Randomized trial of two doses of vitamin D(3) in preterm infants <32 weeks: Dose impact on achieving desired serum 25(OH)D(3) in a NICU population

BACKGROUND: Recommendations for vitamin D supplementation for preterm infants span a wide range of doses. Response to vitamin D supplementation and impact on outcomes in preterm infants is not well understood. OBJECTIVE: Evaluate serum 25(OH)D(3) concentration changes after 4 weeks in response to two different doses of vitamin D(3) supplementation in a population of premature infants and quantify the impact on NICU outcomes. DESIGN: 32 infants born at 24–32 weeks gestation were prospectively randomized to receive 400 or 800 IU/day vitamin D(3) supplementation. Serum 25(OH)D(3) levels were measured every 4 weeks. The Wilcoxon signed rank test was used to compare serum levels of 25(OH)D(3) at 4 weeks and each subsequent time point. A p-value of <0.05 was considered statistically significant. RESULTS: Serum 25(OH)D(3) levels at birth were 41.9 and 42.9 nmol/l for infants in the 400 IU group and 800 IU group, respectively (p = 0.86). Cord 25(OH)D(3) concentrations significantly correlated with gestational age (r = 0.40, p = 0.04). After 4 weeks of D(3) supplementation, median 25(OH)D(3) levels increased in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day respectively, with significantly more improvement in the higher dose (p = 0.048). Infants in the 400 IU group were significantly more likely to have dual energy x-ray absorptiometry (DEXA) bone density measurements <10 percentile (56% vs 16%, p = 0.04). CONCLUSIONS: Improvement in 25(OH)D(3) levels at 4 weeks, bone density, and trends towards improvement in linear growth support consideration of a daily dose of 800 IU of vitamin D for infants <32 weeks cared for in the NICU.