Vitamin A supplementation for preventing morbidity and mortality in very low birthweight infants

B A Darlow, P J Graham
Cochrane Database of Systematic Reviews 2002, (4): CD000501

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 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 June 2002, Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002), 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 </=1500g, and which reported clinical outcomes (death, chronic lung disease or bronchopulmonary dysplasia) and/or vitamin A concentrations were considered for the review.

DATA COLLECTION AND ANALYSIS: Data on mortality, requirement for supplemental oxygen at one month of age and at 36 weeks post-menstrual age, retinopathy of prematurity and nosocomial sepsis were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.

MAIN RESULTS: Seven eligible trials were identified, one having a much larger sample size than the others combined. The meta-analysis suggests supplementation with vitamin A results in benefit in terms of reducing death or oxygen requirement at one month of age [summary RR 0.93 (0.88, 0.99), RD -0.05 (-0.10, -0.01), NNT 20 (10, 100) and oxygen requirement at 36 weeks post-menstrual age [summary RR 0.87 (0.77, 0.99), RD -0.07 (-0.14, -0.01), NNT 14 (7, 100)], and trends towards reduction in oxygen requirement in survivors at one month of age [summary RR 0.93 (0.86, 1.01) and death or oxygen requirement at 36 weeks post-menstrual age [summary RR 0.91 (0.83, 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.

REVIEWER'S 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 amongst survivors at 36 weeks post-menstrual age, with this latter outcome being confined to infants with birthweight less than 1000g. 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. 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.

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