1. Paixao, Maria Jose Gois MSc, RN


Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. For more information, see


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What is the effect of synthetic vitamin A supplementation on morbidity, mortality, and adverse events in infants, one to six months of age, in low- and middle-income countries?



This is a Cochrane intervention review of 12 randomized or quasi-randomized controlled trials.



Vitamin A deficiency suppresses the immune system, thereby increasing the risk of infections, xerophthalmia, and blindness. Because vitamin A is not produced by the body, it must come from external sources. During pregnancy, adequate vitamin A is transferred from mother to fetus regardless of maternal dietary intake. During lactation, however, vitamin A concentration in breast milk is more sensitive to variations in maternal intake, putting newborns of malnourished mothers at risk for vitamin A deficiency. Infants in low- and middle-income regions are at even greater risk for vitamin A deficiency because they tend to have low liver stores at birth, decreased absorption, and increased losses due to recurrent gastrointestinal infections.


Vitamin A supplementation has been shown to reduce morbidity and mortality in children ages six to 59 months; one to six months of age is an advantageous time for delivery of vitamin A supplementation, however, because it can be done along with routine vaccination, ensuring that more infants receive it.



This review included 12 studies for a total of 24,846 infants ages one to six months. Synthetic vitamin A supplementation was compared with placebo in eight studies and with no intervention in four. The studies were conducted in eight countries: Bangladesh (4); Nepal (2); Indonesia (1); Turkey (1); Ghana (2); Kenya (1); and India, Ghana, and Peru (1).


In the seven studies reporting the primary outcome of all-cause mortality, there was a 5% increased risk of mortality in the intervention group, but this was not statistically significant. There were no statistically significant effects of vitamin A supplementation on the secondary outcomes of morbidity or mortality due to diarrhea or acute respiratory tract infection. There was also no increased risk of adverse events such as vomiting, irritability, diarrhea, fever, and convulsions. The intervention group had a threefold increased risk of bulging fontanelle compared with controls, but there were no subsequent complications from this adverse event. Finally, vitamin A supplementation did not decrease vitamin A deficiency in the intervention group compared with controls.



Vitamin A supplementation in infants one to six months of age did not decrease the risk of mortality or morbidity and did not have any demonstrable effect on immune response to vaccination. These results support the 2011 World Health Organization recommendation that vitamin A supplementation in infants one to five months of age is not recommended for the reduction of morbidity and mortality.



Most of the research on the effects of vitamin A supplementation in this review was conducted about 20 years ago; it is not clear if there would be beneficial effects now that the overall prevalence of vitamin A deficiency is decreasing. Future research might provide further insight into which characteristics of younger infants are detrimentally effected by vitamin A supplementation.




Imdad A, et al. Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age. Cochrane Database Syst Rev 2016;9:CD007480.