SummaryBackgroundVitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D3 (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population.MethodsWe did a randomised placebo-controlled trial to compare oral 100 000 IU (2·5 mg) vitamin D3 with placebo given to children aged 1–11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379.Findings1524 children were assigned to receive vitamin D3 and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129–0·164) and the placebo group (0.137, 0·121–0·155); the incidence rate ratio was 1·06 (95% CI 0·89–1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group—a toxic level.InterpretationsQuarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting.FundingWellcome Trust and British Council.

WHAT'S KNOWN ON THIS SUBJECT: Hypovitaminosis D is common among children. Although there is prolific biochemical literature linking vitamin D to enteric immunologic function, there is a paucity of prospective data exploring the role of supplementation in prevention of diarrheal illnesses. WHAT THIS STUDY ADDS:In a high-risk population, quarterly supplementation with 100 000 IU of vitamin D 3 did not reduce the risk for first or recurrent diarrheal illnesses in a population of children aged 1 to 29 months in a low-income inner city setting. abstract OBJECTIVE: To investigate the effect of vitamin D 3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. METHODS:This double-blind placebo-controlled trial randomized 3046 high-risk 1-to 11-month-old infants to receive 6 quarterly doses of oral vitamin D 3 (cholecalciferol 100 000 IU) or placebo in inner city Kabul. Data on diarrheal episodes ($3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using KaplanMeier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. RESULTS:No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per childyear (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D 3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. CONCLUSIONS:Quarterly supplementation with vitamin D 3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D 3 supplementation for prevention of diarrheal diseases.

IntroductionChildhood diarrheal illnesses are a major public health problem. In low-income settings data on disease burden and factors associated with diarrheal illnesses are poorly defined, precluding effective prevention programs. This study explores factors associated with recurrent diarrheal illnesses among children in Kabul, Afghanistan.MethodsA cohort of 1–11 month old infants was followed for 18 months from 2007–2009. Data on diarrheal episodes were gathered through active and passive surveillance. Information on child health, socioeconomics, water and sanitation, and hygiene behaviors was collected. Factors associated with recurrent diarrheal illnesses were analyzed using random effects recurrent events regression models.Results3,045 children were enrolled and 2,511 (82%) completed 18-month follow-up. There were 14,998 episodes of diarrheal disease over 4,200 child-years (3.51 episodes/child-year, 95%CI 3.40–3.62). Risk of diarrheal illness during the winter season was 63% lower than the summer season (HR = 0.37, 95%CI 0.35–0.39, P<0.001). Soap for hand washing was available in 72% of households and 11.9% had toilets with septic/canalization. Half of all mothers reported using soap for hand washing. In multivariate analysis diarrheal illness was lower among children born to mothers with post-primary education (aHR = 0.79, 95%CI 0.69–0.91, p = 0.001), from households where maternal hand washing with soap was reported (aHR = 0.83, 95%CI 0.74–0.92, p<0.001) and with improved sanitation facilities (aHR = 0.76, 95%CI 0.63–0.93, p = 0.006). Malnourished children from impoverished households had significantly increased risks for recurrent disease [(aHR = 1.15, 95%CI 1.03–1.29, p = 0.016) and (aHR = 1.20, 95%CI 1.05–1.37, p = 0.006) respectively].ConclusionsMaternal hand washing and improved sanitation facilities were protective, and represent important prevention points among public health endeavors. The discrepancy between soap availability and utilization suggests barriers to access and knowledge, and programs simultaneously addressing these aspects would likely be beneficial. Enhanced maternal education and economic status were protective in this population and these findings support multi-sector interventions to combat illness.Trial Registration www.ClinicalTrials.gov NCT00548379 https://www.clinicaltrials.gov/ct2/show/NCT00548379

BACKGROUND AND OBJECTIVES: Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children. METHODS:In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D 3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score .1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated.RESULTS: Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: 20.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming .300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores.CONCLUSIONS: Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth.