reduction in Western Europe, North America, and Australasia. JPOG NOV/DEC 2013 • 245 225


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

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 different 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 constiThe financial burden is traditionally divided

tutes part of the spectrum of asthma and whether

into direct and indirect costs. Direct costs relate to

symptoms early in life can predict progression of

costs of hospital admission, emergency room, out-

disease through childhood and into adult life. In

patient and community practitioner visits, medicinal

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

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

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

cal appointments, as well as the cost of altering the

century the main thrust has been to separate phe-

home such as purchase of non-allergenic bedding.

notypes into episodic (viral) wheeze or multi-trigger

Indirect costs are calculated as days missed from

wheeze. Other terms such as persistent wheeze

school, days missed from work for the parent to look

and intermittent recurrent wheeze only confuse

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

the picture. The triggers that may instigate non-

a child dies from asthma, it is possible to calculate

viral wheeze are tobacco smoke, exercise, emotion,

the loss of potential earnings the child would have

and various aeroallergens. An excellent review of



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PAEDIATRICS

preschool wheezing can be found in the European

I

PAEDIATRICS Peer Reviewed

What’s new?

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

• P revalence and hospital admissions are beginning to fall in English-speaking countries • Good asthma control means a much lower financial burden • Very severe asthma management requires a tertiary care, multidisciplinary team • Recent smoking legislation may benefit children with asthma

is agreed is that the more severe and persistent the symptoms, the more likely they are to persist. Although epidemiological studies try to separate episodic viral wheeze and multiple-trigger wheeze, be-

tive process. In sensitized asthmatic bronchial epi-

cause of the overlap, it is much more difficult when

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

dealing with an individual child. The relationship

processes are not induced; this leads to very high

between atopy and disease progression has been

viral load and the development of inflammation.

closely studied and the single most useful indicator

A Swedish cohort study has consistently sug-

of persistence of symptoms is the presence of al-

gested a relationship between early RSV infection,

lergen sensitization on skin-prick testing at 2 years

early sensitization and asthma patterns throughout

4

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

childhood,6 whereas most others have not. This

taken by most UK clinicians in very young children.

study managed to follow up 46 of the original 47 infants with RSV infection and 92 of the 93 control

MECHANISMS OF SYMPTOM DEVELOPMENT AND PROGRESSION

subjects for 18 years.

GENERAL MANAGEMENT OF ASTHMA

Children sensitized at an early age to the common aeroallergens (house-dust mite and cat being the

There are multiple local, national and international

two most common sources) react differently to res-

guidelines on asthma management. The Scottish

piratory viruses than those not sensitized. Although

Intercollegiate Guidelines Network (SIGN)/British

respiratory syncytial virus (RSV) results in repeated

Thoracic Society guidelines are regularly updated;

wheezing and coughing episodes in childhood, rhi-

their outline can be found in the British National

novirus is thought to be more important in causing

Formulary for Children. A step-wise approach is

asthma exacerbations in children.

5

recommended, but the step most often forgotten

In normal bronchial epithelial cells, the pres-

is to step down when control has been achieved

ence of virus leads to rapid induction of interferon-β

following a reasonable period of stability. Parents

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

understand this and often reduce or stop treatment

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

if there are no symptoms. There is no evidence that

bonuclease and protein kinase R join in to kill and

this is inappropriate and, indeed, we know that the

phagocytose the virus, thereby limiting the infec-

long-term use of inhaled corticosteroids (ICS) has no JPOG NOV/DEC 2013 • 227


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Peer Reviewed

Table 1. Passive smoke exposure and incidence of wheeze

re-checked 20 minutes later. Repeated increases clearly indicate non-adherence with prescribed

Smoking exposure

Age at outcome (y)

Number of studies

Pooled odds ratio

Prenatal maternal Maternal Paternal

≤2

11 2 0

1.44 1.72


3–4

7 4 0

1.25 1.77


5–18

5 2 2

1.38 1.65 1.31

Passive smoke exposure and incidence of wheeze (adapted from Royal College of Physicians report ‘Passive smoking and children’ 2010; page 85).

treatment and need addressing. This can be more difficult than it may seem. The reasons for nonadherence are complex and multiple.

VERY SEVERE ASTHMA IN CHILDREN In the majority of children, asthma is relatively easy to diagnose and manage by following guideline 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 β 2-agonists

effect on the natural history of the disease. When

and other treatments, such as theophyllines or leu-

ICS are stopped after many years usage, those with

kotriene-receptor antagonists (LTRAs). These need

persisting active disease eventually show falls in

specialist assessment by tertiary respiratory teams.

lung function and increases in symptoms.

It is imperative to assess the family background. Is there a lack of adherence to treatments? Is the home

ARE THERE NEW WAYS OF MONITORING CLINICAL PROGRESS?

environment contributing to poor control? Are there contributory psychosocial factors? Discussions with primary care personnel, checking with the pharmacist that prescriptions are collected regularly, and

Asthma is an inflammatory condition. Studies have

visits to the family are often necessary to establish

assessed enhanced control by measuring inflamma-

the cause for poor control. The gathering of all the

tory markers in the blood and sputum and measur-

relevant information needs a multidisciplinary team

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

that includes specialist paediatricians, respiratory

portable FeNO monitors became available, there

nurses, psychologists, and social workers. The role

was hope that FeNO would be clinically helpful.

of nurse-led home visits is now well established.

After a decade of usage, the general belief is that

Invasive procedures such as bronchoscopy may be

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

needed.

7

ful as an adjunct to good clinical history-taking and

In keeping with the recognition that more se-

careful clinical examination. The clinical assess-

vere disease continues into adult life, one of the

ment should include lung function testing (spirom-

longest followed-up asthma cohorts has recently

etry) in all children old enough to produce reliable

been published from Melbourne, Australia. 8 Pa-

values for forced vital capacity and forced expira-

tients were recruited from a 1957 birth cohort at the

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

age of 7 years and reviewed regularly to 50 years of

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

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

given 6–10 puffs of salbutamol and have spirometry

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



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PAEDIATRICS

participated in the follow-up at 50 years and 197 of these completed questionnaires and lung function

I


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

testing. Chronic obstructive pulmonary disease was diagnosed in 28 adults (14%) and 24 of these were

Upper 95% CI

from the very severe cohort introduced at 10 years

Smoothed hospitalizations Lower 95% CI

of age. The authors comment that early aggressive

8

the future, prevent airway remodelling and reduce

7

both the symptoms of asthma throughout life and the development of chronic obstructive pulmonary disease as a long-term complication.

It was believed that ‘wheezy bronchitis’ was part of the asthma spectrum, but in the 21st century the main thrust has been to

Asthma admissions (number/day)

therapy for very severe asthma in childhood may, in

6 5 4 3 2 1 0 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

separate phenotypes into episodic (viral) wheeze or multi-trigger wheeze

cigarettes per day. The odds ratio for wheeze in relation 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 Children’s Charter early in 2011. Having undertaken a

THE ENVIRONMENT AND WHEEZE/ASTHMA

confirmatory survey amongst UK children, the Charter’s first point is ‘Children should be able to enjoy a smoke-free environment both inside and out-

The Royal College of Physicians published ‘Pas9

side the home’. The British Lung Foundation went

sive smoking and children’ in 2010. The single

on to recommend a change in UK law prohibiting

most useful measure that may reduce the preva-

parents from smoking in cars when children were

lence and influence the symptoms of wheeze and

present. Scotland banned smoking in public places

asthma in children is to encourage the birth and

and workplaces in March 2006. Over the next 3.6

rearing of children in an environment free from

years, there was a significant fall in daily hospital

tobacco smoke. The developing fetus in a mother

admissions for asthma in children. This can be seen

who smokes receives as much nicotine and other

in Figure 1, including 95% confidence intervals and

tobacco constituents as an adult who smokes 20

smoothed admissions for children with asthma. JPOG NOV/DEC 2013 • 229


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

INCIDENCE AND CONTROL OF WHEEZING THROUGHOUT CHILDHOOD

NEWER PHARMACEUTICAL TREATMENTS The Early Years

The profile of asthma incidence seen in the 2008 Ger10

In the preschool age group, children with episodic

man asthma cohort study can be replicated through-

viral wheeze respond to short-acting β 2-agonists

out all Western European countries. The numbers are

when given through a spacer (with facemask at-

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

tached in those under 3 years old). Those with

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

repeated symptoms affecting activity, sleep, and

nology Assessment–funded MASCOT study, opened

nursery attendance require preventative treatment

in 2009 with the intention of enrolling 900 children

but respond less well to ICS than children with mul-

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

tiple trigger wheeze. LTRAs in the form of montelu-

alone) of the SIGN national asthma guidelines. It had

kast granules or chewable tablets (4 mg) have been

difficulty recruiting children and closed early in Janu-

used increasingly in this age group. Studies from

11

ary 2011. A positive inference may be that there are

UK, Europe, and Australasia have reported varying

fewer poorly controlled asthmatic children in the UK

outcomes, but the SIGN national guidelines (up-

than there were 10 years ago.

dated in June 2009) recommend LTRAs in this age



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group. Their administration to very young children

I


Practice points

is often easier for parents than the use of spacer devices for ICS delivery.

The School Age Years Little has changed over the past 5 years in relation 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 lowdose ICS are insufficient to maintain good clinical control, but a North American study 12 confirmed that the first step-up therapy should be combination

• E ncourage families to ensure their child has a smoke-free environment • Episodic viral wheeze is extremely common in the first 3 years • M ulti-trigger wheeze persists longer, but there is overlap with episodic viral wheeze in many young children • Strive for good asthma control • K now where your nearest tertiary care asthma centre is for referral of children with very severe asthma symptoms despite conventional treatment

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 13

symptoms. At present, the National Institute for

A UK safety study

Health and Clinical Excellence has not approved its

examined whether tolerance to LABAs was a clini-

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

undertaken in all age groups. 14

cal concern. The general consensus is that, when

subcutaneous injection either fortnightly or monthly

used in addition to ICS, LABAs are effective and

depending on body weight and the absolute concen-

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

tration of serum IgE.

studies as children are underrepresented in clinical trials compared with adults with asthma. An exciting development has been the licens-

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

ing of omalizumab, an anti-IgE monoclonal an-

About the Author

tibody, for use in children aged 6 years and over

Warren 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.

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 revolutionized the lives of a few patients with very severe

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 treatment of wheezing disorders in preschool children: 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 children: a useful distinction for clinicians? Paediatr Respir Rev 2011;12:160–164. 5. Friedlander SL, Busse WW. The role of rhinovirus in asthma exacerbations. J All Clin Immunol 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. Wheezing in childhood: incidence, longitudinal patterns 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 corticosteroids. New Engl J Med 2010;362:975– 985. 13. Salpeter SR, Buckley NS, Ormiston TM, Salpeter 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 randomized controlled trial. Pediatr Allergy Immunol 2010;21:336–344.



12/4/13 5:16 PM

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Professor Josef Smolen talks about early intervention and treatment targets in rheumatoid arthritis

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The Journey of Cervical Cancer Prevention Pentingnya perhatian 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 Ginekologi RS. H. Adam Malik, Medan - Fakultas Kedokteran Universitas Sumatera Utara

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 tertinggi 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 kematian mencapai 20-25 pasien per hari. Lebih dari 70% kasus berada di stadium lanjut (di atas stadium IIIb). Dapat dikatakan setiap 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 (tidak menyebabkan kanker seperti HPV tipe 6 & 11). Di dunia, diketahui ada 15 HPV tipe onkogenik, dan HPV tipe 16 & 18 menyebabkan 70% kasus kanker serviks. Sekitar 30% penyebab lainnya adalah HPV onkogenik tipe 31, 33, 45, 51, dll. Dari data penelitian 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 tidak seperti infeksi lainnya, karena HPV adalah virus yang “cerdas” . Virus Human Papilloma ini tidak dapat menembus membran basalis dan tidak menyebabkan viremia sehingga tubuh kita tidak dapat mengenali virus yang masuk ke dalam tubuh. Respon antibodi terhadap infeksi alamiah pun hanya dijumpai pada 50% wanita yang pernah terinfeksi oleh HPV. Dari penelitian, diketahui bahwa perempuan yang terinfeksi alamiah memiliki serum antibodi yang rendah sehingga antibodi dari infeksi alamiah tidak dapat memberikan perlindungan terhadap re-infeksi. Di sisi lain infeksi HPV pada epitel serviks mudah terjadi dan hanya memerlukan waktu

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 penelitian yang dilakukan oleh Prof. Andrijono, infeksi yang dijumpai pada LSIL (low grade squamous epithelial lesion) umumnya HPV tipe 6 atau 11, yang merupakan tipe HPV yang tidak menyebabkan progresivitas ke derajat yang lebih tinggi. 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 tipe 16 & 18 (lihat tabel 1 dibawah ini) Tabel 1. Perjalanan Kanker Serviks

Regresi LSIL (NIS I) HSIL (NIS II) HSIL (NIS III)

57% 43% 32%

Persistent

Progres ke NIS III

Progres ke Karsinoma

32% 35% 56%

11% 22% -

1% 5% >12%

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 prakanker dan kanker serviks, tetapi tidak dapat mencegah terjadinya infeksi HPV yang dapat menyebabkan kanker serviks. Sedangkan pencegahan primer dengan vaksinasi dapat menginduksi antibodi sehingga mencegah infeksi HPV tipe onkogenik menjadi kanker serviks yang invasif. Pencegahan primer dengan edukasi pun tidak kalah pentingnya untuk meningkatkan kesadaran akan kanker serviks dan pencegahannya. Vaksinasi yang diikuti dengan skrining memberikan perlindungan terbaik dalam mencegah kanker serviks.

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 Komposisi vaksin HPV 16/18 mengandung antigen HPV 16 dan 18 dengan suatu sistem adjuvant AS04 (garam aluminium + Monophosphoryl lipid A/ MPL - untuk memperkuat respon imun). Antigen vaksin berupa VLP (Virus-like Particles) tanpa materi genetik DNA yang bersifat non-infeksius dan non-onkogenik. Dari studi yang dilakukan oleh Rotelli-Martins dkk (dimuat di jurnal Human Vaccine & Immunotherapeutic pada tahun 2012), didapatkan bahwa kadar antibodi terhadap HPV tipe 16 & 18 tetap tinggi dan bertahan hingga 8,4 tahun. Pada lanjutan studi yang sama, vaksin HPV 16/18 dengan adjuvant AS04 ini masih konsisten menunjukkan kadar antibodi HPV 16 dan 18 yang tinggi 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 negative untuk 14 tipe HPV onkogenik dan seronegatif untuk HPV tipe 16 & 18. Sebagaimana telah diketahui bahwa HPV tipe 16 & 18 berkaitan dengan 70% dari kanker serviks, dan ada 30% HPV onkogenik lainnya yang juga menyebabkan kanker serviks. Untuk kelompok studi ini, hasil efikasi terhadap lesi derajat tinggi (CIN3+) yang berkaitan dengan HPV 16/18 mencapai 100%. Hasil efikasi terhadap lesi derajat tinggi (CIN3+) tanpa melihat tipe HPV Onkogenik, hasilnya mencapai 93,2% pada kelompok studi TVCnaïve. (lihat tabel 1 dan tabel 2) Tabel 1. PATRICIA: Hasil efikasi terhadap lesi derajat tinggi tanpa melihat tipe HPV

Endpoint

Group

N

n

Vaccine efficacy, % (95% CI)

CIN3+

Vaccine Control

5,466 5,452

3 44

93,2 (78.9-98.7)

Efikasi menyeluruh vaksin HPV 16/18 terhadap CIN 3+ sebesar 93.2% terlepas dari tipe 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 tipe 16 & 18. Pemberian vaksinasi lengkap terdiri dari 3 dosis dengan jadwal yang direkomendasikan adalah bulan 0, 1, dan 6 secara intramuskular di bagian deltoid (tidak 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 suntikan. Yang perlu diingat pada pemberian vaksin ini adalah bahwa vaksinasi merupakan tindakan memasukkan antigen ke dalam tubuh yang mungkin menyebabkan reaksi anafilaksis (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) tipe onkogenik. HPV tipe onkogenik tipe 16 & 18 menyebabkan 70% kasus kanker serviks dan HPV tipe onkogenik lainya seperti HPV tipe 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, setiap 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 penelitian yang sudah dimuat di jurnal internasional

Tabel 2. PATRICIA: Hasil efikasi terhadap lesi derajat tinggi yang berasosiasi dengan HPV 16/18

menunjukkan kadar antibodi terhadap HPV tipe 16 & 18 tetap tinggi dan bertahan lama sampai 9,4 tahun. • Studi penelitian terbaru dari vaksin HPV 16/18 (studi PATRICIA),

Endpoint

Group

N

n

Vaccine efficacy, % (95% CI)

yang juga sudah dimuat di jurnal internasional, menunjukkan bahwa untuk kelompok studi TVC-naïve, vaksin ini memberikan hasil efikasi terhadap CIN3+ sebesar 93,2% tanpa melihat tipe HPV.

CIN3+

Vaccine Control

5,466 5,452

0 27

100,0 (85.5-100.0)

• 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.

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GYNAECOLOGY PAEDIATRICS

II

Peer Peer Reviewed Reviewed

Ovarian Cancer: Current Management Painful Bladder Syndrome and Future Directions Maria Vella, MRCOG; Dudley Robinson, MD, FRCOG; Linda Cardozo, MD, FRCOG 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 extended 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 Society 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 bladder biopsy. JPOG NOV/DEC 2013 • 232


12/4/13 5:16 PM

GYNAECOLOGY

PREVALENCE Large population-based studies are thought to be

I GYNAECOLOGY Peer Reviewed

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

the most accurate way of identifying the prevalence of the disease. However, accurate epidemiologic 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 studies quote a prevalence rate of 18.1/100,000 women, whereas, more recently, a rate of 197/100,000 women has been quoted. It typically affects premenopausal 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 depending 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-

cell activation are thought to have a role. Both are

quency, were compared in the same population. The

thought to be implicated and are generally found in

prevalence rate using the former was 0.57%. This

histological samples of most ulcerative and some

was in marked contrast to the 12.6% prevalence

non-ulcerative BPS.

rate obtained using the Pelvic Pain and Urgency/

Other theories include the possible implication

Frequency questionnaire, hence highlighting the

of infection as an initial trigger, although document-

need for a more standardized questionnaire to be

ed evidence of a urinary tract infection at the onset

used for epidemiologic studies. In a recent large

of symptoms has only been found in a limited num-

telephone survey in the United States, a prevalence

ber of patients. Furthermore, no particular organism

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

or class of organisms has ever been demonstrated.

associated diseases like fibromyalgia).

Autoantibodies, namely antinuclear antibodies, have been found in some patients with BPS.

AETIOLOGY AND PATHOGENESIS

This, together with similar clinical and histological features found in some patients with autoimmune

The aetiology and pathogenesis of PBS is very poor-

disorders, has prompted the possibility of an un-

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

derlying autoimmune theory in the pathogenesis of

ries have been put forward. Inflammation and mast

some patients with BPS. JPOG NOV/DEC 2013 • 233


12/4/13 5:16 PM

GYNAECOLOGY

I

Peer Reviewed

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

thelium by a primary insult. This may be in the form of bacterial cystitis, bladder trauma, an autoimmune disorder, toxins, etc. The triggering factor will

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



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-

Leakage of urine constituents into urothelitum

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-









Immunogenic response



Bladder injury ± chronic neuropathic pain





cells and their interaction with other inflammatory are implicated in the pathogenesis.



C-fibre activation

This figure also highlights the importance of mast cells and the nervous system. All of these factors

Damage to bladder epithelium which fails to repair the damage

Mast cell activation and release of histamine

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

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

More recently, there is some evidence to sug-

ally start off having mild episodic symptoms last-

gest that PBS may be part of a generalized somatic

ing for several days, which tend to become more

disorder, thus explaining the possible co-existence

severe and consistent with time. The episodic and

with other chronic conditions such as fibromyalgia

non-specific nature of the disease is generally re-

and irritable bowel syndrome. They share features

sponsible for a delay in making a diagnosis.

like symptoms of fatigue and pain and also show an

Patients generally present with pain and lower

association with ‘stress’ and psychosocial factors.

urinary tract symptoms (these are the two essential

Both fibromyalgia and BPS/IC patients display sub-

diagnostic criteria). Pain is commonly suprapubic,

stantial clinical overlap, and studies have shown

although it may also be experienced in the lower

that the latter display diffusely increased periph-

abdominal region, vulva or vagina, urethra, or even

eral nociception as seen in patients with fibromy-

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

algia. It may therefore be speculated that the same

lower abdominal pressure sensation or urethral pain

types of central mechanisms that contribute to the

experienced when passing urine. Urinary symptoms

pathogenesis of fibromyalgia may be operative in

typically include frequency and, less commonly, ur-

the pathogenesis of BPS/IC.

gency. Nocturia is less common in these patients.

The general consensus is that the pathogen-

A variety of factors may exacerbate symptoms,

esis involves damage occurring to the bladder epi-

including certain acidic foods like tomatoes and al-



12/4/13 5:16 PM

GYNAECOLOGY

cohol, spicy foods, caffeine, and chocolate. Some patients claim that their symptoms are exacerbated


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

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 systemic and autoimmune disorders like rheumatoid arthritis 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 Examination Investigation 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 focus 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)

examination of the lower abdomen. This helps iden-

perceived to be related to the urinary bladder, as-

tify scars from previous surgery, any obvious organ

sociated with lower urinary tract symptoms of more

enlargement as well as any areas of tenderness.

than 6 weeks duration, in the absence of infection

Hernial orifices should also be examined.

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

In addition, a pelvic examination should be

During history taking, emphasis should be

performed in order to be able to map pain over

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

the vulval area. A bimanual examination aims to

relationship of the pain to bladder filling and emp-

identify any enlarged organs as well as eliciting

tying should be noted. Any associated lower urinary

any tender points over the urethra, bladder, levator

tract symptoms, any bladder or urological previous

muscles, or adnexae. This helps in diagnosing BPS

diseases, and any past history of pelvic surgery,

and also to exclude any other diseases that may be

pelvic irradiation, or autoimmune diseases should

part of the differential diagnosis.

all be enquired about. Any exacerbating or relieving factors or any specific pattern of the symptoms

Investigations

should also be identified.

A number of investigations are available in order

A thorough physical examination should also

to make an accurate diagnosis, exclude any confus-

be carried out, including a general assessment and

able diseases, and define the severity of the illness. JPOG NOV/DEC 2013 • 235


12/4/13 5:16 PM

GYNAECOLOGY

I

Peer Reviewed

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

Frequency volume chart – a 3-day voiding diary is recommended in the first instance. This simple investigation helps identify patients with

Investigation

Level of evidence Grade of recommendation

Urodynamics

4

C

Cystoscopy

2

B

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 recommended that the severity of pain should be recorded using a visual analogue score for pain over 24

There is however no single investigation or test

hours. A visual analogue score may also be used

that will identify PBS.

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 evaluate quality of life in anybody presenting with lower urinary tract symptoms. The O’Leary-Sant symptom

The general consensus

score should be used for this purpose in patients

is that the pathogenesis

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

involves damage occurring to the bladder epithelium by a primary insult

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 epithelial permeability. A volume of normal saline is initially instilled into the bladder via a urinary cath-

Initial Investigations

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

Laboratory testing – a urinary dipstick and uri-

tient is asked to rank their urgency and pain on a

nalysis for culture, and sensitivity and cytology are

6-point analogue scale. The bladder is then drained

essential initial investigations. Specific testing for

and a 0.4-M potassium chloride solution is instilled.

Ureaplasma urelyticum, Mycoplasma hominis, and

Once again, patients are asked to rank their sense

Chlamydia may be helpful in some patients. These

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

initial investigations may help exclude patients

positive test is one that elicits pain and provocation

with lower urinary tract symptoms secondary to

of symptoms. Whilst this test has not been shown

infection and may help to identify the necessary

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

diagnostic and treatment pathway that needs to be

the diagnostic algorithm of these patients, it may

followed.

have some prognostic value in being able to predict



12/4/13 5:16 PM

GYNAECOLOGY

response to treatment. Further studies are needed to fully evaluate the potential use of this test.


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

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 hydrodistension is considered an optional investigation, although it is mandatory in all patients presenting with haematuria. Classical features include glomerulations (described as punctuate petechial

Treatment

Level of evidence Grade of recommendation

Behavioural modification

3

C

Physical therapy

3

C

Stress reduction

4

C

Dietary modification

4

C

haemorrhages occurring after hydrodistension) and Hunner’s ulcers (patches of red mucosa exhibiting small vessels radiating to a central pale scar). How-

our of the fluid checked for the degree of bleeding.

ever, cystoscopic findings do not generally correlate

The total volume drained is the measured maximum

with the degree of symptoms exhibited, although

bladder capacity. During a second filling, the blad-

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

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

ciated with generalized body pain and urinary ur-

of the bladder capacity to achieve optimal vision for

gency.

inspection and biopsies. The bladder should not be

There has been a great variation in the degree

filled to maximum capacity or distended again to

of hydrodistension. The European Society for the

avoid further provocation of changes with doubtful

Study of PBS/IC has therefore suggested a stand-

reproducibility.’

ardized procedure for cystoscopy and hydrodistension. ‘A rigid cystoscope is preferred to facilitate

Other Investigations

taking of adequate biopsies. Glycine or correspond-

Biomarkers – in a quest to develop a non-invasive

ing filling fluid should be used to allow for coagula-

diagnostic test for these patients, a number of bio-

tion after biopsies. Infusion height should be ap-

markers have been studied. These include tryptase,

proximately 80 cm above the symphysis pubis. A

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

dripping chamber is used and the bladder is filled

liferative factor. Antiproliferative factor has been

until fluid dribbling stops. If necessary a digital

extensively studied and is shown to be increased in

block is applied around the urethra to prevent leak-

patients with documented BPS and may therefore be

age. Pre-distension inspection includes observation

used as a potential biomarker. However, whilst it has

for radiating vessels, coagulum or fibrin deposits,

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

white spots, hyperaemia, oedema, cracks, scars or

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

any other mucosal changes. Continuous inspection

it also needs to be reproducible in other laboratories.

while filling the bladder is advised. When maximum

It has as yet not been replicated and the biological

capacity is reached, the distension is maintained

assay has not been proven for commercial use. The

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

search for an adequate biomarker continues. JPOG NOV/DEC 2013 • 237


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GYNAECOLOGY

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

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

Treatment

Level of evidence

Recommendation

Analgesics (see text)

4

C

Amitriptyline

2

B

3

C

Gabapentin

4

C

Sodium pentosanpolysulfate

1

D

Hydroxyzine

1

Cimetidine

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 effects.

Antibiotics

4

D D

Stress reduction – it has previously been shown that mental stress aggravates the symptoms of BPS. Consequently, it is thought that stressrelieving mechanisms may help improve these patients’ quality of life. Different strategies ad-

Treatment

vised have included taking regular exercise, trying

A combination of the lack of definitive diagnostic

to work shorter hours, and trying to create a less

tests and standardized clinical criteria make BPS a

stressful home environment. Furthermore, a number

difficult condition to treat. The mainstay of treat-

of patient education and support groups are avail-

ment is targeted at trying to obtain symptomatic re-

able, and patients are encouraged to take part in

lief, and over the years a variety of different forms

these.

of treatment have been tried. These can be broadly

Dietary manipulation – some foods are

divided into conservative measures, oral medica-

thought to exacerbate symptoms. These gener-

tion, intravesical therapies, neuromodulation, and

ally include caffeine-based products (tea, coffee,

surgery.

chocolate), fizzy drinks, citrus fruits and juices, alcohol, spicy foods, and acidic foods like, for ex-

Conservative Measures

ample, tomatoes. The influence of these foods is

These, in combination with analgesia, form the ini-

very variable, and the general consensus is not

tial management of patients presenting with BPS.

to put patients on a strict diet but to advise them

Table 2 summarizes their levels of evidence and

to experiment with different foods and try to find

grades of recommendation.

out which foods tend to aggravate their symptoms

Behavioural modification – this is the cor-

themselves.

nerstone of treatment for these patients. Patient motivation is essential. It includes timed voiding,

Medical Management

controlled fluid intake (generally limited to about

The main categories of medication used in bladder

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

pain syndrome include analgesics, antidepressants,

tended voiding interval), and pelvic floor muscle

immunosuppressants, antihistamines, and glycosa-



12/4/13 5:16 PM

GYNAECOLOGY

minoglycans. Table 3 summarizes their levels of evidence and grades of recommendation.


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

Analgesics – pain is one of the main symptoms these patients present with. Its evaluation and adequate analgesia are therefore fundamental to their management. Pain evaluation should include categorical scales (rating as mild, moderate, and severe), visual analogue scales, and pain questionnaires like the McGill questionnaire. It is sometimes 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-steroidal anti-inflammatory drugs, such as ibuprofen and diclofenac. Whilst paracetamol is widely available 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 paracetamol 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 gastrointestinal 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 therapy should be made by an appropriately trained specialist in consultation with another physician (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. JPOG NOV/DEC 2013 • 239


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GYNAECOLOGY

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

possibly blood checks to ensure that the drug is being taken as prescribed and that non-prescribed drugs are not being taken – inappropriate aggressive behaviour associated with demanding the drug will not be accepted – h ospital specialist review will normally occur at least once a year –t he patient may be requested to attend a specialist psychiatric/psychology review – f ailure to comply with the above may result in the patient being referred to a drug dependency agency and the use of therapeutic, analgesic opioids being stopped • Morphine is the first-line drug, unless there are contraindications to morphine or special indications for another drug. The drug should be prescribed in a slow-release/modified slow-release form. Short-acting preparations are undesirable and should be avoided where possible. Parenteral dosing is undesirable and should be avoided where possible.”

Neuropathic analgesics. These include tricyclic antidepressants, serotonin reuptake inhibitors, and anticonvulsants. There is good evidence for the use of tricyclic antidepressants in the management of pelvic pain. The most widely used is amitriptyline. They • The patient should undergo a trial of opioids.

are used in much lower doses than they would be

• The dose required needs to be calculated by

used for mood problems. They are thought to work

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

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 antidepressants. Anticonvulsants have been used in the man-

– the drugs will be prescribed for fixed periods

agement of pain for many years. Although there is

of time, and a new prescription will not be

little evidence to show their effectiveness in man-

available until the end of that period

aging acute pain, they are useful in managing neu-

– t he patient will be subjected to spot urine and

ropathic pain and may therefore be used to manage



12/4/13 5:16 PM

GYNAECOLOGY

some of these patients. Antihistamines – the rationale behind using


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

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. Hydroxyzine works as an H 1-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-

Treatment

Level of evidence

Recommendation

Dimethyl sulfoxide

2

B

Hyaluronic acid

1

D

Chondroitin sulfate

4

D

Oxybutynin

4

D

Botulinum toxin

4

D

domized controlled trial (RCT) has failed to show its efficacy. It is still used as one of the first-line treatments.

more common ones). Its safety and clinical efficacy

Cimetidine, an H2-receptor antagonist, has

have been reported in several short-term RCTs.

also been shown to be beneficial in a small RCT

More recently, its long-term efficacy and safety

and is sometimes used.

were also demonstrated in a study where patients

Immunosuppressants – cyclosporin, an im-

were followed up for a mean time of 2 years.

munosuppressant routinely used in organ trans-

Antibiotics – there are conflicting reports of

plantation, has shown some promising results. It is

antibiotic use for patients with BPS. Some studies

thought to act by inhibiting the activation of mast

suggest that empirical treatment with doxycycline

cells and T cells. Its beneficial effects only last for

may be beneficial, while others report no long-

the duration of time patients are taking the drug.

term improvement following antibiotic treatment.

Furthermore, it is associated with multiple side

At present, there is no evidence to suggest rec-

effects like impairment of renal function and in-

ommending antibiotics in the routine treatment of

creased susceptibility to infection. Hence, caution

patients with BPS.

must be exerted when taken long-term. Glycosaminoglycans – sodium pentosan-

Intravesical Therapies

polysulfate is a synthetic sulfated polysaccharide

Intravesical treatments are widely used in the treat-

which theoretically works by replenishing the dam-

ment of these patients. Evidence for their use is

aged glycosaminoglycan layer overlying the transi-

limited. Table 4 summarizes the levels of evidence

tional epithelium in patients with BPS. In addition,

and recommendations for the different intravesical

it is also thought to inhibit histamine release from

therapies in use.

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

Dimethyl sulfoxide – Dimethyl sulfoxide

drug approved by the Food and Drug Administration

has been used for the treatment of BPS patients

for symptoms associated with BPS. It is generally

for a long time. It is the only intravesical therapy

well tolerated with few side effects (gastrointes-

approved for use in these patients by the Food and

tinal upset, abdominal pain, and headache are the

Drug Administration. Its mechanism of action is JPOG NOV/DEC 2013 • 241


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GYNAECOLOGY

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Peer Reviewed

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

fore not recommended in clinical practice. Chondroitin sulfate – this is another mucopolysaccharide. Some reports have shown it to be

Treatment

effective when used in combination with hyaluronic

Level of evidence

Recommendation

Hydrodistension

3

C

Ulcer resection

3

C

used in combination with bladder retraining has

Cystoplasty

3

C

been reported to be beneficial in some patients. Its

Urinary diversion ± cystectomy

3

C

long-term effects are however unknown.

acid. Oxybutynin – intravesical oxybutynin when

Botulinum toxin – intravesical injection of botulinum toxin A may be used in cases of refractory BPS. A systematic review involving three RCTs and seven prospective studies showed that some

not fully understood, although it is thought to act

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

by inhibition of mast cell activation, hence reduc-

sis could not be performed due to the heterogeneity

ing inflammation. Some small studies have shown

of reported outcomes. There was a trend towards

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

short-term benefit, but the systematic review con-

weeks. Treatment is then suspended until symp-

cluded that more robust evidence from further well-

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

designed trials is needed.

fects, although its long-term effects are unknown. Neuromodulation

Sacral neuromodulation may be recommended in patients with persistent symptoms which are refractory to oral and intravesical therapies. It in-

[Dimethyl sulfoxide] is the only intravesical

volves the implantation of a permanent electrode to stimulate S3 or S4 nerve roots. Several studies have shown promising results with success rates

therapy approved for

after implantation ranging from 60% to 77% with

use in... patients by

follow-up ranging between 19 and 36 months.

the Food and Drug Administration

Whilst initial results appear promising, there is however currently insufficient evidence to determine its role in the treatment of BPS. Further larger prospective trials are needed. Surgery

This should be reserved for those patients with Hyaluronic acid – this is a mucopolysac-

severely debilitating symptoms who have failed

charide which is thought to work by repairing the

all other forms of treatment. Surgical options are

GAG layer of the bladder mucosa. Studies have not

listed in Table 5.

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

Hydrodistension – this technique is used



12/4/13 5:16 PM

GYNAECOLOGY

both for diagnostic purposes and for treatment of


Practice points

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 period of time. Ulcer resection – this was initially described as an open procedure by Hunner for treatment of patients with IC. It was later abandoned owing to the associated morbidity and recurrence of symptoms. More recently, transurethral resection has been reported. A large clinical series has reported significant improvement in most of their patients, with symptomatic relief lasting for about

• 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.

23 months. Transurethral resection, coagulation, or laser ablation of Hunner’s lesions is a recommended 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 functional 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 refractory 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-

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

verse clinical presentation. It is therefore a difficult condition to treat, with limited effective treatment options.

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

About the Authors

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

Maria 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 Hospital, London, UK.



12/4/13 5:16 PM

PRACTICE IIN Inn P Practice ractice I I Peer Peer Reviewed Reviewed

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

CASE HISTORY A 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 prominent. 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.

What is the diagnosis of this enlarging lesion occurring on a 13-year-old boy’s neck? (Answers on p. 254)

Clinical Case Rectal Bleeding in Pregnancy: Don’t Assume It’s Benign Christopher S Pokorny, MB BS, FRACP, FRCP, FACG

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 addition, 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. Does Angela require investigation at this stage or can this be deferred until after her baby is born? (Answers on p. 255) JPOG NOV/DEC 2013 • 244


12/4/13 5:16 PM

10th International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Outreach Course, Singapore

in conjunction with 5th Scientific Congress of the College of Obstetricians & Gynaecologists, Singapore (COGS)

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

Long term Outcome Growth and Development Snapshot of Allergic Children

Dr. Sumadiono, Sp.A(K)

DR. Dr. Ahmad Suryawan, Sp.A(K)

FK Universitas Gajah Mada RSU. Sardjito - Yogyakarta

FK Universitas Airlangga RSUD Dr. Soetomo - Surabaya

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 anafilaksis, 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 fisik pada pasien alergi merupakan pendekatan lini pertama. Sedangkan untuk memastikan diagnosis, dilakukan pemeriksaan IgE mediated (skin prick test/SPT, dan IgE spesifik 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 spesifik 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

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 flutikason 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 grafik 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 fisiologis dan

no growth impairment

+. 70 +. 60 +. 50 +. 40 +. 30 +. 20

EFFECT SIZE

+. 10 - . 00 - . 10

growth impairment

- . 20 - . 30

Low High Dosage Dosage Low Severity

Low High Dosage Dosage High Severity

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

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 anakanak sehat dengan anak-anak dengan asma. Keluaran jangka panjang dinilai dengan CHIP-AE (Child Health and Illness Profile, Adolescent Edition) dan hasilnya anak-anak dengan asma akan mengalami persepsi kesejahteraan yang lebih rendah, lebih banyak pembatasan fisik, 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.

Instructions FOR AUTHORS

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.

CATEGORIES OF ARTICLES Clinical Reviews

Case Studies

Systematic 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.

The text should not exceed 1,000 words. References should be limited to 20. Case studies should be divided into the following sections: • Presentation • History • Clinical and Laboratory Examination • Diagnosis • Treatment • Comment

Reviews with substantial educational value will be included as continuing medical education articles. Authors of selected articles are requested to include 10 true/false questions for readers to respond. Please provide answers separately 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: • Test significant content and avoid trivial statements; • Write statements that can be classified unequivocally as either true or false and avoid ambiguity; • Avoid taking statements verbatim from the text, which a candidate could easily check back. Paraphrase statements wherever possible; • Not deliberately try to “trick” candidates with questions;

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Letters to the Editor Letters may be sent to the Editorial Office by e-mail to [email protected] or posted on the JPOG website at www.jpog.com. Letters should not exceed 300 words, have no more than five references and contain no more than one illustration. Letters may be edited prior to publication.

• Construct statements that have only one major point;

Book Reviews

• Avoid using negative statements, as these are unnecessarily confusing; and

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

• Avoid referring to information that cannot be found in the article or is not inferred by the article’s content.

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.

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

Criteria

Copyright and Disclaimer

Only 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.

Authors of accepted manuscripts are required to sign and return a disclaimer form, disclosing any financial interest and confirming acceptance of author responsibility and transferral of copyright to Journal of Paediatrics Obstetrics and Gynaecology. Authors are responsible to ensure that permission is obtained for the use of any copyrighted text or illustrations.

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

MANUSCRIPT PREPARATION Title Page

References

A title page should contain the following information: • Title of the paper • Full names of all authors • Academic qualifications of all authors • Titles and affiliations of all authors • E-mail, mailing address, telephone and fax numbers of the corresponding author

References must be numbered consecutively in order of appearance in the text. When listing references, follow the Vancouver style. Journal names should be abbreviated according to Index Medicus. List all authors and/or editors up to six; if more than six, list the first three and et al. Examples for referencing style:

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

Illustrations/Figures Illustrations include photographs, pho-tomicrographs, charts and diagrams; they must be of professional quality and of a size permitting some reduction in the final copy. Patient identification should be obscured, and transfer arrows should be used to indicate subtle but salient points.

Tables Each column should have a short or abbre-viated heading. Place explanatory matter in footnotes, not in the heading. Non-standard abbreviations used in each table should be defined in the footnotes.

Language and Style British spelling is used. Système Inter-national (SI) units are used except for blood pressure values which are to be reported in mm Hg. For the expression of length, area, mass and volume, metric system is used. Temperatures are to be given in degree Celsius. Non-proprietary names of medical substances should be used unless the specific brand/trade name of a drug is directly relevant to the discussion.

Journal article: 1. McCaffery K, Forrest S, Waller J, et al. Attitudes towards HPV testing: a qualitative study of beliefs among Indian, Pakistani, African-Caribbean and white British women in the UK. Br J Cancer 2003;88:42-46.

Book: 2. Lask B, Bryant-Waugh R. Anorexia Nervosa and Related Eating Disorders in Childhood and Adolescence. 2nd ed. Hove: Psychology Press; 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. Accessed December 10, 2001.

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

PAEDIATRICS

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Chronic Fatigue Syndrome in Imaging Paediatric Children and Brain Young People Tumours Carrie Mackenzie, FRCPCH, DCCH, MD; MMed Alison Wray, BA, MPhil CPsychol Tang PhuaMBChB, Hwee, MBBS, FRCR, Diagnostic Radiology

INTRODUCTION Chronic fatigue syndrome (CFS) or myalgic encephalomyopathy (ME) is a relatively common 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 presentation 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 variable and, for some children and young people, never takes place. Inevitably, the lack of positive investigative findings coupled with the ongoing debate about the pathophysiological basis of the condition leads to considerable and confusing debate amongst professionals 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 development 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 management. JPOG NOV/DEC 2013 • 245


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

• NICE guidance – Chronic fatigue syndrome/myalgic encephalomyopathy 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 fatigue 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

CFS and ME are two separate and distinct entities, which share features with other conditions such as ‘medically unexplained symptoms’ or other func-

DEFINITION

tional somatic disorders and overlap with chronic pain syndromes. In making the diagnosis, it is cru-

The fact that the terminology associated with this

cial to also ‘demedicalize’ the condition, drawing

condition has created such controversy over a num-

a line under all that has gone before in terms of

ber of years indicates the difficulties inherent in

investigating the constellation of presenting symp-

labelling such a heterogeneous group of individu-

toms and reaching agreement with the affected

als who present with a wide range of physical and

child or young person and their carers that the way

emotional symptoms. However, the persisting and

forward is by means of rehabilitation from the point

disabling fatigue universal in this group of children

they now find themselves at. Indeed if this does not

and young people has lead to our team favouring

happen, it may prove difficult to engage the child

the use of the term chronic fatigue syndrome. We

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

believe this reduces confusion and assists in acceptance of the diagnosis when used in conjunction

EPIDEMIOLOGY

with a sympathetic explanation of the very variable nature of the condition, which includes both physi-

Prevalence data for CFS are heterogeneous and

cal and psychological symptoms. The term favoured

confusing as a result of different study methodolo-

and adopted by the Royal College of Paediatrics

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

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

ferent age limits. A number of studies report preva-

the term ME carries with it a much more physical

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

or medical basis which patients and carers often

Most studies focus on the condition in adolescents;

confuse with conditions such as multiple sclerosis.

those reporting prevalence rates in younger chil-

Moreover, there are still those who believe that

dren show it to be markedly lower. There remains



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

a distinct need for further research to truly under-

an autoimmune process in genetically predisposed

stand the prevalence of CFS in the child and adoles-

individuals, but the evidence for this does not yet

cent population.

exist and it seems likely that the causation is multi-

The evidence on gender remains inconclusive.

factorial. Various aetiological factors, such as level

Some studies report no significant gender differ-

of exercise taken, personal and maternal psycho-

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

logical well being, gender, socioeconomic status,

Our own figures based on 176 children and young

birth weight, birth order, coexistence of atopic con-

people under 16 show a ratio of two boys to every

ditions, exposure to certain viruses, school attend-

three girls.

ance, and achievement, have all been considered, but as yet their contribution, if any, remains un-

PATHOLOGY AND PATHOGENESIS

clear. Any hope of intervention to prevent CFS in future generations will demand a better understand-

There has been a plethora of research into CFS, but

ing of the aetiological factors at play. However, the

the very wide and varied nature of the hypotheses

once popular stereotypical picture of the affected

being pursued indicates the clear lack of under-

individual being female, highly intelligent, and high

standing of the pathophysiological basis for this

achieving is not borne out by our experience.

condition. Many of our children and young people

DIAGNOSIS AND DIFFERENTIAL prior to the onset of their fatigue, but the exact na- DIAGNOSIS can describe an intercurrent illness immediately

ture of this usually relatively minor illness is often unclear and it is by no means a universal precursor.

The diagnosis of CFS relies not only on the exclu-

It may well be that some external ‘trigger’ provokes

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Table 2. Investigations

INVESTIGATIONS As a minimum, we require that the child or young

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

person will have undergone the screening investigations set out in the NICE guidance and that the results of these tests are normal when seen for initial assessment by the specialist CFS team. Diagnosis marks the start of a long and challenging journey for the child or young person and their carers. It is important to demedicalize and demystify the condition and positively and confidently recognize the symptom clusters shared by CFS sufferers. A further key feature of the initial consultation is to explain the nature of the condition, acknowledge the difficulties they have encountered 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

directed investigations but also on the presenta-

people with CFS recover and go on to achieve

tion of symptom clusters shared by other children

academic qualifications. Ninety-nine percent of

and young people with the condition in addition to

young people aged 16 seen by our specialist team

persistent and disabling fatigue. These symptoms

achieved some academic qualifications and were

may classically include malaise, sleep disorder,

able to progress to the next stage of their educa-

headache, dizziness, poor temperature control, ab-

tion or training. The vast majority of children and

dominal pain, nausea, anorexia, sore throat, tender

young people will not require transition to adult

lymphadenopathy, arthralgia, myalgia, and cognitive

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

difficulties such as poor short-term memory, im-

ing and disabling illness.

paired concentration, anxiety, and low mood. Since many of these symptoms overlap with diagnoses rel-

“I visited the clinic and was diagnosed with

evant to many disciplines such as gastroenterology,

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

rheumatology, endocrinology, neurology, infectious

ing symptoms had a name. After more than 9

diseases and immunology, oncology, and haematol-

months of feeling so terrible, someone could

ogy, as well as childhood and adolescent mental

finally tell me what was wrong.”

health, it is beholden upon us to ensure that appropriate paediatric subspecialists have been consulted

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

and the necessary investigations undertaken. How-

better knowing than being left worrying or try-

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

ing to guess.”

and, often, normal examination findings are key in making the diagnosis (see Table 2).

The fact that CFS is a heterogeneous group is



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

now generally agreed and evidence is growing to support this. One study has identified three phenotypes in CFS in children that are differentially associated with severity; the musculoskeletal phenotype is associated with muscle and joint pain and these children have worse fatigue. The migraine phenotype which is associated with headache, abdominal 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 condition has a profound impact, not only on the child or young person, but also on their families. It is associated 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 ist, and clinical psychologist may need to be involved. Evidence-based guidelines recommend the follow-

Once children and young people and their families have gained an understanding of the condition, the

ing:

basis of treatment and an optimistically realistic

Activity management: this is a person-centred,

expectation of what the future might hold, a coordi-

goal-directed approach to managing a child or young

nated multidisciplinary approach to management is

person’s symptoms. It uses analysis of activity and

required in the majority of cases. Commonly, occu-

graded activity through learning the skills of pacing to

pational therapist, physiotherapist, nurse special-

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Figure 1. Vicious cycle.

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 increased very slowly depending on progress. The

CFS

aim of graded exercise therapy is to increase fitness and stamina. The primary aim of management is to re-

Sleep Sleep disorder/ disorder/ muscle muscle weakness weakness

establish the child or young person in a sustainable routine and then to help them learn to self Increased rest/ reduced activity

Further rest

manage the condition. At the outset of treatment, this commonly involves three aspects: sleep hygiene, activity/energy management, and school liaison.

Worsening of symptoms on exercise

Fatigue/aches and pains

In the absence of a clear understanding of the cause of CFS, we make use of a number of analogies which ‘fit’ well with patients’ experience of

More inactivity

Reduced activity Loss of control

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).

Cognitive behaviour therapy: this is an individualized psychological therapy which incorpo-

SLEEP HYGIENE

rates two major components: the cognitive element which focuses on the identification and modifica-

Disordered sleep patterns are commonly found in

tion of thoughts, beliefs, and assumptions which

CFS including day/night reversal, interrupted sleep,

may shape the child or young person’s understand-

insomnia, or hypersomnia. It is therefore important

ing of their condition, and the behavioural element

to establish effective and positive sleep routines

which aims to gradually and consistently introduce

which include

a change in behaviour, eg, an increase in activity

• Establishing a regular waking time

or return to school. A cognitive behaviour therapy

• Avoiding prolonged sleep and day time sleeps

model can include treatment of accompanying anxi-

• Always sleep at night in own bedroom and avoid

ety or depression and can be tailored to include involvement of the family. Graded exercise therapy: this is a struc-

use of computer/TV prior to bed • Relaxation to aid falling asleep and consistent bedtime routine

tured and supervised programme of exercise agreed

Melatonin and/or amitriptyline are used in

between doctor, therapist (usually a physiothera-

some cases to support good sleep hygiene and im-



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prove the quality of sleep.

I


Table 3. Top tips for management from our team

ACTIVITY/ENERGY MANAGEMENT The young person needs to keep a diary to establish their baseline of activity. Activity meaning everything 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

These patients take time • in clinic, so it is useful to book appointments at the end of clinic • to recover Stay confident when the inevitable relapse occurs Remember progress is always slower than you expect There is no quick fix Involve parents

that they avoid the boom and bust pattern of activity which hinders recovery. It can be useful to think in terms of the different energy demands of situations, eg, high or low.

The key professional needs to be prepared

Increase in activity levels needs to take place

to put considerable time into liaising with educa-

gradually and be carefully monitored. We would

tional services. In our experience, this patient group

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

needs more time for liaison than other children with

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

a chronic illness.

SCHOOL LIAISON

MANAGEMENT OF SPECIFIC PHYSICAL SYMPTOMS

Chronic fatigue syndrome has a negative impact on education, and many children and young people are

We find that as the child or young person learns

unable to attend full-time school. A crucial element

to manage their fatigue effectively and their well

of any successful management plan, therefore, is

being begins to improve so other troubling symp-

the establishment of a sustainable educational

toms such as nausea, abdominal pain, myalgia,

routine. This may involve the home tuition services

and joint pain all decrease. We therefore tend to

initially, followed by a carefully managed plan for

avoid specific pharmacological agents. Gastrointes-

school re-integration. It is very likely to involve

tinal symptoms can be managed through diet and

part-time school attendance. A recent study sug-

ensuring healthy eating and adequate fluid intake,

gests that the factor most strongly associated with

avoiding caffeine and sugary drinks. Small frequent

reduced school attendance is poor physical func-

meals are often better than three heavy meals. Pain

tion. It is therefore important to ensure that the

is managed with simple analgesics like paraceta-

child or young person is fully engaged with treat-

mol and/or ibuprofen. In addition, relaxation and

ment to improve physical function. However, it is

cognitive behaviour techniques may be considered

also necessary to be aware of the cognitive impact

in parallel to improve pain.

of CFS and to ensure teachers are informed of the effects of CFS on memory, information processing,

ROLE OF THE FAMILY

and concentration. Children with CFS are entitled to exam concessions when taking public exams if

The role of the family is crucial in helping a child

requested by a doctor.

or young person learn to manage this condition. JPOG NOV/DEC 2013 • 251


12/4/13 5:16 PM

PAEDIATRICS

I

Peer Reviewed

Practice points

Family life • 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 disorders have been excluded • CFS is a genuine physical illness and this needs to be communicated 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 investigations 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

is affected and families have to adjust their expectations of what they can do together.

every 3–4 weeks. At the end of this, we hold a multidisciplinary 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 appropriate 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

Family life is affected and families have to adjust

if mildly affected, there are still only 13 specialist

their expectations of what they can do together.

teams in Britain and these are often small with lim-

Some parents have to stop work in order to care for

ited capacity. The burden of treating this condition

their child. Support and encouragement from family

for the majority therefore lies with paediatricians

members is valued by children and young people; it

and local therapy services. However, the special-

is therefore important that parents understand the

ist teams now have considerable experience of this

condition fully and are involved in treatment.

perplexing, enigmatic condition. We would encour-

The package of care we have developed in-

age professionals working with CFS to consult with

volves an initial period of treatment of six sessions

a specialist team. In recognition of the scarcity of



12/4/13 5:16 PM

PAEDIATRICS

resources, we have been instrumental in setting up

I


make good recoveries.

a clinical network in North and Central England for those working with CFS in order to improve knowl-

“To me keeping positive and determination I

edge and services.

think were really important in my recovery. I think it was really important to keep trying –

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 service where available, with expertise in managing the condition seems likely to be in the best interest of the affected individuals and their families. Since CFS affects not only the child or young person but also those around them, the sooner appropriate 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 psychological 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-

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 guideline no 53. London: NICE, 2007. Royal College of Paediatrics and Child Health. Evidence based guidelines 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, Uiterwaal 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.

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

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

understanding of the causes and course of the con-

About the Authors

dition. However, it is clear that early diagnosis and

Carrie 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.

appropriate management greatly facilitate recovery, and the majority of children and young people



12/4/13 5:16 PM

Formula Presinutri, nutrisi presisi untuk mendukung tumbuh kembang optimal Ananda yang diperkaya dengan: DHA, AA, Kolin mendukung perkembangan kognitif bayi1-2

Prebiotik FOS Inulin menstimulasi pertumbuhan bifidobacteria di intestinal3

Zinc mendukung proses enzimatis metabolisme4

Zat Besi membantu mencegah anemia5 dan vitamin c membantu penyerapannya

11 Asam Amino Esensial mendukung pertumbuhan fisik6

Karena Anda mengerti yang terbaik untuk Ananda 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.

ASI adalah yang Terbaik


SGM Ananda Presinutri

SIMPOSIUM HIGHLIGHT

Diagnosis dan Tata Laksana Alergi Susu Sapi

K

ejadian 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 Scientific 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).

dr. Sumadiono, Sp.A(K) Bagian Ilmu Kesehatan Anak Fakultas Kedokteran - Universitas Gajah Mada RSUP Dr. Sardjito - Yogyakarta Draft Revisi Diagnosis dan Tata Laksana Alergi Susu Sapi Angka 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 defisiensi 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 spesifik, 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 specific 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

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%

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 ringansedang, 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. TATA LAKSANA ALERGI SUSU SAPI PADA BAYI DENGAN SUSU FORMULA Curiga 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 defisiensi besi -Demam atopik (DA), angiedema, urtikaria -Pilek, batuk kronik, mengi -Kolik persisten (> 3 jam perhari/minggu) selama lebih dari 3 minggu

ASS berat Satu/lebih gejala dibawah ini: -Gagal tumbuh karena diare dan atau regurgitasi, muntah dan atau anak tidak mau makan -Anemia defiseinsi 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 defisiensi besi -Laringoedema akut atau obstruksi bronkus dengan kesulitan bernapas -Syok anafilaksis

Bila ragu-ragu Konsultasikan/ periksakan: Uji tusuk kulit IgE spesifik

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

Tidak ada perbaikan - 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

- Uji provokasi terbuka - Berikan susu formula susu sapi dibawah pengawasan

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

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

Tidak ada perbaikan

Perbaikan

Evaluasi diagnosis

Uji provokasi

Rujuk ke dokter spesialis anak konsultan Diet eliminasi susu sapi Formula asam amino minimal 2-4 minggu #

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

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).

SGM Soya Presinutri formula isolat protein1 kedelai untuk mendukung pertumbuhan optimal Ananda yang alergi protein susu sapi

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. Mendukung pertumbuhan fisik yang optimal. Mencegah anemia defisiensi besi. Stimulasi pertumbuhan bakteri baik untuk saluran cerna sehat. Mendukung perkembangan otak yang optimal. 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 Clinic An Enlarging Lesion on the Neck Gayle Fischer, MB BS, MD, FACD

Answer:

VERRUCOUS EPIDERMAL NAEVUS

verrucous) and seborrhoeic keratoses, they

associated with any other abnormali-

have little in common with these lesions.

ties. They can easily be differentiated

• Viral warts are very unlikely to have

from a viral wart on histopathology, but

their onset in a patient’s first year of life

they may be confused with a seborrhoeic

or to persist unchanged for more than 2

keratosis unless the pathologist is aware

The correct diagnosis in this case is a verru-

or 3 years. It is also unusual for many

of the age of the patient.

cous epidermal naevus, a birthmark that occurs

viral warts to be grouped on the shoul-

mainly on the trunk and limbs. These lesions

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

may be congenital, but in over half of cases

although this presentation is not uncom-

DIAGNOSIS

TREATMENT

the onset is in the first year after birth. They

mon on the hands (Figure 2) and feet.

Treatment is often requested for verrucous

may spread beyond their original size with age,

• Seborrhoeic keratoses generally oc-

epidermal naevi for cosmetic or functional

usually over a few months but sometimes sev-

cur from middle age, and they present as

reasons. Although there are superficial abla-

eral years. It is not unusual for them to become

discrete lesions (Figure 3). The back is a

tive procedures such as laser ablation that

more raised and ‘warty’ at puberty.

typical location, but they can be found on

are effective, these lesions will often recur

any part of the skin.

afterwards. Naevi that have any protruding

The colour of verrucous epidermal

areas or are interfering with function need

naevi ranges from flesh-coloured to brown

CAUSE

complete excision to avoid recurrence.

or whorled distribution. On the chest, there

The cause of verrucous epidermal naevi

© 2013 Medicine Today Pty Ltd. Initially published in

is often a dramatic cut-off at the midline.

is unknown, but they are believed to arise

and black. They may occur as single or multiple grouped lesions and can have a linear

from a post-zygotic mutation resulting in

DIFFERENTIAL DIAGNOSIS

epidermal mosaicism. The lesions are harmless and have

Although verrucous epidermal naevi resem-

no potential for malignant transformation

ble common viral warts (hence the name

and, particularly when localized, are rarely

Figure 2. True viral warts.

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

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

Figure 3. A typical seborrhoeic keratosis in a woman aged in her 60s.



12/4/13 5:16 PM

IN IN PPract ractice ice

II

I N Reviewed PRACTICE Peer Peer Reviewed

Clinical Case Rectal Bleeding in Pregnancy: Don’t Assume It’s Benign Christopher S Pokorny, MB BS, FRACP, FRCP, FACG

Answer:

COMMENTARY

given the duration of her symptoms and the intermittent nature of her rectal bleeding.

Possible Causes

A rapid onset of symptoms, particularly in

Rectal bleeding at anytime requires con-

the presence of nausea, vomiting, abdomi-

sideration of the underlying cause (see the

nal pain, and fever does, however, raise

box on this page listing the possible caus-

the possibility of an infectious cause. In

es). The passage of bright blood suggests

such instances, stool microscopy and cul-

a source in the rectum or sigmoid. Minor

ture should be requested. It is important to

rectal bleeding as a result of small tears,

remember that parasitic infections such as

fissures, or haemorrhoids is not uncommon

Giardia do not cause rectal bleeding.

during pregnancy as constipation devel-

Inflammatory bowel disease (eg, ul-

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

cerative proctitis) can occur for the first

1

nant women. In most cases, constipation

time during pregnancy, especially in the

responds to an increase in dietary fibre and

first trimester, and Angela’s symptoms are

fluid intake. Iron supplements may also

in keeping with this. 3 Apart from urgency,

contribute to constipation and may need to

mucus may be passed as well as blood,

be ceased if the constipation is severe.

and the stool volume is generally small in

Causes of rectal bleeding in pregnancy

Common • H aemorrhoids • Tears and fissures Uncommon • Infectious colitis • Inflammatory bowel disease • D iverticular disease • C olorectal malignancy/ polyps • Ischaemic colitis

Anal fissures tend to be accom-

such cases. Specific questioning about ex-

tis), erythema nodosum, and aphthous

panied by marked pain (as opposed to

traintestinal manifestations is sometimes

ulcers. There may also be a family his-

haemorrhoids that are usually painless)

of help – for example, peripheral arthritis,

tory of inflammatory bowel disease. 4

and generally result from straining. When

low back pain, red eyes (episcleritis, uvei-

Given Angela’s age, a rectal or distal

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 gastroenteritis can cause bloody diarrhoea, this is unlikely in Angela’s case, particularly JPOG NOV/DEC 2013 • 255


12/4/13 5:16 PM


asymptomatic individuals. The next investigation should be direct visualization by flexible sigmoidoscopy after an enema to evacuate the rectum 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 biopsies to be taken.5 If these tests fail to provide the answer 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 possible this should be deferred until after her baby is born. However, if necessary before then, it can be safely performed especially

Figure. An example of rectal cancer viewed at sigmoidoscopy.

in the later stages of pregnancy.

OUTCOME colonic malignancy or polyp, diverticular

include a full blood count, but anaemia is

disease, or ischaemic colitis are much

not unusual in pregnancy. There is abso-

In Angela’s case, flexible sigmoidoscopy

less likely. In addition, ischaemic colitis

lutely no point in faecal occult blood test-

was performed and sadly revealed a rectal

generally occurs in the context of signifi-

ing as this is only of potential benefit in

cancer (see Figure). Although rectal bleed-

cant vascular disease or atrial fibrillation. However, these conditions need to

ing is not uncommon in pregnancy, this

be considered in the differential diagno-

Although rectal

ses, although rectal bleeding from more

bleeding is not

proximal malignant lesions tends to be dark in colour and diverticular bleeding usually is profuse.

Gentle digital examination of the rectum

propriately. However, in the vast majority of cases the cause will be benign.

uncommon in pregnancy, this case highlights

Investigations

case highlights the need to investigate ap-

the need to

with careful inspection of the perianal

investigate

area should be performed at the time of

appropriately

consultation. Initial investigation should

© 2012 Medicine Today Pty Ltd. Initially published in Medicine Today June 2012;13(6):73–74. Reprinted with permission.

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

REFERENCES 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 pregnancy. Gastrointest Endosc Clin N Am 2006;16:131.



12/4/13 5:16 PM

Peran dan Keamanan Susu Formula Soya pada Alergi Susu Sapi Dr. E.M. Dadi Suyoko, SpA(K) 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

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

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. 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

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 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.

Continuing Medical Education P 5 SK

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)

INTRODUCTION

studied (eg, age, body build, ethnic origins). The United States reported an

Gestational diabetes mellitus (GDM) is a

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

controversial subject in obstetrics. It is

in more recent publications. The United

defined by the National Diabetes Data

Kingdom reported an incidence of 2% 6

Group in 1985 as carbohydrate intolerance

and Canada described 3.8%. 7 In Hong

of variable severity with onset or first rec-

Kong, a study 8 performed in a university

ognition during pregnancy.1 The first case

teaching hospital, Queen Mary Hospital,

report of GDM appeared in 1824, which

showed that of the 16,383 women

described a mother with thirst, polyuria

managed in the period 1998–2001, the

and glycosuria and the death of a mac-

prevalence of GDM increased from 1.3%

rosomic infant from shoulder impaction.

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

Historically, there has been a lot of contro-

(25–29 years), 10.3% (30–34 years),

versy over most aspects of GDM, includ-

21.7% (35–39 years), and 31.9% (≥ 40

of diabetes after pregnancy. Following the

ing screening, diagnosis, risks, treatment,

years), respectively, from the youngest

publication of the HAPO study, the Interna-

and the relationship between GDM and

to the oldest cohort (P < 0.001). Another

tional Association of Diabetes and Preg-

type II diabetes mellitus. Recently, several

study performed in a different university

nancy Study Groups (IADPSG) established

major studies have substantially resolved

teaching hospital in Hong Kong, Prince

a new set of diagnostic guidelines (Figure

these areas of controversy, eg, the Hyper-

of Wales Hospital, found that the

1).10 As more and more women suffer from

glycaemia and Adverse Pregnancy Out-

prevalence of GDM was 14.2%. In

diabetes before pregnancy, the IADPSG

2

comes (HAPO) study, the Australian Car-

our hospital, a regional hospital with

recommends screening women with risk

bohydrate Intolerance Study in Pregnant

around 6,000 deliveries per year, the

factors at the booking visit by using ran-

Women (ACHOIS), 3 and the Maternal-Fetal

incidences of GDM in 2008 and 2009

dom plasma glucose, fasting plasma glu-

Medicine Units Network treatment of mild

were 13.2% and 14.2%, respectively.

cose, or glycated haemoglobin A1c paired

9

gestational diabetes (MFMUN-GDM) clin-

with diagnostic thresholds, according to

4

ical trials, which will be discussed further

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

SCREENING AND DIAGNOSIS

in this article.

the current guidelines for the diagnosis of pre-existing diabetes. Moreover, GDM

INCIDENCE

The diagnostic criteria of GDM were ini-

can be diagnosed at the booking visit with

tially established more than 40 years ago,

a fasting plasma glucose between 5.1

and these criteria were not designed to

mmol/L and 7.0 mmol/L, hence lowering

GDM

identify pregnant women at increased risk

the thresholds of GDM in most guidelines.

varies with diagnostic criteria and

for adverse perinatal outcomes but rather

They also recommend that all women who

characteristics of the population being

women at higher risk for the development

do not have diabetes should be screened

The

reported

incidence

of


JPOG_NovDec_2013_CME_Final_ID.indd 257

12/4/13 7:40 PM

Figure 1. Flow chart showing guidelines as suggested by IADPSG10

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

DM if FG ≥ 7.0 mmol/L, or HbA1c ≥ 6.5%, or RG ≥ 11.1 mmol/L

GDM if FG ≥ 5.1 mmol/L, but < 7.0 mmol/L

Normal

75-g OGTT at 24–28 weeks

GDM if FG ≥ 5.1 mmol/L, or 1hG ≥ 10.0 mmol/L, or 2hG ≥ 8.5 mmol/L

DM if FG ≥ 7.0 mmol/L

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.

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

Applying this system of testing and diag-

plasma glucose ≥ 8.9 mmol/L. It showed

oral glucose tolerance test. In contrast

nostic criteria will probably double the in-

an unambiguous, linear, positive asso-

to the World Health Organization criteria

cidence of GDM.

ciation between maternal glycaemia and

11

which use an abnormal fasting or 2-hour plasma glucose for the diagnosis of diabe-

adverse pregnancy outcomes (eg, birth

RISKS

weight > 90th percentile, caesarean sec-

tes, the IADPSG suggests that an abnormal

tion, cord plasma C-peptide level reflec-

1-hour plasma glucose is adequate for the

The HAPO study was a 10-year, prospec-

tive of fetal hyperinsulinemia, neonatal

diagnosis. They also take into account the

tive, blinded, multicentre study, which

hypoglycaemia, excess neonatal adiposity,

continuous association between maternal

enrolled 25,505 pregnant women. It aimed

shoulder dystocia or birth injury, neonatal

blood glucose concentrations and adverse

at studying the associations between the

hyperbilirubinaemia, pre-eclampsia). 12,13

perinatal outcomes as seen in HAPO. The

risks of adverse pregnancy outcomes and

The risk factors and health risks of GDM

agreed thresholds represent an odds ratio

the degrees of maternal glucose intoler-

are summarized in Tables 1 and 2.

of 1.75 for birth weight, cord C-peptide,

ance less severe than overt diabetes.

and fetal body weight being greater than

Exclusion criteria include fasting plasma

the 90th percentile, relative to the odds of

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

those outcomes at mean glucose values.

ma glucose ≥ 11.2 mmol/L, or a random

2

TREATMENT The ACHOIS 3 and the MFMUN-GDM 4



12/4/13 7:40 PM

Continuing Medical Education

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 glucose monitoring, and, if needed, insulin treatment. In the ACHOIS trial,3 a composite measure of serious perinatal complications (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 (relative risk, 0.87; 97% CI, 0.72–1.07; P =

Table 1. Risks factors of gestational diabetesa

Risk factors

Odds ratio

References

Overweight

2

Torloni et al, Chu et al

Obesity

3.7


Severe obesity

7


Prior gestational diabetes

23

McGuire et al

Prior macrosomic infant

3.3

McGuire et al

Maternal age greater than 25 y

1.4

Cypryk et al

Maternal age greater than 35 y

2.3

Xiong et al

Multiple gestation

2.2b

Rauh-Hain et al

South East Asian

7.6

b

Dornhorst et al

Hispanic

2.4

b

Dooley et al

African American

1.8

b

Dooley et al

Polycystic ovarian syndrome

2.9

Toulis et al

Parent with diabetes

3.2

Kim et al

Sibling with diabetes

7.1

Kim et al

Periodontal disease

2.6

Xiong et al

Low maternal birth weight

1.9

Seghieri et al

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

0.14). In both studies, rates of large-forgestational-age (LGA)/macrosomia, preeclampsia and maternal pregnancy weight gain were reduced by intervention. Rates of shoulder dystocia and caesarean section were significantly decreased by treatment in the MFMUN-GDM trial only. Rates of induction of labour and of admission to the neonatal unit were increased by treatment in the ACHOIS trial only. Generally, these two trials showed that identification and treatment of GDM with a standard approach improved pregnancy outcomes.

DIETARY MODIFICATION The scientific evidence for making nutritional recommendations for women with

Table 2. Health risks of gestational diabetesa Mother

Fetus

Newborn

Child/Adult

Birth trauma

Hyperinsulinaemia

Obesity

Increased caesarean delivery Pre-eclampsia/ Gestational hypertension Type 2 diabetes

Cardiomyopathy

Respiratory distress syndrome Hypoglycaemia

Stillbirth

Hypocalcaemia

Metabolic syndrome

Large for gestational age/ macrosomia Birth trauma

Hypomagnesaemia

Metabolic syndrome

Type 2 diabetes

Hyperviscosity Polycythaemia Hyperbilirubinaemia Cardiomyopathy

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



12/4/13 7:40 PM

GDM is limited. Referral to nutritional

study showed that in women with GDM,

on Gestational Diabetes recommends the

counselling should ideally occur within

carbohydrate restriction to < 42% led

following blood glucose concentrations:

48 hours of the diagnosis of GDM. The

to fewer LGA infants, reduced rates of

fasting plasma glucose, 5.0–5.5 mmol/L;

first meeting with a professional dietitian

caesarean sections for macrosomia and

1-hour postprandial plasma glucose, < 7.8

should be arranged within 1 week of the

cephalopelvic disproportion, and reduced

mmol/L; and 2-hour postprandial plasma

referral, and a total of three visits are sug-

need for insulin treatment, compared with

glucose, < 6.7–7.1 mmol/L.22 The NICE

gested. 16 Throughout the pregnancy, the

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

guidelines19 recommend drug treatment

diet should be adjusted and individualized

Few studies have focused on the benefit

if diet and exercise cannot control the

to meet the patient’s food choice, financial

of carbohydrates with a low glycaemic in-

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

needs, culture, habits, weight gain, physi-

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

sound shows possible fetal macrosomia

cal activity, and blood glucose goals.

each gram of available carbohydrate in

(abdominal circumference above the 70th

The Dietary Reference Intakes rec-

the food increasing a person’s blood glu-

percentile) at diagnosis.

ommends no increase in calories for the

cose level following consumption of the

first trimester but an additional 340 kcal/

food, relative to consumption of glucose.

day during the second trimester and 452

Food with carbohydrates that break down

kcal/day during the third trimester. 17 In

quickly during digestion and release glu-

Glyburide (or glibenclamide) is a sec-

obese women with GDM, a 30% caloric

cose rapidly into the bloodstream tend to

ond-generation sulfonylurea. It binds to

restriction help to avoid ketonuria or an

have a high GI, while food with carbohy-

receptors that are associated with the

while im-

drates that break down more slowly, re-

adenosine triphosphate-dependent po-

proving glycaemic control. A more severe

leasing glucose more gradually into the

tassium channels of pancreatic β cells to

caloric restriction is not recommended.

bloodstream, tend to have a low GI. There

increase insulin secretion and insulin sen-

The National Institute for Clinical Excel-

have been no randomized studies with

sitivity of peripheral tissues. The onset of

lence (NICE) guidelines19 in the UK recom-

sufficient sample size to draw a conclu-

action takes approximately 1 hour with the

mend that women with GDM whose pre-

sion on the benefits of carbohydrates with

peak level at 4 hours after intake. Stud-

pregnancy body mass index is above 27

a low GI. Increased dietary fibre intake

ies on the placental transfer of glyburide

kg/m should restrict caloric intake (to 25

is traditionally recommended for women

are contradictory. In vitro studies showed

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

with GDM, as it may reduce the postpran-

minimal placental transfer, but the fetal

ate exercise (of at least 30 minutes daily).

dial blood glucose. But no proof exists that

response to various dosages of glyburide

The goal of fractionating food intake

extra dietary fibre intake is beneficial in

is not completely known. 23 A meta-analy-

these women.

sis by Moretti et al24 reported no differ-

15

increase in free fatty acids,

18

2

into three meals and two to three snacks

ences between the insulin and glyburide

in between meals is to distribute the glucose intake throughout the day in order to

Oral Hypoglycaemic Agents

PHARMACOTHERAPY

groups with regard to birthweight, LGA/ macrosomia, gestation at delivery, admis-

control the postprandial glucose, while at the same time maintaining a satisfac-

Drug treatment is necessary in 7–20% of

sions to neonatal units, or neonatal hypo-

tory nutritional intake. The evening snack

women with GDM when, despite dietary

glycaemia.

decreases the night-time ketogenesis re-

modification, there is insufficient glucose

Metformin belongs to the biguanide

lated to fasting.

control, high levels of fasting glucose, sub-

group. It inhibits hepatic gluconeogenesis

Generally, 40–45% of the calories in

optimal weight gain (due to caloric restric-

and glucose absorption, and stimulates

the daily diet come from carbohydrates,

tion), or persistent hunger sensation. The

glucose uptake in peripheral tissues. The

One

Fifth International Workshop-Conference

onset of action takes approximately 1 hour

but this must be individualized.

20



12/4/13 7:40 PM

Continuing Medical Education

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

the standard treatment for diabetes, espe-

take. Metformin does cross the placenta.

cially when diet and exercise fail to con-

Because it acts as an insulin sensitizer in

trol the maternal blood glucose and there

Once GDM is diagnosed, visits to health

peripheral tissues rather than as an insu-

is no risk of placental transfer of insulin

carers or dietitians by the pregnant women

lin analogue, it is believed that fetal me-

to the fetus.

should be made at least every 1–2 weeks

ANTENATAL MANAGEMENT

tabolism is less likely to be affected. The

Insulin requirements are not constant

and more frequently if complications oc-

Metformin in Gestational Diabetes (MiG)

throughout the day: it is low at night with

cur. There is no consensus on the frequen-

trial of 751 women showed similar peri-

a sharp rise at dawn, followed by a grad-

cy and timing of antenatal surveillance

natal complications in both the metformin

ual decrease during the rest of the day.

tests in women with GDM. It is crucial to

and insulin groups, with better acceptabil-

Women in the first trimester are at risk of

manage women, who do not comply with

ity in the metformin group; but subsequent

hypoglycaemic events because of emesis,

advice, require drugs, have macrosomic or

insulin was indicated in 46.3% of women

and blood glucose levels should be closely

growth-restricted fetuses, or have other

taking metformin.

monitored with appropriate adjustment of

obstetric complications, as though they

25

26

Long-term safety data on infants

insulin. After the second trimester, insulin

had pre-existing diabetes and to begin

whose mothers were treated with glybur-

requirements rise. During labour, short-

close antenatal monitoring (eg, the NICE

ide or metformin are lacking. Early neona-

acting insulin should be used to achieve

guidelines19 suggest anomaly scan, echo-

tal complications, such as hypoglycaemia,

optimal glucose levels of between 4 and 8

cardiography, growth scan at 28, 32 and 36

are not common and do not differ very much

mmol/L and to prevent neonatal hypogly-

weeks’ gestation, tests of fetal well-being

from those resulting from insulin therapy.

caemia. After delivery, glycaemic control

after 38 weeks’ gestation). History review,

When counselling patients, health carers

must be relaxed to prevent maternal hy-

blood pressure measurement, and urine

can reassure them that the rates of con-

poglycaemia, especially in breastfeeding

albumin testing to diagnose pre-eclampsia

genital malformations with the use of oral

women. Insulin therapy should be stopped

are also essential at every visit. In an at-

hypoglycaemic agents and insulin do not

in women who have not taken insulin be-

tempt to prevent macrosomia and to guide

differ. The maternal glucose control (fast-

fore pregnancy, while those women who

the treatment, a randomized trial 29 com-

ing blood glucose and 2-hour postprandial)

are taking insulin for pre-existing diabetes

pared ultrasound performed at 32 weeks’

by oral hypoglycaemic agents and insulin

should resume their pre-pregnant insulin

gestation with ultrasound at both 28 and

is also comparable.

dosages.

32 weeks’ gestation. The rate of macroso-

Acarbose, an alpha glucosidase in-

There are two types of insulin: hu-

mia was significantly higher in the group

hibitor, has been used less often. Prelimi-

man insulin and insulin analogue. The

assessed only at 32 weeks (71.1% vs

nary studies showed that it was effective

short-acting insulin analogue aspart has

33.3%; P < 0.005).

in decreasing postprandial hyperglycae-

been shown to be safe in pregnancy in a

The mode and timing of delivery of

mia in GDM, but its use has been limited

randomized trial and has been registered

women with GDM is controversial because

by its side effects, like abdominal cramp-

for this indication. The short-acting insu-

sufficient data are lacking to make a rec-

ing. Further studies are needed to better

lin analogue lispro has also been shown

ommendation.

evaluate the potential placental transfer

to be safe in observational studies. How-

Induction of labour in women with

of this drug, as small amounts of acarbose

ever, there is no safety data available on

insulin-treated diabetes at 38 weeks’

can be absorbed into the bloodstream.

the long-acting insulin analogues detemir

gestation is intended to reduce the risk

and glargine; both are prescribed off-

of stillbirth. One study 30 failed to detect a

label. Therefore, long-acting human insu-

benefit to expectant management beyond

lin should be used instead.

38 weeks’ gestation, as the rate of caesar-

27

Insulin Traditionally, insulin has been regarded as

28



12/4/13 7:40 PM

ean delivery was not reduced but rather

POSTPARTUM MANAGEMENT

varies from annual to triennial. Advice on postpartum weight loss, which may help

the rates of LGA infants and shoulder dystocia were increased. For uncompli-

Approximately 50% of women with GDM

reduce the occurrence of type 2 diabetes

cated GDM, no strong evidence exists to

will develop type 2 diabetes within 5 to

mellitus, includes breastfeeding, dietary

support earlier induction of labour, which

10 years.

was also confirmed by a Cochrane review

that GDM is a stronger predictor of later

of randomized trials on elective delivery in

metabolic syndrome after adjustments for

women with diabetes.

pre-pregnancy body mass index and age.

31

32

An Italian study

33

showed

modification, and exercising for at least 150 minutes every week.35

CONCLUSION

Prophylactic pre-labour caesarean

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

section using estimated fetal weight by ul-

in Denmark, 68% of the 481 women with

Without further cost analyses and confir-

trasound has been proposed but is contro-

previously diagnosed GDM had impaired

mation of results from randomized inter-

versial. Recommendations concerning the

glucose regulation, 59% had elevated

vention trials, the IADPSG guidelines are

lower estimated fetal weight thresholds

fasting serum insulin, 54% had central

unlikely to be widely adopted worldwide.

for prophylactic caesarean section vary

obesity, 28% had hypertension, and 35%

Without a uniform diagnosis, research on

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

had dyslipidemia, presenting with higher

risks and management is difficult. Women

College of Obstetricians and Gynecologists

triglycerides levels and lower high-density

with GDM should be treated with dietary

and the Royal College of Obstetricians and

lipoprotein cholesterol levels compared

modification, appropriate exercise, and

Gynaecologists recommend prophylactic

with the control group.

34

drugs, if necessary. Oral hypoglycaemic

caesarean section if the estimated fetal

Diagnostic testing for diabetes is

agents (eg, glyburide, metformin) are as

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

appropriate 6 weeks after delivery. It is

useful as but not better than insulin alone

inaccuracy of ultrasound in estimating

unclear whether a traditional 2-hour 75-g

in terms of early pregnancy outcomes.

fetal weight, which leads to an increase

oral glucose tolerance test or fasting

in unnecessary caesarean deliveries and,

plasma glucose test may be more useful

About the Authors

therefore, caesarean-associated mater-

at this time. The frequency of follow-up

nal and fetal morbidities, and additional

blood glucose tests for early detection of

health-care costs.

impaired glucose tolerance or diabetes

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

References 1. National Diabetes Data Group. Classification 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. Hyperglycemia 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 Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. 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 Medicine 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. Universal 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 mellitus. Diabetes Care 2006;29:948–949. 9. Ko GTC, Tam WH, Chan JCN, Rogers M. Prevalence 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 Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification 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 anthropometrics. Diabetes 2009;58:453–459. 13. HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol 2010;202:255.e1–255.e7. 14. Pridjian G, Benjamin TD. Update on gestational 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. Impact of gestational diabetes mellitus nutrition practice guidelines implemented by registered dietitians on pregnancy outcomes. J Am Diet Assoc 2006;106:1426–1433. 17. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; 2002.

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



12/4/13 7:40 PM

CME CME Questions Questions

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:

P 5 SK

Gestational Diabetes Jawab pertanyaan di bawah ini dengan Benar atau Salah 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 MFMUNGDM 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.



12/4/13 7:40 PM

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JPOG 2013 Annual Index Section

First Author

Issue

Page

Adolescent, 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

Adenomyosis, 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

Aetiology, 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

Acute 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

CME

Lee VCY

May/Jun

125

Dermatology

Gynaecology

OBSTETRICS

Paediatrics

ReProductive medicine Aetiology, artificial insemination, fertilization in vitro, male infertility, semen analysis

JPOG Nov/Dec 2013 • 264

JPOG_NovDec_2013_Annual Index_P264_Final_ID.indd 264

12/4/13 1:53 PM

Chronic Fatigue Syndrome in Children and Young People. Gestational Diabetes. Painful Bladder Syndrome. Asthma in Children

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