Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

Systematic review and meta-analysis of randomized and cluster-randomized trials in community-dwelling children aged 6 months to 5 years, largely from low- and middle-income countries. The evidence base included multiple trials with placebo or control comparators and occasional factorial designs that tested vitamin A alone and in combination with other interventions.

Oral vitamin A supplementation was evaluated across randomized trials in children aged 6 months to 5 years, most commonly as high-dose retinol palmitate capsules given every 4 to 6 months, with age-based dosing such as 50,000 IU, 100,000 IU, or 200,000 IU. Some trials used weekly low-dose regimens or single-dose supplementation, but the overarching intervention was vitamin A versus placebo or control.

Vitamin A supplementation reduced all-cause mortality and several important morbidity outcomes in young children. Pooled all-cause mortality was lower with vitamin A, with RR 0.88 (0.83 to 0.93) in the fixed-effect model and RR 0.76 (0.66 to 0.88) in the random-effects model; diarrhoea mortality was also reduced, RR 0.88 (0.79 to 0.98). Vitamin A lowered diarrhoea incidence, RR 0.85 (0.82 to 0.87), and measles incidence, RR 0.50 (0.37 to 0.67), while reducing vitamin A deficiency status, RR 0.71 (0.65 to 0.78). Short-term vomiting was increased, RR 1.97 (1.44 to 2.69).

Heterogeneity was substantial for some morbidity outcomes, especially diarrhoea-related measures, and the review included trials with different dose schedules, follow-up periods, and settings. Several estimates were influenced by very large studies, including DEVTA, and some trials had incomplete arm-level reporting or clustered designs that limit direct comparability. The authors also note that placebo-controlled trials are ethically problematic in settings with known vitamin A deficiency.