Association between early postnatal serum 25-hydroxyvitamin D and necrotizing enterocolitis in very preterm infants: a retrospective cohort study

Vitamin D plays an important role in intestinal immune regulation and epithelial barrier function, but its association with necrotizing enterocolitis (NEC) in very preterm infants remains uncertain. We investigated whether early postnatal serum 25-hydroxyvitamin D [25(OH)D] concentrations were associated with subsequent NEC in very preterm infants. We retrospectively included very preterm infants who underwent early postnatal serum 25(OH)D measurement on postnatal days 5–7 between January 2023 and December 2024. Restricted cubic spline (RCS) analysis, multivariable logistic regression, sensitivity analyses, subgroup analyses, and receiver operating characteristic analysis were performed to evaluate the association between 25(OH)D and NEC. Among the 228 infants, 70 developed Bell stage II or III NEC. Infants with NEC had significantly lower serum 25(OH)D concentrations than those without NEC (23.8 ± 9.2 vs. 36.7 ± 11.7 ng/mL, P < 0.001). Lower serum 25(OH)D concentrations remained independently associated with subsequent NEC after adjustment for major perinatal and neonatal covariates. RCS analysis demonstrated a significant non-linear association, with NEC risk decreasing as serum 25(OH)D concentrations increased before reaching a plateau at approximately 25–30 ng/mL. The association remained consistent across sensitivity and subgroup analyses. Addition of serum 25(OH)D improved discrimination beyond gestational age and birth weight alone. Among very preterm infants who underwent early serum 25(OH)D measurement, lower early postnatal serum 25(OH)D concentrations were independently associated with subsequent NEC. Future prospective multicenter studies are warranted to validate these findings. Not applicable.