Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants.

Systematic review and meta-analysis of randomized trials in very low birth weight preterm infants, generally defined as birth weight <=1500 g or gestation <32 weeks, comparing vitamin A with placebo or no supplementation. Ten trials reported outcomes for 1460 infants in pooled analyses, with 735 assigned to vitamin A and 725 to control.

Vitamin A supplementation was evaluated in multiple regimens, most commonly intramuscular dosing; the largest trial used 5000 IU intramuscularly three times weekly for 4 weeks. Other studies used oral vitamin A 5000 IU daily to day 28 or vitamin A delivered in intravenous lipid emulsion during parenteral nutrition, with doses ranging from 1500 to 10,000 IU depending on the trial.

Vitamin A supplementation produced a modest overall benefit for very low birth weight infants, with a small reduction in death or oxygen use at 1 month and a marginal reduction in chronic lung disease or oxygen use at 36 weeks postmenstrual age. There was no clear long-term neurodevelopmental benefit or harm; follow-up at 18 to 22 months showed no difference (RR 0.89, 95% CI 0.74 to 1.08). No adverse effects were reported in the trials, although intramuscular injections were painful. Overall, the evidence supports a small respiratory benefit, but the effect size is modest and the optimal dosing strategy remains uncertain.

The evidence base was heterogeneous, with different routes, doses, and timing of vitamin A delivery across trials. Several studies were small, and long-term neurodevelopmental data were limited. Intramuscular treatment acceptability is also a practical limitation because injections were painful, and the review did not show clear advantages for alternative dosing regimens.