Does Vitamin D–Binding Protein Predict Response to Vitamin D Supplementation in Term and Preterm Newborns? A Prospective Cohort Study

Background: Vitamin D–binding protein (DBP) is the principal carrier of circulating 25-hydroxyvitamin D3 [25(OH)D₃] and is independently synthesized by the neonate. Whether neonatal DBP at birth adds predictive value beyond baseline 25(OH)D₃ for supplementation response remains unclear. Methods: This single-center prospective cohort study enrolled 101 neonates. Neonates with 25(OH)D₃ <20 ng/mL (supplementation-response cohort; n = 59: 29 preterm, 30 term) received 800 IU/day oral cholecalciferol for 8 weeks; neonates with 25(OH)D₃ ≥20 ng/mL served as baseline reference controls (n = 42). Serum 25(OH)D₃ and DBP were measured at baseline and week 8 in the supplementation-response cohort. Results: Median baseline 25(OH)D₃ was 8.60 [6.70–12.05] ng/mL and median baseline DBP was 4.97 [3.70–8.19] µg/mL. After supplementation, 25(OH)D₃ increased significantly (median Δ = 17.70 ng/mL; p <0.001), with 55/59 (93.2%) achieving sufficiency. In multivariable regression, gestational age was the strongest independent predictor of Δ25(OH)D3 (β = −0.440, p = 0.001), followed by baseline 25(OH)D3 (β = −0.314, p = 0.015); baseline DBP was not significant (β = 0.072, p = 0.551). Conclusions: Baseline DBP did not independently predict supplementation response. Lower gestational age and lower baseline 25(OH)D₃ were associated with greater increases in 25(OH)D₃ after supplementation, whereas baseline DBP provided no additional predictive value. Supplementation with 800 IU/day for 8 weeks was effective across gestational-age categories. Routine DBP measurement does not appear to provide additional clinical value for guiding neonatal vitamin D supplementation.