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 D [25(OH)D] and is independently synthesized by the neonate. Whether neonatal DBP at birth adds predictive value beyond baseline 25(OH)D for supplementation response remains unclear. Methods: This single-center prospective cohort study enrolled 101 neonates. Neonates with 25(OH)D < 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)D ≥ 20 ng/mL served as baseline reference controls (n = 42). Serum 25(OH)D and DBP were measured at baseline and week 8 in the supplementation-response cohort. Results: Median baseline 25(OH)D was 8.6 [6.7–12.0] ng/mL and median baseline DBP was 4.9 [3.7–8.1] µg/mL. After supplementation, 25(OH)D increased significantly (median Δ = 17.7 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)D (β = −0.440, p = 0.001), followed by baseline 25(OH)D (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)D were associated with greater increases in 25(OH)D 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.