A controlled trial of the effects of vitamin A supplementation for low birth-weight neonates did not show any beneficial effects and suggested the possibility of harm in girls.

Vitamin A supplementation for babies around 6 months old is widely used in low-income countries and has been shown to be associated with mortality reductions. It is not clear whether neonatal supplementation has benefits, however, and this paper reports the results of one of two parallel trials examining this issue. In this study, carried out in Guinea-Bissau, infants who weighed less than 2.5kg at birth were randomised to receive vitamin A 25,000 units or placebo. They were followed to age 12 months, and the primary outcome was mortality, calculated as mortality rate ratios (MRR).

There were 1,736 babies randomised to treatment, of whom 1,717 were eligible for the final analysis. Vitamin A supplementation at birth was not significantly associated with mortality: MRR for supplementation compared with placebo was 1.08 (95% CI 0.79 to 1.47).

A pre-specified analysis stratified by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046). MRR for supplementation was 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. The parallel trial examined supplementation in normal birthweight infants, and when data from the studies were combined, the combined estimate of the effect of supplementation on mortality was 1.08 (95% CI 0.87 to 1.33). Stratified by sex, the MMR were 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex).

The authors conclude that the combined trial results indicate that neonatal vitamin A supplementation would not be justified for Guinea-Bissau. While the data should be taken with caution, they suggest a possible harmful effect in girls: this would justify re-analysis of the data from similar previous studies stratified by sex.