Ajpp January -March 2014 by IJCP

Online Submission

IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine and Faculty Dean Harvard Medical School Group Consultant Editor

Asian Journal of

Paediatric Practice

Volume 16, No. 3, 2013

Dr Deepak Chopra Chief Editorial Advisor

Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal

FROM THE DESK OF EDITOR

Group Editor-in-Chief

Dr Veena Aggarwal

MD, Group Executive Editor Anand Gopal Bhatnagar Editorial Anchor

Swati Y Bhave

AJPP Speciality Board Chief Editor Dr Swati Y Bhave Editorial Board National Dr Alagiriswamy Parthasarathy Dr Ajay Kalra Dr K Nedunchelian Dr Yagnesh Popat Dr Chhaya Prasad Dr Atul Agarwal Dr Anoop Verma Dr Vijay Zawar Dr J S Tuteja Dr Surekha Joshi Editorial Board International Dr Professor Antonio An Tung Chuh Dr Jay E Berkelhamer Dr Neil Wigg Professor Andreas Konstantopoulos Ahmaduddin Maarij Professor Leyla Namazova-Baranova Dr Angelo Neeneo Dr Yoshikatsu Eto Dr Peter Cooper

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran, Dr Jayakar Thomas Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

FROM THE DESK OF GROUP EDITOR-IN-CHIEF 6 Duration of CPR may be a Factor in Kidsâ&#x20AC;&#x2122; Survival

KK Aggarwal

REVIEW ARTICLE 7 Pediatric Oropharyngeal Trauma: A Retrospective Study with Brief Review of Literature

Neeru Chugh, Neelima Gupta, Lakshmi Vaid

11 Role of Zinc in Pediatric Diarrhea

Chaitali Bajait, Vijay Thawani

ORIGINAL ARTICLE 16 Impact of Tonsillectomy on Quality-of-life in Children: Our Experience

Neelima Gupta, Lakshmi Vaid, PP Singh

CLINICAL STUDY

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

20 Exclusive Breastfeeding: Is Motivation the Only Issue?

M Girish, N Mujawar, V Dandge, P Pazare, K Gaikwad

Printed at SR Offset Art Printers, Chennai ÂŠ Copyright 2013 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

CASE REPORT 25 Retinoblastoma: A Curse to Childhood

Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Harpal Singh Jhagta, Prachi Jain, Manoj Gupta, Ashish Bajaj

29 Neonatal Bartter Syndrome

Meetu Rawat Gupta, Subandhu Gupta, Anand S Vasudev, RN Srivastava

32 Acute Disseminated Encephalomyelitis Presenting as Fever of Unknown Origin: Case Report

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FROM THE DESK OF EDITOR

Dr Swati Y Bhave

Chief Editor Executive Director, AACCI, (Association of Adolescent and Child Care in India) Senior Visiting Consultant Indraprastha Apollo Hospitals, New Delhi

Dear Readers I wish you all a very happy and prosperous new year 2013. Febrile illness in children younger than 36 months is common and has potentially serious consequences. With the widespread use of immunizations against Streptococcus pneumoniae and Haemophilus influenzae type b, the epidemiology of bacterial infections causing fever has changed. Although an extensive diagnostic evaluation is still recommended for neonates, lumbar puncture and chest radiography are no longer recommended for older children with fever but no other indications. With an increase in the incidence of urinary tract infections in children, urine testing is important in those with unexplained fever. Signs of a serious bacterial infection include cyanosis, poor peripheral circulation, petechial rash and inconsolability. Parental and physician concern have also been validated as indications of serious illness. Rapid testing for influenza and other viruses may help reduce the need for more invasive studies. Hospitalization and antibiotics are encouraged for infants and young children who are thought to have a serious bacterial infection. Suggested empiric antibiotics include ampicillin and gentamicin for neonates; ceftriaxone and cefotaxime for young infants; and cefixime, amoxicillin, or azithromycin for older infants. Abstracts from various journals on Zinc in health make interesting reading in the news and event section.

Dr Swati Y Bhave

Address for correspondence IJCP Group of Publications E - 219, Greater Kailash, Part - 1, New Delhi - 110 048

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

FROM THE DESK OF GROUP EDITOR-IN-CHIEF

Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, Elect IMA Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Duration of CPR may be a Factor in Kids’ Survival Some children with in-hospital cardiac arrest can benefit from longer duration of cardiopulmonary resuscitation (CPR), a study has found. In the study among survivors, neurological outcome was favorable for the majority of patients. Of the 3,419 children included in the study, 28% survived to hospital discharge and 16.6% of these survivors had CPR longer than 35 minutes, according to Renée Matos, MD, MPH, of the University of Pittsburgh School of Medicine and colleagues. A total of 60% of these survivors with longer-duration CPR achieved a favorable neurologic outcome, as reported in the study published in Jan. 21 issue of Circulation: Journal of the American Heart Association. In the mid-1990s, authorities considered pediatric CPR futile beyond 20 minutes’ duration or when more than two doses of epinephrine were provided. Even though longer-duration CPR can benefit some children, the reality is that after the first 15 minutes of CPR, survival rate declines rapidly. Survival decreased by 2.1% for every minute of chest compressions over 15 minutes. When CPR was longer than 35 minutes, those in the Surgical Cardiac category had the best survival to hospital discharge rate (25%), followed by, Medical Cardiac - 21%; General Surgical - 13%; General Medical - 10% and Trauma - 8%. (Medpage Today)

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

REVIEW ARTICLE

Pediatric Oropharyngeal Trauma: A Retrospective Study with Brief Review of Literature NEERU CHUGH*, NEELIMA GUPTA**, LAKSHMI VAIDâ&#x20AC;

ABSTRACT Background: Children often present in emergency with history of trauma in the oral cavity. This review was done to evaluate our treatment protocol and compare it with the protocol followed in the developed world. Material and methods: Retrospective review of cases of trauma to the oral cavity and oropharynx from 2006 to 2010 in a tertiary care hospital. Results: Twenty-four patients were included in the study. The average age was 4.3 years and male-to-female ratio was 3:1. Seventy-nine percent patients underwent surgical intervention. Four patients were admitted for antibiotics and observation only. Conclusion: The outcome in all patients was satisfactory. In our setting, where poor compliance is common and parents may not be vigilant enough to recognize complications, we suggest a protocol of admission and repair of the wound rather than a conservative approach advocated by western world. In our knowledge, no Indian studies are available with which we can compare our treatment protocol. Keywords: Pediatric, oropharyngeal trauma, impalement injury palate

njuries of oral cavity and oropharynx are common in pediatric patients, the common site being the soft palate. Most of the injuries occur from a fall while carrying a pointed object in mouth. Various treatment protocols have been cited in studies, ranging from no treatment, observation and conservative management to hospitalization and surgical repair of the wound. Carotid artery injury and subsequent neurological sequelae are rare but well-documented complications of penetrating injuries of lateral oropharynx in the medical literature. We planned this study with the objective of studying the epidemiology and clinical presentation of children with oropharyngeal injuries and the subsequent management approach with outcome in these patients. The evaluation was aimed at helping the care giver in formulating a management protocol for patients presenting with such injuries.

*Ex-Resident **Associate Professor â&#x20AC; Professor Dept. of ENT University College of Medical Sciences and GTB Hospital, New Delhi Address for correspondence Dr Neelima Gupta A-304, Abhyant Apartments Vasundhara Enclave, New Delhi - 96 E-mail: write2drneelima@yahoo.com

MATERIAL AND METHODS Data was collected retrospectively of all pediatric patients admitted with impalement injuries of oral cavity and oropharynx over a five year period from 2006 to 2010 at ENT department of a tertiary care hospital. Patients were evaluated for age, sex, mechanism of injury, object causing injury, site of injury, type of wound, time lag in presenting to hospital, presenting complaints, treatment received, hospital stay and postoperative course. The common presenting complaints were bleeding from the mouth after history of a fall or running against a wall with some object inside the mouth; pain in the throat, drooling and difficulty in swallowing food. The salient observations are presented in Table 1. OBSERVATIONS AND RESULTS Case records of 24 patients with injuries to oral cavity and oropharynx were reviewed. The demographic characteristics are shown in Table 1. The most common mechanism of injury was falling down while playing with an object in mouth. Majority of children were brought immediately to hospital due to bleeding from mouth. All the patients were admitted and were put on intravenous (IV) antibiotics and analgesics. The lacerations were located laterally or in midline, either at junction of hard and soft palate or involving only hard or soft palate. Only

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

REVIEW ARTICLE Table 1. Clinical Details and Management of Patients with Penetrating Injuries of Oral Cavity and Oropharynx Age zz zz

Range: 1-12 years Mean: 4.3 years

Sex zz zz

Male: 18 Female: 6

Site of injury Left: 10 zz Right: 8 zz Midline: 6 zz

Hard palate alone: 6 Soft palate alone: 11 Hard and soft palate both: 6 Buccal mucosa: 1

Objects causing injury Wooden stick: 6 Metal rod: 3 Sugarcane: 3 Flute: 2 Plastic pen: 2 Nail head: 1 Toothbrush: 3 Miscellaneous: 4 Type of wound Linear and superficial to deep: 18 Avulsion flap type: 6 Treatment Conservative management: 4 Surgical repair under GA: 19 Absconded: 1

one case in our study involved buccal mucosa injury between second and third molar. Injuries were mostly linear and superficial (75%). Twenty-five percent injuries resulted in creation of a flap of the palate. None of the injuries resulted in palatal perforation and none of them had any retained foreign bodies. None of the patients presented with or developed any neurovascular complications. Nineteen of the patients underwent surgical repair of wound under general anesthesia. Postoperative recovery was uneventful and we achieved our objective of good primary healing and restoration of function.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

DISCUSSION Palatal and lateral oropharyngeal injuries are common in children. They commonly present with pain and transient oral bleeding. Usual occurrence is due to fall during playing while carrying an object in mouth, as also observed in our study. Other mechanisms involved in injury are, direct force applied to an object held in mouth and falling onto a stationary object with mouth open.1 The result can be either a penetrating or a nonpenetrating injury. The term â&#x20AC;&#x2DC;pencil injuryâ&#x20AC;&#x2122; was coined by Bickerstaff for intraoral injuries caused by sharp objects in 1964. The mean age of our patients was 4.3 years, comparable to that of four years in a study involving review of 131 patients with oropharyngeal impalement injuries.1 Male children are injured more commonly, reflecting more outdoor activity in males; M:F ratio, (3:1, our study), (2:1),1 and (9:4).2 There was no significant site preponderance observed in our cases, as compared to higher incidence of left side (53%) involvement in a previous study.1 The common objects causing injury were wooden sticks, metal rods, sugarcane, flute and pens, etc. Wooden sticks, pens, toothbrushes, plastic toys, straws were the commonly implicated agents in other studies also.1,2 We admitted all patients and started IV antibiotics and analgesics. Surgical repair was done in 19 cases and four patients were managed conservatively. In a review of 131 cases, only 18% patients underwent surgical exploration and antibiotics were administered in 88% cases.1 In another review,2 bleeding was controlled by suturing in only one case. Surgical intervention was reserved for cases with large avulsion flap or in cases where wound exploration was required for a foreign body. Similar view is advocated in more recent reviews.3,4 Antibiotic administration is advocated if laceration is over 1-2 cm in length. Commonly these injuries heal uneventfully without complications. Complications reported include internal carotid artery thrombosis,5,6 and rarely internal jugular vein thrombosis.7 It is proposed that the internal carotid artery gets compressed between the penetrating object and the second or third vertebra leading to disruption of intima and resultant thrombosis.6 A lucid period of 3-48 hours between injury and appearance of neurologic sequelae has been reported. Signs indicative of severe injury are dysphagia, drooling and subcutaneous emphysema of the neck.6 Occurrence of torticollis, cervical tenderness or neck swelling should

REVIEW ARTICLE alert the physician. Occasionally an injury may lead to retropharyngeal abscess or pneumomediastinum,8 meningitis and brain abscess.9 None of the reported complications occurred in any of our patients, but, we admitted all patients in order to observe for signs of impending complication. The serious nature of these complications has prompted investigators to develop their algorithms and management protocols.10

REFERENCES 1. Hellmann JR, Shott SR, Gootee MJ. Impalement injuries of the palate in children: review of 131 cases. Int J Pediatr Otorhinolaryngol 1993;26(2):157-63. 2. Takenoshita Y, Sasaki M, Horinouchi Y, Ikebe T, Kawano Y. Impalement injuries of the oral cavity in children. ASDC J Dent Child 1996;63(3):181-4. 3. Randall DA, Kang DR. Current management of penetrating injuries of the soft palate. Otolaryngol Head Neck Surg 2006;135(3):356-60.

None of the studies have demonstrated any correlation between mechanism of injury or degree of injury with the potential for neurovascular complications.

4. Younessi OJ, Alcaino EA. Impalement injuries of the oral cavity in children: a case report and survey of the literature. Int J Paediatr Dent 2007;17(1):66-71.

Most of the studies reviewed, advocate conservative management with non-admission contingent on assurance of reliable adult supervision at home. Indicators prompting immediate re-evaluation include: Fever, poor oral intake for >24 hours, drooling, difficulty in breathing, neck pain, vomiting, irritability, lethargy or excessive drowsiness and vision changes.8 Studies have also however advised admission and observation if anticipated follow-up is poor or social conditions warrant concern;1 or if distance from the hospital is too much.8

5. Borges G, Bonilha L, Santos SF, Carelli EF, Fernandes YB, Ramina R, et al. Thrombosis of the internal carotid artery secondary to soft palate injury in children and childhood. Report of two cases. Pediatr Neurosurg 2000;32(3):150-3. 6. Mains B, Nagle M. Thrombosis of the internal carotid artery due to soft palate injury. J Laryngol Otol 1989;103(8): 796-7. 7. Kaplan DM, Fliss DM, Peiser Y, Greenberg D, Leiberman A. Internal jugular vein thrombosis in a child due to a ‘pencil point injury’ of the palate. Int J Pediatr Otorhinolaryngol 1998;44(2):183-7. 8. Schoem SR, Choi SS, Zalzal GH, Grundfast KM. Management of oropharyngeal trauma in children. Arch Otolaryngol Head Neck Surg 1997;123(12):1267-70.

SUMMARY In the developing world, with the constraints of unreliable supervision of adults at home, patients coming from far off distances and anticipated poor compliance of instructions, we feel that admission with observation or primary surgical intervention will avoid missing any serious complications.

9. Chang CJ, Huang LT, Lui CC, Huang SC. Oral wooden stick injury complicated by meningitis and brain abscess. Chang Gung Med J 2002;25(4):266-70. 10. Raska GM, Cordova SW, Lema R, Goldwasser MS. Management of penetrating trauma to the soft palate: a case report. J Oral Maxillofac Surg 2007;65(7):1279-85.

GERD Label in Infants Encourages Parents to Medicate Parents who were told that fussy infants had gastrointestinal reflux disorder (GERD) were more interested in giving them medications – even when told the drugs would likely be ineffective – than when the children were not diagnosed with a disease, according to a new study. (Source: Medscape)

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

REVIEW ARTICLE

Role of Zinc in Pediatric Diarrhea CHAITALI BAJAIT, VIJAY THAWANI

ABSTRACT Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions/salts (ORS), can reduce the duration and severity of diarrheal episodes for up to three months. The World Health Organization (WHO) and UNICEF recommend daily 20 mg zinc supplements for 10-14 days for children with acute diarrhea, and 10 mg per day for infants under six months old, to curtail the severity of the episode and prevent further occurrences in the ensuing-two to three months, thereby decreasing the morbidity considerably. This article reviews the available evidence on the efficacy and safety of zinc supplementation in pediatric diarrhea and convincingly concludes that zinc supplementation has a beneficial impact on the disease outcome. Keywords: Acute diarrhea, oral rehydration solutions/salts, zinc salts

cute diarrhea remains a leading cause of childhood deaths despite the undeniable success of oral rehydration therapy (ORT). Worldwide, diarrheal diseases are the leading cause of pediatric morbidity and mortality, with 1.5 billion episodes and 1.5-2.5 million deaths estimated annually among children below five years of age.1,2 In developing countries, the scenario is worse due to infection, malnutrition, and illiteracy. One out of every five children who die of diarrhea worldwide is an Indian. Daily around 1,000 children die of diarrhea in India, which means 41 children lose their lives every hour.3 Giving oral fluids using an oral rehydration solution (ORS) saves childrenâ&#x20AC;&#x2122;s lives, but does not seem to have any effect on the length of time the children suffer with diarrhea.

Many countries have changed diarrhea management policies to include low osmolarity ORS and zinc, but there is a gap between policy change and effective program implementation, with very few children currently being appropriately treated.5 Although the Government of India has initiated the provision of zinc in addition to low osmolarity ORS through the public health system, under the National Rural Health Mission, a survey conducted by UNICEF in India documented less than 1% prescriptions for zinc. One of the main reasons for this is the lack of knowledge and awareness among the care providers on how to implement the existing cost-effective interventions. The challenge is to achieve a greater coverage of these interventions in resource poor settings.6

Hence, new revised recommendations have been formulated by the World Health Organization (WHO) and the United Nations International Childrenâ&#x20AC;&#x2122;s Emergency Fund (UNICEF), in collaboration with the United States Agency for International Development (USAID) and other experts. It recommends zinc salt along with low osmolarity ORS, with reduced levels of glucose and salt, during acute diarrhea, which reduces the duration and severity of the episode; and zinc supplementation given for 10-14 days lowers the incidence of diarrhea in the following two to three months.4

MECHANISM OF ACTION OF ZINC IN DIARRHEA

Despite the evidence of benefit, there has been little progress on the widespread introduction of low osmolarity ORS and zinc for the treatment of diarrhea.

The physiological effect of zinc on intestinal ion transport has not yet been established thoroughly. Therefore, the fundamental information of the mechanism by which zinc may be effective in improving diarrhea is needed. A very recent publication has established that zinc inhibits cAMP-induced, chloridedependent fluid secretion by inhibiting basolateral potassium (K) channels, in in-vitro studies with rat ileum. This study has also shown the specificity of Zn to cAMP-activated K channels, because zinc did not block the calcium (Ca)-mediated K channels. As this study was not performed in Zn-deficient animals, it provides evidence that Zn is probably effective in the absence of Zn deficiency.7,8 Zinc also improves

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

REVIEW ARTICLE the absorption of water and electrolytes, improves regeneration of the intestinal epithelium, increases the levels of brush border enzymes, and enhances the immune response, allowing for a better clearance of the pathogens.9 Another report has recently provided evidence that zinc inhibits toxin-induced cholera, but not Escherichia coli heat-stable, enterotoxin-induced, ion secretion in cultured Caco-2 cells.10 Thus, zinc plays an important role in modulating the host resistance to infectious agents and reduces the risk, severity, and duration of diarrheal diseases. It also plays a critical role in metallo-enzymes, polyribosomes, and the cell membrane and cellular function, giving credence to the belief that it plays a central role in cellular growth and in the function of the immune system.11

Pharmacokinetics of Zinc in Diarrhea12 Absorption The molecular weight of elemental zinc is 65.37 and zinc sulfate is 287.5. Crude zinc sulfate is also known as white vitriol. Each gram of zinc sulfate represents 3.5 millimoles of Zn. Its solubility is 1 in 0.6 ml of water and it is insoluble in alcohol. Zinc and its salts are poorly absorbed from the gastrointestinal tract (GIT) (only 20 to 30%), duodenum, and ileum. Endogenous zinc is reabsorbed in the ileum and colon, creating enterohepatic circulation. Distribution After absorption zinc is bound to protein metallothionein in the intestines. Zinc is widely distributed throughout the body. It is primarily stored in RBCs, WBCs, muscles, bones, skin, kidneys, liver, pancreas, retina, and prostate. The extent of binding is 60-70% to plasma albumin, 30-40% to alpha 2 macroglobulins or transferring and 1% to amino acids like histidine and cysteine. Peak plasma concentration occurs in approximately two hours. Elimination Zinc is excreted mainly in the feces (90%) and only traces are found in the urine, as the kidney plays a small role in regulating the body Zn content.

Clinical Evidence Convincing evidence for the clinical importance of zinc has come from randomized controlled trials (RCTs) evaluating the impact of zinc supplementation during acute and persistent diarrhea.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

Zinc supplements reduce the severity and duration of acute diarrhea A study tested the hypothesis that daily supplementation of zinc had an effect on the clinical course of acute diarrhea, that is, frequency of stool, stool amount, and duration of acute diarrhea, in 117 children, of age six to fifty-nine months. Reduction in stool frequency per day was found to be 62% in the zinc-supplemented group and 26% reduction was found in the placebo-supplemented group, with an obvious difference of 36% between the two groups from day 1 to day 3 and day 5, which was found to be statistically significant. Similarly a significant difference was observed for reduction in amount of stool per day from day 1 to day 3 and day 5, with an obvious difference of 45% between the study groups.13 A meta-analysis of 12 studies examined the impact of zinc supplements on the management of acute diarrhea, 11 of which showed a reduction in the duration of the diarrheal episode. In eight of these, the reduction was statistically significant. Five of these studies also collected data on stool volume and frequency, and found that zinc supplements reduced stool output and frequency. The data showed that zinc supplementation had a significant and beneficial impact on the clinical course of acute diarrhea, reducing both its duration and severity.4 Another meta-analysis of 18 trials with 6165 enrolled participants showed that in acute diarrhea, zinc resulted in a shorter diarrhea duration (MD - 12.27 hours, 95% CI -23.02 to -1.52 hours; 2741 children, nine trials), and less diarrhea by day three (RR 0.69, 95% CI 0.59 to 0.81; 1073 children, two trials), day five (RR 0.55, 95% CI 0.32 to 0.95; 346 children, two trials), and day seven (RR 0.71, 95% CI 0.52 to 0.98; 4087 children, seven trials). Zinc also reduced the duration of persistent diarrhea (MD -15.84 hours, 95% CI -25.43 to - 6.24 hours; 529 children, five trials). Few trials reported the severity, but the results were inconsistent.14 The results of a recent systematic review suggest that zinc supplementation reduced the mean duration of acute diarrhea by approximately 20%, and persistent diarrhea by 15-30%, but had no significant effect on stool frequency or stool output. There was a high degree of statistically significant heterogeneity across the published studies for the effects of zinc supplementation on mean diarrheal duration and risk of vomiting following the administration of zinc.15 Zinc supplementation in prevention of acute and persistent diarrhea Studies evaluating the effect of zinc supplementation on diarrheal diseases found a preventive and long-lasting impact. These showed that 10 mg to 20 mg of zinc per

REVIEW ARTICLE day, for 10-14 days, reduced the number of episodes of diarrhea in 2-3 months after the supplementation.4,16 The WHO and UNICEF, therefore, recommend 20 mg zinc supplements daily, for 10-14 days, for children with acute diarrhea, and 10 mg per day for infants under six months of age, to curtail the severity of the episode and prevent further occurrences in the ensuing 2-3 months.

parameters were explored with one-way sensitivity analyses. In this study, the ORS was found to be less cost-effective than was previously thought. The use of zinc as an adjunct therapy, however, significantly improved the cost-effectiveness of the standard management of diarrhea for dysenteric as well as nondysenteric illnesses.20

Zinc supplementation in the treatment of persistent diarrhea

Zinc supplementation and irrational use of antimicrobials

An RCT in 40 infants (6-18 months old) with persistent diarrhea (greater than two weeksâ&#x20AC;˛ duration) evaluated the effect of oral zinc supplementation. It concluded that in persistent diarrhea there was depletion of zinc with the progression of the disease and oral zinc administration improved the zinc status.17

Excessive use of antimicrobials (AMs) for diarrhea is a major contributing factor toward increasing rates of AM-resistance in developing countries. A study of AM use in a rural area of Bangladesh found that 26% of the purchased medicines were AMs, which were most frequently purchased for children aged 0-4 years to use for diarrhea. A community-based controlled trial was conducted in Bangladesh where there were 30 service areas (clusters), around the Matlab Treatment Center, each with about 200 children between the ages of 3 and 59 months, who were randomly allocated to intervention or comparison areas. All children between the ages of 3 and 59 months were included in the study. The significant reduction in AM use and related behavior in the intervention group demonstrated that the benefits of zinc supplementation extend well beyond reducing childhood morbidity and mortality. Zinc supplementation for diarrhea with education programs, in addition to ORT, can reduce inappropriate AM use that leads to resistant pathogens.21

A pooled analysis of four RCTs has been reported on the effects of supplementary oral zinc in children, under the age of five, with persistent diarrhea. The Cox survival regression analysis was used to evaluate the overall effect of zinc on the continuation of diarrhea and possible differential effects in the subgroups. Zincsupplemented children with persistent diarrhea had a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) than those in the control group.18 Zinc supplementation in the treatment and prevention of bloody diarrhea Studies conducted during acute shigellosis showed that zinc therapy was associated with enhanced antigenspecific antibody responses. The bactericidal antibody titers against Shigella increased the proportions of B cells and plasma cells, as also higher lymphocyte proliferation responses in the peripheral circulation, during the early convalescent phase of shigellosis. For all these reasons, it is clear that zinc supplementation should be given as an adjunct to antimicrobial (AM) treatment in bloody diarrhea.19 Zinc supplementation and cost-effectiveness A study analyzed the incremental costs, effects, and cost-effectiveness when zinc was used as an adjunct therapy to the standard treatment of acute childhood diarrhea, including dysentery, and reassessed the cost-effectiveness of standard case management with ORS. The probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single

Recommended dose of zinc in diarrhea22 Elemental zinc is used orally, as an adjunct to ORT in acute diarrhea, in infants (under six months): 10 mg daily for 10-14 days; and in children (six months - five years): 20 mg daily for 10-14 days. How to administer zinc salt?22 Zinc sulfate, acetate, and gluconate are all acceptable zinc salt formulations, of which zinc sulfate is low-cost, efficacious, safe, and therefore, optimal for the national program. Zinc sulfate tablets may be dispersed in breast milk, in oral rehydration solutions, or in water on a small spoon; older children may chew the tablets or swallow them with water. Zinc sulfate dispersible tablet is also available in the market, containing 20 mg of elemental zinc. Pediatric zinc sulfate tablets are also available.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

REVIEW ARTICLE Drug Interaction22-24 If zinc is given concomitantly with the following, drug interaction may occur. Phytate, which is present in staple foods like cereals, corn, and rice, decreases zinc absorption from composite meals. Experiments in vitro have shown that zinc is precipitated by phosphate and phytate at pH values close to those of the intestinal lumen. Dairy products and brown bread decrease zinc absorption. Coffee also inhibits zinc absorption. Iron supplements inhibit absorption of Zn and therefore Zn supplements are administered two hours before iron supplements. Penicillamine and other chelators reduce absorption of Zn. Calcium salts reduce absorption of zinc. Oral tetracyclines reduce absorption of Zn, and hence, Zn supplements are administered two hours before tetracyclines. Amino acids, such as histidine and methionine, and other low-molecular-weight ions, such as EDTA and organic acids (e.g., citrate), enhance zinc absorption. Zn inhibits copper absorption from the intestine. Thiazide diuretics increase urinary excretion of Zn. Zinc reduces absorption of Ciprofloxacin, Levofloxacin, and Ofloxacin. Absorption of both zinc salts and ferrous salts will reduce if used concomitantly. Side effects of zinc supplementation To date there have been no reports of severe adverse reactions from any form of zinc supplementation used in the treatment of diarrhea. A zinc dose of 40 mg has been approved as being safe to use by the Food and Drug Administration (FDA), and a zinc dosage of more than this can pose certain risks. Too much zinc will probably interfere with the metabolism and absorption of other essential minerals in the body, especially iron, magnesium, and copper, reduce the bodyâ&#x20AC;&#x2122;s immune function, and reduce the HDL level. Oral zinc sulfate supplements can also cause side effects such as stomach upset, heartburn, and nausea. Rare side effects include fever, sore throat, mouth sores, weakness, and fatigue. Trials have included more than 8,500 children who participated in efficacy trials in both the placebo and zinc study arms, with nearly 12,000 child-years of observation, from one large effectiveness trial. No differences in adverse reactions based on the different zinc salts (sulfate, acetate, and gluconate) were noted in the supplementation trials. One trial reported higher vomiting in the zinc versus the control group, when zinc was given with multiple micronutrients, but not when given alone. The copper status has been evaluated in four trials. Three of these have not found a difference in the serum copper status after supplementation. However, one trial did find

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a significant trend of decreased copper level when comparing zinc-supplemented children with non-zinc supplemented children. However, these children were malnourished with persistent diarrhea at baseline. Overall, there is no substantial evidence of short-term zinc supplementation for the treatment of diarrhea adversely affecting the copper status.25 RECOMMENDATIONS The Indian Academy of Pediatrics, WHO, and UNICEF have already endorsed the use of zinc as a supplement to ORS in the management of diarrhea. A dosage of 20 mg of elemental zinc per day has been shown to be effective and safe in age group six months - to five years. Administration of zinc is recommended through a primary healthcare. For maximum impact on diarrheal diseases, zinc and ORS should be made available at the community level. Community-based programs increase the use of zinc and the introduction of zinc increases the use of ORS in the same communities The revitalization of community-health workers with a reach into the least fortunate communities will be critical to achieving the targeted coverage rates. In addition, incorporating the private sector, the medical and non-medical sectors, and the formal and informal sectors, may help reach additional segments of the population. CONCLUSION Oral zinc administration provides substantial benefit in the reduction of stool output, frequency, and duration, combined with safety, efficacy, and affordability in acute diarrhea. Thus, it can be concluded that oral zinc supplementation is a simple and effective therapeutic intervention in the management of acute diarrhea. REFERENCES 1. Kosek M, Bern C, Guerrant RL. The global burden of diarrheal diseases as estimated from studies published between 1992 and 2000. Bull World Health Organ 2003;81:197-204. 2. Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet2003;361:2226-33. 3. Diarrhea claims nearly 1000 children in India every day: Report. Available from: http://www.medindia. net/news/Diarrhea-Claims-Nearly-1000-Children-inIndia-Every-Day-Report-26603-1.htm. [Last cited on 2010 Feb 121].

REVIEW ARTICLE 4. WHO / UNICEF Joint Statement - Clinical management of acute diarrhea. WHO/FCH/CAH/04.7. May 2004.

acute and persistent diarrhea: a systematic review. PLoS ONE 2010;5:e10386.

5. Fischer Walker CL, Fontaine O, Young MW, Black RE. Zinc and low osmolarity oral rehydration salts for diarrhea: A renewed call to action. Bull World Health Organ 2009;87:780-6.

16. Scrimgeour AG, Lukaski HC. Zinc and diarrheal disease: Current status and future perspectives. Curr Opin Clin Nutr Metab Care 2008;11:711-7. 17. Sachdev HP, Mittal NK, Yadav HS. Oral zinc supplementation in persistent diarrhea in infants. Ann Trop Paediatr 1990;10:63-9.

6. Management practices for childhood diarrhea in India. Survey of 10 districts. New Delhi: UNICEF; 2009.

18. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: Pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516-22.

7. Hoque KM, Rajendran VM, Binder HJ. Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum. Am J Physiol 2005;288:G956-63. 8. Hoque KM, Binder HJ. Zinc in the Treatment of Acute Diarrhea: Current Status and Assessment. Gastroenterology 2006;130:2201-05.

19. Roy SK, Raqib R, Khatun W, Azim T, Chowdhury R, Fuchs GJ, et al. Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh. Eur J Clin Nutr. 2008;62:849-55.

9. Zinc supplementation helps diarrhea symptoms. Available from:http://www.newsmedical.net / news / 2008 / 02 / 04 / 34888.aspx. [Last cited on 2010 Feb 6].

20. Robberstad B, Strand T, Black RE, Sommerfelt H. Cost effectiveness of zinc as adjunct therapy for acute childhood diarrhea in developing countries. Bull World Health Organ 2004;82:523-31.

10. Berni CR, Cirillo P, Buccigrossi V, Ruotolo S, Annalisa P, De Luca P, et al. Zinc inhibits cholera toxin induced, but not Escherichia coli heat stable enterotoxininduced, ion secretion in human enterocytes. J Infect Dis 2005;191:1072-7.

21. Baqui AH, Black RE, El Arifeen S, Yunus M, Zaman K, Begum N, et al. Zinc therapy for diarrhea increased the use of oral rehydration therapy and reduced the use of antibiotics in Bangladeshi children. J Health Popul Nutr 2004;22:440-2.

11. Implementing the new recommendations on the clinical management of diarrhea-Guidelines for policy makers and programme managers. Geneva: WHO; 2006.

22. Medicines for diarrhea in children. In: Stuart MC, Kouimtzi M, Hill SR, editors. WHO Model Formulary.2008:351.

12. Ramanujam TR. Role of zinc in health and disease. Available from: http:/www.medindia.net/articles/roleofzinc.asp. [Last cited on 2010 Nov 15].

23. LĂśnnerdal B. Dietary factors influencing zinc absorption. J Nutr 2000;130:1378S-83.

13. Trivedia SS, Chudasamab RK, Patel N. Effect of zinc supplementation in children with acute diarrhea: Randomized double blind controlled trial. Gastroenterol Res 2009;2:168-74.

24. PĂŠcoud A, Donzel P, Schelling JL. Effect of foodstuffs on the absorption of zinc sulfate. Clin Pharmacol Ther 1975;17:469-74. 25. Fischer C, Harvey P. Low risk of adverse effects from zinc supplementation. MOST, The USAID Micronutrient Program.

14. Lazzerini M, Ronfani L. Oral zinc for treating diarrhea in children. Cochrane Database Syst Rev 2008:CD005436.

Citation: Bajait C, Thawani V. Role of zinc in pediatric diarrhea. Indian J Pharmacol 2011;43;232-5.

15. Patel A, Mamtani M, Dibley MJ, Badhoniya N, Kulkarni H. Therapeutic value of zinc supplementation in

ESA Dose Predicts Death in Kids on Peritoneal Dialysis In children receiving chronic peritoneal dialysis (PD), anemia and high requirements for erythropoiesis-stimulating agents (ESAs) independently predict mortality, according to results from a global cohort study published online March 7 in the Journal of the American Society of Nephrology. (Source: Medscape)

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ORIGINAL ARTICLE

Impact of Tonsillectomy on Quality-of-life in Children: Our Experience NEELIMA GUPTA*, LAKSHMI VAID**, PP SINGH†

ABSTRACT An important requirement of contemporary medicine is the assessment of patient benefit or change in health status resulting from medical or surgical intervention. Tonsillectomy is a commonly performed surgery in children. Its indications and benefits have been documented in the literature but to the best of our knowledge, there have been no Indian studies to measure the quality-of-life (QoL), post-tonsillectomy in children. Objective: To assess QoL of children after tonsillectomy, with or without adenoidectomy. Study design and setting: Retrospective study in a tertiary referral center. Methodology: The sample consisted of 136 children who had undergone tonsillectomy with or without adenoidectomy over a period of two years. The parents of these children were sent a questionnaire to assess their QoL six months after the surgery. The questionnaire used is a modified version of Glasgow Children’s Benefit Inventory (GCBI), a post intervention, health-related benefit measure. Results: Forty-four questionnaires were returned (32.2% response rate). Four questionnaires were declared invalid. Two parents reported worsening of a few symptoms, resulting in a negative score. In the remainder the total score ranged from 2.08 to 91.6. Conclusions: Sixty-eight percent of the parents were extremely satisfied after the surgery. Overall the parents reported change for the better in various observed aspects of the life of their children as reflected in the positive scores after intervention. Most of them reported decreased number of visits to the doctor and decreased need for antibiotic prescription i.e. there was an improvement in the ‘physical health’ aspect of the life of children. But, there was no change observed in the ‘emotional and psychosocial’ aspect of behavior in children. Keywords: Quality-of-life, tonsillectomy, children

onsillectomy and adenotonsillectomy are common surgical procedures performed in children. But, their indications are still variable and differ from center-to-center. In the past, the most frequent indication for surgery was recurrent tonsillitis. There has been a rise in obstructive sleep apnea as a significant indication from 0% in 1978 to 19% in 1986.1 Various studies have studied the effect of tonsillectomy in children suffering from upper airway obstruction. This study was designed to study the effect of tonsillectomy on the quality-of-life (QoL) of children, with the idea that the beneficial effects of tonsillectomy could be ascertained and more pertinent recommendations for surgery may be formulated. As far as our knowledge goes, there are very few Indian studies that have studied the effect of tonsillectomy on QoL of children. *Associate Professor **Professor †Professor and Head Dept. of ENT University College of Medical Sciences and GTB Hospital, New Delhi Address for correspondence Dr Neelima Gupta A-304, Abhyant Apartments 2, Vasundhara Enclave, New Delhi - 100 096 E-mail: write2drneelima@yahoo.com

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METHODOLOGY Study design: Retrospective study. Study area: Children operated for tonsillectomy or adenotonsillectomy in a hospital setting. Case selection: One hundred thirty-six children consecutively operated over a period of two years were selected from records. Twelve years was taken as the upper age limit. Questionnaires were mailed to all of them with a self-addressed envelope. Only 44 parents returned questionnaires (response rate of 32%). Out of the respondents the age group of children ranged from 4 to 12 years with the mean being 8.45 years. The maleto-female ratio was 1.2:1. We adapted the questionnaire from the Glasgow Children’s Benefit Inventory (GCBI), which has 24 questions on the consequences of a specified intervention on various aspects of the child’s day-to-day life, without reference to any specific symptoms.2 The questionnaire was modified and translated into Hindi (mother tongue) and was pre-tested among a group of parents prior to its administration. It was also tested for its consistency and internal validity. We also added one question (Question number 25), which asked for the

ORIGINAL ARTICLE parents overall satisfaction with the intervention. The questionnaire was self-administered and was filled-up by either parent of the operated child. The questions were worded to apply to child of any age. The pattern of responses assesses the child’s QoL in terms of emotion, physical health, learning and vitality. For each question, a response was given on a 5-point Likert type rating scale, with the central point being ‘no change’ and the extremes representing ‘much better’ and ‘much worse’. Assigning the individual responses a numerical value from –2 to +2, adding the total score and dividing by 24, calculated a summary score for the questionnaire. The score was multiplied by 50 to produce a result on a scale from –100 (maximum harm) to + 100 (maximum benefit). OBSERVATION AND RESULTS Forty-four questionnaires were returned out of 136. Four were declared invalid since a few questions were unanswered in these forms. On calculating the scores, two questionnaires had a negative score of –8.33 and –20.83. The rest had positive scores ranging from 2.08 to 91.6. Responses related to questions pertaining to selfconsciousness, embarrassment, easy distraction, selfesteem, confidence and self-care addressing the factor of ‘emotion’ were mostly responded to as ‘no change’. Similarly, the questions assessing change in learning, concentration, liveliness, fun with friends and leisure activities addressing the factors of ‘learning’ and ‘vitality’ were responded to as ‘no change’. Questions relating to overall life, absences from school, colds, visit to the doctor and need for antibiotic prescriptions, addressing the factor of ‘physical health’ were uniformly answered with ‘much better’ as shown in Table 1, which shows the number of parents who gave a particular response. The figures in bold indicate that this is the response ticked by the maximum number of parents. No statistically significant difference was observed in responses regarding change in food habits; sleep pattern, learning and progress of the child; as they were either answered with ‘little better’ or ‘no change’. Limitations of the study: Ideally, a pre- and postcomparison on QoL of the patients should have been done, but due to logistic constraints a comparative study could not be undertaken. Similarly, no matched control group of unoperated children was available. The attrition rate was very high, as only 32% respondents returned the filled

up questionnaire may be because of the socioeconomic background, lack of permanent addresses and literacy level constraints of our population. But, considering that there are few Indian studies in this area, our findings add substantively to the existing knowledge regarding impact of tonsillectomy on the QoL of the children. DISCUSSION As decisions concerning resource allocation become increasingly stringent it is important to understand the personal impact of diseases and their treatment beyond the standard medical morbidity or functional limitations so that this can be incorporated into the decision-making process. This has led to studies pertaining to outcome measures and effect of disease and management on QoL. On review of literature we encountered various studies that assessed the QoL before and after an intervention. We used a retrospective measure of assessment of QoL after tonsillectomy. The advantages of the retrospective approach are that it halves the burden of questionnaires for the parents, it is much more sensitive to change, and it can be used in conditions for which a sizeable cohort of patients can take years to build up.2 It has been shown in a few studies that trials commonly use serial measurements by the patients at two points in time while clinicians use the patient’s retrospective assessment of change made at one point in time. Retrospective measures were found to be more sensitive to change than serial measures and correlated more strongly with patient’s satisfaction with change.3 Therefore, we chose to use a retrospective measure. Paradise and Bluestone et al4 studied the efficacy of tonsillectomy for recurrent throat infection in 187 children in randomized as well as nonrandomized trials. They found that tonsillectomy with or without adenoidectomy was unequivocally effective for two years, and probably for one more year in reducing the frequency and severity of episodes of throat infection. Differences between the treatment groups in regard to secondary outcome measures such as number of visits on which isolated cervical lymphadenopathy was found, number of parent reported sore-throat days and school absent days due to sore-throat, were less clear cut and of uncertain clinical importance. In our study, majority of parents reported decrease in visits to the doctor, improvement in school attendance and decrease in episodes of cold. Our study has a follow-up of only six months; so, we have not studied infection rate following tonsillectomy.

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ORIGINAL ARTICLE In a study comprising of 138 children, compared with children who had not undergone adenotonsillectomy, parents of the adenotonsillectomy group more frequently reported improvement in breathing, snoring, excessive daytime sleepiness and QoL postoperatively. Parental reporting of asthma, bedwetting, concentration, school performance and intellectual or developmental progress were not statistically different between the two groups.5 In our analysis also 67.5% of the parents observed â&#x20AC;&#x2DC;no changeâ&#x20AC;&#x2122; in level of concentration or intellectual progress of the child after intervention.

and otolaryngologists should advice parents that adenotonsillectomy most likely results in improvement in breathing, sleep and QoL but should be guarded in promising improvement in behavior and development. Some studies have shown improvement in all aspects of the life of children. Goldstein7 in a pilot study demonstrated a high prevalence (28%) of abnormal behavior in children undergoing T & A for chronic upper airway obstruction. The Child Behavior Checklist (CBCL) scores significantly improved following T & A. Subclasses that showed improvement were withdrawn behavior, somatic complaints, attention problems and thought problems. Similarly De Serres et al8 in their study of 101 children found large, moderate and small improvements in QoL in 74.5%, 6.1% and 7.1% of children, respectively. Sleep disturbance, caregiver concern and physical suffering were the most improved domains, although significant changes also occurred

Ali and his group6 concluded from their study on 33 children, that following surgery relief of mildto-moderate sleep-disordered breathing improves behavior and functioning. In our study, 50% of the parents said they had observed no change in behavior of the child after surgery while 30% said that the behavior had changed for the better. Pediatricians

Table 1. Number of Responses to the Questions Assessing Various Aspects of QoL Question

Much better

Little better

No change

Little worse

Much worse

Overall life

Things they do

Behavior

Progress and development

Liveliness

Sleep

Food

Self-consciousness

Family harmony

Fun with friends

Embarrassment

Distractibility

Learning

Absences from school

Concentration

Irritability

Self-esteem

Happiness

Confidence

Self-care

Leisure

Colds

Visits to doctor

Need for medication

Overall satisfaction

The figures in bold indicate the response given by maximum number of parents.

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ORIGINAL ARTICLE for speech and swallowing problems, emotional disturbance and activity limitations. However, in our study 57.5% and 67.5% parents observed no change in the child’s activities and his interaction with friends, respectively as shown in Table 1.

rate. However, these limitations not withstanding we conclude that tonsillectomy has a positive impact on QoL of children. REFERENCES

In their study on 64 children who underwent tonsillectomy, Goldstein et al9 found that behavioral and emotional difficulties are found in children with sleep disordered breathing before treatment and improve after intervention. They used the CBCL total problem T scores as their outcome measure. Flanary10 studied both short-term and long-term effect of adenotonsillectomy on general and disease specific QoL in children suffering from upper airway obstruction secondary to adenotonsillar hypertrophy. This study used both Children’s Health Questionnaire Parent Form-28 and OSA-18 QoL measures and found that CHQPF-28 psychosocial summary scores did not show significant improvement in the short-term or longterm results. Mitchell11 also confirmed that caregiver concerns were reduced after tonsillectomy and the domain with the most significant improvement was sleep disturbance while least improvement was seen in emotional distress. We observed in our study that 42.5% parents reported ‘a little better’ sleep pattern in their children while 27.5% parents observed no change in sleep pattern.

1. Rosenfeld RM, Green RP. Tonsillectomy and adenoidectomy: changing trends. Ann Otol Rhinol Laryngol 1990;99(3 Pt 1):187-91. 2. Kubba H, Swan IR, Gatehouse S. The Glasgow Children’s Benefit Inventory: a new instrument for assessing healthrelated benefit after an intervention. Ann Otol Rhinol Laryngol 2004;113(12):980-6. 3. Fischer D, Stewart AL, Bloch DA, Lorig K, Laurent D, Holman H. Capturing the patient’s view of change as a clinical outcome measure. JAMA 1999;282(12):1157-62. 4. Paradise JL, Bluestone CD, Bachman RZ, Colborn DK, Bernard BS, Taylor FH, et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children. Results of parallel randomized and nonrandomized clinical trials. N Engl J Med 1984;310(11):674-83. 5. Constantin E, Kermack A, Nixon GM, Tidmarsh L, Ducharme FM, Brouillette RT. Adenotonsillectomy improves sleep, breathing, and quality of life but not behavior. J Pediatr 2007;150(5):540-6, 546.e1. 6. Ali NJ, Pitson D, Stradling JR. Sleep disordered breathing: effects of adenotonsillectomy on behaviour and psychological functioning. Eur J Pediatr 1996;155(1): 56-62. 7. Goldstein NA, Post JC, Rosenfeld RM, Campbell TF. Impact of tonsillectomy and adenoidectomy on child behavior. Arch Otolaryngol Head Neck Surg 2000;126(4):494-8.

CONCLUSION Tonsillectomy definitely leads to an improvement in the QoL in children and 68% of parents were extremely satisfied with the surgical outcome. Almost all the parents reported decrease in visits to the doctor and in antibiotic prescription but there were no significant changes observed in the emotional aspects and personality of the children. The low response rate led to a small sample size so we could not apply any tests of statistical significance. A control group of children who are followed-up with no surgical intervention will help in concluding that improvement is because of the surgical intervention. Also, our results can only give insight into short-term QoL improvements because we thought that if we send the questionnaires any later it will lead to further reduction in response

8. De Serres LM, Derkay C, Sie K, Biavati M, Jones J, Tunkel D, et al. Impact of adenotonsillectomy on quality of life in children with obstructive sleep disorders. Arch Otolaryngol Head Neck Surg 2002;128(5):489-96. 9. Goldstein NA, Fatima M, Campbell TF, Rosenfeld RM. Child behavior and quality of life before and after tonsillectomy and adenoidectomy. Arch Otolaryngol Head Neck Surg 2002;128(7):770-5. 10. Flanary VA. Long-term effect of adenotonsillectomy on quality of life in pediatric patients. Laryngoscope 2003;113(10):1639-44. 11. Mitchell RB, Kelly J, Call E, Yao N. Quality of life after adenotonsillectomy for obstructive sleep apnea in children. Arch Otolaryngol Head Neck Surg 2004;130(2):190-4.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

CLINICAL STUDY

Exclusive Breastfeeding: Is Motivation the Only Issue? M GIRISH*, N MUJAWAR**, V DANDGE**, P PAZARE†, K GAIKWAD‡

ABSTRACT Objectives: The aim of the study was: (1) To know the frequency of suboptimal infant breastfeeding behavior (SIBB), delayed onset of lactation (DOL) and excess neonatal weight loss (EWL) in mother-infant pairs with a high motivation to breastfeed; (2) to see if SIBB influenced lactational problems represented by: a] DOL, b] EWL; (3) in addition, we have tried to assess the risk factors for SIBB and other risk factors for DOL and EWL. Material and methods: A longitudinal hospital-based observational study. Infant breastfeeding behavior was assessed by IBFAT score, DOL was measured by maternal perception of breast fullness and maternal motivation by an initial interview based on breastfeeding self-efficacy scale. Results: Frequency of SIBB was 13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7. DOL occurred in 11.8% of mothers and excess weight loss in 17.7% of infants. Prolonged labor, medications given during labor, inadequacy of sleep during peripartum and use of supplementary feeds were found to be significantly associated with SIBB. Infants with SIBB on Day 0 were 17 times more likely to have SIBB on Day 3 and they were also four times more likely to have excess weight loss. Failure of exclusive breastfeeding (EBF) occurred in 8.1% and showed a significant association with SIBB, but at two weeks all were breastfeeding exclusively. Conclusion: Infant behavior plays an important role in the success of early breastfeeding and if suboptimal, contributes to failure of EBF. Both infant behavior and onset of lactation constitute significant predictors of excessive weight loss and short-term failure of exclusive breastfeeding and help in determining the need for intensive lactation counseling in high-risk cases. Keywords: Suboptimal infant breastfeeding behavior, exclusive breastfeeding, neonatal weight loss, onset of lactation

he mother-baby symbiotic dyad can be considered to last for 15 months, connected by the umbilical cord for the first nine months and by breastfeeding for the next six months. The infant’s health is imperiled not just if the first period of nine months is shortened but also if the second period is pruned. Exclusive breastfeeding (EBF) remains uncommon in most countries (both developed and developing), even in countries with high rates of breastfeeding initiation.1,2 Studies investigating failure of EBF3,4 have put the spotlight on the mother or the environmental influences acting on the mother (lack of support for breastfeeding by social workers and healthcare providers, emotional stress in mothers and their perception of not having enough breast milk, and pressure from close relatives to introduce other liquid foods, unsupportive hospital practices that

*Associate

Professor

**Professor †Lecturer

‡Assistant

Lecturer Dept. of Pediatrics NKP Salve Institute of Medical Sciences and Research Center Nagpur, Maharashtra

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delay early initiation of breastfeeding and maternal employment). While psychosocial and cultural barriers are reported as important contributing factors, there have been instances where mothers were highly motivated to breastfeed but were discouraged within the first few weeks due to insufficient milk and suboptimal breastfeeding behaviors among newborns leading to excessive weight loss and other medical complications, even death.5,9 Based on the hypothesis that even highly motivated mothers can face problems in breastfeeding including problems with infant behavior we decided to study the phenomenon of suboptimal infant breastfeeding behavior (SIBB) and other lactation problems in this group of mothers. AIMS AND OBJECTIVES The aim of the study was: (1) To know the frequency of SIBB, delayed onset of lactation (DOL) and excess neonatal weight loss (EWL) in mother-infant pairs with a high motivation to breastfeed; (2) to see if SIBB influenced lactational problems represented by: a) DOL, b) EWL; (3) in addition, we have tried to assess the risk factors for SIBB and other risk factors for DOL and EWL.

CLINICAL STUDY MATERIAL AND METHODS This observational longitudinal study was conducted in a tertiary care hospital in Nagpur, Maharashtra after taking approval from the Institutional Ethics Committee. A pilot study was done and the prevalence of SIBB was found to be 11%. In the absence of Indian data, 11% prevalence at 95% confidence interval (CI) and 80% power was considered to calculate the sample size. All mothers who delivered their babies during the period between April and September 2009, were interviewed and included if: (1) They delivered term appropriate for age babies with no perinatal morbidities; (2) they were motivated to breastfeeding exclusively (based on a shortened version of the breastfeeding selfefficacy scale) and (3) they resided near the hospital area and were willing to participate in the study. Infant’s behavior was assessed using the Infant Breastfeeding Assessment Tool (IBFAT), which includes ratings for arousal, rooting, time to latch and feed well, sucking effectiveness. Each point is worth 0-3 with a total maximum score of 12. A score of <10 was considered SIBB. Onset of lactation (OL) was determined by maternal report of breast fullness changes; DOL was defined as breast fullness perceived after 72 hours. EWL was defined as loss of weight ≥10% of birthweight by Day 3. At the time of delivery, information was collected from the medical record concerning the duration of Stage I and II labor (from onset of regular contractions to cervical dilation of 10 cm and from full dilation to the delivery of the infant, respectively), mode of delivery, labor medications, infant resuscitation, gravida, parity and infant birth weight. Breastfeeding guidance was given by the first author within 24 hours of delivery and then at every opportunity, emphasizing correct positioning and latching on to the breast and the importance of demand feeding and avoidance of supplements. The mother was interviewed for following information: ÂÂ

The interval without sleep before delivery.

ÂÂ

Infant feeding pattern since birth (when first put to breast since the time of birth; infant interest in nursing in the form of smacking or licking lips, opening and closing mouth, sucking on lips, tongue, hands, fingers, increased alertness and movements of arms and legs, number of breastfeeds; use of supplemental fluids/feeds).

ÂÂ

Family support during delivery.

ÂÂ

Previous experience of breastfeeding.

ÂÂ

Her confidence in her ability to exclusively breastfeed her infant for six months (on a scale of 1 = no confidence, to 5 = very confident).

Breastfeeding observation was done by a research assistant who worked exclusively on this project for six months. Data regarding nipple type (flat/inverted/ normal), maternal and infant positioning, suckling behavior and mother’s report of pain during feeding was recorded. IBFAT score was recorded on Days 0, 3, 7 (counting the day of birth as 0) and lactation guidance was continued. The guidance provided was as per the ILCA (International Lactation Consultant Association) guidelines. On Day 3 additional information collected were: a) Frequency of feeding; b) level of breast fullness (on a scale of 1-5; with 1 = no change and 5 = uncomfortably full); c) the approximate time postpartum when breast fullness first reached 3; d) supplemental feeds given; e) the level of support received from other family members (1 = most not supportive, 2 = some supportive, 3 = a lot of support) and f) any pain or discomfort encountered during feeding. Infant’s weight was taken on an electronic weighing scale. Any baby who had excess weight loss was given appropriate management (either close observation or neonatal intensive care unit [NICU] admission). Maternal body mass index (BMI) was measured on Day 14. STATISTICAL ANALYSIS Bivariate associations between five outcome variables, namely, SIBB on Days 0, 3, 7, DOL, excessive weight loss and 13 independent variables were examined using χ2 tests or Fisher’s test. Multiple logistic regression analysis was used to control for associations among the independent variables. Stepwise selection was used to construct the preliminary models (p level for inclusion or removal = 0.05). The independent variables for each preliminary model were chosen based on whether: a) There was a theoretical basis for an association between the independent variable and the outcome; b) the independent variable preceded the outcome variable in occurrence, potential interaction with parity and mode of delivery were examined, wherever there was a significant outcome for a given independent variable in the bivariate analyses. In preliminary analyses, potential interactions with parity and delivery mode were also examined, but these were not included in the regression models

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CLINICAL STUDY because there was little evidence that the association of the outcomes with any of the independent variables differed in mothers with vaginal versus cesarean section delivery or in primipara versus multipara. Bivariate associations among the five outcome variables were also examined. RESULTS One hundred thirty-five mother-infant pairs were included for the final analysis. Attitude towards breastfeeding were strongly positive with 84.4% mothers confident about breastfeeding exclusively for six months and 93.3% reporting full family support for same. About 8.1% babies received supplementation in the form of cow’s milk, water or glucose supplementation. The mean maternal age was 22.4 years and 50% were primiparous. Majority of mothers were educated upto middle school (63.7%). About 32.2% mothers underwent cesarean section, 80% of which was performed on primipara. The duration of labor was longer in primipara, analgesics during labor were given to only 14% and 12.5% received oxytocin, all in primipara. Early breastfeeding (within half an hour after normal delivery and 4 hours after cesarean section) was influenced more by the mode of delivery (delayed in 36% of cesarean) than by the parity. Average breastfeeding frequency was 8 ± 2 on Day 0. Frequency of SIBB was 13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7. SIBB was significantly associated with prolonged labor (SIBB Day 0), medications given during labor especially oxytocin and maternal analgesics (SIBB Day 0), inadequacy of sleep in the mother during the peripartum period (SIBB Days 0 and 3), use of supplementary feeds (SIBB Days 3 and 7). DOL occurred in 11.8% of mothers. There was significant association with the use of supplementary feeds in the babies and the type of family (nuclear/joint). Excess weight loss occurred in 23.7% of infants and was also significantly associated with use of supplementary feeds and type of family (more common in nuclear family). Infants with SIBB on Day 0 were 17 times more likely to have SIBB on Day 3 (p < 0.002, lower CL 2.6 and upper CL 125.7, Fisher exact test) and they were also nearly four times more likely to have excess weight loss. No significant association was found between SIBB on Day 0 and SIBB on Day 7 as well as DOL in the mother. At two weeks, all the babies were on exclusive breastfeeding.

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DISCUSSION The results indicate that lactation difficulties are not uncommon during first few days postpartum even among mothers who were highly motivated to breastfeed exclusively, though the incidence of SIBB reported in our study (13.3% on Day 0, 6.6% on Day 3 and 2.9% on Day 7) population is much lower than that observed in a similar study done in California, USA.10 But, the incidence of excess weight loss is much higher in our study (21.7%) as compared to western data.11 Significant association between SIBB on Day 0 and the risk of excess weight loss and SIBB on Days 3 and 7 with the use of supplementary feeds indicates that infant breastfeeding behavior assessment would help in identifying babies at high-risk for breastfeeding complications. In our study, all the babies with a low SIBB score were given repeated and intensive lactation counseling and this may explain the fact that the incidence of SIBB decreased progressively by Day 7, SIBB on Day 0 improved and weight gain occurred by Day 7 and more importantly, the fact that all the mothers were giving exclusive breastfeeding at two weeks. DOL occurred in 11.8% but we found no significant association with suboptimal infant behavior either on Day 0 or Day 3. DOL was significantly associated with the use of supplementary feeds in the first 48 hours and this finding has been corroborated by several other studies.12-15 The vicious cycle of supplementary feeding and lactational problems have been highlighted and emphasized in the past. Early supplementary feeds lead to DOL resulting in further supplementation thereby perpetuating the cycle. This may also prime future decisions to supplement, leading to an earlier introduction of top feeds. Exclusive breastfeeding indicates that the baby will receive only breast milk and no prelacteals or supplementary feeds with the exception of drops or syrups consisting of vitamins, mineral supplements or medicines.16 By this definition, all the babies who received supplementary feeds in our study (8.1%) represent failure of exclusive breastfeeding and towards this end, both SIBB (on Days 0 and 3) and DOL contributed towards temporary failure in exclusive breastfeeding but the trend was reversed successfully through timely intervention. There have been conflicting reports on association of labor medications and infant suckling behavior.17-20 We studied induction of labor with oxytocin and IV analgesics during labor and found that they significantly affected breastfeeding behavior on first day of life. Two other factors found to be associated with a greater risk of SIBB on Day 0 were prolonged

CLINICAL STUDY labor (total duration >12 hours) and adequacy of sleep before labor pains in the mother. We presume that the longer duration of labor and inadequate sleep could increase stress in the mother during the postpartum period and this may affect mother infant bonding. These findings imply that modification of the labor and delivery experience should improve early lactation success, a recommendation often made in various studies.21-23 The role of joint family system on the success of exclusive breastfeeding is controversial. While administration of prelacteals and supplementary feeds is usually attributed to family pressures in a joint family system, we found that supplementary feeds were more often used and delayed lactation occurred more commonly in mothers belonging to nuclear families thus reinforcing the need for the traditional joint family system; of course lactation guidance should be given to the entire family! CONCLUSION In the list of factors conducive for exclusive breastfeeding in healthy neonates the thrust so far has been on maternal factors. In this study, we have tried to turn the spotlight also on infant behavior as an important variable, which deserves attention. Infant behavior plays an important role in the success of early breastfeeding and if suboptimal, contributes to failure of EBF. Evaluation of infant breastfeeding behavior as well as onset of lactation in the early days could predict excessive weight loss and possibility of supplementary feeding in the neonate. Suboptimal infant breastfeeding behavior is amenable to intervention (lactation management counseling, avoidance of supplementary feeds, modifications in use of labor medications). All women with breastfeeding problems initially can eventually establish an adequate milk supply but the phenomenon should be taken seriously and every opportunity should be taken to address all the issues responsible for this including infant behavior, not only because it can lead to poor breastfeeding outcome in the short-term but it is known to lead to shorter duration of exclusive breastfeeding.7

3. Froozani MD, Permehzadeh K, Motlagh AR, Golestan B. Effect of breastfeeding education on the feeding pattern and health of infants in their first 4 months in the Islamic Republic of Iran. Bull World Health Organ 1999;77(5):381-5. 4. Imdad A, Yakoob MY, Bhutta ZA. Effect of breastfeeding promotion interventions on breastfeeding rates, with special focus on developing countries. BMC Public Health 2011;11 Suppl 3:S24. 5. Banapurmath CR, Nagaraj MC, Banapurmath S, Kesaree N. Breastfeeding practices in villages of central Karnataka. Indian Pediatr 1996;33(6):477-9. 6. Hall RT, Mercer AM, Teasley SL, McPherson DM, Simon SD, Santos SR, et al. A breast-feeding assessment score to evaluate the risk for cessation of breast-feeding by 7 to 10 days of age. J Pediatr 2002;141(5):659-64. 7. McLeod D, Pullon S, Cookson T. Factors influencing continuation of breastfeeding in a cohort of women. J Hum Lact 2002;18(4):335-43. 8. Mathur GP, Chitranshi S, Mathur S, Singh SB, Bhalla M. Lactation failure. Indian Pediatr 1992;29(12):1541-4. 9. Neifert MR. Prevention of breastfeeding tragedies. In: The Pediatric Clinics of North America, Breastfeeding 2001, Part II: The Management of Breastfeeding. Volume 48. Schanler RJ (Ed.), WB Saunders: Philadelphia, PA 2001:p.273-98. 10. Chapman DJ, Pérez-Escamilla R. Identification of risk factors for delayed onset of lactation. J Am Diet Assoc 1999 ;99(4):450-4; quiz 455-6. 11. Dewey KG, Nommsen-Rivers LA, Heinig MJ, Cohen RJ. Risk factors for suboptimal infant breastfeeding behavior, delayed onset of lactation, and excess neonatal weight loss. Pediatrics 2003;112(3 Pt 1):607-19. 12. Manganaro R, Mamì C, Marrone T, Marseglia L, Gemelli M. Incidence of dehydration and hypernatremia in exclusively breast-fed infants. J Pediatr 2001;139(5):673-5. 13. Ransjö-Arvidson AB, Matthiesen AS, Lilja G, Nissen E, Widström AM, Uvnäs-Moberg K. Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying. Birth 2001; 28(1):5-12. 14. Kramer MS, Barr RG, Dagenais S, Yang H, Jones P, Ciofani L, et al. Pacifier use, early weaning, and cry/fuss behavior: a randomized controlled trial. JAMA 2001;286(3):322-6.

REFERENCES

15. ABM Clinical Protocol #3. Hospital Guidelines for the Use of Supplementary Feedings in the Healthy Term Breastfed Neonate, Revised 2009. The Academy of Breast Feeding Medicine Protocol Committee. Breast Feeding Medicine 2009:4(3):175-82.

1. Dimond HJ, Ashworth A. Infant feeding practices in Kenya, Mexico and Malaysia. The rarity of the exclusively breast-fed infant. Hum Nutr Appl Nutr 1987;41(1):51-64.

16. WHO Geneva. Indicators for assessing breastfeeding practices. WHO Geneva Switzerland: WHO Document WHO/CDD/SER1991;9:14.

2. Perez-Escamilla R. Breastfeeding in Africa and the Latin American and Caribbean region: the potential role of urbanization. J Trop Pediatr 1994;40(3):137-43.

17. Crowell MK, Hill PD, Humenick SS. Relationship between obstetric analgesia and time of effective breast feeding. J Nurse Midwifery 1994;39(3):150-6.

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CLINICAL STUDY 18. Riordan J, Gross A, Angeron J, Krumwiede B, Melin J. The effect of labor pain relief medication on neonatal suckling and breastfeeding duration. J Hum Lact 2000;16(1):7-12.

analgesia on newborn breastfeeding behaviors. J Obstet Gynecol Neonatal Nurs 2003;32(3):322-31. 22. Ounsted MK, Hendrick AM, Mutch LM, Calder AA, Good FJ. Induction of labour by different methods in primiparous women. I Some perinatal and postnatal problems. Early Hum Dev 1978;2(3):227-39.

19. MacMullen NJ, Dulski LA. Factors related to sucking ability in healthy newborns. J Obstet Gynecol Neonatal Nurs 2000;29(4):390-6. 20. Halpern SH, Levine T, Wilson DB, MacDonell J, Katsiris SE, Leighton BL. Effect of labor analgesia on breastfeeding success. Birth 1999;26(2):83-8.

23. Zuppa AA, Vignetti M, Romagnoli C, Tortorolo G. Assistance procedures in the perinatal period that condition breast feeding at the time of discharge from the hospital. Pediatr Med Chir 1984;6(3):367-72.

21. Radzyminski S. The effect of ultra low dose epidural

Impact of Zinc Supplementation in Malnourished Children with Acute Watery Diarrhea Objective: To evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). Design: A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhea. After decoding it was observed that 44 children received zinc sulfate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrolment. Result: All the children (100%) in the zinc supplemented group and 32 (89%) children in the placebo group recovered within five days of hospitalization (p=0.04). The zinc supplemented group had a significantly shorter duration of diarrhea (70.4 ± 10.0 vs 103.4 ± 17.1; p=0.0001), passed less liquid stool (1.5 ± 0.7 vs 2.4 ± 0.7 kg; p=0.0001), consumed less oral rehydration solution (2.5 ± 1.0 vs 3.6 ± 0.8 liter; p=0.0001) and other liquids (867.0 ± 466.1 vs 1354.7 ± 675.6 ml; p=0.0001) as compared to the placebo group. Conclusion: Above findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhea. Dutta P, Mitra U, Datta A, et al. J Trop Padiatr 2000;46(5):259-63.

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CASE REPORT

Retinoblastoma: A Curse to Childhood HARPAL SINGH JHAGTA*, PRACHI JAIN**, MANOJ GUPTA†, ASHISH BAJAJ‡

ABSTRACT Retinoblastoma is the most common intraocular malignancy in children. With the improvement in diagnostic and treatment modalities, early diagnosis and prompt treatment have remarkably improved the survival and salvageable vision in retinoblastoma patients. We report a case of a 14-month-old female child who presented to us with intermittent deviation of both eyes and white reflex in both eyes along with redness and photophobia in right eye, she was diagnosed to liver bilateral retinoblastoma. Keywords: Retinoblastoma, poor vision, Schiotz tonometer

etinoblastoma is the most common intraocular malignancy in children. The current incidence ranging from one in 15,000 to one in 18,000 live births.1 The average age at diagnosis is 18 months, with unilateral cases being diagnosed at around 24 months and bilateral cases before 12 months. Out of the newly diagnosed cases of retinoblastoma only 6% are familial while 94% are sporadic. It is bilateral in about 25-35% of cases. Bilateral retinoblastomas involve germinal mutations in all cases. Out of the unilateral cases, approximately 15% are caused by germinal mutations while the 85% are sporadic.2 With the improvement in diagnostic and treatment modalities, early diagnosis and prompt treatment have remarkably improved the survival and salvageable vision in retinoblastoma patients, which otherwise would have succumbed to death in pre-revolutionary era in medical science. CASE REPORT A 14-month-old female child presented to us with intermittent deviation of both eyes and white reflex in both eyes for last three months, along with redness and photophobia in right eye for last 15 days. On examination, child resisted occlusion of left eye signifying poor vision in right eye. Right eye conjunctiva was congested, cornea was hazy and edematous and anterior chamber was full of fluffy clumps with hypopyon of approximately 1 mm (Fig. 1).

*Sankara Eye Hospital, Ludhiana, Punjab **Regional Institute of Ophthalmology, PGIMS, Rohtak, Haryana

Figure 1. Leucocoria in left eye with mid-dilated pupil, not reacting to light.

Fundus details could not be seen due to hazy media. Intraocular pressure was unrecordably low. Patient had leucocoria in left eye with mid-dilated pupil, which was not reacting to light (Fig. 1). On fundus examination, yellow white mass with dense vitreous seeding was seen in left eye. Intraocular pressure was 17.3 mmHg with Schiotz tonometer in left eye. On USG, diffuse vitreous seeding is seen in right eye (Fig. 2) and welldefined hypoechoic endophytic lesion with calcific foci and overlying retinal detachment in posterior segment was seen in left eye (Fig. 3). Choroidal thickness of 1.4 mm in right eye and 1.6 mm in left eye was seen. On CT scan soft tissue mass with calcification was seen in both eyes (Fig. 4). No retrobulbar extension was seen. Family history was negative for retinoblastoma. After observing history, examination and finding on USG and CT scan diagnosis of retinoblastoma Group E

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CASE REPORT in right eye and retinoblastoma Group D in left eye was made and child was referred to higher center for further management. GENETICS

Figure 2. USG showing diffuse vitereous seeding in right eye.

Only 6% of retinoblastoma cases are found to be familial while remaining 94% are sporadic in origin. All bilateral cases are thought to be hereditary. Knudson proposed two hit hypothesis for the occurrence of retinoblastoma.3 According to this, two chromosomal mutations are required for the occurrence of retinoblastoma. Those having familial disease inherit one germinal mutation from the parents (first hit) while another mutation occurs sporadically while development of retina (second hit). Sporadic cases encounter both the mutations during retinal development. Familial cases, because of underlying germinal mutation, are also predisposed to other nonocular malignancies like osteosarcoma. CLINICAL PRESENTATION

Figure 3. USG showing well-defined hypoechoic endophytic lesion with calcific foci and overlying retinal detachment in posterior segment in left eye.

The clinical presentation of retinoblastoma depends on the stage of the disease.4 Early lesions are likely to be missed, unless an indirect ophthalmoscopy is performed. Leucocoria (56%) is the most common clinical presentation of retinoblastoma followed by strabismus (20%). Leucocoria is observed mainly in endophytic growth of tumor that has gained substantial size to be observed through the pupil as grayish white reflex. Strabismus occurs when the tumor is involving fovea thus interfering with the normal fixation pattern of child. Other clinical presentations include diminished vision, red painful eye, asymptomatic, hyphema, vitreous hemorrhage, proptosis or orbital cellulitis. Three types of tumor growth patterns are observed: ÂÂ

Endophytic: Extension into vitreous cavity.

ÂÂ

Exophytic: Extension into subretinal space.

ÂÂ

Infilterating: Diffusely involving retina causing placoid thickening. This type is diagnosed late and is usually seen in older children.

Retinoblastoma may spread locally via scleral emissary veins to involve orbital tissues and central nervous system (CNS) involvement through optic nerve or hematogenous spread. Distant metastasis may involve pre-auricular or cervical lymph nodes and bone marrow. DIAGNOSIS Figure 4. CT scan showing soft tissue mass with calcification.

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A child with suspected retinoblastoma must undergo complete ophthalmic evaluation including a dilated

CASE REPORT fundus examination under anesthesia. Diagnosis is usually clinical, aided by USG B-scan of the eye revealing tumor extension and intralesional calcification.4 Computed tomogrophy (CT) scan and magnetic resonance imaging (MRI) are reserved in cases with atypical presentation, extraocular extension or those having diagnostic dilemma. CT scan helps to delineate tumor extension and co-existent pinealoblastoma can be detected (trilateral tumor). MRI is useful when optic nerve or intracranial extension is suspected. Intralesional calcification on CT scan or USG B-scan is highly suggestive finding for retinoblastoma. On histopathology, poorly differentiated tumor consists of small to round cells having scanty cytoplasm and hyperchromatic nuclei. Well-differentiated tumors show rosettes and flueretes formation, which is highly suggestive of photoreceptor differentiation of tumor cells. Flexner-Wintersteiner rosettes consist of columnar cells arranged around a lumen and are highly characteristic of retinoblastoma. Grouping (Shields) Group A

Small tumor Retinoblastoma <3 mm in basal dimensions

Group B

Larger tumor Retinoblastoma >3 mm in basal dimensions Macular location (<3 mm from foveola) zz Juxtapapillary location (<1.5 mm from optic disc) zz Clear subretinal fluid <3 mm from tumor margin

Staging Stage 0

No enucleation

Stage I

Enucleation, tumor completely resected

Stage II

Enucleation, microscopic residual tumor

Stage III

Regional extension zz zz

Stage IV

Overt orbital disease Pre-auricular or cervical lymph node involvement

Metastatic disease Hematogenous metastasis Single lesion Multiple lesions zz CNS extension Prechiasmatic lesion CNS mass Leptomeningeal disease zz

INTERNATIONAL CLASSIFICATION SYSTEM FOR RETINOBLASTOMA The International Classification system includes grouping and staging of retinoblastoma. Grouping is done preoperatively to plan lines of management and prognosticate organ salvage while grouping is done postenucleation to prognosticate the survival of the patient.5

zz zz

Group C

Focal seeding C1 subretinal seeds <3 mm from retinoblastoma zz C2 vitreous seeds <3 mm from retinoblastoma zz C3 both subretinal and vitreous seeds <3 mm from retinoblastoma zz

Group D

Diffuse Seeding D1 subretinal seeds >3 mm from retinoblastoma zz D2 vitreous seeds >3 mm from retinoblastoma zz D3 both subretinal and vitreous seeds >3 mm from retina zz

Group E

Extensive retinoblastoma Occupying >50% globe or Neovascular glaucoma zz Spontaneous vitreous hemorrhage or hyphema zz Invasion of optic nerve, choroid (thickness >2 mm), sclera, orbit, anterior chamber zz zz

MANAGEMENT The management of retinoblastoma needs a multidisciplinary team approach including an ocular oncologist, pediatric oncologist, radiation oncologist, radiation physicist and an ophthalmic oncopathologist. The primary aim is to save the life of a child. Management of retinoblastoma is highly individualized and depends upon age at presentation, laterality, tumor location, tumor staging, visual prognosis, systemic condition and socioeconomic status. Genetic counseling is an important aspect in the management of retinoblastoma.6 Current protocol suggests management of small intraocular tumors, unilateral or bilateral, by focal cryotherapy alone or in combination with standard dose 6 cycle chemotherapy with vincristine, etoposide and carboplatin. Focal therapy should be deferred until 6 cycles of chemotherapy for tumors located in visually crucial areas and residual disease is treated with transpupillary thermotherapy or plaque brachytherapy (I 125 or Ru 106 for 36-72 hours). Extensive disease described under Group D and E of International Classification system is managed by

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CASE REPORT high dose chemotherapy followed by aggressive focal therapy. Primary enucleation should be considered in overt disease without salvageable vision. External beam radiotherapy using linear accelerator is delivered after high dose chemoreduction in cases with residual orbital disease.7 Cases with metastatic disease are usually managed on palliative grounds. CNS metastasis can be managed with high dose chemotherapy along with intrathecal chemotherapy.8

3. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68 (4):820-3.

The recent advances such as identification of genetic mutations, early diagnosis and improved treatment modalities like chemoreduction with adjuvant focal therapy have contributed to better survival, improved eye salvage and potential for optimal visual recovery.

6. Kiran VS, Kannabiran C, Chakravarthi K, Vemuganti GK, Honavar SG. Mutational screening of the RB1 gene in Indian patients with retinoblastoma reveals eight novel and several recurrent mutations. Hum Mutat 2003;22(4):339.

4. Murthy R, Honavar SG, Naik MN, Reddy VA. Retinoblastoma. In: Modern Ophthalmology. Dutta LC (Ed.), Jaypee Brothers: New Delhi 2004:p.849-59. 5. Chantada G, Doz F, Antoneli CB Grundy R Clare Stannard FF, Dunkel IJ. A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer 2006;47:(6)801-5.

7. Honavar SG, Reddy VAP, Murthy R, Naik M, Vemuganti GK. Management of orbital retinoblastoma. XI International Congress of Ocular Oncology. Hyderabad, India, 2004:p.51.

REFERENCES 1. Bishop JO, Madson EC. Retinoblastoma. Review of current status. Surv Ophthalmol 1975;19(6):342-66.

8. Pratt CB, Crom DB, Howarth C. The use of chemotherapy in extraocular retinoblastoma. Med and Pediatr Oncol 1985;13(6):330-3.

2. Shields JA, Shields CL. Intraocular tumors - A text and Atlas. WB Saunders Company: Philadelphia, PA, USA 1992.

Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in Children Objective: To determine whether zinc with oral rehydration solution (ORS) is more cost-effective than ORS alone in treatment of acute diarrhea. Study Design and Setting: Cost-effectiveness analysis among patients consulting the emergency room of a government institution. Method: Cost of treatment and outcome of participants of a randomized trial of zinc+ORS versus ORS alone for acute diarrhea were investigated. Included were subjects 2-59 months with diarrhea <7 days and no dehydration. The direct medical, nonmedical and indirect costs were obtained, using the societal perspective. The incremental cost-effectiveness ratio (ICER) was calculated. Results: Sixty patients were given zinc + ORS and 57 were given ORS alone. Mean duration of diarrhea was 17 hours shorter and mean total cost of treatment was 5% cheaper in the zinc + ORS than ORS group. Conclusion: Use of zinc with ORS reduced the total cost and duration of acute diarrhea. Gregorio GV, Dans LF, Cordero CP, et al. J Clin Epidemiol 2007;60(6):560-6.

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CASE REPORT

Neonatal Bartter Syndrome MEETU RAWAT GUPTA*, SUBANDHU GUPTA**, ANAND S VASUDEV†, RN SRIVASTAVA†

ABSTRACT Bartter syndrome is characterized by hypokalemia, metabolic alkalosis, increased urinary excretion of sodium, potassium and chloride and normal blood pressure. A rare subset of the disorder occurs in the newborn period, which prompts us to report two such cases. Both showed satisfactory response to treatment with indomethacin. Keywords: Neonatal Bartter syndrome, hypokalemic metabolic alkalosis

artter syndrome is an inherited renal tubular disorder characterized by hypokalemia, hypochloremic metabolic alkalosis, normal blood pressure with hyperreninemia and increased urinary loss of sodium, potassium and chloride. The neonatal form of Bartter syndrome is rare and clinically manifests with failure to thrive, polyuria and episodes of dehydration. We report two infants with neonatal Bartter syndrome, who had typical clinical features, but early diagnosis was not made. Both improved with administration of indomethacin and potassium supplements.

CASE REPORT

Case 1 A 15-month-old boy was referred with complaints of failure to thrive since birth. He was a term small for gestational age (birth weight 1.8 kg) and was a product of nonconsanguineous marriage. Maternal polyhydramnios was detected in the fifth month of pregnancy. There was no history of birth asphyxia. He was exclusively breastfed for the first three months of life after which cow milk was given and by 5th month of life, complementary feeds were introduced, which were poorly tolerated. He showed poor oral acceptance for solids yet would consume liquids in large amounts and pass urine frequently. He developed vomiting,

around 2-3 times a day, nonbilious, nonprojectile, being partially relieved by antiemetics. The weight gain was poor (4.5 kg at 12 months). At age of 14 months, he developed fever with respiratory distress, needing hospital admission for 10 days and was treated with intravenous antibiotics. Metabolic alkalosis was detected and he was referred to this hospital. There was no history of child neglect or parental discordance. There was no history of loose stools, cyanotic spells, seizures, altered sensorium and focal neurological deficits. Examination showed weight 4 kgs (expected 11.21 kgs), length 60 cm (expected 79.4 cm) and head circumference 42 cm (<3rd centile). He had no dysmorphic features. The blood pressure was normal. Systemic examination was within normal limits and neurological examination did not disclose any localizing signs. Detailed laboratory evaluation showed hypochloremic metabolic alkalosis, hypokalemia, increased urinary losses of K+, Ca++ and raised aldosterone level (Table 1), confirming the diagnosis of Bartter syndrome. Ultrasound abdomen revealed bilateral medullary nephrocalcinosis. The child was managed with indomethacin 2 mg/kg, potassium supplementation and supportive treatment along with dietary advice. On discharge, there was clinical and biochemical improvement with serum potassium of 4.2 mEq/l. On regular follow-up visit upto present age of five years, he has showed consistent gain in weight.

Case 2 *Pediatric Registrar **Senior Resident †Senior Consultant Dept. of Pediatric Nephrology Indraprastha Apollo Hospitals, New Delhi

A 7½ month-old baby boy, resident of Kabul, Afghanistan, presented with complaints of failure to thrive, cough and polyuria since four months. He was a product of second degree consanguineous

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CASE REPORT Table 1. Laboratory Investigations of the Two Cases Investigations

Case 1

Case 2

Serum potassium

2.4 mEq/l

3 mEq/l

Serum calcium

10 mg/dl

7.9 mg/dl

Serum magnesium

3.3 mg/dl

1.6 mg/dl

Serum chloride

98 mEq/l

99 mEq/l

Serum aldosterone

1087.4 IU/l

7.6

7.46

Bicarbonate

40.7 mEq/l

28.17 mEq/l

Urine sodium

41 mEq/l

3,000 mEq/l

Urine potassium

9.9 mEq/l

2 mEq/l

Urine calcium

2.5 mEq/l

1.8 mEq/l

Urine creatinine

11.1 mg/dl

13 mg/dl

0.22

0.28

42 mEq/l

< 15 mEq/l

Urine calcium: Creatinine ratio Urine chloride

marriage born as a term appropriate for gestational age by vaginal delivery. There was maternal history of polyhydramnios. There was no history of birth asphyxia. Family history was not significant. The child required frequent hospitalizations for persistent cough in Kabul and Pakistan. Investigations on blood had shown low Na+, K+, Cl-, Mg+ and a high HCO3-, aldosterone, PGE, renin along with metabolic alkalosis. Ultrasound abdomen showed hyperechogenic kidneys. The chest X-ray was normal. Nuclear scan was positive for gastroesophageal reflux. A provisional diagnosis of Bartter syndrome was made and he was referred to this hospital. On examination, his weight was 4.86 kg (expected 8.64 kg), length 62.5 cm (expected 69.5 cm) and head circumference 38 cm (<3rd centile). He had mild pallor and normal BP. Systemic examination was within normal limits. Laboratory investigations (Table 1) showed metabolic alkalosis and increased urinary excretion of K+ and Ca+. The chest X-ray and ultrasound abdomen were normal. Child was managed with indomethacin, potassium supplementation and supportive treatment and discharged in stable condition. On follow-up, he showed marked clinical and biochemical improvement. DISCUSSION The two patients we described had typical abnormalities of Bartter syndrome. Although, the typical features were present almost since birth, the diagnosis

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

wasÂ delayed by several months. There was marked clinical improvement with initiation of indomethacin and potassium supplements. Bartter syndrome is an inherited renal tubulopathy, which may manifest during the neonatal period, infancy or childhood.1 The sodium potassium 2 chloride cotransporter NKCC2 or the luminal potassium channel ROMK causes neonatal Bartter syndrome, where tubular losses of sodium, potassium, chloride and water cause secondary hyperaldosteronism.1,3 Bhamkar and Gajendragadkar have recently described a case report on antenatal Bartter syndrome with sensorineural deafness.2 Gitelman syndrome however is a phenotypically related channelopathy instead of being a variant of Bartterâ&#x20AC;&#x2122;s syndrome, affecting sodium chloride cotransporter. NCCT present in the distal convoluted tubule. Linkage analysis and mutational studies have revealed defects in the gene encoding sodium chloride co-transporter NCCT.3 The neonatal variant is particularly uncommon. Antenatal features include polyhydramnios and premature delivery.4 Amniotic fluid shows consistently elevated chloride levels. After birth, rapid weight loss may occur.5-7 Lethargy and poor feeding often develop.8 Special facial features like triangular face, prominent forehead, large eyes, strabismus, protruding ears, drooping mouth exist as also sensorineural deafness, convulsions and increased susceptibility to infections.4 Metabolic alkalosis with hypokalemia occurs in the first week of life. Urine has low specific gravity with very high sodium, chloride and calcium levels while potassium is normal.8 However, after 1-3 weeks, the level of potassium in the urine rises with relatively less level of sodium than in the first week of life. Prostaglandin levels are high, both in blood and in urine.8,9 Hyperprostaglandin E2 is a secondary phenomenon due to fluid and electrolyte loss, and is suppressed by appropriate fluid and electrolyte replacement over a period of time. Serum renin and aldosterone levels are also very high, and are important in establishing the diagnosis. Untreated infants fail to thrive, and may die in a few days as a result of dehydration, poor feeding or severe electrolyte disturbance. Mild mental retardation is linked to delay in diagnosis and treatment.8 Therapeutic efforts should be directed to correct dehydration and electrolytic imbalance.10 The treatment of Bartter syndrome consists of supplementation of potassium (1-3 mEq/kg/day) and after 6-12 weeks of life, administration of indomethacin (2-3 mg/kg/ day).1,4 Ibuprofen (30 mg/kg/day) has similar effect,

CASE REPORT but indomethacin has been more widely used. The treatment results in striking clinical improvement although serum potassium levels may not increase to above 3.5 mEq/l. Potassium sparing diuretics and angiotensin converting enzyme inhibitors have also been used.1

RM, Jenson HB, Behrman RE, Stanton BF (Eds.), Saunders Publications: Philadelphia 2007:p.2201-2. 4. Kumar PS, Deenadayalan M, Janakiraman L, Vijayakumar M. Neonatal Bartter syndrome. Indian Pediatr 2006;43(8):735-7. 5. Bartter FC, Pronove P, Gill JR Jr, Maccardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. Am J Med 1962;33:811-28.

Prenatal diagnosis can be made by the high chloride content of the amniotic fluid and mutational analysis of genomic DNA extracted from cultured amniocytes.11

6. Massa G, Proesmans W, Devlieger H, Vandenberghe K, Van Assche A, Eggermont E. Electrolyte composition of the amniotic fluid in Bartter syndrome. Eur J Obstet Gynecol Reprod Biol 1987;24(4):335-40.

Bartter syndrome and other renal tubulopathies should be considered in an infant with no obvious cause of failure to thrive and unexplained polyuria. Early investigation and treatment should begin to prevent long-term side effects like growth failure, nephrocalcinosis and renal failure.

7. Ohlsson A, Sieck U, Cumming W, Akhtar M, Serenius F. A variant of Bartter’s syndrome. Bartter’s syndrome associated with hydramnios, prematurity, hypercalciuria and nephrocalcinosis. Acta Paediatr Scand 1984;73(6):868-74. 8. Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156(9):669-79.

REFERENCES

9. Amirlak I, Dawson KP. Bartter syndrome: an overview. QJM 2000;93(4):207-15.

1. Srivastava RN, Bagga A. Renal tubular disorders. In: Pediatric Nephrology. 4th edition, Srivastava RN, Bagga A, (Eds.), Jaypee Brothers Publishers: New Delhi 2005:p.278-9. 2. Bhamkar RP, Gajendragadkar A. Antenatal Bartter’s syndrome with sensorineural deafness. Indian J Nephrol 2009;19(1):23-6.

10. Proesmans W, Massa G, Vanderschueren-Lodeweyckx M. Growth from birth to adulthood in a patient with the neonatal form of Bartter syndrome. Pediatr Nephrol 1988;2(2):205-9.

3. Dell KM, Avner ED. Bartter/Gitelman syndromes and other inherited tubular transport abnormalities. In: Nelson Textbook of Pediatrics. 18th edition, Kliegman

11. Proesmans W, Massa G, Vandenberghe K, Van Assche A. Prenatal diagnosis of Bartter syndrome. Lancet 1987;1(8529):394.

Zinc in the Treatment of Acute Diarrhea: Current Status and Assessment Aim: To review the role of oral rehydration solution (ORS) in the treatment of acute diarrhea with particular attention to recent efforts to develop improved ORS formulations. Conclusion: One promising approach is the administration of zinc. Based on its beneficial effects in infections, including pneumonia, zinc has been shown to be effective in the treatment of acute diarrhea in several randomized controlled trials including subsequent meta-analyses. Hoque KM, Binder HJ. Gastroenterology 2006;130(7):2201-5

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

CASE REPORT

Acute Disseminated Encephalomyelitis Presenting as Fever of Unknown Origin: Case Report MARGHERITA DI COSTANZO, MARIA ERMINIA CAMARCA, MARIA GIOVANNA COLELLA, GIUSEPPE BUTTARO, ANDREA ELEFANTE, ROBERTO BERNI CANANI

ABSTRACT Background: Fever of unknown origin (FUO) can be defined as a body temperature higher than 38.3°C on several occasions over more than 3 weeks, the diagnosis of which remains uncertain after 1 week of evaluation. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system with a wide range of clinical manifestations. The highest incidence of ADEM is observed during childhood and it usually occurs following a viral or bacterial infection or, more rarely, following a vaccination, or without a preceding cause. Case presentation: Here, we describe an atypical case of ADEM that initially manifested as several weeks of FUO in a fifteen years old boy. Conclusions: This case report suggests a new possible syndromic association between ADEM and FUO, which should be considered in the clinical examination of patients with FUO, especially in the presence of also modest neurologic or neuropsychiatric symptoms. Keywords: Fever of unknown origin, acute disseminated encephalomyelitis

ever of unknown origin (FUO) can be defined as a body temperature higher than 38.3°C on several occasions over more than 3 weeks, the diagnosis of which remains uncertain after 1 week of evaluation.1 Evaluation of FUO in children is complex, because of a wide range of possible etiologies. The most common causes of FUO in childhood are viral infections, while in older patients frequent causes are inflammatory illnesses (rheumatic diseases, vasculitides, polymyalgia rheumatic, sarcoidosis), infections and neoplasms.1,2 Acute disseminated encephalomyelitis (ADEM) is uncommon inflammatory demyelinating disease of the central nervous system (CNS) with a wide range of clinical manifestations. The highest incidence of ADEM is observed during childhood and it usually occurs following a viral or bacterial infection or, more rarely, following a vaccination, or without a preceding cause.3 Onset of the disorder is sudden. According to the classic definition, ADEM is a monophasic disease, but it can also present a relapsing course, being described as “recurrent” if the affected districts are always the same or “multiphasic” if there is dissemination in space and time of the lesions.4 Irritability and lethargy are common first signs of ADEM. Fever and headache are reported about in half of patients. Fever in ADEM is frequently associated with the development of neurologic symptoms, which can occur after hours or weeks from the onset of illness. The most common neurologic symptoms are visual field deficits; language disturbances; mental status abnormalities ranging from irritability and lethargy to coma; psychiatric changes

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

which include depression, personality changes and psychosis. Meningeal signs are reported in children with severe disease. Weakness, which may be hemiparetic or generalized and symmetric, is more commonly detected than sensory defects. Other reported symptoms are cranial nerve palsies, generalized or focal seizures and ataxia.5-8 Here we describe an atypical case of ADEM presenting as FUO. CASE PRESENTATION The patient was an Italian boy of fifteen years old who was admitted to the pediatric department of the University of Naples “Federico II” for persistent fever from 25 days with inconstant headache, asthenia and a state of anxiety. He was in a poor state of health. The clinical examination didn’t reveal any sign of localization of fever. Familial history was unremarkable except for his sister who had used drugs in the past and was suffering from hepatitis C virus (HCV) infection. Personal history revealed only allergic rhinitis with positive skin prick test. The past medical history revealed that he had a motorcycle accident seven months before. On that occasion a CT of skull was negative. Six months before hospital admission he presented flu like syndrome. A few months before he showed a state of anxiety characterized by tachycardia and agitation. For these symptoms a neurologist recommended a drug therapy (levosulpiride, ademetionine and hypothalamic phospholipid liposomes). One week prior to admission at our hospital, he was admitted at

CASE REPORT Table 1. Laboratory Data: Complete and Differential Blood Count, Inflammatory Indexes (Erythrocyte Sedimentation Rate (ESR), C-reactive Protein (CRP), Serum Protein Electrophoresis (SPEP), Assay of Immunoglobulins). White blood cells (× 103/μL)

8.81

Red blood cells (× 106/μL)

5.02

Platelets (×

103/μL)

256

Hemoglobin (g/dL)

12.9

Hematocrit (%)

38.3

Neutrophils (%)

71.9

Lymphocytes (%)

19.7

Monocytes (%)

7.5

Eosinophils (%)

0.6

Basophils (%)

0.3

ESR (mm/h)

CRP (mg/L)

0.03

Total protein (g/dL)

6.6

IgG (mg/dl)

1112

IgA (mg/dl)

309

IgM (mg/dl)

Albumin (g/dL)

64.4

Alpha 1 (g/dL)

2.7

Alpha 2 (g/dL)

10.1

Beta (g/dL)

9.0

Gamma (g/dL)

13.8

A/G

1.81

the pediatric unit of Formia hospital for high-spiking fever, which was poor responsive to paracetamol, and inconstant headache. During the previous admission, a definitive documentation of fever and exclusion of factitious fever were obtained. A total body CT scanning was performed in order to exclude consequences of the previous motorcycle accident. The following laboratory studies, which were carried out on several occasions, resulted within the normal range: complete blood count (CBC); peripheral blood smear; inflammatory indexes (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum protein electrophoresis (SPEP), assay of immunoglobulins) (Table 1); serum chemistry; urine and blood culture; throat and urethral swab; serology for viral hepatitis, human immunodeficiency virus (HIV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex viruses (HSV), rubella and bartonella infection, brucellosis, chlamydial diseases, typhoid and paratyphoid A and B fever, rickettsiosis, syphilis and toxoplasmosis; Mantoux test and rapid

test for Malaria; immunologic screening (antinuclear antibodies, antimitochondrial antibodies, rheumatologic factor and C3-C4); thyroid hormones, cortisol, ACTH, aldosterone, angiotensin-converting enzyme; blood lead and toxicological investigations for benzodiazepines, opiates, methadone, cocaine, cannabis, amphetamines. The patient also underwent the following exams: chest and skull radiography, abdominal ultrasonography, total body CT scanning and color flow Doppler echocardiography, but these imaging studies failed to disclose the diagnosis. Appropriate consultations were indicated based on patient history, including the following: infectious disease specialist, hematologist and neurologist. Hematologist asked for a bone marrow aspirate, which resulted negative for the research of leukemia and other myeloproliferative disorders. This detailed workup was helpful to exclude the most common causes of FUO: factitious fever, infectious diseases, neoplasms, immunodeficiencies, autoimmune diseases, vasculitides, endocrine disorders, drug fever and inflammatory bowel diseases. Despite negative exams, he still had fever and was in a poor state of health. The clinical examination did not show any sign of localization of fever. His headache and panic state got worse, so an immediate ophthalmologic visit was performed. The exam of fundus oculi showed: fade borders of optical disc, raised on retinal surface (left eye > right eye). Normal macula. Increased vascular tortuosity. A cranial magnetic resonance imaging (MRI)

Figure 1. Transverse T2-weighted MRI brain image shows small high-signal lesions on the lateral right side of the pontine tegmentum.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

CASE REPORT was urgently ordered. The MRI showed some areas of hyperintensity in T2-weighted and Fluid-attenuated Inversion Recovery (FLAIR) images. These areas were in several regions of brain. They were typical of an inflammatory autoimmune disease, like ADEM (Figure 1). The next day the patient underwent an EEG, which showed suffering of temporal right areas of brain. A lumbar puncture with cerebrospinal fluid (CSF) analysis revealed elevated protein content (92 mg/dl), normal glucose content (5.2 mmol/L, compared to a random blood glucose level 7.5 mmol/L) and leukocytosis, predominantly lymphocytosis (100 lymphocytes cell/mm3). The opening pressure was normal (17 cm CSF). CSF oligoclonal bands of IgG were negative. Their presence was more often associated with Multiple Sclerosis (MS), the most important alternative diagnosis to ADEM. CSF culture and an extensive microbiologic workup for bacterial and viral infection of CNS have been helpful in distinguishing ADEM from various infectious forms of meningoencephalitis. Acute infectious encephalitis may be caused by a wide range of viruses but the most important is herpes simplex encephalitis (HSE) because of its severity, especially if untreated, and its good response to specific treatment with acyclovir. Analysis of the CSF for HSV DNA using the Polymerase Chain Reaction (PCR) has been a significant advance in the diagnosis of HSE as this test has a very high sensitivity and specificity especially with appropriate sample timing.9 In our patient serology for HSV and analysis of CSF for HSV DNA resulted negative, thus the diagnosis of HSE was ruled out. CNS vasculitides may also result in syndromes resembling ADEM, but negative serum markers of inflammation, immunologic screening and CSF analysis didn’t favor this diagnostic hypothesis. Moreover neuroimaging showed demyelization areas, typical of an autoimmunitary inflammatory disease like ADEM, so we immediately started therapy with high doses of glucocorticoids i.v. The patient received 1 g/day of methylprednisolone for 5 days, and then he continued the therapy with progressive decreased doses of methylprednisolone by oral way.4,8 Patient conditions quickly improved. Fever disappeared and headache decreased. He still had panic and anxiety, so he started a therapy with dipotassium clorazepate (5 mg/day), with improvement of symptoms. After 6 days of therapy, the patient repeated ophthalmologic visit; fundus oculi still showed mild signs of intracranial hypertension. After 13 days of therapy patient repeated cranial MRI, which showed complete resolution of the lesions. The patient was discharged in a good state of health, with a domiciliary therapy. He stopped glucocorticoids

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

therapy after 1 month. He also underwent a last ophthalmologic visit and the fundus oculi was normal. After three and six months, at follow up examination no neurologic symptoms were found. At the followup we re-evaluated the diagnosis of ADEM, because many patients initially diagnosed with ADEM develop clinically definite MS. The final diagnosis of ADEM was only established because there was no evidence of a second clinical and neuroradiologic episode of CNS demyelination. CONCLUSIONS Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelization that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination10 and is more frequent in children. Today the exact incidence of ADEM is little known. In one study of children with ADEM living in San Diego County, California, the incidence was estimated to be at least 0.4/100,000/year,11 but in the last decade ADEM has been increasingly diagnosed as more magnetic resonance imaging studies are performed on patients with acute encephalopathy. Based on its immune-mediated etiology, ADEM is commonly treated with high-dose steroids. Factors influencing treatment efficacy and possible alternative options for steroid resistant cases remain unclear. In a portion of patients who fail to respond to steroid therapy, intravenous immunoglobulin has been used with some benefit. Unsolved issues regard clinical predictors to best select therapy for groups of patients. Plasmapheresis and cytostatic drugs are alternative treatment options in patients who do not respond to steroid and/or to intravenous immunoglobulins.8 An acute encephalopathy with multifocal neurologic signs and deficits is usually the first clinical manifestation, but ADEM has a wide range of presenting features. We described an atypical case of ADEM that initially manifested as several weeks of FUO. A successful diagnosis of the underlying disease required an intensive and rational diagnostic evaluation of the wide spectrum of possible etiologies of FUO. This case report suggests a new possible syndromic association between ADEM and FUO, which should be considered in the clinical examination of patients with FUO, especially in the presence of also modest neurologic or neuropsychiatric symptoms.

CASE REPORT 7. La Mantia L, Erbetta A: Headache and inflammatory disorders of the central nervous system. Neurol Sci 2004, 25(Suppl 3):S148-53.

REFERENCES 1. Williams J, Bellamy R: Fever of unknown origin. Clin Med 2008, 8(Suppl 5):526-30.

8. Ravaglia S, Piccolo G, Ceroni M, Franciotta D, Pichiecchio A, Bastianello S, Tavazzi E, Minoli L, Marchioni E: Severe steroid-resistant post-infectious encephalomyelitis: general features and effects of IVIg. J Neurol 2007, 254(Suppl 11):1518-23.

2. Chiappini E, Galli L, Bonsignori F, Venturini E, Principi N, de Martino M: Self-reported pediatriciansâ&#x20AC;&#x2122; management of the well-appearing young child with fever without a source: first survey in an European country in the antipneumococcal vaccine era. BMC Public Health 2009, 9:300.

9. Kennedy PG. Viral encephalitis: J Neurol 2005, 252 (Suppl 3):268-72.

3. Menge T, Kieseier BC, Nessler S, Hemmer B, Hartung HP, StĂźve O: Acute disseminated encephalomyelitis: an acute hit against the brain. Curr Opin Neurol 2007, 20 (Suppl 3):247-54.

10. Tenembaum S, Chitnis T, Ness J, Hahn JS: International Pediatric MS Study Group. Acute disseminated encephalomyelitis. Neurology 2007, 68(16 Suppl 2): S23-36.

4. Marchioni E, Tavazzi E, Minoli L, Del Bue S, Ferrante P, Piccolo G, Bastianello S, Ravaglia S: Acute disseminated encephalomyelitis. Neurol Sci 2008, 29(Suppl 2):S286-8.

11. Leake JA, Albani S, Kao AS, Senac MO, Billman GF, Nespeca MP, Paulino AD, Quintela ER, Sawyer MH, Bradley JS: Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004, 23(Suppl 8):756-64.

5. Young NP, Weinshenker BG, Lucchinetti CF: Acute Disseminated Encephalomyelitis: Current Understanding and Controversies. Semin Neurol 2008, 28:84-94. 6. Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean JM: Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 2001, 56:1308-12.

Citation: Di Costanzo et al.: Acute disseminated encephalomyelitis presenting as fever of unknown origin: case report. BMC Pediatrics 2011, 11:103

Zinc Supplementation and Serum Zinc During Diarrhea Objective: Zinc deficiency is very common in developing countries and is more pronounced during an episode of diarrhea. Supplementation with zinc improves diarrhea and might correct zinc deficiency in both the short and longer term. Method: A nested study was conducted within a cluster randomized treatment trial. Fifty children with diarrhea living in the zinc treated clusters, 50 children with diarrhea living in control clusters and 50 healthy children living in the control clusters were enrolled. Serum zinc at the start of the diarrhea episode was assessed (1-3 days after supplementation began in zinc treated children), and again one week after the diarrhea ended and supplementation ceased. Baseline characteristics and serum zinc concentration were assessed. Result: Serum zinc was low in 44% of healthy children at the first blood draw. Compared to healthy controls, serum zinc was 3.1 mmol/l higher among children with diarrhea who were supplemented with zinc at first blood draw and 1.3 mmol/l higher 3 weeks later. Conclusion: Zinc supplementation enhances serum zinc concentration when given as a treatment for diarrhea and helps children maintain a more adequate zinc status during the convalescent period. Baqui AH, Black RE, Fischer Walker CL, et al. Indian J Pediatr 2006;73(6):493-7.

Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

Asian Journal of

Paediatric Practice Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Asian Journal of Paediatric Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

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Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

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Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

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Asian Journal of Paediatric Practice, Vol. 16, No. 3, 2013

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