High-Dose Vitamin D and Low-Dose Vitamin A May Reduce Bronchopulmonary Dysplasia in Preterm Infants

This network meta-analysis evaluated the effects of different supplemental doses of vitamins A and D on the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. The analysis included 4357 preterm infants from randomized controlled trials, though the specific number of trials, settings, and follow-up durations were not reported. The intervention consisted of various doses of vitamin A and D supplementation, compared with placebo and other supplementation strategies. The primary outcome was the incidence of BPD, with secondary outcomes including mortality and duration of mechanical ventilation.

For the primary outcome, high-dose vitamin D (≥800 IU/d) showed the most notable reduction in BPD incidence. However, no effect size, absolute numbers, confidence intervals, or p-values were reported for this finding. The direction of effect was favorable for high-dose vitamin D. For mortality, low-dose vitamin A (<3330 IU/d) exhibited the lowest mortality among all strategies, but there were no statistically significant differences between any supplementation strategy or placebo. Again, specific numerical data were not provided. For mechanical ventilation duration, high-dose vitamin A (≥3330 IU/d) was associated with the shortest duration, though effect sizes and statistical measures were not reported.

Safety and tolerability data, including adverse events, serious adverse events, and discontinuations, were not reported in this meta-analysis. The study did not report any specific limitations, funding sources, or conflicts of interest. The authors noted that this is a network meta-analysis of RCTs, so results are pooled estimates and represent associations only, not causal relationships.

Compared to prior studies, this analysis synthesizes evidence on both vitamins A and D for BPD prevention, which is a common and serious complication in preterm infants. Previous individual trials have shown mixed results, and this meta-analysis attempts to clarify optimal dosing. However, the lack of reported effect sizes and confidence intervals limits the ability to compare these results directly with prior landmark studies.

Key methodological limitations include the absence of reported p-values and confidence intervals for the main outcomes, which prevents assessment of statistical precision and clinical significance. Additionally, the study did not specify the number of trials included, the quality of the trials, or the heterogeneity among them. The lack of safety data is a significant gap, as vitamin supplementation at high doses may carry risks such as toxicity.

Clinically, these findings suggest that high-dose vitamin D (≥800 IU/d) and low-dose vitamin A (<3330 IU/d) may be considered for prevention of BPD in preterm infants. However, given the absence of robust statistical data and safety information, clinicians should interpret these results with caution. The mortality benefit of low-dose vitamin A was not statistically significant, so it should not be assumed to reduce mortality.

Several questions remain unanswered. The optimal duration of supplementation, the long-term outcomes of high-dose vitamin D, and the potential for adverse effects are not addressed. Future research should focus on well-designed RCTs with adequate sample sizes, clear reporting of effect sizes and confidence intervals, and comprehensive safety monitoring to confirm these findings and establish definitive clinical guidelines.