Abstract: Eleven trials met the inclusion criteria. Ten trials (1460 infants) compared vitamin A supplementation with a control and one (120 infants) compared different regimens of vitamin A supplementation. Compared to the control group, vitamin A appeared to have a small benefit in reducing the risk of death or oxygen requirement at one month of age (typical RR 0.93, 95% CI 0.88 to 0.99; typical RD −0.05, 95% CI −0.10 to −0.01; NNTB 20, 95% CI 10 to 100; 6 studies, 1165 infants) and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (typical RR 0.87, 95% CI 0.77 to 0.99; typical RD −0.07, 95% CI −0.13 to −0.01; NNTB 11, 95% CI 6 to 100; 5 studies, 986 infants) (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (typical RR 0.92, 95% CI 0.84 to 1.01; typical RD −0.05, 95% CI −0.11 to 0.01; 4 studies, 1089 infants). Neurodevelopmental assessment of 88% of the surviving infants in the largest trial showed no difference between the groups at 18 to 22 months of age, corrected for prematurity (low-quality evidence). There is no evidence to support different vitamin A dosing regimens. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.

Plain-language summary: Eleven trials were included in this review, ten comparing vitamin A with a control (placebo or no supplementation) and one comparing different vitamin A regimens. The search for eligible trials was updated in May 2016. Compared to the control group, supplementing very low birth weight infants with vitamin A appears to have a small benefit in reducing the risk of death or oxygen requirement at one month of age and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (moderate-quality evidence). Although there is a statistical reduction in chronic lung disease, these findings are consistent with either a meaningful impact on chronic lung disease or a negligible impact. The one trial that investigated neurodevelopmental status at 18 to 22 months of age correcting for prematurity found no evidence of benefit or harm associated with vitamin A supplementation compared to control (low-quality evidence). No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.