Safety of Early Vitamin D Supplementation in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD) and Growth Failure (P11-070-19)

To determine safety and efficacy profiles of enteral vitamin D in extremely preterm infants (< 28 weeks of gestation) exposed to early vitamin D supplementation. We analyzed demographic, clinical, and supplementation data of 74 study participants randomly assigned to receive three different regimens of early vitamin D supplementation: placebo (G1), 200 IU/day (G2) or 800 IU/day (G3) (CT.gov: NCT01600430). Study participants included in this analysis received ≥ 70 doses (0.5 ml of vitamin D or placebo every 6 hours through an orogastric tube) in the first 28 days after birth. We defined safety outcomes based on 25 (OH) vitamin D concentrations at birth (D0), postnatal day 14 (D14), and postnatal day 28 (D28). Efficacy outcomes were defined using the new BPD classification and length z-scores. The median gestational age of study participants was 26 weeks and the mean birth weight was 815g [+ /- 199]. Thirty-one participants received placebo (42%), 20 received 200 IU/day (27%), and 23 received 800 IU/day (31%). Half were male and 56% were black. Most infants received the first dose of vitamin D on or before D5 (90%). The median value of vitamin D doses given was 90 [IQR: 84-94]. The mean difference between 25 (OH) D concentrations (in ng/ml) at D14 and 25 (OH) D concentrations at D0 was + 5 in G1, + 18 in G2, + 33 in G3 (P < 0.05). The increase in 25 (OH) D concentrations from D0 to D14 was higher among black participants (26 vs 14; P < 0.05). The mean difference between 25 (OH) D concentrations at D28 and 25 (OH) D concentrations at D14 was + 2 in G1, + 6 in G2, and + 25 in G3. Vitamin D concentrations in G3 at D14 (57, IQR: 41–67) were not significantly different than vitamin D concentrations in G2 at D28 (38, IQR: 21–50; P = 0.08). At 36 weeks postmenstrual age, moderate or severe BPD was more common in infants that received placebo (31% vs 16%; P = 0.16). A decline in length-for-age Z score of > 1.2 SD was also more common in infants that received placebo (85% vs. 75%; P = 0.33). In this secondary analysis, a vitamin D dose of 800 IU/day increased vitamin D concentrations to target range by D14 and a vitamin D dose of 200 IU/day increased vitamin D concentrations to target range by D28. A combination of these two supplementation regimens seems ideal to avoid toxicity. KPRI.