Response of Vitamin D binding protein and free Vitamin D concentrations to Vitamin D supplementation in hospitalized premature infants

Objective: The objective of this study was to evaluate the relationship between 25(OH)D, Vitamin D Binding Protein (DBP), and free vitamin D in premature infants. Methods: Thirty-two infants <32 weeks' gestation were randomized to two different levels of vitamin D3 supplementation (400 vs. 800 IU/day). 25(OH)D levels were measured by LC-MS/MS; DBP was measured by validated ELISA. Free vitamin D was calculated using molar ratios of 25(OH)D and DBP. The Wilcoxon signed rank test was used to compare DBP, free D and 25(OH)D levels; Spearman's correlation coefficients were used to assess correlations. Results: The mean gestational age at birth was 30.5 weeks; mean birth weight was 1405 g. Mean 25(OH)D levels at birth were 17.3 ng/mL; DBP levels were 297 mg/L, and estimated free vitamin D levels were 18.9. There was a statistically significant change in 25(OH)D levels after 8 weeks (24.6 vs. 39.1 ng/mL in the 400 vs. 800 group, respectively, p=0.02). DBP levels from birth to 8 weeks showed a statistically significant decrease (267 vs. 208, p=0.04). Estimated free 25(OH)D concentrations increased over the study period, from 18.9 at birth to 64.7 at 8 weeks of age (p=0.0001). Free vitamin D levels at birth were associated with global DEXA bone mineral content at discharge from the NICU (r=0.58, p=0.05). Conclusion: Supplementation with vitamin D3 increased the free portion of the vitamin D metabolite, providing increased bioavailable substrate. Improved free vitamin D levels may improve measurable outcomes such as bone mineral content and deserve further evaluation.