Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age

Aamer Imdad, Zunirah Ahmed, Zulfiqar A Bhutta

Vitamin A deficiency is a significant public health problem in low- and middle-income countries. Vitamin A supplementation provided to infants less than six months of age is one of the strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity. To evaluate the effect of synthetic vitamin A supplementation in infants one to six months of age in low- and middle-income countries, irrespective of maternal antenatal or postnatal vitamin A supplementation status, on mortality, morbidity and adverse effects. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 5 March 2016), Embase (1980 to 5 March 2016) and CINAHL (1982 to 5 March 2016). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised, individually or cluster randomised trials involving synthetic vitamin A supplementation compared to placebo or no intervention provided to infants one to six months of age were eligible. Two review authors assessed the studies for eligibility and assessed their risk of bias and collected data on outcomes. The review included 12 studies (reported in 22 publications). The included studies assigned 24,846 participants aged one to six months to vitamin A supplementation or control group. There was no effect of vitamin A supplementation for the primary outcome of all-cause mortality based on seven studies that included 21,339 (85%) participants (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.89 to 1.25; I(2) = 0%; test for heterogeneity: P = 0.79; quality of evidence: moderate). Also, there was no effect of vitamin A supplementation on mortality or morbidity due to diarrhoea and respiratory tract infection. There was an increased risk of bulging fontanelle within 24 to 72 hours of supplementation in the vitamin A group compared to control (RR 3.10, 95% CI 1.89 to 5.09; I(2) = 9%, test for heterogeneity: P = 0.36; quality of evidence: high). There was no reported subsequent increased risk of death, convulsions or irritability in infants who developed bulging fontanelle after vitamin A supplementation, and it resolved in most cases within 72 hours. There was no increased risk of other adverse effects such as vomiting, irritability, diarrhoea, fever and convulsions in the vitamin A supplementation group compared to control. Vitamin A supplementation did not have any statistically significant effect on vitamin A deficiency (RR 0.86, 95% CI 0.70 to 1.06; I(2) = 27%; test for heterogeneity: P = 0.25; quality of evidence: moderate). There is no convincing evidence that vitamin A supplementation for infants one to six months of age results in a reduction in infant mortality or morbidity in low- and middle-income countries. There is an increased risk of bulging fontanelle with vitamin A supplementation in this age group; however, there were no reported subsequent complications because of this adverse effect.