Vitamin A Supplementation for Prevention of Bronchopulmonary Dysplasia: Cornerstone of Care or Futile Therapy?

OBJECTIVE: To review the evidence on vitamin A supplementation (VAS) and bronchopulmonary dysplasia (BPD) in extremely-low-birth-weight infants. We also discuss the impact of a vitamin A shortage on BPD rates.

DATA SOURCES: A PubMed search inclusive of dates 1946 to March 2016 was performed using the search terms bronchopulmonary dysplasia, chronic lung disease (CLD), and vitamin A STUDY SELECTION AND DATA EXTRACTION: All English-language studies were evaluated. Only those investigating VAS by intramuscular administration were included.

DATA SYNTHESIS: A total of 6 studies were evaluated. Additionally, a report on the incidence of BPD during a national shortage was reviewed. Investigators found mixed results with VAS and incidence of CLD or death in a varying number of neonates. In the largest evaluation, investigators found a statistically significant decrease in the rate of death or BPD: 55% in the VAS group versus 62% in the placebo group. The number needed to treat to prevent 1 case of BPD was 15 infants. Few studies found an increased incidence of adverse events following VAS. A report over a 2-year shortage period found that whereas the rate of VAS declined dramatically, BPD rates remained stable. This large observational evaluation calls into question the place of vitamin A in BPD prevention.

CONCLUSIONS: VAS has been identified as a strategy to decrease the incidence of BPD. Initial large-scale prospective evaluations have shown clear benefit of VAS in reducing the incidence of CLD or death. However, changing definitions of BPD and implementation of noninvasive ventilation strategies limit the application of early studies. During a drug shortage, VAS declined dramatically, but BPD rates remained stable. With concerns of sepsis and necrotizing enterocolitis in small-scale studies, and in light of the recent shortage evidence, further evaluations are necessary before VAS can be recommended as a cornerstone of BPD prevention.