JPOG December 2013 ID

JAN/FEB 2012 Nov/Dec 2013Vol. Vol.38 39No. No.
16
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
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ISSN 1016-0124 (INDONESIA)
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

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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 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 specic maternal morbidity
221
224
Editorial Board
Board Director, Paediatrics 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
Professor Biran Affandi University of Indonesia Dr Karen Kar-Loen Chan The University of Hong Kong Professor Oh Moh Chay KK Womens and Childrens Hospital, Singapore Associate Professor Anette Jacobsen KK Womens and Childrens Hospital, Singapore Professor Rahman Jamal Universiti Kebangsaan Malaysia Dato Dr Ravindran Jegasothy Hospital Kuala Lumpur, Malaysia Associate Professor Kenneth Kwek KK Womens and Childrens 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
Dr Tak-Yeung Leung Chinese University of Hong Kong Professor Tzou-Yien Lin Chang Gung University, Taiwan Professor Somsak Lolekha Ramathibodi Hospital, Thailand Professor Lucy Chai-See Lum University of Malaya, Malaysia Professor SC Ng National University of Singapore Professor Hextan Yuen-Sheung Ngan The University of Hong Kong Professor Carmencita D Padilla University of the Philippines Manila Professor Seng-Hock Quak National University of Singapore Dr Tatang Kustiman Samsi University of Tarumanagara, Indonesia Professor Alex Sia KK Womens and Childrens Hospital, Singapore
Dr Raman Subramaniam Fetal Medicine and Gynaecology Centre, Malaysia Professor Walfrido W Sumpaico MCU-FDT Medical Foundation, Philippines Professor Cheng Lim Tan KK Womens and Childrens Hospital, Singapore Professor Kok Hian Tan KK Womens and Childrens Hospital, Singapore Professor Surasak Taneepanichskul Chulalongkorn University, Thailand Professor Eng-Hseon Tay Thomson Women Cancer Centre, Singapore Professor PC Wong National University of Singapore Adjunct Professor George SH Yeo KK Womens and Childrens Hospital, Singapore Professor Hui-Kim Yap National University of Singapore Professor Tsu-Fuh Yeh China Medical University, Taiwan
JPOG NOV/DEC 2013 i
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.
SHORT TERM IMPACT
Early Life Nutrition
Mendukung perkembangan otak sejak awal Mendukung perkembangan sistem daya tahan tubuh sejak awal Mendukung pertumbuhan sejak awal
LONG TERM BENEFIT
Kemampuan belajar dan kognitif yang optimal
Perkembangan sistem daya tahan tubuh untuk mengurangi alergi dan infeksi
Komposisi tubuh yang optimal untuk mengurangi resiko terkena penyakit tidak menular (non-communicable diseases)
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. 2. 3. 4. 5. Gibson R.A, et al. Maternal and Child Nutrition 2011. pp17-26 Arslanoglu Set al. j, Nutr. 2008;13B:1091-1095 Dupont C. Protein requirements during the first year of life. Am J Clin Nutr 2003;77(suppl):1544S-9S. Flynn A. The role of dietary calcium in bone health. Proceeding of the Nutrition Society (2003), 62: 851 858. 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
225
Review Article Gynaecology
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 PregnancyDont Assume Its Benign
Christopher S Pokorny
Publisher
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Publication Manager
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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 eld or elds. 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 inuence on editorial content or presentation. MIMS Pte Ltd does not guarantee, directly or indirectly, the quality or efcacy 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 Ofce 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.
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JPOG NOV/DEC 2013 iii
Persembahan SGM Presinutri untuk Bayi dengan Kebutuhan Medis Khusus
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NO V / DEC Vol. 39
2013 No. 6
Review Article Paediatrics
245 Chronic Fatigue Syndrome in Children and Young People

Chronic fatigue syndrome is a relatively common and serious condition in children and young people, having a significant impact on their physical, emotional, and cognitive well being. This review explores the best practice approach to assessment, diagnosis, and management of chronic fatigue syndrome in children and young people. Carrie Mackenzie, Alison Wray
245
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
Comprehensive reviews providing the latest clinical information on all aspects of the management of medical conditions affecting children and women.
Case Studies
Interesting cases seen in general practice and their management.
The Cover: Chronic Fatigue Syndrome 2013 MIMS Pte Ltd
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: enquiry@jpog.com
Lisa Low, Illustrator
JPOG NOV/DEC 2013 iv
PEER REVIEWED
Journal Watch
In total, 498 (87.8%) of the women received
the Wide Range Assessment of Visual Motor Abilities at ages 3 and 7 years, and the Kaufman Brief Intelligence Test and Wide Range Assessment of Memory and Learning at age 7 years. Adjustments were made for sociodemographic background, maternal intelligence, and home environment. Longer breastfeeding duration was associated with a higher Peabody Picture Vocabulary Test score at age 3 (0.21; 95% CI, 0.030.38 points per month breastfed) and higher intelligence on the Kaufman Brief Intelligence Test at age 7 (0.35; 95% CI, 0.160.53). Beneficial effects of breastfeeding on Wide Range Assessment of Visual Motor Abilities at age 3 appeared to be greater for women who consumed 2 servings of fish per week compared with < 2 servings per week (0.24; 95% CI, 0.000.47 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
GYNAECOLOGY
at least one dose of medication during the openlabel study. Compared with baseline in the randomized trial, at the end of the open-label study
3IQ safe and effective for diagnosing urgency urinary incontinence
fesoterodine was linked to a reduction in the mean total number of incontinence (4.64 vs 1.16) and urgency incontinence (3.95 vs 0.90) episodes per day (P < 0.0001 for both). Patient satisfaction increased from 89% at 3 months to 92% and 93% at 6 and 9 months, respectively. Twenty-six women experienced one or more serious adverse events, but only one was considered to be treatment-related. Specialist evaluation of 22 women found that the 3IQ had misclassified five but without any adverse outcomes.
Hess R et al. Long-term efcacy and safety of questionnaire-based initiation of urgency urinary incontinence treatment. Am J Obstet Gynecol 2013; doi:10.1016/j.ajog.2013.05.008.
PAEDIATRICS
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 Incontinence Questions (3IQ) have been developed to aid primary care providers in diagnosing and initiating treatment, and a recent study has shown that long-term fesoterodine therapy initiated on the basis of the 3IQ is both safe and effective. Researchers invited 567 women who had completed a 12-week randomized controlled trial of fesoterodine therapy for urgency urinary incontinence diagnosed by the 3IQ to participate in a 9-month open-label continuation study. They collected data on incontinence and voiding episodes using voiding diaries. Patient satisfaction was determined by questionnaire, and safety was evaluated by monitoring post-void residual volumes and adverse events. Nutrients in breast milk may benefit the developing brain, but no exact relationship between maternal diet during lactation and childhood cognition has been determined to date. Now, a study has found that longer duration and greater exclusivity of breastfeeding is associated with better receptive language at age 3 and higher verbal and non-verbal IQ at age 7. The prospective, longitudinal, Project Viva study evaluated feeding practices among a US prebirth cohort of 1,312 mothers and assessed the cognitive capabilities of their children at ages 3 and 7 years (1,224 at age 3; 1,037 at age 7) using the Peabody Picture Vocabulary Test at age 3 years,
Wide Range Assessment of Memory and Learning scores. An accompanying editorial notes that the pu-
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 breastfeeding through to age 6 months. The suggestion is made that large-scale structural changes are required to support mothers in this endeavour.
Belfort MB et al. Infant feeding and childhood cognition at ages 3 and 7 years: effects of breastfeeding duration and exclusivity. JAMA Pediatr 2013; doi:10.1001/jamapediatrics.2013.455; Christakis DA. Breastfeeding and cognition: can IQ tip the scale? Ibid: doi:10.1001/ jamapediatrics.2013.470 (editorial).
Consumption of sugar-sweetened beverages linked to weight gain in young children

Although consumption of sugar-sweetened beverages (SSBs) has been linked to weight gain in
JPOG NOV/DEC 2013 221
school-aged children and adolescents, results for younger children have been mixed. Now, a US study has shown that consumption of SSBs is also linked to weight gain in 2- to 5-year-old children. The researchers compared the consumption of SSBs (soda pop, sports drinks, and fruit drinks that are not 100% fruit juice) and body mass index (BMI) z scores among 9,600 children followed up as part of the US-based Early Childhood Longitudinal SurveyBirth Cohort study (a representative survey of the US population of children born in 2001). Adjustments were made for race/ethnicity, socioeconomic status, mothers BMI, and TV viewing.
sis also showed that children who were already exposed to such beverages at age 2 had a greater subsequent increase in BMI z score over the following 2 years than infrequent/non-drinkers ( P < 0.05). The researchers suggest that paediatricians and parents should discourage the consumption of SSBs to avoid potential unhealthy weight gain in children.
DeBoer MD et al. Sugar-sweetened beverages and weight gain in 2- to 5-year-old children. Pediatrics 2013;132:18.
breastfeeding at age 67 months was associated with a decreased risk of being overweight (odds ratio [OR], 0.85; 95% CI, 0.691.05) or obese (OR, 0.55; 95% CI, 0.390.78) at ages 7 and 8 (underweight: OR, 0.84; 95% CI, 0.681.03; obese: OR, 0.44; 95% CI, 0.310.63). 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 other factors have a greater impact on obesity,
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 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 2001 through 2009 during the ongoing nationwide Longitudinal Survey of Babies in the 21st century were undertaken. All 43,367 singleton children born after 37 gestational weeks with available information on feeding during infancy were eligible, but some were excluded because of missing data Increased consumption of SSBs compared with infrequent/no consumption of such beverages was associated with higher BMI z scores among children aged 4 (0.756 0.048 vs 0.644 0.024; P < 0.05) and 5 (0.849 0.051 vs 0.662 0.018; P < 0.01), but not among those aged 2 (0.362 0.087 vs 0.461 0.039; P > 0.05). Moreover, children aged 5 who regularly consumed SSBs (ie, 1 serving/day) had a higher odds ratio (OR) for being obese than infrequent/non-drinkers (< 1 serving/day) (OR, 1.43; 95% CI, 1.101.85; P < 0.01). A prospective analyor were lost to follow-up. In total, 29,907 were included in the analysis at age 7 and 30,780 at age 8. Data were adjusted for the childrens sex and screen time as well as for maternal educational attainment, and smoking and working status. At age 7, 7.3% of the children were classified as overweight and 2.1% as obese, according to the International Obesity Task Force body mass index cut-off points based on sex and age. The corresponding values at age 8 were 7.8% and 1.9%. In addition, compared with formula feeding, exclusive
Yamakawa M et al. Breastfeeding and obesity among schoolchildren: a nationwide longitudinal survey in Japan. JAMA Pediatr 2013; doi:10.1001/jamapediatrics2013.2230; Bovbjerg ML et al. Breastfeeding and childhood obesity: where do we go from here? Ibid: doi:10.1001/ jamapediatrics.2013.2854 (editorial).
Late preterm infants not at higher risk of ADHD, learning disabilities

Late preterm infants have previously been suggested to be at greater risk of learning and behavioural problems than term infants, but most studies have evaluated clinic-referred children at early school age, and findings have been mixed. Now, a population-based study suggests that late preterm infants are not at greater risk of developing attention deficit/hyperactivity disorder (ADHD) and learning disabilities compared with term infants. The study included 5,699 children born in Rochester, Minnesota, US, between 1976 and 1982, who were still resident in the community after 5 years and who did not have a severe intellectual disability. The cumulative incidence of ADHD and learning disabilities in reading, written language, and math by age 19 was determined by comparing
PEER REVIEWED
Journal Watch
medical and school records for former late preterm (34 to < 37 weeks) and term (37 to < 42 weeks) infants. Adjustments were made for maternal education and perinatal complications. No statistically significant differences were observed between former late preterm (n = 256) and term (n = 4,419) infants at age 19 in terms of the cumulative incidence of ADHD (7.7% vs 7.2%; P = 0.84) or of learning disabilities relating to reading (14.2% vs 13.1%; P = 0.57), written language (13.5% vs 15.7%; P = 0.36), and math (16.1% vs 15.5%; P = 0.89). The researchers conclude that former late preterm infants have similar rates of ADHD and learning disabilities as term infants.
Harris MN et al. ADHD and learning disabilities in former late preterm infants: a population-based birth cohort. Pediatrics 2013;132:e630e636.
the frequency of eating breakfast. Moreover, the amount of time spent viewing TV decreased and the consumption of sweets and sweetened beverages declined. Although a trend towards weight gain remainedthe average BMI increased from 20012002 to 20052006there was no increase in average BMI between 20052006 and 2009 2010, which may indicate that obesity rates are beginning to stabilize. The researchers comment that these findings indicate that public health initiatives may be beginning to have an effect. However, they note that paediatricians should be aware of age-, sex-, and ethnicity-based differences in behaviour when interpreting these findings. A number of these differences are noted in the study. For example, older adolescents were more frequent users of computers, consumed fewer fruits and vegetables and
Early-term infants have higher rates of neonatal morbidity, NICU admission

Full-term neonates born between 37 and 41 weeks gestational age have traditionally been considered a homogenous, low-risk group. However, a recent study has provided further evidence that earlyterm births (37 0/7386/7 weeks) are associated with higher rates of neonatal morbidity and neonatal intensive care unit (NICU) or neonatology service admission than term births (390/7416/7 weeks). The retrospective, population-based birth cohort study evaluated 33,488 live births at major birthing hospitals in Erie County, New York, between January 1, 2006, and December 31, 2008. Data on NICU or neonatology service admission were extracted from medical records. Of the 33,488 live births, 29,741 were at a gestational age between 37 and 416/7 weeks and 9,031 (27%) were early-term. Compared with term neonates, early-term neonates were at significantly higher risk for NICU or neonatology service admission (8.8% vs 5.3%; adjusted odds ratio [OR], 1.64), duration of hospital stay 5 days (1.9% vs 1.2%; adjusted OR, 1.37), respiratory morbidity (5.4% vs 3.3%; adjusted OR, 1.58), respiratory support (2.0% vs 1.1%; adjusted OR, 1.93), mechanical ventilation or intubation (0.6% vs 0.1%; adjusted OR, 4.57),
Obesity rates among US adolescents may be stabilizing

Obesity rates among US adolescents have been of concern for some time given that obesity is a risk factor for many leading causes of mortality. However, a recent study has indicated that obesity rates among US adolescents may be stabilizing and that this may be due to changes in obesogenic behaviours. Nationally representative US students in grades 610 anonymously completed the Health Behavior in School-aged Children (HBSC) survey, which assesses body mass index (BMI), physical activity, and sedentary and dietary behaviours, in 20012002, 20052006, and 20092010. AfricanAmerican and Hispanic students were oversampled to obtain better estimates for these populations. Obesogenic behaviours remained common over the study period, but the amount of time spent engaging in physical activity increased over time, as did the consumption of fruit and vegetables and
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, 20012009. Pediatrics 2013;132:606-614.
surfactant use (0.3% vs 0.05%; adjusted OR, 6.29), hypoglycaemia (4.9% vs 2.5%; adjusted OR, 1.92), administration of intravenous fluids (7.5% vs 4.4%; adjusted OR, 1.68), and treatment with intravenous antibiotics (2.6% vs 1.6%; adjusted OR, 1.62). In addition, significantly more early-term neonates were delivered by caesarean section than term neonates (38.4% vs 29.3%). Caesarean delivery was found to increase the risk for NICU or neonatology service admission and morbidity, but even earlyterm infants delivered vaginally had a significantly higher rate of NICU or neonatology service admis-
sion than term infants. An accompanying editorial notes that these findings reinforce the conception of maturation as a continuum and highlight the difficulties associated with using a preset gestational age as an index of separation between immaturity and maturity.
Sengupta S et al. Adverse neonatal outcomes associated with early-term birth. JAMA Pediatr. 2013; doi:10.1001/jamapediatrics.2013.2581. Oh W et al. Not all term infants are created equal. JAMA Pediatr. 2013; doi:10.1001/jamapediatrics.2013.2593 (editorial).
and these women may face the greatest risks. The researchers comment that although a short consent time does not necessarily imply a poor-quality conversation regarding potential risks, it is unlikely that a high-quality informed consent process can occur in under 50 minutes. They suggest that an alternative approach should be adopted, such as the inclusion of informed consent discussions during routine prenatal care. An accompanying editorial and roundtable discussion support this suggestion.
to 1,601,253 women without pregnancy complications who delivered singletons at 3742 completed weeks gestation. The rate of postpartum haemorrhage requiring blood transfusion was increased by labour induction at 38 weeks (adjusted rate ratio [aRR], 1.28; 95% CI, 1.111.49), 39 weeks (aRR, 1.21; 95% CI, 1.061.38), and 40 weeks (aRR, 1.12; 95% CI, 1.001.26) gestation. Similarly, induction at 38 and 39 weeks gestation was associated with higher rates of puerperal sepsis (aRR, 1.27; 95% CI, 1.131.99; and aRR, 1.24; 95% CI, 1.091.82, respectively) and induction at 38 weeks gestation with higher rates of venous thromboembolism (aRR, 2.94; 95% CI, 1.595.46). However, the absolute increase in morbidity rates was small, and the number needed to harm was substantial for all
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).
Currently, the standard practice for obtaining informed consent to caesarean delivery in the US is to obtain the patients consent at the time the decision to perform a caesarean is made. However, a novel study has shown that this approach does not allow sufficient time for patients to evaluate potential risks, particularly among women who are at greatest risk. The retrospective chart review of 90 patients who underwent caesarean delivery during labour compared the time from consent to incision to actual delivery among women with and without fetal heart rate indications. The median consent time among all women was 48 minutes (interquartile range, 2572 minutes), but it was < 30 minutes in 28.9% of women and < 15 minutes in 10%. Moreover, after adjusting for potential confounders, the odds of delivery < 30 minutes after consent were 4.7 times higher (95% CI, 1.415.2; P = 0.01) among women with fetal heart rate indications. In addition, the consent time was not higher among obese women or those who had previously experienced a caesarean delivery,
Early-term labour induction linked to higher rates of specic maternal morbidity

Labour induction is widely used to prevent adverse maternal, fetal, and infant outcomes. Although generally considered safe, problems such as prolonged labour, chorioamnionitis, fetal death, and uterine rupture can occur. In a recent study, researchers in Canada compared the gestational age-specific effects of labour induction on severe obstetric morbidity and found that women who were induced at an earlier term had higher rates of specific severe maternal morbidity than similar women who were treated expectantly, although the absolute risks were low. The researchers compared data from hospital records collated in the Discharge Abstract Database of the Canadian Institute for Health Information for 20032011 (excluding Quebec). The database includes all maternal hospital admissions for delivery as well as links to newborn infant admissions. The analysis was performed using a pregnancies-at-risk approach and was restricted
three conditions.
Liu S et al. Gestational age-specic severe maternal morbidity associated with labor induction. Am J Obstet Gynecol 2013; 209:209.e1-8.
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).
diperlihatkan, antara lain pemberian susu formula hidrolisat, susu formula rendah atau bebas laktosa atau terapi antirefluks. Bila dalam 2 minggu hingga maksimum 1 bulan tidak ada respons, maka perlu dipikirkan diagnosis lain. Medikasi dengan simethicone yang memiliki efek menurunkan gas dalam lambung dibuktikan pada 2 studi tidak menunjukkan manfaat, sedangkan obat golongan antikolinergik (dicylomine, pipenazolate bromide) pada review didapatkan sedikit lebih efektif dari plasebo hanya selama beberapa hari pertama saja dan selanjutnya tidak berbeda bermakna dengan plasebo. Efek samping terapi yang dilaporkan, bayi menjadi letargi, apnea pada pemberian dicycloine dan tidak dapat digunakan pada bayi berusia < 6 bulan serta menyebabkan kantuk. Golongan Proton pump inhibitors/PPI pada kolik bayi dilaporkan beberapa studi tidak menunjukkan manfaat. Sedangkan pada studi perbandingan probiotik L reuteri protectis vs. plasebo pada kolik bayi dilaporkan probiotik dapat menurunkan kejadian bayi rewel (75% vs. 38%) terutama pada 7 hari pertama. Hormon melatonin dalam ASI memiliki efek hipotonik dan relaksasi otot polos gastrointestinal yang diekskresikan oleh ibu pada malam hari, sehingga memperbaiki waktu tidur bayi dan mengurangi kolik. Gas berlebih dalam saluran cerna (Fussiness and gassiness) Sejumlah udara dalam saluran cerna adalah keadaan normal, namun bila berlebihan akan menyebabkan distensi abdominal dan rasa nyeri. Riwayat klinis dan pemeriksaan fisik dapat diidentifikasi etiologinya pada 66,3% kasus. Pemeriksaan tes tambahan dilakukan berdasarkan temuan klinis. Telusuri adanya red flag sebagai skrining pada kasus ini, dan buktikan lebih dulu penyebabnya apakah ada kecurigaan terhadap faktor organik. Bila tidak ada red flag tetapi terdapat ruam popok dan tanda intoleransi laktosa, maka bila bayi mendapat ASI, pemberian ASI tetap diteruskan. Bila bayi mendapat susu formula, sebaiknya diberikan yang kadar laktosanya diturunkan. Bila gejala tidak membaik rujuk ke dokter anak konsultan gastroenterologi. (lihat gambar 2). Kesimpulan : 1. Abdominal discomfort sangat sering pada bayi. 2. Abdominal discomfort tidak hanya sekedar gangguan fungsional, tetapi merupakan keadaan yang perlu mendapat perhatian. 3. Studi tersamar ganda dan intervensi prospektif masih sangat terbatas dilakukan pada bayi dengan abdominal discomfort. 4. Diperlukan pedoman pendekatan tata laksana bayi dengan abdominal discomfort.
Infantile Colic
3 month of age Fussiness, irritability, or crying >> 3 hours/day 3 days/week At least one week
Organic cause Red Flag
Consider GERD, CMA, low lactase activity, or other GI disease
No Evaluate and establish correct feeding technique and baby comfort Maintain support Improvement? Consider modication of infant diet and try an eHF/CM-free diet in BF No Improvement? Yes No
Yes Evaluate and treat: Anxiety in parents Maternal depression Absence of mother child reciprocity Yes
Yes
No Refer to pediatric gastroenterologist
Refer to Psychology/psychiatry
Consider diagnosis of CMA
Gambar 1. Tata laksana infantile colic
Fussiness, Gassiness: Accompanied by Crying

Excessive Crying/Gas/Fussiness Breastfed infant RED FLAGS? Failure to thrive Frequent regurgitation, vomiting, and cough episodes Sandifers position Family history of atopy Respiratory/dermatological symptoms of atopy GI bleeding Formula fed infant
Yes
Organic cause? Refer to pediatric GI specialist
No
No
The patient has: Diaper rash, or Diarrhea post-gastroenteritis, or Reducing substances in feces
Yes
BF: no change Formula-fed: lactose may be withdrawn from the diet temporarily
Education Reassurances
No
Refer to pediatric GI specialist
Problem solved??
Yes
Discharge
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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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 67 and 1314 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
PAEDIATRIC S PAEDIATRICS
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The nancial 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 into direct and indirect costs. Direct costs relate to costs of hospital admission, emergency room, outpatient and community practitioner visits, medicinal costs, family costs for travel to hospital or to medical appointments, as well as the cost of altering the home such as purchase of non-allergenic bedding. Indirect costs are calculated as days missed from school, days missed from work for the parent to look after the child when ill, and, although uncommon, if a child dies from asthma, it is possible to calculate the loss of potential earnings the child would have
tutes part of the spectrum of asthma and whether symptoms early in life can predict progression of disease through childhood and into adult life. In the 1970s, it was believed that wheezy bronchitis was part of the asthma spectrum, but in the 21st century the main thrust has been to separate phenotypes into episodic (viral) wheeze or multi-trigger wheeze. Other terms such as persistent wheeze and intermittent recurrent wheeze only confuse the picture. The triggers that may instigate nonviral wheeze are tobacco smoke, exercise, emotion, and various aeroallergens. An excellent review of
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preschool wheezing can be found in the European Respiratory Society (ERS) Task Force paper in the European Respiratory Journal 2008.3 It discusses the overlap in phenotypes and the finding that a childs phenotype may change from one to the other when followed prospectively for 1 year or more. It is very difficult, therefore, at any single time point to give clear advice to parents about the likelihood of symptoms continuing or disappearing. What is agreed is that the more severe and persistent the symptoms, the more likely they are to persist. Although epidemiological studies try to separate episodic viral wheeze and multiple-trigger wheeze, because of the overlap, it is much more difficult when dealing with an individual child. The relationship between atopy and disease progression has been closely studied and the single most useful indicator of persistence of symptoms is the presence of allergen sensitization on skin-prick testing at 2 years
4 of age. However, this is not an investigation under-
Whats new?
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
tive process. In sensitized asthmatic bronchial epithelial cells, IFN- is greatly reduced so anti-viral processes are not induced; this leads to very high viral load and the development of inflammation. A Swedish cohort study has consistently suggested a relationship between early RSV infection, early sensitization and asthma patterns throughout childhood,6 whereas most others have not. This study managed to follow up 46 of the original 47 infants with RSV infection and 92 of the 93 control subjects for 18 years.
taken by most UK clinicians in very young children.
MECHANISMS OF SYMPTOM DEVELOPMENT AND PROGRESSION

Children sensitized at an early age to the common aeroallergens (house-dust mite and cat being the two most common sources) react differently to respiratory viruses than those not sensitized. Although respiratory syncytial virus (RSV) results in repeated wheezing and coughing episodes in childhood, rhinovirus is thought to be more important in causing asthma exacerbations in children.
5
GENERAL MANAGEMENT OF ASTHMA

There are multiple local, national and international guidelines on asthma management. The Scottish Intercollegiate Guidelines Network (SIGN)/British Thoracic Society guidelines are regularly updated; their outline can be found in the British National Formulary for Children. A step-wise approach is recommended, but the step most often forgotten is to step down when control has been achieved following a reasonable period of stability. Parents understand this and often reduce or stop treatment if there are no symptoms. There is no evidence that this is inappropriate and, indeed, we know that the long-term use of inhaled corticosteroids (ICS) has no
In normal bronchial epithelial cells, the presence of virus leads to rapid induction of interferon- (IFN- ). This then induces more of itself as well as interferon- (IFN- ). Other compounds such as ribonuclease and protein kinase R join in to kill and phagocytose the virus, thereby limiting the infec-
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Table 1. Passive smoke exposure and incidence of wheeze
re-checked 20 minutes later. Repeated increases clearly indicate non-adherence with prescribed treatment and need addressing. This can be more difficult than it may seem. The reasons for nonadherence are complex and multiple.
Smoking exposure Prenatal maternal Maternal Paternal Prenatal maternal Maternal Paternal Prenatal maternal Maternal Paternal
Age at outcome (y) 2
Number of studies 11 2 0 7 4 0 5 2 2
Pooled odds ratio 1.44 1.72 1.25 1.77 1.38 1.65 1.31
34
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 2-agonists (LABAs), multiple doses of short-acting 2-agonists
518
Passive smoke exposure and incidence of wheeze (adapted from Royal College of Physicians report Passive smoking and children 2010; page 85).
effect on the natural history of the disease. When ICS are stopped after many years usage, those with persisting active disease eventually show falls in lung function and increases in symptoms.
and other treatments, such as theophyllines or leukotriene-receptor antagonists (LTRAs). These need specialist assessment by tertiary respiratory teams. It is imperative to assess the family background. Is there a lack of adherence to treatments? Is the home environment contributing to poor control? Are there contributory psychosocial factors? Discussions with primary care personnel, checking with the pharmacist that prescriptions are collected regularly, and visits to the family are often necessary to establish the cause for poor control. The gathering of all the relevant information needs a multidisciplinary team that includes specialist paediatricians, respiratory nurses, psychologists, and social workers. The role of nurse-led home visits is now well established. needed. In keeping with the recognition that more severe disease continues into adult life, one of the longest followed-up asthma cohorts has recently been published from Melbourne, Australia. 8 Patients were recruited from a 1957 birth cohort at the age of 7 years and reviewed regularly to 50 years of age. At 10 years, a cohort of very severe asthmatic children was included. Of the total cohort, 346 (76%)
7
ARE THERE NEW WAYS OF MONITORING CLINICAL PROGRESS?

Asthma is an inflammatory condition. Studies have assessed enhanced control by measuring inflammatory markers in the blood and sputum and measuring fractional exhaled nitric oxide (FeNO). As small, portable FeNO monitors became available, there was hope that FeNO would be clinically helpful. After a decade of usage, the general belief is that FeNO is a marker of atopy but is probably not helpful as an adjunct to good clinical history-taking and careful clinical examination. The clinical assessment should include lung function testing (spirometry) in all children old enough to produce reliable values for forced vital capacity and forced expiratory volume in 1 second (FEV1). The child with low FEV1 (eg, below 80% expected) values should be given 610 puffs of salbutamol and have spirometry
Invasive procedures such as bronchoscopy may be
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participated in the follow-up at 50 years and 197 of these completed questionnaires and lung function testing. Chronic obstructive pulmonary disease was diagnosed in 28 adults (14%) and 24 of these were from the very severe cohort introduced at 10 years of age. The authors comment that early aggressive therapy for very severe asthma in childhood may, in both the symptoms of asthma throughout life and the development of chronic obstructive pulmonary disease as a long-term complication. the future, prevent airway remodelling and reduce
Figure 1. Daily hospital admissions for asthma among children between January 2000 and October 2009.
Upper 95% CI Smoothed hospitalizations Lower 95% CI
8 Asthma admissions (number/day) 7 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
It was believed that wheezy bronchitis was part of the asthma spectrum, but in the 21st century the main thrust has been to separate phenotypes into episodic (viral) wheeze or multi-trigger wheeze
Adapted from NEJM 2010;363: page 1141
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 Childrens Charter early in 2011. Having undertaken a
THE ENVIRONMENT AND WHEEZE/ASTHMA

The Royal College of Physicians published Passive smoking and children in 2010. The single most useful measure that may reduce the prevalence and influence the symptoms of wheeze and asthma in children is to encourage the birth and rearing of children in an environment free from tobacco smoke. The developing fetus in a mother who smokes receives as much nicotine and other tobacco constituents as an adult who smokes 20
9
confirmatory survey amongst UK children, the Charters first point is Children should be able to enjoy a smoke-free environment both inside and outside the home. The British Lung Foundation went on to recommend a change in UK law prohibiting parents from smoking in cars when children were present. Scotland banned smoking in public places and workplaces in March 2006. Over the next 3.6 years, there was a significant fall in daily hospital admissions for asthma in children. This can be seen in Figure 1, including 95% confidence intervals and smoothed admissions for children with asthma.
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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

The prole of asthma incidence seen in the 2008 German asthma cohort study can be replicated throughout all Western European countries. The numbers are greatest in the rst few years of life, falling to low levels by 12 years of age. A UK study, the Health Technology Assessmentfunded MASCOT study, opened in 2009 with the intention of enrolling 900 children with asthma poorly controlled at step 3 (low-dose ICS alone) of the SIGN national asthma guidelines. It had difculty recruiting children and closed early in January 2011. A positive inference may be that there are fewer poorly controlled asthmatic children in the UK than there were 10 years ago.
NEWER PHARMACEUTICAL TREATMENTS

The Early Years
In the preschool age group, children with episodic viral wheeze respond to short-acting 2-agonists when given through a spacer (with facemask attached in those under 3 years old). Those with repeated symptoms affecting activity, sleep, and nursery attendance require preventative treatment but respond less well to ICS than children with multiple trigger wheeze. LTRAs in the form of montelukast granules or chewable tablets (4 mg) have been used increasingly in this age group. Studies from UK, Europe, and Australasia have reported varying outcomes, but the SIGN national guidelines (updated in June 2009) recommend LTRAs in this age
10
11
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group. Their administration to very young children is often easier for parents than the use of spacer devices for ICS delivery.
Practice points
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 therapy rather than the addition of LTRA. Because of safety issues of LABA usage, raised by the Food and Drug Administration, meta-analyses have been undertaken in all age groups.
14 13
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
symptoms. At present, the National Institute for Health and Clinical Excellence has not approved its use in children under 12 years of age. It is given by subcutaneous injection either fortnightly or monthly depending on body weight and the absolute concentration of serum IgE.
2012 Elsevier Ltd. Initially published in Medicine 2012;40(5):238242.
A UK safety study
examined whether tolerance to LABAs was a clinical concern. The general consensus is that, when used in addition to ICS, LABAs are effective and safe in children, but there is still a need for further studies as children are underrepresented in clinical trials compared with adults with asthma. An exciting development has been the licensing of omalizumab, an anti-IgE monoclonal antibody, for use in children aged 6 years and over with very severe asthma. This will be used only in a very small number of children but can have a dramatic impact on symptoms and has revolutionized the lives of a few patients with very severe
About the Author

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.
REFERENCES
1. Pearce N, At-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;62:758766. 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;60:315335. 3. Brand PLP, Baraldi H, Bisgaard AL, et al; ERS Task Force. Denition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J 2008;32:10961110. 4. Schultz A, Brand PLP. Episodic viral wheeze and multiple trigger wheeze in preschool children: a useful distinction for clinicians? Paediatr Respir Rev 2011;12:160164. 5. Friedlander SL, Busse WW. The role of rhinovirus in asthma exacerbations. J All Clin Immunol 2005;116:267273. 6. Sigurs N, Alijassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the rst year of life. Thorax 2010;65:10451052. 7. Bracken M, Fleming L, Hall P, et al. Results of nurse-led home visits for children with difcult 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, Grber C, et al. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J 2008;32:585592. 11. Lenney W, Perry S, Price D. Clinical trials and tribulations: The MASCOT Study. Thorax 2011;66:457458. 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 -agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med 2006;144:904912. 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;21:336344.
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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 32% 35% 56%
Progres ke NIS III 11% 22% -
Progres ke Karsinoma 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-nave 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 ekasi terhadap lesi derajat tinggi (CIN3+) yang berkaitan dengan HPV 16/18 mencapai 100%. Hasil ekasi terhadap lesi derajat tinggi (CIN3+) tanpa melihat tipe HPV Onkogenik, hasilnya mencapai 93,2% pada kelompok studi TVCnave. (lihat tabel 1 dan tabel 2)
Tabel 1. PATRICIA: Hasil ekasi terhadap lesi derajat tinggi tanpa melihat tipe HPV
Ekasi menyeluruh vaksin HPV 16/18 terhadap CIN 3+ sebesar 93.2% terlepas dari tipe HPV onkogenik pada kelompok TVC-nave. 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 analaksis (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
Endpoint CIN3+
Group Vaccine Control
N 5,466 5,452
n 3 44
Vaccine efficacy, % (95% CI) 93,2 (78.9-98.7)
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 ekasi 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 CIN3+
Group Vaccine Control
N 5,466 5,452
n 0 27
Vaccine efficacy, % (95% CI) 100,0 (85.5-100.0)
yang juga sudah dimuat di jurnal internasional, menunjukkan bahwa untuk kelompok studi TVC-nave, vaksin ini memberikan hasil ekasi terhadap CIN3+ sebesar 93,2% tanpa melihat tipe HPV.
Pemberian vaksinasi lengkap terdiri dari 3 dosis dengan
jadwal yang direkomendasikan adalah bulan 0,1 dan 6 secara intramuskular di bagian deltoid. Hingga saat ini pemberian booster belum diperlukan.
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GYNAECOLOGY PAEDIATRICS
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Ovarian Cancer: Current Management Painful Bladder Syndrome and Future Directions
Maria Vella, MRCOG; Dudley Robinson, MD, FRCOG; Linda Cardozo, MD, FRCOG Sin 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 Hunners 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.
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PREVALENCE
Large population-based studies are thought to be 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 OLeary-Sant questionnaire and the Pelvic Pain and Urgency/Frequency, were compared in the same population. The prevalence rate using the former was 0.57%. This was in marked contrast to the 12.6% prevalence rate obtained using the Pelvic Pain and Urgency/ Frequency questionnaire, hence highlighting the need for a more standardized questionnaire to be used for epidemiologic studies. In a recent large telephone survey in the United States, a prevalence rate of 37% was identified (only soft markers or associated diseases like fibromyalgia).
Epidemiologic studies on painful bladder syndrome are hindered by various factors, resulting in widely varying prevalence rates.
cell activation are thought to have a role. Both are thought to be implicated and are generally found in histological samples of most ulcerative and some non-ulcerative BPS. Other theories include the possible implication of infection as an initial trigger, although documented evidence of a urinary tract infection at the onset of symptoms has only been found in a limited number of patients. Furthermore, no particular organism or class of organisms has ever been demonstrated. Autoantibodies, namely antinuclear antibodies, have been found in some patients with BPS. This, together with similar clinical and histological features found in some patients with autoimmune disorders, has prompted the possibility of an underlying autoimmune theory in the pathogenesis of some patients with BPS.
AETIOLOGY AND PATHOGENESIS

The aetiology and pathogenesis of PBS is very poorly understood. Over the years, a number of theories have been put forward. Inflammation and mast
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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 then set off the cascade of events seen in Figure 1. This figure also highlights the importance of mast cells and their interaction with other inflammatory cells and the nervous system. All of these factors are implicated in the pathogenesis. Genetics may also play a role in the aetiology. A study using a combined mail-in and telephone survey concluded that adult female first-degree relatives have a prevalence rate of BPS 17 times that of the normal population, suggesting a possible genetic susceptibility to the condition. A potential ge-
Insult to urothelium by, e.g, bacterial cystitis, bladder trauma, etc Damage to bladder epithelium which fails to repair the damage Leakage of urine constituents into urothelitum Mast cell activation and release of histamine
C-bre activation
Immunogenic response
netic role was also shown in a twin study that demonstrated a higher concordance of BPS amongst monozygotic compared with dizygotic twins.
Bladder injury chronic neuropathic pain
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 suggest that PBS may be part of a generalized somatic disorder, thus explaining the possible co-existence with other chronic conditions such as fibromyalgia and irritable bowel syndrome. They share features like symptoms of fatigue and pain and also show an association with stress and psychosocial factors. Both fibromyalgia and BPS/IC patients display substantial clinical overlap, and studies have shown that the latter display diffusely increased peripheral nociception as seen in patients with fibromyalgia. It may therefore be speculated that the same types of central mechanisms that contribute to the pathogenesis of fibromyalgia may be operative in the pathogenesis of BPS/IC. The general consensus is that the pathogenesis involves damage occurring to the bladder epiJPOG NOV/DEC 2013 234
ally start off having mild episodic symptoms lasting for several days, which tend to become more severe and consistent with time. The episodic and non-specific nature of the disease is generally responsible for a delay in making a diagnosis. Patients generally present with pain and lower urinary tract symptoms (these are the two essential diagnostic criteria). Pain is commonly suprapubic, although it may also be experienced in the lower abdominal region, vulva or vagina, urethra, or even rectum. It may be described as a burning pain, as a lower abdominal pressure sensation or urethral pain experienced when passing urine. Urinary symptoms typically include frequency and, less commonly, urgency. Nocturia is less common in these patients. A variety of factors may exacerbate symptoms, including certain acidic foods like tomatoes and al-
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cohol, spicy foods, caffeine, and chocolate. Some patients claim that their symptoms are exacerbated by sexual intercourse. This may cause a significant negative impact on their relationships. In some women, symptoms are significantly worse in their premenstrual week. A higher prevalence of systemic and autoimmune disorders like rheumatoid arthritis and Sjogrens 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.
Patients with painful bladder syndrome usually present with pain (commonly suprapubic) and lower urinary tract symptoms.
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) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or any other identifiable cause (Hanno et al ). During history taking, emphasis should be made on the site of the pain and its character. The relationship of the pain to bladder filling and emptying should be noted. Any associated lower urinary tract symptoms, any bladder or urological previous diseases, and any past history of pelvic surgery, pelvic irradiation, or autoimmune diseases should all be enquired about. Any exacerbating or relieving factors or any specific pattern of the symptoms should also be identified. A thorough physical examination should also be carried out, including a general assessment and examination of the lower abdomen. This helps identify scars from previous surgery, any obvious organ enlargement as well as any areas of tenderness. Hernial orifices should also be examined. In addition, a pelvic examination should be performed in order to be able to map pain over the vulval area. A bimanual examination aims to identify any enlarged organs as well as eliciting any tender points over the urethra, bladder, levator muscles, or adnexae. This helps in diagnosing BPS and also to exclude any other diseases that may be part of the differential diagnosis.
Investigations
A number of investigations are available in order to make an accurate diagnosis, exclude any confusable diseases, and define the severity of the illness.
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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 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
Investigation Urodynamics Cystoscopy
Level of evidence Grade of recommendation 4 2 C B
There is however no single investigation or test that will identify PBS.
hours. A visual analogue score may also be used in conjunction with a frequency volume chart and quality of life scores in order to monitor disease progression or response to treatment. Assessment of impact on quality of life it is considered good clinical practice to evaluate quality of life in anybody presenting with lower urinary tract symptoms. The OLeary-Sant symptom
The general consensus is that the pathogenesis involves damage occurring to the bladder epithelium by a primary insult
score should be used for this purpose in patients with BPS. It may also be used in order to monitor the response to any treatment.
Further Investigations
These may be necessary. The levels of evidence and their grades of recommendation are summarized in Table 1. Potassium testing this test works on the principle that these patients have increased 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 patient is asked to rank their urgency and pain on a 6-point analogue scale. The bladder is then drained and a 0.4-M potassium chloride solution is instilled. Once again, patients are asked to rank their sense of urgency and pain on the same 6-point scale. A positive test is one that elicits pain and provocation of symptoms. Whilst this test has not been shown to be of any clinical value and is not really used in the diagnostic algorithm of these patients, it may have some prognostic value in being able to predict
Laboratory testing a urinary dipstick and urinalysis for culture, and sensitivity and cytology are essential initial investigations. Specific testing for Ureaplasma urelyticum , Mycoplasma hominis , and Chlamydia may be helpful in some patients. These initial investigations may help exclude patients with lower urinary tract symptoms secondary to infection and may help to identify the necessary diagnostic and treatment pathway that needs to be followed.
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response to treatment. Further studies are needed to fully evaluate the potential use of this test. Urodynamics urodynamic studies are not mandatory and are not recommended on a routine basis. However, they may be very useful in order to exclude other conditions like detrusor overactivity, particularly in patients presenting with confusing symptoms. Cystoscopy cystoscopy with or without hydrodistension is considered an optional investigation, although it is mandatory in all patients presenting with haematuria. Classical features include glomerulations (described as punctuate petechial haemorrhages occurring after hydrodistension) and Hunners ulcers (patches of red mucosa exhibiting small vessels radiating to a central pale scar). However, cystoscopic findings do not generally correlate with the degree of symptoms exhibited, although the presence of a Hunners lesion is usually associated with generalized body pain and urinary urgency. There has been a great variation in the degree of hydrodistension. The European Society for the Study of PBS/IC has therefore suggested a standardized procedure for cystoscopy and hydrodistension. A rigid cystoscope is preferred to facilitate taking of adequate biopsies. Glycine or corresponding filling fluid should be used to allow for coagulation after biopsies. Infusion height should be approximately 80 cm above the symphysis pubis. A dripping chamber is used and the bladder is filled until fluid dribbling stops. If necessary a digital block is applied around the urethra to prevent leakage. Pre-distension inspection includes observation for radiating vessels, coagulum or fibrin deposits, white spots, hyperaemia, oedema, cracks, scars or any other mucosal changes. Continuous inspection while filling the bladder is advised. When maximum capacity is reached, the distension is maintained for 3 minutes. The bladder is emptied and the col-
Table 2. Levels of evidence and grades of recommendation for conservative therapy
Treatment Behavioural modification Physical therapy Stress reduction Dietary modification
Level of evidence Grade of recommendation 3 3 4 4 C C C C
our of the fluid checked for the degree of bleeding. The total volume drained is the measured maximum bladder capacity. During a second filling, the bladder is filled to approximately one-third to two-thirds of the bladder capacity to achieve optimal vision for inspection and biopsies. The bladder should not be filled to maximum capacity or distended again to avoid further provocation of changes with doubtful reproducibility.
Other Investigations
Biomarkers in a quest to develop a non-invasive diagnostic test for these patients, a number of biomarkers have been studied. These include tryptase, urinary histamine, IL-6 and, more recently, antiproliferative factor. Antiproliferative factor has been extensively studied and is shown to be increased in patients with documented BPS and may therefore be used as a potential biomarker. However, whilst it has both a high specificity (90.6%) and a high sensitivity (91.4%) for BPS in order to be an effective biomarker, it also needs to be reproducible in other laboratories. It has as yet not been replicated and the biological assay has not been proven for commercial use. The search for an adequate biomarker continues.
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Table 3. Levels of evidence and grades of recommendation for medical therapy Treatment Analgesics (see text) Amitriptyline Cimetidine Gabapentin Sodium pentosanpolysulfate Hydroxyzine Antibiotics Level of evidence 4 2 3 4 1 Recommendation C B C C D
training. There are no associated side effects. It is thought to be particularly useful in patients who complain of frequency and urgency in addition to bladder pain, and there have been reports of up to 50% of patients showing improvement. Physical therapy pelvic floor biofeedback and soft tissue massage may stimulate relaxation of pelvic floor muscles and can therefore reduce pelvic pain. This therapy tends to work better in patients who are highly motivated and who also have associated symptoms of urinary frequency and urgency. In addition, it does not carry any side effects. 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-
1 4
D D
Treatment
A combination of the lack of definitive diagnostic tests and standardized clinical criteria make BPS a difficult condition to treat. The mainstay of treatment is targeted at trying to obtain symptomatic relief, and over the years a variety of different forms of treatment have been tried. These can be broadly divided into conservative measures, oral medication, intravesical therapies, neuromodulation, and surgery.
Conservative Measures
vised have included taking regular exercise, trying to work shorter hours, and trying to create a less stressful home environment. Furthermore, a number of patient education and support groups are available, and patients are encouraged to take part in these. Dietary manipulation some foods are thought to exacerbate symptoms. These generally include caffeine-based products (tea, coffee, chocolate), fizzy drinks, citrus fruits and juices, alcohol, spicy foods, and acidic foods like, for example, tomatoes. The influence of these foods is very variable, and the general consensus is not to put patients on a strict diet but to advise them to experiment with different foods and try to find out which foods tend to aggravate their symptoms themselves.
Medical Management
These, in combination with analgesia, form the initial management of patients presenting with BPS. Table 2 summarizes their levels of evidence and grades of recommendation. Behavioural modification this is the cornerstone of treatment for these patients. Patient motivation is essential. It includes timed voiding, controlled fluid intake (generally limited to about 1.5 L per day), bladder retraining (gradually extended voiding interval), and pelvic floor muscle
The main categories of medication used in bladder pain syndrome include analgesics, antidepressants, immunosuppressants, antihistamines, and glycosa-
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minoglycans. Table 3 summarizes their levels of evidence and grades of recommendation. 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.
Pain evaluation and adequate analgesia are fundamental to the management of painful bladder syndrome.
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 patients 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.
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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.
The patient should undergo a trial of opioids. The dose required needs to be calculated by careful titration. The patient should be made aware (and possibly give written consent): t hat opioids are strong drugs and associated with addiction and dependency t he opioids will normally only be prescribed from one source t he drugs will be prescribed for fixed periods of time, and a new prescription will not be available until the end of that period t he patient will be subjected to spot urine and
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 are used in much lower doses than they would be used for mood problems. They are thought to work by increasing the levels of norepinephrine and/or serotonin. Similarly, serotonin reuptake inhibitors also act by inhibiting reuptake of serotonin. However, they appear to be less effective than tricyclic antidepressants. Anticonvulsants have been used in the management of pain for many years. Although there is little evidence to show their effectiveness in managing acute pain, they are useful in managing neuropathic pain and may therefore be used to manage
G YNA ECOLOGY
some of these patients. Antihistamines the rationale behind using antihistamines for the treatment of bladder pain syndrome is the theory that mast cells releasing an increased level of histamine may be involved in the pathogenesis leading to interstitial cystitis. Both hydroxyzine and cimetidine have been used, the former being the more widely used of the two. 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 randomized controlled trial (RCT) has failed to show its efficacy. It is still used as one of the first-line treatments. Cimetidine, an H2-receptor antagonist, has also been shown to be beneficial in a small RCT and is sometimes used. Immunosuppressants cyclosporin, an immunosuppressant routinely used in organ transplantation, has shown some promising results. It is thought to act by inhibiting the activation of mast cells and T cells. Its beneficial effects only last for the duration of time patients are taking the drug. Furthermore, it is associated with multiple side effects like impairment of renal function and increased susceptibility to infection. Hence, caution must be exerted when taken long-term. Glycosaminoglycans sodium pentosanpolysulfate is a synthetic sulfated polysaccharide which theoretically works by replenishing the damaged glycosaminoglycan layer overlying the transitional epithelium in patients with BPS. In addition, it is also thought to inhibit histamine release from mast cells. It is an oral preparation and is the only drug approved by the Food and Drug Administration for symptoms associated with BPS. It is generally well tolerated with few side effects (gastrointestinal upset, abdominal pain, and headache are the
Table 4. Levels of evidence and grades of recommendation for intravesical therapy
Treatment Dimethyl sulfoxide Hyaluronic acid Chondroitin sulfate Oxybutynin Botulinum toxin
Level of evidence 2 1 4 4 4
Recommendation B D D D D
more common ones). Its safety and clinical efficacy have been reported in several short-term RCTs. More recently, its long-term efficacy and safety were also demonstrated in a study where patients were followed up for a mean time of 2 years. Antibiotics there are conflicting reports of antibiotic use for patients with BPS. Some studies suggest that empirical treatment with doxycycline may be beneficial, while others report no longterm improvement following antibiotic treatment. At present, there is no evidence to suggest recommending antibiotics in the routine treatment of patients with BPS.
Intravesical Therapies
Intravesical treatments are widely used in the treatment of these patients. Evidence for their use is limited. Table 4 summarizes the levels of evidence and recommendations for the different intravesical therapies in use. Dimethyl sulfoxide Dimethyl sulfoxide has been used for the treatment of BPS patients for a long time. It is the only intravesical therapy approved for use in these patients by the Food and Drug Administration. Its mechanism of action is
GYNAECOLOGY
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 effective when used in combination with hyaluronic acid. Oxybutynin intravesical oxybutynin when used in combination with bladder retraining has been reported to be beneficial in some patients. Its long-term effects are however unknown. Botulinum toxin intravesical injection of botulinum toxin A may be used in cases of refractory BPS. A systematic review involving three RCTs and seven prospective studies showed that some
Treatment Hydrodistension Ulcer resection Cystoplasty Urinary diversion cystectomy
Level of evidence 3 3 3 3
Recommendation C C C C
not fully understood, although it is thought to act by inhibition of mast cell activation, hence reducing inflammation. Some small studies have shown its beneficial effect. It is instilled weekly for 68 weeks. Treatment is then suspended until symptoms recur. It is thought to have limited side effects, although its long-term effects are unknown.
improvement in eight of the studies. A meta-analysis could not be performed due to the heterogeneity of reported outcomes. There was a trend towards short-term benefit, but the systematic review concluded that more robust evidence from further welldesigned trials is needed.
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 therapy approved for use in... patients by the Food and Drug Administration
volves the implantation of a permanent electrode to stimulate S3 or S4 nerve roots. Several studies have shown promising results with success rates after implantation ranging from 60% to 77% with follow-up ranging between 19 and 36 months. Whilst initial results appear promising, there is however currently insufficient evidence to 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 mucopolysaccharide which is thought to work by repairing the GAG layer of the bladder mucosa. Studies have not shown it to be superior to placebo, and it is thereJPOG NOV/DEC 2013 242
severely debilitating symptoms who have failed all other forms of treatment. Surgical options are listed in Table 5. Hydrodistension this technique is used
G YNA ECOLOGY
both for diagnostic purposes and for treatment of BPS. Most studies reported are retrospective and uncontrolled. Poor results are reported in the more recent studies with symptomatic relief obtained in only a small proportion of patients for a short 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 23 months. Transurethral resection, coagulation, or laser ablation of Hunners 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 bladders 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.
Practice points
Painful bladder syndrome is a chronic debilitating condition that is difficult to treat. Its aetiology and pathogenesis are largely unknown, although mast cells and destruction of the glycosaminoglycan layer in the bladder are thought to play an essential role. It is generally a diagnosis of exclusion. Cystoscopy may show glomerulations and a Hunners 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.
CONCLUSION
Bladder pain syndrome is a chronic debilitating clinical condition that is still poorly understood. It is thought to have variable aetiology and a diverse clinical presentation. It is therefore a difficult condition to treat, with limited effective treatment options.
Urodyn 2002;21:167. Van de Merwe J, Nordling J, Bouchelouche K, et al. Diagnostic criteria, classication, 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;4:18441857. Hanno P, Lin A, Nordling J, et al. Bladder pain syndrome international consultation on incontinence. Neurourol Urodyn 2010;29:191198. 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;171:21382141. Parsons CL. Bladder surface glycosaminoglycan: efcient mechanism of environmental adaptation. Urology 1986;27:9. Al-Zahrani AA, Gajewski JB. Long term efcacy and tolerability of pentosan polysulfate sodium in the treatment of painful bladder syndrome. Can Urol Assoc J Apr 2011;5:113118. 2012 Elsevier Ltd. Initially published in Obstetrics, Gynaecology and Reproductive Medicine 2012;22(2):4449.
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 Kings College Hospital, London, UK. Dudley Robinson is a Consultant Urogynaecologist at Kings College Hospital, London, UK. Linda Cardozo is Professor of Urogynaecology at Kings College Hospital, London, UK.
IN PRACTICE I In nP 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 patients voice broke recently. The lesion is not symptomatic but it often gets caught on his collar.
What is the diagnosis of this enlarging lesion occurring on a 13-year-old boys neck?
(Answers on p. 254)
Figure 1. The lesion occurring on the patients neck, which has recently enlarged and become more prominent.
Clinical Case
Rectal Bleeding in Pregnancy: Dont Assume Its 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)
10th International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Outreach Course, Singapore
in conjunction with 5th Scientic Congress of the College of Obstetricians & Gynaecologists, Singapore (COGS)
4-6th May 2014

Rafes City Convention Centre, Singapore
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College of Obstetricians & Gynaecologists, Singapore Academy of Medicine, Singapore 81 Kim Keat Road, #11-00 NKF Centre Singapore 328836 DID: (65) 6593 7868 Fax: (65) 6593 7880 E-mail: liszt_jimenez@ams.edu.sg / yvonne_poon@ams.edu.sg
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The 6th Child Health Annual Scientiic Meeting Indonesian Pediatric Society
Long term Outcome Growth and Development Snapshot of Allergic Children
Dr. Sumadiono, Sp.A(K)

FK Universitas Gajah Mada RSU. Sardjito - Yogyakarta
DR. Dr. Ahmad Suryawan, Sp.A(K)

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 analaksis, 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 sik pada pasien alergi merupakan pendekatan lini pertama. Sedangkan untuk memastikan diagnosis, dilakukan pemeriksaan IgE mediated (skin prick test/SPT, dan IgE spesik 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 spesik 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 utikason sebagai terapi asma ringan sampai sedang pada anak, menyebabkan penurunan kecepatan pertumbuhan linier masing-masing sebesar 1,51 cm / tahun dan 0,43 cm / tahun. Sedangkan studi meta-analisis lain, oleh Allen DB dkk, membandingkan kortikosteroid inhalasi beclomethasone dipropionate dan oral dan hasilnya menunjukkan inhalasi beclomethasone dipropionate tidak berkaitan dengan penurunan tinggi badan liner. Baik beclomethasone dosis tinggi maupun rendah pada anak dengan alergi tingkat rendah maupun tinggi. Studi Allen ini akhirnya menyimpulkan bahwa secara statistik tidak terbukti adanya keterkaitan antara beclomethasone dipropionate dosis tinggi dan terapi jangka panjang yang diberikan pada pasien asma berat. (lihat grak 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 siologis 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
Grak 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 Prole, Adolescent Edition) dan hasilnya anak-anak dengan asma akan mengalami persepsi kesejahteraan yang lebih rendah, lebih banyak pembatasan sik, namun tidak mempengaruhi prestasi akademik maupun prestasi dalam pekerjaan. Skor perubahan perilaku dapat digunakan sebagai prediktor yang baik untuk memprediksi apakah anak yang mengalami dermatitis atopi akan berkembang menjadi asma (OR adjusted 1.15 ; 95% CI 1.02-1.29). Dimasa mendatang perlu dibangun suatu pondasi status kesehatan bagi anak-anak dengan alergi dan merangkul berbagai disiplin ilmu dalam suatu kerangka kerja. Dengan demikian, kualitas hidup anak akan meningkat. Selain itu, perlu diterapkan upaya preventif dan intervensi alergi jangka panjang maupun jangka pendek, dan pentingnya diadakan suatu registrasi/registry. Penelitian lanjut diperlukan untuk mengurangi miss-diagnosis dan terapan manajemen yang tepat berdasarkan rekomendasi IDAI. Salah satu langkah wawasan kedepan yang kini telah dilakukan adalah diluncurkannya revisi rekomendasi diagnosis, tata laksana alergi susu sapi 2013. Kesimpulan o Alergi pada anak berpengaruh pada tumbuh kembang dan untuk penanganan yang komprehensif perlu melibatkan disiplin ilmu kesehatan anak lainnya. o Untuk meningkatkan kualitas hidup anak dengan alergi perlu dibuat suatu pondasi dari berbagai disiplin ilmu dan kerangka kerja yang kuat.
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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.
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.
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.
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 dened in the footnotes.
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.
Language and Style

British spelling is used. Systme 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 specic brand/trade name of a drug is directly relevant to the discussion.
Thesis:
5. King L. Modern Literary Apparitions and Their Mind-Altering Effects [masters thesis]. Evanston, Ill: Northwestern University; 1994.
PA EDIA TRICS
PEER REVIEWED
Chronic Fatigue Syndrome in Imaging Paediatric Children and Brain Young People Tumours
Carrie Mackenzie, MBChB, FRCPCH, DCCH, MD; MMed Alison Wray, BA, MPhil CPsychol Tang Phua 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.
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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 persons 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
The fact that the terminology associated with this condition has created such controversy over a number of years indicates the difficulties inherent in labelling such a heterogeneous group of individuals who present with a wide range of physical and emotional symptoms. However, the persisting and disabling fatigue universal in this group of children and young people has lead to our team favouring the use of the term chronic fatigue syndrome . We believe this reduces confusion and assists in acceptance of the diagnosis when used in conjunction with a sympathetic explanation of the very variable nature of the condition, which includes both physical and psychological symptoms. The term favoured and adopted by the Royal College of Paediatrics and Child Health is CFS/ME, but in our experience the term ME carries with it a much more physical or medical basis which patients and carers often confuse with conditions such as multiple sclerosis. Moreover, there are still those who believe that
tional somatic disorders and overlap with chronic pain syndromes. In making the diagnosis, it is crucial to also demedicalize the condition, drawing a line under all that has gone before in terms of investigating the constellation of presenting symptoms and reaching agreement with the affected child or young person and their carers that the way forward is by means of rehabilitation from the point they now find themselves at. Indeed if this does not happen, it may prove difficult to engage the child and family fully in a treatment programme (Table 1).
EPIDEMIOLOGY
Prevalence data for CFS are heterogeneous and confusing as a result of different study methodologies (eg, settings and diagnostic criteria) and different age limits. A number of studies report prevalence rates from 0.1% to 2% of children under 18. Most studies focus on the condition in adolescents; those reporting prevalence rates in younger children 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 understand the prevalence of CFS in the child and adolescent population. The evidence on gender remains inconclusive. Some studies report no significant gender difference, whereas others report a female excess of 2:1. Our own figures based on 176 children and young people under 16 show a ratio of two boys to every three girls.
an autoimmune process in genetically predisposed individuals, but the evidence for this does not yet exist and it seems likely that the causation is multifactorial. Various aetiological factors, such as level of exercise taken, personal and maternal psychological well being, gender, socioeconomic status, birth weight, birth order, coexistence of atopic conditions, exposure to certain viruses, school attendance, and achievement, have all been considered, but as yet their contribution, if any, remains unclear. Any hope of intervention to prevent CFS in future generations will demand a better understanding of the aetiological factors at play. However, the once popular stereotypical picture of the affected individual being female, highly intelligent, and high achieving is not borne out by our experience.
PATHOLOGY AND PATHOGENESIS

There has been a plethora of research into CFS, but the very wide and varied nature of the hypotheses being pursued indicates the clear lack of understanding of the pathophysiological basis for this condition. Many of our children and young people can describe an intercurrent illness immediately
DIAGNOSIS AND DIFFERENTIAL prior to the onset of their fatigue, but the exact na- DIAGNOSIS
ture of this usually relatively minor illness is often unclear and it is by no means a universal precursor. It may well be that some external trigger provokes The diagnosis of CFS relies not only on the exclusion of other pathology by means of appropriately
PEER REViEWED
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 presentation of symptom clusters shared by other children and young people with the condition in addition to persistent and disabling fatigue. These symptoms may classically include malaise, sleep disorder, headache, dizziness, poor temperature control, abdominal pain, nausea, anorexia, sore throat, tender lymphadenopathy, arthralgia, myalgia, and cognitive difficulties such as poor short-term memory, impaired concentration, anxiety, and low mood. Since many of these symptoms overlap with diagnoses relevant to many disciplines such as gastroenterology, rheumatology, endocrinology, neurology, infectious diseases and immunology, oncology, and haematology, as well as childhood and adolescent mental health, it is beholden upon us to ensure that appropriate paediatric subspecialists have been consulted and the necessary investigations undertaken. However, in the absence of any other disease, the history and, often, normal examination findings are key in making the diagnosis (see Table 2).
people with CFS recover and go on to achieve academic qualifications. Ninety-nine percent of young people aged 16 seen by our specialist team achieved some academic qualifications and were able to progress to the next stage of their education or training. The vast majority of children and young people will not require transition to adult CFS services. About 5% continue to have a persisting and disabling illness. I visited the clinic and was diagnosed with CFS. It was a relief to know that my debilitating symptoms had a name. After more than 9 months of feeling so terrible, someone could finally tell me what was wrong. It helped when I knew I had CFS. It was far better knowing than being left worrying or trying to guess. The fact that CFS is a heterogeneous group is
PA EDIA TRICS
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.
One aspect in the management of chronic fatigue syndrome involves establishing a good sleep hygiene.
IMPACT OF THE CONDITION

It is one of the loneliest illnesses in the world because we dont 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 didnt 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. Once children and young people and their families have gained an understanding of the condition, the basis of treatment and an optimistically realistic expectation of what the future might hold, a coordinated multidisciplinary approach to management is required in the majority of cases. Commonly, occupational therapist, physiotherapist, nurse specialing: Activity management: this is a person-centred, goal-directed approach to managing a child or young persons symptoms. It uses analysis of activity and graded activity through learning the skills of pacing to improve physical and cognitive function.
Evidence-based guidelines recommend the follow-
PEER REViEWED
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 inCFS creased very slowly depending on progress. The aim of graded exercise therapy is to increase fitness and stamina. The primary aim of management is to reestablish the child or young person in a sustainable routine and then to help them learn to self Increased rest/ reduced activity manage the condition. At the outset of treatment, this commonly involves three aspects: sleep hygiene, activity/energy management, and school liaison. 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 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 in-
Sleep Sleep disorder/ disorder/ muscle muscle weakness weakness Further rest Worsening of symptoms on exercise More inactivity Loss of control
Reduced activity
dividualized psychological therapy which incorporates two major components: the cognitive element which focuses on the identification and modification of thoughts, beliefs, and assumptions which may shape the child or young persons understanding of their condition, and the behavioural element which aims to gradually and consistently introduce a change in behaviour, eg, an increase in activity or return to school. A cognitive behaviour therapy model can include treatment of accompanying anxiety or depression and can be tailored to include involvement of the family. Graded exercise therapy: this is a structured and supervised programme of exercise agreed between doctor, therapist (usually a physiotheraJPOG NOV/DEC 2013 250
SLEEP HYGIENE
Disordered sleep patterns are commonly found in CFS including day/night reversal, interrupted sleep, insomnia, or hypersomnia. It is therefore important to establish effective and positive sleep routines which include Establishing a regular waking time Avoiding prolonged sleep and day time sleeps Always sleep at night in own bedroom and avoid use of computer/TV prior to bed Relaxation to aid falling asleep and consistent bedtime routine Melatonin and/or amitriptyline are used in some cases to support good sleep hygiene and im-
PA EDIA TRICS
prove the quality of sleep.
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 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. Increase in activity levels needs to take place gradually and be carefully monitored. We would recommend a 15% increase in activity, eg, if able to read for 30 minutes a day increase to 35 minutes. The key professional needs to be prepared to put considerable time into liaising with educational services. In our experience, this patient group needs more time for liaison than other children with a chronic illness. 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
SCHOOL LIAISON
Chronic fatigue syndrome has a negative impact on education, and many children and young people are unable to attend full-time school. A crucial element of any successful management plan, therefore, is the establishment of a sustainable educational routine. This may involve the home tuition services initially, followed by a carefully managed plan for school re-integration. It is very likely to involve part-time school attendance. A recent study suggests that the factor most strongly associated with reduced school attendance is poor physical function. It is therefore important to ensure that the child or young person is fully engaged with treatment to improve physical function. However, it is also necessary to be aware of the cognitive impact of CFS and to ensure teachers are informed of the effects of CFS on memory, information processing, and concentration. Children with CFS are entitled to exam concessions when taking public exams if requested by a doctor.
MANAGEMENT OF SPECIFIC PHYSICAL SYMPTOMS

We find that as the child or young person learns to manage their fatigue effectively and their well being begins to improve so other troubling symptoms such as nausea, abdominal pain, myalgia, and joint pain all decrease. We therefore tend to avoid specific pharmacological agents. Gastrointestinal symptoms can be managed through diet and ensuring healthy eating and adequate fluid intake, avoiding caffeine and sugary drinks. Small frequent meals are often better than three heavy meals. Pain is managed with simple analgesics like paracetamol and/or ibuprofen. In addition, relaxation and cognitive behaviour techniques may be considered in parallel to improve pain.
ROLE OF THE FAMILY

The role of the family is crucial in helping a child or young person learn to manage this condition.
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 34 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 their expectations of what they can do together. Some parents have to stop work in order to care for their child. Support and encouragement from family members is valued by children and young people; it is therefore important that parents understand the condition fully and are involved in treatment. The package of care we have developed involves an initial period of treatment of six sessions
if mildly affected, there are still only 13 specialist teams in Britain and these are often small with limited capacity. The burden of treating this condition for the majority therefore lies with paediatricians and local therapy services. However, the specialist teams now have considerable experience of this perplexing, enigmatic condition. We would encourage professionals working with CFS to consult with a specialist team. In recognition of the scarcity of
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resources, we have been instrumental in setting up a clinical network in North and Central England for those working with CFS in order to improve knowledge and services.
make good recoveries. To me keeping positive and determination I think were really important in my recovery. I think it was really important to keep trying you go through such bad times and good times with this condition it is important to know you will get there eventually.
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.
FURTHER READING
Chalder T, Goodman R, Wessely S, Meltzer R. The epidemiology of fatigue in children. Br Med J 2003;327:654655. 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;94:752756. Davies S, Crawley E. Chronic fatigue syndrome in children aged 11 years old and younger. Arch Dis Child 2008;93:419421. Garralda M, Chalder T. Practitioner review: chronic fatigue syndrome in childhood. J Child Psychol Psychiatry 2005;46:11431151. 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;94:757762. Jelbert R, Stedmon J, Stephens A. A qualitative exploration of adolescents experience of chronic fatigue syndrome. Clin Child Psychol Psychiatry 2010;15:267283. 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;90:10201024. Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome in adults: national birth cohort study. Br Med J 2004;329:941943. 2013 Elsevier Ltd. Initially published in Paediatrics and Child Health 2013;23(1):3539.
CONCLUSION
Chronic fatigue syndrome is a disabling and serious condition affecting physical and mental function and compounded by the uncertain and unpredictable course of the illness. There is still much to understand about this enigmatic condition and both clinicians and researchers have a duty to develop understanding of the causes and course of the condition. However, it is clear that early diagnosis and appropriate management greatly facilitate recovery, and the majority of children and young people
About the Authors

Carrie Mackenzie is Consultant Paediatrician in the Childrens Hospital, Sheffield, UK. Alison Wray is Principal Clinical Psychologist in the Dept of Clinical Psychology at the Childrens Hospital, Sheffield, UK.
SGM Ananda Presinutri
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 bidobacteria di intestinal3
Zinc
mendukung proses enzimatis metabolisme4
Zat Besi
membantu mencegah anemia5 dan vitamin c membantu penyerapannya
11 Asam Amino Esensial

mendukung pertumbuhan sik6
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
SIMPOSIUM HIGHLIGHT
Diagnosis dan Tata Laksana Alergi Susu Sapi

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 specic 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 Diet eliminasi dengan formula susu terhidrolisat ekstensif minimal 2-4 minggu * Perbaikan - Uji provokasi terbuka - Berikan susu formula susu sapi dibawah pengawasan 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 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
Rujuk ke dokter spesialis anak konsultan Diet eliminasi susu sapi Formula asam amino minimal 2-4 minggu #
Tidak ada perbaikan Evaluasi diagnosis
Perbaikan Uji provokasi
Gejala (-) Diberikan protein susu sapi dan dimonitor
Gejala (+) Eliminasi protein susu sapi dari makanan selama 9-12 bulan dan minimal selama 6 bulan Ulangi uji provokasi
Tidak ada perbaikan Evaluasi diagnosis
Perbaikan 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
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
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 DIAGNOSIS

The correct diagnosis in this case is a verrucous epidermal naevus, a birthmark that occurs mainly on the trunk and limbs. These lesions may be congenital, but in over half of cases the onset is in the rst year after birth. They may spread beyond their original size with age, usually over a few months but sometimes several years. It is not unusual for them to become more raised and warty at puberty. The colour of verrucous epidermal naevi ranges from flesh-coloured to brown and black. They may occur as single or multiple grouped lesions and can have a linear or whorled distribution. On the chest, there is often a dramatic cut-off at the midline.
verrucous) and seborrhoeic keratoses, they have little in common with these lesions. Viral warts are very unlikely to have their onset in a patients first year of life or to persist unchanged for more than 2 or 3 years. It is also unusual for many viral warts to be grouped on the shoulder or neck (as in this patients case), although this presentation is not uncommon on the hands (Figure 2) and feet. Seborrhoeic keratoses generally occur from middle age, and they present as discrete lesions (Figure 3). The back is a typical location, but they can be found on any part of the skin.
associated with any other abnormalities. They can easily be differentiated from a viral wart on histopathology, but they may be confused with a seborrhoeic keratosis unless the pathologist is aware of the age of the patient.
TREATMENT
Treatment is often requested for verrucous epidermal naevi for cosmetic or functional reasons. Although there are supercial ablative procedures such as laser ablation that are effective, these lesions will often recur afterwards. Naevi that have any protruding areas or are interfering with function need complete excision to avoid recurrence.
2013 Medicine Today Pty Ltd. Initially published in Medicine Today August 2013;14(8):5859. Reprinted with permission.
CAUSE
The cause of verrucous epidermal naevi is unknown, but they are believed to arise from a post-zygotic mutation resulting in epidermal mosaicism. The lesions are harmless and have no potential for malignant transformation and, particularly when localized, are rarely
DIFFERENTIAL DIAGNOSIS
Although verrucous epidermal naevi resemble common viral warts (hence the name
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 2. True viral warts.

Figure 3. A typical seborrhoeic keratosis in a woman aged in her 60s.
IN IN P PRACT ractice iCE
II
I N REVIEWED PRACTICE PEER PEER REViEWED
Clinical Case
Rectal Bleeding in Pregnancy: Dont Assume Its Benign
Christopher S Pokorny, MB BS, FRACP, FRCP, FACG
Answer:
COMMENTARY
Possible Causes
Rectal bleeding at anytime requires consideration of the underlying cause (see the box on this page listing the possible causes). The passage of bright blood suggests a source in the rectum or sigmoid. Minor rectal bleeding as a result of small tears, fissures, or haemorrhoids is not uncommon during pregnancy as constipation develops at some stage in up to 40% of pregnant women. In most cases, constipation responds to an increase in dietary fibre and fluid intake. Iron supplements may also contribute to constipation and may need to be ceased if the constipation is severe. Anal fissures tend to be accompanied by marked pain (as opposed to haemorrhoids that are usually painless) and generally result from straining. When haemorrhoids are painful, a degree of prolapse, thrombosis, or strangulation may be present. A number of factors are associated with the development of haemorrhoids during pregnancy. These include mechanical compression of veins because of the enlarging uterus, straining as a result of worsening constipation, and hormone-related vascular changes.
2 1
given the duration of her symptoms and the intermittent nature of her rectal bleeding. A rapid onset of symptoms, particularly in the presence of nausea, vomiting, abdominal pain, and fever does, however, raise the possibility of an infectious cause. In such instances, stool microscopy and culture should be requested. It is important to remember that parasitic infections such as Giardia do not cause rectal bleeding. Inflammatory bowel disease (eg, ulcerative proctitis) can occur for the first time during pregnancy, especially in the first trimester, and Angelas symptoms are in keeping with this. 3 Apart from urgency, mucus may be passed as well as blood, and the stool volume is generally small in such cases. Specific questioning about extraintestinal manifestations is sometimes of help for example, peripheral arthritis, low back pain, red eyes (episcleritis, uvei-
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
tis), erythema nodosum, and aphthous ulcers. There may also be a family history of inflammatory bowel disease. 4 Given Angelas age, a rectal or distal
In
Angelas 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 Angelas case, particularly
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 Angelas 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 disease, or ischaemic colitis are much less likely. In addition, ischaemic colitis generally occurs in the context of significant vascular disease or atrial fibrillation. However, these conditions need to be considered in the differential diagnoses, although rectal bleeding from more proximal malignant lesions tends to be dark in colour and diverticular bleeding usually is profuse. include a full blood count, but anaemia is not unusual in pregnancy. There is absolutely no point in faecal occult blood testing as this is only of potential benefit in In Angelas case, flexible sigmoidoscopy was performed and sadly revealed a rectal cancer (see Figure). Although rectal bleeding is not uncommon in pregnancy, this case highlights the need to investigate appropriately. However, in the vast majority of cases the cause will be benign.
2012 Medicine Today Pty Ltd. Initially published in Medicine Today June 2012;13(6):7374. Reprinted with permission.
Although rectal bleeding is not uncommon in pregnancy, this case highlights
Investigations
Gentle digital examination of the rectum with careful inspection of the perianal area should be performed at the time of consultation. Initial investigation should
the need to investigate appropriately
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 inflammatory bowel disease in pregnancy. Am J Gastroenterol 1985;80:365. 4. Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996;334:841848. 5. Cappell MS. Sedation and analgesia for gastrointestinal endoscopy during pregnancy. Gastrointest Endosc Clin N Am 2006;16:131.
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 cows 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.

P 5 SK
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
Gestational diabetes mellitus (GDM) is a controversial subject in obstetrics. It is defined by the National Diabetes Data Group in 1985 as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy.1 The first case report of GDM appeared in 1824, which described a mother with thirst, polyuria and glycosuria and the death of a macrosomic infant from shoulder impaction. Historically, there has been a lot of controversy over most aspects of GDM, including screening, diagnosis, risks, treatment, and the relationship between GDM and type II diabetes mellitus. Recently, several major studies have substantially resolved these areas of controversy, eg, the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study,2 the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), and the Maternal-Fetal
3
studied (eg, age, body build, ethnic origins). The United States reported an incidence of 38%, 5 with a rising trend in more recent publications. The United Kingdom reported an incidence of 2% 6 and Canada described 3.8%. 7 In Hong Kong, a study 8 performed in a university teaching hospital, Queen Mary Hospital, showed that of the 16,383 women managed in the period 19982001, the prevalence of GDM increased from 1.3% ( 20 years), 2.5% (2024 years), 6.2% (2529 years), 10.3% (3034 years), 21.7% (3539 years), and 31.9% ( 40 years), respectively, from the youngest to the oldest cohort ( P < 0.001). Another study performed in a different university
9
Diagnosis and treatment of gestational diabetes can help reduce the risk of many adverse pregnancy outcomes due to this condition.
of diabetes after pregnancy. Following the publication of the HAPO study, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) established a new set of diagnostic guidelines (Figure 1).10 As more and more women suffer from diabetes before pregnancy, the IADPSG recommends screening women with risk factors at the booking visit by using random plasma glucose, fasting plasma glucose, or glycated haemoglobin A1c paired with diagnostic thresholds, according to the current guidelines for the diagnosis of pre-existing diabetes. Moreover, GDM can be diagnosed at the booking visit with a fasting plasma glucose between 5.1 mmol/L and 7.0 mmol/L, hence lowering the thresholds of GDM in most guidelines. They also recommend that all women who do not have diabetes should be screened
teaching hospital in Hong Kong, Prince of Wales Hospital, found that the prevalence of GDM was 14.2%. In our hospital, a regional hospital with around 6,000 deliveries per year, the incidences of GDM in 2008 and 2009 were 13.2% and 14.2%, respectively.
Medicine Units Network treatment of mild gestational diabetes (MFMUN-GDM) clin4
ical trials, which will be discussed further in this article.
SCREENING AND DIAGNOSIS

The diagnostic criteria of GDM were ini-
INCIDENCE
The reported incidence of GDM
tially established more than 40 years ago, and these criteria were not designed to identify pregnant women at increased risk for adverse perinatal outcomes but rather women at higher risk for the development
varies with diagnostic criteria and characteristics of the population being
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
Normal
GDM if FG 5.1 mmol/L, but < 7.0 mmol/L
75-g OGTT at 2428 weeks
DM if FG 7.0 mmol/L
GDM if FG 5.1 mmol/L, or 1hG 10.0 mmol/L, or 2hG 8.5 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 2428 weeks gestation with the 75-g oral glucose tolerance test. In contrast to the World Health Organization criteria which use an abnormal fasting or 2-hour plasma glucose for the diagnosis of diabetes, the IADPSG suggests that an abnormal 1-hour plasma glucose is adequate for the diagnosis. They also take into account the continuous association between maternal blood glucose concentrations and adverse perinatal outcomes as seen in HAPO. The agreed thresholds represent an odds ratio of 1.75 for birth weight, cord C-peptide, and fetal body weight being greater than the 90th percentile, relative to the odds of those outcomes at mean glucose values.
Applying this system of testing and diagnostic criteria will probably double the incidence of GDM.11
plasma glucose 8.9 mmol/L. It showed an unambiguous, linear, positive association between maternal glycaemia and adverse pregnancy outcomes (eg, birth weight > 90th percentile, caesarean section, cord plasma C-peptide level reflec-
RISKS
The HAPO study was a 10-year, prospec2
tive of fetal hyperinsulinemia, neonatal hypoglycaemia, excess neonatal adiposity, shoulder dystocia or birth injury, neonatal hyperbilirubinaemia,pre-eclampsia). 12,13 The risk factors and health risks of GDM are summarized in Tables 1 and 2.
tive, blinded, multicentre study, which enrolled 25,505 pregnant women. It aimed at studying the associations between the risks of adverse pregnancy outcomes and the degrees of maternal glucose intolerance less severe than overt diabetes. Exclusion criteria include fasting plasma glucose > 5.8 mmol/L, or the 2-hour plasma glucose 11.2 mmol/L, or a random
TREATMENT
The ACHOIS 3 and the MFMUN-GDM 4
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, 0.140.75; 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, 0.721.07; P = 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.
Table 1. Risks factors of gestational diabetesa
Risk factors
Overweight Obesity Severe obesity Prior gestational diabetes Prior macrosomic infant Maternal age greater than 25 y Maternal age greater than 35 y Multiple gestation South East Asian Hispanic African American Polycystic ovarian syndrome Parent with diabetes Sibling with diabetes Periodontal disease Low maternal birth weight
a b
Odds ratio
2 3.7 7 23 3.3 1.4 2.3 2.2 7.6 2.4 1.8 2.9 3.2 7.1 2.6 1.9
b b b b
References
Torloni et al, Chu et al Torloni et al, Chu et al Torloni et al, Chu et al McGuire et al McGuire et al Cypryk et al Xiong et al Rauh-Hain et al Dornhorst et al Dooley et al Dooley et al Toulis et al Kim et al Kim et al Xiong et al Seghieri et al
Reprinted from Obstetrics and Gynecology Clinics of North America, 37(2), Pridjian et al, Update on gestational diabetes, 255267, 2010, with permission from Elsevier. Relative risk compared with white race.
Table 2. Health risks of gestational diabetesa Mother Birth trauma Increased caesarean delivery Pre-eclampsia/ Gestational hypertension Type 2 diabetes Metabolic syndrome Fetus Hyperinsulinaemia Cardiomyopathy Stillbirth Newborn Respiratory distress syndrome Hypoglycaemia Hypocalcaemia Child/Adult Obesity Type 2 diabetes Metabolic syndrome
DIETARY MODIFICATION
The scientific evidence for making nutritional recommendations for women with
Large for gestational age/ macrosomia Birth trauma
Hypomagnesaemia Hyperviscosity Polycythaemia Hyperbilirubinaemia Cardiomyopathy
a Reprinted from Obstetrics and Gynecology Clinics of North America, 37(2), Pridjian et al, Update on gestational diabetes, 255267, 2010, with permission from Elsevier.
GDM is limited. Referral to nutritional counselling should ideally occur within 48 hours of the diagnosis of GDM. The
15
study showed that in women with GDM, carbohydrate restriction to < 42% led to fewer LGA infants, reduced rates of caesarean sections for macrosomia and cephalopelvic disproportion, and reduced need for insulin treatment, compared with a higher carbohydrate content (4550%).21 Few studies have focused on the benefit of carbohydrates with a low glycaemic index (GI), which is a measure of how much each gram of available carbohydrate in the food increasing a persons blood glucose level following consumption of the food, relative to consumption of glucose. Food with carbohydrates that break down quickly during digestion and release glucose rapidly into the bloodstream tend to have a high GI, while food with carbohydrates that break down more slowly, releasing glucose more gradually into the bloodstream, tend to have a low GI. There have been no randomized studies with sufficient sample size to draw a conclusion on the benefits of carbohydrates with a low GI. Increased dietary fibre intake is traditionally recommended for women with GDM, as it may reduce the postprandial blood glucose. But no proof exists that extra dietary fibre intake is beneficial in these women.
on Gestational Diabetes recommends the following blood glucose concentrations: fasting plasma glucose, 5.05.5 mmol/L; 1-hour postprandial plasma glucose, < 7.8 mmol/L; and 2-hour postprandial plasma glucose, < 6.77.1 mmol/L.22 The NICE guidelines19 recommend drug treatment if diet and exercise cannot control the blood glucose for 12 weeks, or if ultrasound shows possible fetal macrosomia (abdominal circumference above the 70th percentile) at diagnosis.
first meeting with a professional dietitian should be arranged within 1 week of the referral, and a total of three visits are suggested. 16 Throughout the pregnancy, the diet should be adjusted and individualized to meet the patients food choice, financial needs, culture, habits, weight gain, physical activity, and blood glucose goals. The Dietary Reference Intakes recommends no increase in calories for the first trimester but an additional 340 kcal/ day during the second trimester and 452 kcal/day during the third trimester. 17 In obese women with GDM, a 30% caloric restriction help to avoid ketonuria or an increase in free fatty acids,18 while improving glycaemic control. A more severe caloric restriction is not recommended. The National Institute for Clinical Excellence (NICE) guidelines in the UK recom19
Oral Hypoglycaemic Agents

Glyburide (or glibenclamide) is a second-generation sulfonylurea. It binds to receptors that are associated with the adenosine triphosphate-dependent potassium channels of pancreatic cells to increase insulin secretion and insulin sensitivity of peripheral tissues. The onset of action takes approximately 1 hour with the peak level at 4 hours after intake. Studies on the placental transfer of glyburide are contradictory. In vitro studies showed minimal placental transfer, but the fetal response to various dosages of glyburide is not completely known. 23 A meta-analysis by Moretti et al24 reported no differences between the insulin and glyburide groups with regard to birthweight, LGA/ macrosomia, gestation at delivery, admissions to neonatal units, or neonatal hypoglycaemia. Metformin belongs to the biguanide group. It inhibits hepatic gluconeogenesis and glucose absorption, and stimulates glucose uptake in peripheral tissues. The onset of action takes approximately 1 hour
mend that women with GDM whose prepregnancy body mass index is above 27 kg/m should restrict caloric intake (to 25
2
kcal/kg/day or less) and engage in moderate exercise (of at least 30 minutes daily). The goal of fractionating food intake into three meals and two to three snacks in between meals is to distribute the glucose intake throughout the day in order to control the postprandial glucose, while at the same time maintaining a satisfactory nutritional intake. The evening snack decreases the night-time ketogenesis related to fasting. Generally, 4045% of the calories in the daily diet come from carbohydrates, but this must be individualized.
20
PHARMACOTHERAPY
Drug treatment is necessary in 720% of women with GDM when, despite dietary modification, there is insufficient glucose control, high levels of fasting glucose, suboptimal weight gain (due to caloric restriction), or persistent hunger sensation. The Fifth International Workshop-Conference
One
with the peak level at 24 hours after intake. Metformin does cross the placenta. Because it acts as an insulin sensitizer in peripheral tissues rather than as an insulin analogue, it is believed that fetal metabolism is less likely to be affected. The
25
the standard treatment for diabetes, especially when diet and exercise fail to control the maternal blood glucose and there is no risk of placental transfer of insulin to the fetus. Insulin requirements are not constant throughout the day: it is low at night with a sharp rise at dawn, followed by a gradual decrease during the rest of the day. Women in the first trimester are at risk of hypoglycaemic events because of emesis, and blood glucose levels should be closely monitored with appropriate adjustment of insulin. After the second trimester, insulin requirements rise. During labour, shortacting insulin should be used to achieve optimal glucose levels of between 4 and 8 mmol/L and to prevent neonatal hypoglycaemia. After delivery, glycaemic control must be relaxed to prevent maternal hypoglycaemia, especially in breastfeeding women. Insulin therapy should be stopped in women who have not taken insulin before pregnancy, while those women who are taking insulin for pre-existing diabetes should resume their pre-pregnant insulin dosages. There are two types of insulin: human insulin and insulin analogue. The short-acting insulin analogue aspart has been shown to be safe in pregnancy in a randomized trial and has been registered
28
ANTENATAL MANAGEMENT
Once GDM is diagnosed, visits to health carers or dietitians by the pregnant women should be made at least every 12 weeks and more frequently if complications occur. There is no consensus on the frequency and timing of antenatal surveillance tests in women with GDM. It is crucial to manage women, who do not comply with advice, require drugs, have macrosomic or growth-restricted fetuses, or have other obstetric complications, as though they had pre-existing diabetes and to begin close antenatal monitoring (eg, the NICE guidelines19 suggest anomaly scan, echocardiography, growth scan at 28, 32 and 36 weeks gestation, tests of fetal well-being after 38 weeks gestation). History review, blood pressure measurement, and urine albumin testing to diagnose pre-eclampsia are also essential at every visit. In an attempt to prevent macrosomia and to guide the treatment, a randomized trial 29 compared ultrasound performed at 32 weeks gestation with ultrasound at both 28 and 32 weeks gestation. The rate of macrosomia was significantly higher in the group assessed only at 32 weeks (71.1% vs 33.3%; P < 0.005). The mode and timing of delivery of women with GDM is controversial because sufficient data are lacking to make a recommendation. Induction of labour in women with insulin-treated diabetes at 38 weeks gestation is intended to reduce the risk of stillbirth. One study 30 failed to detect a benefit to expectant management beyond 38 weeks gestation, as the rate of caesarJPOG NOV/DEC 2013 261
Metformin in Gestational Diabetes (MiG) trial of 751 women showed similar peri26
natal complications in both the metformin and insulin groups, with better acceptability in the metformin group; but subsequent insulin was indicated in 46.3% of women taking metformin. Long-term safety data on infants whose mothers were treated with glyburide or metformin are lacking. Early neonatal complications, such as hypoglycaemia, are not common and do not differ very much from those resulting from insulin therapy. When counselling patients, health carers can reassure them that the rates of congenital malformations with the use of oral hypoglycaemic agents and insulin do not differ. The maternal glucose control (fasting blood glucose and 2-hour postprandial) by oral hypoglycaemic agents and insulin is also comparable. Acarbose, an alpha glucosidase inhibitor, has been used less often. Preliminary studies showed that it was effective in decreasing postprandial hyperglycaemia in GDM, but its use has been limited by its side effects, like abdominal cramping. Further studies are needed to better
27
for this indication. The short-acting insulin analogue lispro has also been shown to be safe in observational studies. However, there is no safety data available on the long-acting insulin analogues detemir and glargine; both are prescribed offlabel. Therefore, long-acting human insulin should be used instead.
evaluate the potential placental transfer of this drug, as small amounts of acarbose can be absorbed into the bloodstream.
Insulin
Traditionally, insulin has been regarded as
ean delivery was not reduced but rather the rates of LGA infants and shoulder dystocia were increased. For uncomplicated GDM, no strong evidence exists to support earlier induction of labour, which was also confirmed by a Cochrane review of randomized trials on elective delivery in women with diabetes.
31
POSTPARTUM MANAGEMENT
Approximately 50% of women with GDM will develop type 2 diabetes within 5 to 10 years.
32
varies from annual to triennial. Advice on postpartum weight loss, which may help reduce the occurrence of type 2 diabetes mellitus, includes breastfeeding, dietary modification, and exercising for at least 150 minutes every week.35
An Italian study
33
showed
that GDM is a stronger predictor of later metabolic syndrome after adjustments for pre-pregnancy body mass index and age. In a large 4- to 23-year follow-up study in Denmark, 68% of the 481 women with previously diagnosed GDM had impaired glucose regulation, 59% had elevated fasting serum insulin, 54% had central obesity, 28% had hypertension, and 35% had dyslipidemia, presenting with higher triglycerides levels and lower high-density lipoprotein cholesterol levels compared with the control group.
34
Prophylactic pre-labour caesarean section using estimated fetal weight by ultrasound has been proposed but is controversial. Recommendations concerning the lower estimated fetal weight thresholds for prophylactic caesarean section vary from 4,000 to 4,500 g. Both the American College of Obstetricians and Gynecologists and the Royal College of Obstetricians and Gynaecologists recommend prophylactic caesarean section if the estimated fetal weight is > 4,500 g. Another issue is the inaccuracy of ultrasound in estimating fetal weight, which leads to an increase in unnecessary caesarean deliveries and, therefore, caesarean-associated maternal and fetal morbidities, and additional health-care costs.
CONCLUSION
Without further cost analyses and confirmation of results from randomized intervention trials, the IADPSG guidelines are unlikely to be widely adopted worldwide. Without a uniform diagnosis, research on risks and management is difficult. Women with GDM should be treated with dietary modification, appropriate exercise, and drugs, if necessary. Oral hypoglycaemic agents (eg, glyburide, metformin) are as useful as but not better than insulin alone in terms of early pregnancy outcomes. About the Authors
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.
Diagnostic testing for diabetes is appropriate 6 weeks after delivery. It is unclear whether a traditional 2-hour 75-g oral glucose tolerance test or fasting plasma glucose test may be more useful at this time. The frequency of follow-up blood glucose tests for early detection of impaired glucose tolerance or diabetes
References
1. National Diabetes Data Group. Classication and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:10391057. 2. Metzger BE, Lowe LP, Dyer AR, et al; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:19912002. 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;352:24772486. 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;361:13391348. 5. Coustan DR. Gestational diabetes. In: Diabetes in America. 2nd ed. NIH Publication No. 951468. Bethesda, MD: National Diabetes Data Group, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases; 1995:703717. 6. Scott DA, Loveman E, McIntyre L, Waugh N. Screening for gestational diabetes: a systematic review and economic evaluation. Health Technol Assess 2002;6:1161. 7. Grifn 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;29:948949. 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 classication of hyperglycemia in pregnancy. Diabetes Care 2010;33:676682. 11. Moses RG. New consensus criteria for GDM: problem solved or Pandoras box? Diabetes Care 2010;33:690691. 12. HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes 2009;58:453459. 13. HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol 2010;202:255.e1255.e7. 14. Pridjian G, Benjamin TD. Update on gestational diabetes. Obstet Gynecol Clin North Am 2010;37:255267. 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;106:14261433. 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.
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
Jawab pertanyaan di bawah ini dengan Benar atau Salah
1. Gestational diabetes mellitus (GDM) can present in the rst 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 signicantly 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.
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JPOG 2013 Annual Index

Section First Author Issue Page
DERMaToLogY
Adolescent, aetiology, differential diagnosis, verrucous epidermal naevus Aetiology, anti-bacterial agents, antiviral agents, child, differential diagnosis, erythema multiforme In Practice In Practice Fischer G Fischer G Nov/Dec Sep/Oct 244 206
GYNaECoLogY
Adenomyosis, endometrial ablation techniques, endometrial hyperplasia, endometrial neoplasms, leiomyoma, metrorrhagia, perimenopause, polyps, progestins, tranexamic acid Adjuvant chemotherapy, CA-125 antigen, gynaecological surgical procedures, ovarian neoplasms, palliative care Aetiology, analgesics, cystoscopy, diagnosis, interstitial cystitis Bone density conservation agents, hormone replacement therapy, postmenopausal osteoporosis, primary prevention, secondary prevention, selective oestrogen receptor modulators Complementary therapies, drug therapy, hormone replacement therapy, hot ushes, menopause Infertility, ovulation induction, polycystic ovary syndrome Clinical Review Clinical Review Clinical Review Clinical Review CME Clinical Review Eden J Taylor SE Vella M Daroszewska A Ang SB Kini S Mar/Apr Jul/Aug Nov/Dec Sep/Oct Jan/Feb May/Jun 74 155 232 181 37 100
OBSTETRICS
Aetiology, diagnosis, haemorrhage, pregnancy, rectal neoplasms, rectum Carbetocin, caesarean section, drug toxicity, oxytocics, pharmacology, postpartum haemorrhage Chronic renal insufciency, kidney transplantation, pregnancy, renal dialysis Dietary modication, gestational diabetes, hypoglycemic agents, insulin, type 2 diabetes mellitus Eclampsia, pre-eclampsia, pregnancy-induced hypertension Ectopic pregnancy, rst pregnancy trimester, habitual abortion, hydatidiform mole, hyperemesis gravidarum, pregnancy complications, spontaneous abortion Ectopic pregnancy, imaging Fever, postpartum period, puerperal infection, sepsis, Streptococcus pyogenes Inherited blood coagulation disorders, postpartum haemorrhage, prenatal diagnosis, thrombocytopenia, thrombotic microangiopathies Krukenberg tumour, pregnancy, prognosis Obstetric labour complications, placenta accreta, placenta praevia, postpartum haemorrhage, prenatal care Prenatal diagnosis, Streptococcus agalactiae Repeat caesarean section, reproductive history, vaginal birth after caesarean In Practice Clinical Review Clinical Review CME Clinical Review Clinical Review CME Clinical Review Clinical Review Case Study Clinical Review CME CME Pokorny CS Yussof SM Hall M Chan LL McCarthy FP Pugsley H Lam SL Glackin KG Lefkou E Mohd Azri MS Jegasothy R Leung KY Yung WK Nov/Dec Sep/Oct Sep/Oct Nov/Dec Mar/Apr Jul/Aug Mar/Apr Jan/Feb Jan/Feb May/Jun May/Jun Sep/Oct Jul/Aug 244 207 195 257 49 146 81 28 15 122 93 213 169
PaEdiaTRiCs
Acute abdomen, appendicitis, children, familial intestinal malrotation, intussusception, peritonitis, vomiting Adolescent, aetiology, child, chronic fatigue syndrome, cognitive therapy, diet therapy, differential diagnosis, intrinsic sleep disorders Adolescent, child, diagnosis, infant, sleep disorders, therapy Asthma, child, respiratory sounds, tobacco smoke pollution Autistic disorder, diagnosis, pervasive child development disorders, symptom assessment Child, constipation, encopresis, infant, laxatives, toilet training Cochlear implantation, deafness, hearing aids, hearing loss, otitis media with effusion Clinical Review Clinical Review Clinical Review Clinical Review Clinical Review Clinical Review Clinical Review Makin E Mackenzie C Wong PPC Lenney W Yates K Dowling T Elloy MD Mar/Apr Nov/Dec Jan/Feb Nov/Dec May/Jun Jul/Aug Jul/Aug 61 245 5 225 112 164 137
REPRodUCTiVE MEdiCiNE
Aetiology, articial insemination, fertilization in vitro, male infertility, semen analysis CME Lee VCY May/Jun 125
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JAN/FEB 2012 Nov/Dec 2013Vol. Vol.38 39No. No.

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