Periodic high-dose vitamin A supplementation at 6-59 months of age is recommended by the World Health Organization (WHO) for the revention of vitamin A deficiency and for reducing the risk of death in children. Vitamin A supplementation for 1-5 month old infants has not been shown to be beneficial in reducing infant mortality and morbidity. There has been considerable interest in research on vitamin A supplementation of infants less than 1 month old (neonatal supplementation) but the results of randomized controlled trials evaluating this intervention are conflicting.
A systematic review of literature commissioned by WHO identified 6 randomized controlled trials (RCTs) involving 42,508 infants that evaluated neonatal vitamin A supplementation (given at <1 month of age). A meta-analysis of these trials suggested no overall reduction in infant mortality in the intervention group (pooled relative risk 0.92, 95% CI 0.75 to 1.12, P=0.393; I2=54.1%, P=0.053). The available evidence however is not enough to either accept or reject neonatal vitamin A supplementation as an intervention with considerable potential for improving infant survival.
A technical consultation convened by WHO in December 2008 recommended a specific set of randomized placebo-controlled trials to produce the necessary evidence to determine the effect of neonatal vitamin A supplementation given within the first two days after birth on mortality in the first six months of life. The trials should be conducted in settings with high infant mortality. Given the limitations of the data available, three trials were recommended: at least two in Africa and one in Asia. Additionally, the experts indicated the need to study the biological mechanisms of action that may explain the possible beneficial effect of vitamin A supplementation on infant survival.
This project therefore aims to assess the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival as well as the potential mechanisms involved. We propose to conduct three large randomized controlled trials, each with enough statistical power to detect a 15% or greater reduction in the risk of death in the first half of infancy in low- and middle-income countries, two in sub-Saharan Africa and one in south Asia. Additionally, we propose to conduct animal and human studies on biological mechanisms that could explain the possible beneficial effects of vitamin A supplementation.
