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

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000501. doi: 10.1002/14651858.CD000501.pub2.


Background: Vitamin A is necessary for normal lung growth and the ongoing 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. Several studies have been undertaken to assess whether vitamin A supplementation beyond that routinely given in multivitamin preparations can reduce the incidence of this outcome.

Objectives: To assess the benefit and risk of supplementation with vitamin A in very low birthweight infants.

Search strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE up to November 2006, Cochrane Central Register of Controlled Trials Register (CENTRAL, The Cochrane Library, Issue 4, 2006), and Science Citation Index. The reference lists of relevant trials, recent issues of paediatric and nutrition journals, abstracts and proceedings from relevant conferences in the English language were hand searched.

Selection criteria: Randomised controlled trials which compared the effects of supplemental vitamin A with standard vitamin A regimes in infants with birthweight </= 1500 g and reported clinical outcomes (death, chronic lung disease or bronchopulmonary dysplasia, long-term neurodevelopmental status) and/or vitamin A concentrations were considered for the review, as were trials which compared vitamin A dosing regimes and reported biochemical outcomes (retinol concentrations at 28 days).

Data collection and analysis: Data on mortality, requirement for supplemental oxygen at one month of age and at 36 weeks postmenstrual age, retinopathy of prematurity, nosocomial sepsis and follow-up at 18 to 22 months, as well as retinol concentrations at 28 days in trials comparing dosage regimes, were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.

Main results: Eight eligible trials comparing vitamin A supplementation with standard regimes were identified, one having a much larger sample size than the others combined. The meta-analysis suggests supplementation with vitamin A is beneficial in reducing death or oxygen requirement at one month of age [typical RR 0.93 (95% CI 0.88, 0.99), RD -0.05 ( 95% CI -0.10, -0.01), NNT 20 (10, 100) and oxygen requirement at 36 weeks postmenstrual age [typical RR 0.87 (95% CI 0.77, 0.98), RD -0.08 ( 95% CI -0.14, -0.01), NNT 13 (7, 100)], and trends towards reduction in oxygen requirement in survivors at one month of age [typical RR 0.93 (95% CI 0.86, 1.01) and death or oxygen requirement at 36 weeks postmenstrual age [typical RR 0.91 (95% CI 0.82, 1.00)]. Meta-analysis of the three studies from which data on retinopathy of prematurity are available suggests a trend towards reduced incidence in vitamin A supplemented infants. Neurodevelopmental assessment of 85% of surviving infants participating in the largest trial showed no differences in outcome between supplementation and placebo groups at 18 to 22 months corrected age.

Authors' conclusions: Supplementing very low birthweight infants with vitamin A is associated with a reduction in death or oxygen requirement at one month of age and oxygen requirement among survivors at 36 weeks postmenstrual age, with this latter outcome being confined to infants with birthweight less than 1000 g. 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. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections, should be assessed in a further trial.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / prevention & control*
  • Infant, Very Low Birth Weight*
  • Lung Diseases / prevention & control*
  • Randomized Controlled Trials as Topic
  • Vitamin A / therapeutic use*
  • Vitamins / therapeutic use*


  • Vitamins
  • Vitamin A