Immunogenicity of measles-rubella vaccine administered under India’s Universal Immunization Programme in the context of measles rubella elimination goal: A longitudinal study

Background & objectives: There is a paucity of data regarding immunogenicity of recently introduced measles–rubella (MR) vaccine in Indian children, in which the first dose is administered below one year of age. This study was undertaken to assess the immunogenicity against rubella and measles 4-6 wk after one and two doses of MR vaccine administered under India’s Universal Immunization Programme (UIP). Methods: In this longitudinal study, 100 consecutive healthy infants (9-12 months) of either gender attending the immunization clinic of a tertiary care government hospital affiliated to a medical college of Delhi for the first dose of routine MR vaccination were enrolled. MR vaccine (0.5 ml, subcutaneous) was administered to the enrolled participants (1st dose at 9-12 months and 2nd dose at 15-24 months). On each follow up (4-6 wk post-vaccination), 2 ml of venous blood sample was collected to estimate the antibody titres against measles and rubella using quantitative ELISA kits. Seroprotection (>10 IU/ml for measles and >10 WHO U/ml for rubella) and antibody titres were evaluated after each dose. Results: The seroprotection rate against rubella was 97.5 and 100 per cent and against measles was 88.7 per cent and 100 per cent 4-6 wk after the first and second doses, respectively. The mean (standard deviation) titres against rubella and measles increased significantly (P<0.001) after the second dose in comparison to the levels after the first dose by about 100 per cent and 20 per cent, respectively. Interpretation & conclusions: MR vaccine administered below one year of age under the UIP resulted in seroprotection against rubella and measles in a large majority of children. Furthermore, its second dose resulted in seroprotection of all children. The current MR vaccination strategy of two doses, out of which the first is to be given to infants below one year of age, appears robust and justifiable among Indian children.

Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in Hospitalized Children

Objectives: To evaluate the antibiotic resistance pattern, clinical profile and predictors for adverse outcomes in children hospitalized due to staphylococcal infection; and the frequency of nasal and axillary carrier states in these children. Methods: This descriptive study enrolled 100 symptomatic children (aged 1 month - 12 years) in whom S. aureus was isolated from cultures of blood, pus or cerebrospinal fluid. All samples were processed as per the Clinical and Laboratory Standards Institute (CLSI) standards. Antimicrobial susceptibility was tested using disc diffusion method; minimum inhibitory concentration (MIC) for vancomycin was measured using E strips. Predictors for poor recovery were determined by univariate and multivariable logistic regression analysis. Results: Skin and soft tissue infections were the most common (47%) followed by respiratory infections (37%). Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 62%, out of which 63% (39/62) were multi-drug resistant. Carrier state was present in 49% (93% MRSA); 80% were axillary carriers. High MIC (>1 µg/mL) for vancomycin was seen in 65% of patients, and was the only factor associated with poor recovery [aOR (95%CI) 5.3 (1.6,18.5); P=0.008] on multivariable logistic regression analysis. Conclusion: MRSA is the predominant strain in severe staphylococcal infections requiring hospitalization, and majority of them are multidrug resistant. High MIC to vancomycin among S. aureus is an emerging concern.

Sunlight Exposure vs Oral Vitamin D Supplementation for Prevention of Vitamin D Deficiency in Infancy: ARandomized Controlled Trial

Objective: To compare the efficacy of sunlight exposure and oral vitamin D3 supplementation to achieve vitamin D sufficiency in infants at 6 months of age. Design: Open-label randomized controlled trial. Setting: Public hospital in Northern India (28.7°N). Participant: Breastfed infants at 6-8 weeks of age. Intervention: Randomized to receive sunlight exposure (40% body surface area for a minimum of 30 minutes/week) or oral vitamin D3 supplementation (400 IU/day) till 6 months of age. Outcome: Primary - proportion of infants having vitamin D sufficiency (>20 ng/mL). Secondary - proportion of infants developing vitamin D deficiency (<12ng/mL) and rickets in both the groups at 6 months of age. Results: Eighty (40 in each group) infants with mean (SD) age 47.8 (4.5) days were enrolled. The proportion of infants with vitamin D sufficiency increased after intervention in the vitamin D group from 10.8% to 35.1% (P=0.01) but remained the same in sunlight group (13.9%) and was significant on comparison between both groups (P=0.037). The mean (SD) compliance rate was 72.9 (3.4)% and 59.7 (23.6)% in the vitamin D and sunlight group, respectively (P=0.01). The geometric mean (95% CI) serum 25(OH) D levels in the vitamin D and sunlight group were 16.23 (13.58-19.40) and 11.89 (9.93-14.23) ng/mL, respectively; (P=0.02), after adjusting baseline serum 25(OH)D with a geometric mean ratio of 1.36 (1.06-1.76). Two infants in sunlight group developed rickets. Conclusion: Oral vitamin D3 supplementation is more efficacious than sunlight in achieving vitamin D sufficiency in breastfed infants during the first 6 months of life due to better compliance.

Aetiology of hospital-acquired diarrhoea in under-five children from an urban hospital in East Delhi, India

Background & objectives: Majority of the studies of hospital-acquired diarrhoea conducted in Western countries have focused on the detection of Clostridium difficile in stool samples. Limited Asian and Indian literature is available on hospital-acquired diarrhoea. This study was aimed to describe the aetiological profile for hospital-acquired diarrhoea in children aged below five years. Methods: One hundred children aged one month to five years who developed diarrhoea (?3 loose stools for >12 h) after hospitalization for at least 72 h were enrolled. Children who were prescribed purgatives or undergoing procedures such as enema and endoscopy or those with underlying chronic gastrointestinal disorders such as celiac disease and inflammatory bowel disease were excluded from the study. Stool samples from the enrolled children were subjected to routine microscopic examination, modified Ziel- Nielson (ZN) staining for Cryptosporidium and culture for various enteropathogens. Multiplex PCR was used to identify the strains of diarrhoeagenic Escherichia coli. Rotavirus detection was done using rapid antigen kit. Toxins (A and B) of C. difficile were detected using enzyme immunoassay. Results: Of the 100 samples of hospital-acquired diarrhoea analysed, diarrhoeagenic E. coli (DEC) was found to be the most common organism, detected in 37 per cent of cases (enteropathogenic E. coli-18%, enterotoxigenic E. coli-8%, enteroaggregative E. coli-4% and mixed infections-7%). Cryptosporidium was detected in 10 per cent of cases. Rotavirus was detected in six per cent and C. difficile in four per cent of cases. Interpretation & conclusions: The findings of this study suggest that the aetiological profile of hospital- acquired diarrhoea appears to be similar to that of community-acquired diarrhoea, with DEC and Cryptosporidium being the most common causes. The efforts for the prevention and management of hospital-acquired diarrhoea should, thus, be directed towards these organisms.

Indian Academy of Pediatrics Consensus Guidelines on Prevention and Management of Suicidal Behavior in Adolescents

Justification: Suicide is an important cause of adolescent mortality and morbidity in India. As pediatricians are often the first point of contact for adolescents and their families in the healthcare system, they need guidelines to screen, assess, manage and prevent adolescent suicidal behavior to ensure survival, health and mental well-being of this vulnerable population. Objectives: To formulate guidelines to aid pediatricians for prevention and management of adolescent suicidal behavior. Process: Indian Academy of Pediatrics, in association with Adolescent Health Academy, formed a multidisciplinary committee of subject experts in June, 2019 to formulate guidelines for adolescent suicide prevention and management. After a review of current scientific literature and preparation of draft guidelines, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by refining of draft guidelines, and discussions over e-mail where suggestions were incorporated and the final document was approved. Guidelines: Pediatricians should screen for mental distress, mental disorders and suicidal and para-suicidal (non-suicidal self-injury) behavior during adolescent health visits. Those with suicidal behavior should be referred to a psychiatrist after providing emergency healthcare, risk assessment, immediate counselling and formulation of a safety plan. Pediatricians should partner with the community and policymakers for primary and secondary prevention of adolescent suicide.

Indian Academy of Pediatrics Consensus Guidelines for Probiotic Use in Childhood Diarrhea

Justification: Several probiotic species and strains, single or combined, have been evaluated in childhood diarrheal disorders, and recommendations have ever been changing as newer trials are published. Therefore, there is a need to develop a guideline for Indian children describing the current role of probiotics in clinical practice. Objectives: To develop a guideline for the use of probiotics in children with diarrhea. Process: A national consultative group (NCG) was constituted by the Indian Academy of Pediatrics (IAP), consisting of subject experts. Sub-topics were allotted to various experts as paired groups for detailed review. Members reviewed the international and Indian literature for existing guidelines, systematic reviews, meta-analyses and trials. Thereafter, two virtual structured meetings of the group were held on 2nd and 22nd August, 2020. The management guidelines were formulated by the group and circulated to the participants for comments. The final guidelines were approved by all experts, and adopted by the IAP executive board. Recommendations: The NCG suggests Lactobacillus GG as a conditional recommendation with low-to-moderate level evidence or Saccharomyces boulardii as a conditional recom-mendation with very low-to-low level evidence as adjuvant therapy in acute diarrhea. The NCG also recommends the use of combination probiotics in neonatal necrotizing enterocolitis (NEC), as these reduce the risk of NEC stage II and above, late-onset sepsis, mortality and also time to achieve full feeds. The NCG does not recommend the use of any kind of probiotics in the therapy of acute dysentery, persistent diarrhea, Clostridium difficile diarrhea and chronic diarrheal conditions such as celiac disease, diarrheapredominant irritable bowel syndrome and inflammatory bowel disease in children. Risk of antibiotic-associated diarrhea (AAD) is high with some antibiotics and most of these cases present as mild diarrhea. The NCG recommends probiotics only in special situations of AAD. L. rhamnoses GG or S. boulardii may be used for the prevention of AAD. VSL#3, a combination probiotic, may be used as an adjuvant in active pouchitis, and for prevention of recurrences and maintenance of remission in pouchitis.

Practical Approach to the Interpretation of Complete Blood Count Reports and Histograms

Improvement in technology and inclusion of new parameters in automated hematology analyzers allows for better and faster detection of anemias. These parameters along with histograms provide details and clues that help to diagnose the etiology of anemia and help bridge the time lag in detection and treatment. Timely and expert interpretation of complete blood counts should not be limited to the pathologist but should also interest the clinician to allow for efficient patient care.

Indian Academy of Pediatrics Consensus Guidelines for Adolescent Friendly Health Services

Justification: Adolescent health is critical to the current and future well- being of the world. Pediatricians need country specific guidelines in accordance with international and national standards to establish comprehensive adolescent friendly health services in clinical practice. Process: Indian Academy of Pediatrics (IAP) in association with Adolescent Health Academy formed a committee of subject experts in June, 2019 to formulate guidelines for adolescent friendly health services. After a review of current scientific literature and drafting guidelines on each topic, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by discussions over e-mail and refining of draft recommendations. The final guidelines were approved by the IAP Executive Board in December, 2021. Objective: To formulate guidelines to enable pediatricians to establish adolescent friendly health services. Recommendations: Pediatricians should coordinate healthcare for adolescents and plan for transition of care to an adult physician by 18 years of age. Pediatricians should establish respectful, confidential and quality adolescent friendly health services for both out-patient and in-patient care. The healthcare facility should provide preventive, therapeutic, and health promoting services. Pediatricians should partner with the multidisciplinary speciality services, community, and adolescents to expand the scope and reach of adolescent friendly health services.

Indian Academy of Pediatrics Guidelines on Screen Time and Digital Wellness in Infants, Children and Adolescents

Justification: Screen-based media have become an important part of human lifestyle. In view of their easy availability and increasing use in Indian children, and their excessive use being linked to physical, developmental and emotional problems, there is a need to develop guidelines related to ensure digital wellness and regulate screen time in infants, children, and adolescents. Objectives: To review the evidence related to effects of screen-based media and excessive screen time on children’s health; and to formulate recommendations for limiting screen time and ensuring digital wellness in Indian infants, children and adolescents. Process: An Expert Committee constituted by the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines. A detailed review document was circulated to the members, and the National consultative meet was held online on 26th March 2021 for a day-long deliberation on framing the guidelines. The consensus review and recommendations formulated by the Group were circulated to the participants and the guidelines were finalized. Conclusions: Very early exposure to screen-based media and excessive screen time (>1-2h/d) seems to be widely prevalent in Indian children. The Group recommends that children below 2 years age should not be exposed to any type of screen, whereas exposure should be limited to a maximum of one hour of supervised screen time per day for children 24-59 months age, and less than two hours per day for children 5-10 years age. Screen time must not replace other activities such as outdoor physical activities, sleep, family and peer interaction, studies, and skill development, which are necessary for overall health and development of the children and adolescents. Families should ensure a warm, nurturing, supportive, fun filled and secure environment at home, and monitor their children’s screen use to ensure that the content being watched is educational, ageappropriate and non-violent. Families, schools and pediatricians should be educated regarding the importance of recording screen exposure and digital wellness as a part of routine child health assessment, and detect any signs of cyberbullying or media addiction; and tackle it timely with expert consultation if needed.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets

Justification: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. Objectives: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. Process: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. Recommendations: The group reiterates the serum 25- hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Seasonal Variation in Serum 25-hydroxy Vitamin D and its Association with Clinical Morbidity in Healthy Infants from Northern India

Objective: To evaluate the seasonal change in serum 25-hydroxyvitamin D (25-OHD) level inhealthy infants and to relate it to common childhood morbidities. Methods: 72 healthybreastfed infants residing in Delhi were enrolled at the end of summer and followed till the endof winter [mean (SD) duration 200 (10) d]. Serum 25-OHD was estimated at baseline andfollow-up. Infants were monitored for common childhood diseases. Results: Mean (SD)serum 25-OHD level was lower at the end of winter (20.7 (8.02) ng/mL) than summer (22.9(8.70) ng/mL) [mean difference (95% CI) –2.14 ng/mL (–3.36, –1.06), P<0.001). Theseasonal distribution of children according to vitamin D status in summer and winter -Deficient(15.3%, 12.5%), Insufficient (19.4%, 30.6%) and Sufficient(65.3%, 56.9%),respectively was comparable P=0.17). The morbidity profile remained unaffected by changein vitamin D status from summer to winter. Conclusions: Seasonal changes in vitamin Dlevels do not have significant clinical effect or effect on overall vitamin D status in apparentlyhealthy infants from North India. This may have implications for results of population surveysfor vitamin D status, irrespective of the season when they are conducted.

Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks

Justification: In view of easy availability and increasing trend of consumption of fast foods and sugar sweetened beverages (fruit juicesand drinks, carbonated drinks, energy drinks) in Indian children, and their association with increasing obesity and related non-communicable diseases, there is a need to develop guidelines related to consumption of foods and drinks that have the potential toincrease this problem in children and adolescents. Objectives: To review the evidence and formulate consensus statements related toterminology, magnitude of problem and possible ill effects of junk foods, fast foods, sugar-sweetened beverages and carbonated drinks;and to formulate recommendations for limiting consumption of these foods and beverages in Indian children and adolescents. Process:A National Consultative group constituted by the Nutrition Chapter of the Indian Academy of Pediatrics (IAP), consisting of variousstakeholders in private and public sector, reviewed the literature and existing guidelines and policy regulations. Detailed review ofliterature was circulated to the members, and the Group met on 11th March 2019 at New Delhi for a day-long deliberation on framing theguidelines. The consensus statements and recommendations formulated by the Group were circulated to the participants and aconsensus document was finalized. Conclusions: The Group suggests a new acronym ‘JUNCS’ foods, to cover a wide variety ofconcepts related to unhealthy foods (Junk foods, Ultra-processed foods, Nutritionally inappropriate foods, Caffeinated/colored/carbonated foods/beverages, and Sugar-sweetened beverages). The Group concludes that consumption of these foods and beveragesis associated with higher free sugar and energy intake; and is associated with higher body mass index (and possibly with adversecardiometabolic consequences) in children and adolescents. Intake of caffeinated drinks may be associated with cardiac and sleepdisturbances. The Group recommends avoiding consumption of the JUNCS by all children and adolescents as far as possible and limittheir consumption to not more than one serving per week. The Group recommends intake of regional and seasonal whole fruits over fruitjuices in children and adolescents, and advises no fruit juices/drinks to infants and young children (age <2 y), whereas for children aged 2-5 y and >5-18 y, their intake should be limited to 125 mL/day and 250 mL/day, respectively. The Group recommends that caffeinatedenergy drinks should not be consumed by children and adolescents. The Group supports recommendations of ban on sale of JUNCSfoods in school canteens and in near vicinity, and suggests efforts to ensure availability and affordability of healthy snacks and foods. TheGroup supports traffic light coding of food available in school canteens and recommends legal ban of screen/print/digital advertisementsof all the JUNCS foods for channels/magazines/websites/social media catering to children and adolescents. The Group further suggestscommunication, marketing and policy/taxation strategies to promote consumption of healthy foods, and limit availability and consumptionof the JUNCS foods

Zinc Supplementation for Promoting Growth in Children Under 5 years of age in Low- and Middle-income Countries: A Systematic Review

Objective: To study the effect of zinc supplementation in children under 5 years of age from low- and middle-income countries (LMICs) onanthropometry and prevalence of malnutrition.Design: Systematic review of randomized controlled trials and cluster randomized trials.Setting: Low- and middle-income countries.Participants: 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specificallydiseased participants and in children with severe acute malnutrition were excluded.Intervention: Zinc supplementation, provided either as medicinal supplementation or through food fortification.Outcome Measures: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalenceof malnutrition.Results: There was no evidence of effect on height-for-age Z score at the end of supplementation period (25 trials; 9165 participants;MD= 0.00 Z; 95% CI -0.07, 0.07; P=0.98; moderate quality evidence) with significant heterogeneity (I² = 57%; P<0.001) related to doseand duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11Z; 95% CI -0.00, 0.21; P=0.05), but the heterogeneity was considerable (I²=94%; P<0.001). There was no evidence of effect on length(6303 participants; MD= 1.18 cm; 95% CI -0.63, 2.99 cm, P=0.20; moderate quality evidence; considerable heterogeneity, I²=99%) but alittle positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate qualityevidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Zscore but a little positive effect on weight (19 trials; 8851 study participants; MD= 0.23 kg; 95% CI 0.03, 0.42; P=0.02; considerableheterogeneity, I²=91%) and change in weight (kg) (23 trials; 10143 study participants; MD= 0.11 kg; 95% CI 0.05, 0.17, P<0.001,substantial heterogeneity, I²=80%). There was no evidence of effect on weight-for-height Z score, and mid upper arm circumference at theend of supplementation period, but there was a little positive effect on change in mid-arm circumference from baseline (8 trials; 1724participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group wasmarginally higher compared to control (2966 study participants; MD= 0.39 cm; 95% CI 0.03, 0.75; P=0.03; substantial heterogeneity,I²=67%). There was no evidence of benefit in stunting (10 trials; 11838 study participants; RR= 1.0; 95% CI 0.95, 1.06; P=0.89; moderatequality evidence; no significant heterogeneity, I²=11%), wasting (7 trials; 8988 study participants; RR= 0.94; 95% CI 0.82, 1.06; P=0.31;moderate quality evidence; no significant heterogeneity, I²=13%) or underweight (7 trials; 8677 study participants; RR= 1.08; 95% CI 0.96,1.21; P=0.19; moderate quality evidence; substantial heterogeneity, I²=73%).Conclusion: Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indicesand malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as apublic health measure to improve growth, therefore, appears unjustified in these settings with scarce resources.

Infantile Colic: An Update

Context: Infantile colic is self-limiting condition but it can be a cause of anxiety for parents and challenge for doctors. The challenge for thedoctors lies in correct identification of the condition and appropriate management. The objective of this review article is to summarize thepathophysiology, treatment options and outcome in infantile colic so that clinicians can have a fair idea about the condition, recentupdates and future prospects.Evidence: A search of the Cochrane Library, PubMed, and Google Scholar was made using the key words “Infant colic”, Infantile colic”,“excessive crying in infants”. All the materials were analyzed and summarized.Results: At present, infantile colic is an area of clinical research both in terms of etiology and treatment. Various etiological theories havebeen proposed but none of them are strong enough to completely describe the condition. Various treatment agents are being tried forcolic like counseling and behavioral modification, dietary modification, lactase and probiotic supplementation, pain relieving agents, andchiropathy. Proper counseling of the parents is the first line of management at present. Simethicone has no role in decreasing thesymptoms of colic and Dicyclomine is not recommended in children younger than six months. No specific recommendations have beenmade on the use of pain relieving agents and manipulative therapies in colic. At present strong evidence is lacking regarding the use ofprobiotics, lactase supplementation and dietary modification.Conclusion: Counseling of parents about the benign nature of the condition is considered first line for now until an effective treatment isestablished. Other treatment options are prescribed on a case-based manner, and based on the parental perception of the condition.

Impact of Water, Sanitation and Hygiene Interventions on Growth, Non-diarrheal Morbidity and Mortality in Children Residing in Low- and Middle-income Countries: A Systematic Review

Objective: To evaluate the impact of water, sanitation and hygiene (WASH) interventions in children (age <18 y) on growth, non-diarrhealmorbidity and mortality in children.Design: Systematic review of randomized controlled trials, non-randomized controlled trials and controlled before-after studies.Setting: Low- and middle-income countries.Participants: 41 trials with WASH intervention, incorporating data on 113055 children.Intervention: Hygiene promotion and education (15 trials), water intervention (10 trials), sanitation improvement (7 trials), all threecomponents of WASH (4 trials), combined water and sanitation (1 trial), and sanitation and hygiene (1 trial).Outcome Measures: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference; (ii) Prevalence of malnutrition; (iii)Non-diarrheal morbidity; and (iv) mortality.Results: There may be little or no effect of hygiene intervention on most anthropometric parameters (low- to very-low quality evidence).Hygiene intervention reduced the risk of developing Acute respiratory infections by 24% (RR 0.76; 95% CI 0.59, 0.98; moderate qualityevidence), cough by 10% (RR 0.90; 95% CI 0.83, 0.97; moderate quality evidence), laboratory-confirmed influenza by 50% (RR 0.5; 95%CI 0.41, 0.62; very low quality evidence), fever by 13% (RR 0.87; 95% CI 0.74, 1.02; moderate quality evidence), and conjunctivitis by51% (RR 0.49; 95% CI 0.45, 0.55; low quality evidence). There was low quality evidence to suggest no impact of hygiene intervention onmortality (RR 0.65; 95% CI 0.25, 1.7). Improvement in water supply and quality was associated with slightly higher weight-for-age Z-score(MD 0.03; 95% CI 0, 0.06; low quality evidence), but no significant impact on other anthropometric parameters or infectious morbidity (lowto very low quality evidence). There was very low quality evidence to suggest reduction in mortality (RR 0.45; 95% CI 0.25, 0.81).Improvement in sanitation had a variable effect on the anthropometry and infectious morbidity. Combined water, sanitation and hygieneintervention improved height-for-age Z scores (MD 0.22; 95% CI 0.12, 0.32) and decreased the risk of stunting by 13% (RR 0.87; 95% CI0.81, 0.94) (very low quality of evidence). There was no evidence of significant effect of combined WASH interventions on non-diarrhealmorbidity (fever, respiratory infections, intestinal helminth infection and school absenteeism) (low- to very-low quality of evidence). AnyWASH intervention (considered together) resulted in lower risk of underweight (RR 0.81; 95% CI 0.69, 0.96), stunting (RR 0.77; 95% CI0.68, 0.86) and wasting (RR 0.12, 0.85) (low- to very-low quality of evidence).Conclusion: Available evidence suggests that there may be little or no effect of WASH interventions on the anthropometric indices inchildren from low- and middle-income countries. There is low- to very-low quality of evidence to suggest decrease in prevalence ofwasting, stunting and underweight. WASH interventions (especially hygiene intervention) were associated with lower risk of non-diarrhealmorbidity (very low to moderate quality evidence). There was very low quality evidence to suggest some decrease to no change inmortality. These potential health benefits lend support to the ongoing efforts for provision of safe and adequate water supply, sanitationand hygiene.

Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Anemia

Objective: To evaluate the proportion of children with moderate to severe iron-deficiencyanemia who have associated celiac disease. Methods: This cross-sectional analytical studywas conducted among children aged 1 to 12 years of age with moderate-to-severe irondeficiency anemia and control children without anemia.Serum IgA-tissue trans-glutaminaselevels were assessed in both cases and controls. All children with positive celiac serologyunderwent upper gastrointestinal endoscopy and duodenal biopsy; biopsy finding of Marshgrade 3 was considered positive for celiac disease. Results: There were 152 anemic childrenand 152 controls with mean (SD) hemoglobinof 7.7 (1.8) and 12.2 (0.74) g/dL, respectively.16 (10.5%) cases and 3 (2%) control patients had positive serology for celiac disease [OR(95% CI) 5.33 (1.52-18.67), P=0.007]. Six (3.9%) children with iron-deficiency anemia andnone of the controls had biopsy features diagnostic of celiac disease. Conclusion:In theNorthern Indian tertiary-care hospital outpatient setting, Celiac disease was associated with4% of children presenting with moderate-to-severe anemia.

Vitamin D Supplementation for Treatment and Prevention of Pneumonia in Under-five Children: A Randomized Double-blind Placebo Controlled Trial.

Objective: To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in under-five children. Design: Randomized, double blind, placebo-controlled trial. Setting: Tertiary-care hospital. Participants: 324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL). Intervention: 100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment. Outcome variables: Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness. Results: Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1·39 (1·11, 1·76); P=0·005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22·8%); vitamin D: 39/156 (25%); RR (95% CI): 1·13 (0·67,1·90); P=0·69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention. Conclusion: There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.