Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in developing countries

Background Vitamin A deficiency is a major public health problem in developing countries. Vitamin A supplementation in children greater than six months of age has been found to be beneficial, with no effect of supplementation between one to five months. Supplementation in the neonatal period has been suggested to have an impact by increasing body stores in early infancy. Objectives To evaluate the role of vitamin A supplementation in term neonates in developing countries with respect to the prevention of mortality and morbidity. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2010), EMBASE and MEDLINE (1966 to May 2010) via PubMed. Selection criteria Randomised and quasi-randomised controlled trials. Trials with factorial designs were also included. Data collection and analysis Two review authors independently assessed trial quality and extracted the data. Main results Seven trials (51,446 neonates) were included in this review, with only few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (where specified) followed by all infants. Data for term neonates from three studies showed a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.82; 95% CI 0.68 to 0.99; I-2 63%). Analysis of data for all infants from five studies showed a 14% reduction in the risk of infant mortality at six months in neonates supplemented with vitamin A compared to control; this reduction was statistically significant (typical RR 0.86; 95% CI 0.77 to 0.97; I-2 39%). These findings should be interpreted with caution, however, due to the small number of included studies, wide confidence intervals with upper levels close to the null effect and statistical heterogeneity. Vitamin A supplementation failed to show any significant effect on infant mortality at 12 months of age compared to control (typical rate ratio 1.03; 95% CI 0.87 to 1.23; I-2 49%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events. Authors' conclusions Considering mortality in early infancy being a major contributory cause of overall child mortality for the under five year old group in developing countries, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation in neonates. Evidence provided in this review does indicate a potential beneficial effect of supplementing neonates with vitamin A at birth for reducing mortality in the first half of infancy. Considering the absence of a clear indication of the biological mechanism and conflicting findings from individual studies in settings with varying levels of maternal vitamin A deficiency and infant mortality, and given four additional ongoing trials with approximately 100,000 neonates being enrolled, we propose a delay in any policy recommendations for neonatal vitamin A supplementation.