Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial.

Three-arm randomized controlled trial in Guinea-Bissau among healthy normal-birth-weight neonates (>2500 g) enrolled at birth and given Bacille Calmette-Guérin vaccination. A total of 6048 infants were randomized in a 1:1:1 allocation to 50,000 IU vitamin A (n=2015), 25,000 IU vitamin A (n=2011), or placebo (n=2022), with mortality followed to 12 months of age.

Neonatal vitamin A supplementation was given as a single oral dose at birth, using retinyl palmitate. Two active regimens were tested: 50,000 IU versus 25,000 IU, each administered into the mouth with a sterile syringe in 0.5 mL oil, compared with placebo.

The lower and higher neonatal vitamin A doses did not differ in their effect on mortality, and neither dose reduced infant mortality versus placebo. Mortality rate ratio for 25,000 IU versus 50,000 IU was 0.96 (95% CI 0.67, 1.38); 50,000 IU versus placebo was 1.31 (0.89, 1.93); and 25,000 IU versus placebo was 1.26 (0.85, 1.86). When both vitamin A groups were combined, the mortality rate ratio versus placebo was 1.28 (0.91, 1.81). Subgroup analyses by sex also showed no clear benefit, with boys at 0.79 (0.48, 1.30) and girls at 1.21 (0.70, 2.08).

The main analysis was limited by relatively few deaths (160) over 4125 person-years, which reduces precision for detecting modest effects. Findings from subgroup and time-window analyses are exploratory and were not consistent with a survival benefit. The trial was conducted in healthy normal-birth-weight neonates in one setting in Guinea-Bissau, which may limit generalizability.