Early Vitamin D Supplementation in Infants Born Extremely Preterm and Fed Human Milk: A Randomized Controlled Trial.

Abstract

To evaluate the effects of vitamin D supplementation on short-term respiratory outcomes in infants born at 28 weeks of gestation or less and fed human milk. This masked, randomized controlled trial included infants born extremely preterm and fed human milk in 2023-2024. Infants received either 800 IU/day vitamin D (intervention) or no additional vitamin D (control) for the first 14 days. Masking was maintained by adding 800 IU of vitamin D to daily feedings. The primary outcome was severity of bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age. Secondary outcomes included reactance and resistance (R_7-19) measurements, obtained using impulse oscillometry at 36 weeks postmenstrual age, and metabolic bone disease (alkaline phosphatase >500 IU/L and phosphorus <5.5 mg/dL) at postnatal day 28. A total of 126 infants were randomized (mean birthweight: 759 ± 228 g; 52% female). The intervention increased 25-hydroxy vitamin D3 concentrations (mean difference: +29 ng/mL; P < .0001). The severity of BPD did not differ between groups (P = .60). area under the reactance curve measurements were comparable (674 ± 207 vs 694 ± 240; P = .64) and R_7-19 measurements were not significantly lower in the intervention group (23 ± 8 vs 25 ± 9; P = .18). On postnatal day 28, the lower risk of metabolic bone disease observed in the intervention group did not reach statistical significance (9% vs 20%; relative risk: 0.43; 95% CI: 0.16, 1.15; P = .08). No serious adverse events related to the intervention were reported. Administering 800 IU/day of vitamin D during the first 2 weeks did not reduce BPD severity but may contribute to improved bone health. ClinicalTrials.gov: NCT05615311. https://clinicaltrials.gov/study/NCT05615311.