Abstract: 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; I2 = 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; I2 = 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; I2 = 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.

Plain-language summary: The review authors searched the medical literature to identify relevant studies that compared the effect of vitamin A supplementation versus control on death, illnesses, and side effects in randomly selected infants aged one to six months. The literature is current to 5 March 2016. The search identified 12 studies that involved 24,846 infants. Most of the studies were well conducted and included children from Asia, Africa, and Latin America. The results of the studies provided no convincing evidence that vitamin A supplementation reduces death or illness in infants one to six months of age (quality of evidence: moderate). Supplementation had no beneficial effects to reduce death or illness due to diarrhoea or pneumonia. Similarly, vitamin A supplementation did not reduce the proportion of children with vitamin A deficiency based on their blood levels of vitamin A (quality of evidence: moderate). Infants who were given vitamin A had an increased risk of development of bulging of soft spot at the top of the head (called bulging fontanelle) and quality of evidence for this side effect was high. However, this adverse effect did not increase subsequent risk of death or fits. In summary, vitamin A supplementation in infants one to six months of age did not reduce death or illness; however, it increased the risk of bulging fontanelle.