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

Abstract

Background: Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth, and this has been associated with increased risk of developing chronic lung disease.

Objectives: To evaluate vitamin A supplementation on the incidence of death and/or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birthweight infants (VLBW); and to consider the effect of the supplementation route, dose, and timing.

Search strategy: In August 2011, the Cochrane Central Regsiter of Controlled Trials (Central, The Cochrane Library), MEDLINE, Science Citation Index and the Oxford Database of Perinatal Trials were searched. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2007.

Selection criteria: Randomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birthweight ≤ 1500 g or < 32 weeks' gestation).

Data collection and analysis: Both review authors screened the search results, extracted data, and assessed the trials' risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data.

Main results: Nine trials met the inclusion criteria, eight compared vitamin A supplementation with a control (1291 infants), and one compared different regimens (120 infants). Compared to the control group, vitamin A appears to be beneficial in reducing death or oxygen requirement at one month of age (RR 0.93, 95% CI 0.88 to 0.99; RD -0.05, 95% CI -0.10 to -0.01; NNTB 20, 95% CI 10 to 100; 1165 infants) and oxygen requirement at 36 weeks' postmenstrual age (RR 0.87, 95% CI 0.77 to 0.98; RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 824 infants). A trend towards a reduction in death or oxygen requirement at 36 weeks' postmenstrual age was also noted (RR 0.91, 95% CI 0.82 to 1.00; 1001 infants). Neurodevelopmental assessment of 88% of surviving infants in the largest trial showed no differences between the groups at 18 to 22 months of age, corrected for prematurity. The different dosage vitamin A regimens showed similar results.

Authors' conclusions: 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 this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.