Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low and middle income countries affecting 190 million children under 5. VAD can lead to many adverse health consequences, including death. OBJECTIVES: To evaluate the effect of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged 6 months to 5 years. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2010, Issue 2),  MEDLINE (1950 to April Week 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), metaRegister of Controlled Trials and African Index Medicus (27 April 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster RCTs evaluating the effect of synthetic VAS in children aged 6 months to 5 years living in the community. We excluded studies of children in hospital and children with disease or infection. We excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion. Data were double abstracted and discrepancies resolved by discussion. Meta-analyses were performed for outcomes including all-cause and cause-specific mortality, disease, vision, and side-effects. MAIN RESULTS: Forty-three trials involving 215,633 children were included. A meta-analysis for all-cause mortality included 17 trials (194,795 children). At follow-up, there was a 24% observed reduction in the risk of all-cause mortality for vitamin A compared with control (Relative risk (RR) = 0.76 (95% confidence interval (CI) 0.69 to 0.83). Seven trials reported diarrhoea mortality and showed a 28% overall reduction for VAS (RR = 0.72 (95% CI 0.57 to 0.91)). There was no significant effect of VAS on cause specific mortality of measles, respiratory disease and meningitis. VAS reduced incidence of diarrhoea (RR = 0.85 (95% CI 0.82 to 0.87)) and measles morbidity (RR = 0.50 (95% CI 0.37 to 0.67)); however, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR = 2.75 (95% CI 1.81 to 4.19)). AUTHORS' CONCLUSIONS: VAS is effective in reducing all-cause mortality and we recommend universal supplementation for children under 5 in areas at risk of VAD. Further placebo-controlled trials of VAS in children between 6 months and 5 years of age are unnecessary, although studies that compare different doses and delivery mechanisms are needed.