Early neonatal vitamin D status and neonatal sepsis: a retrospective cohort study complemented by Mendelian randomization

Vitamin D contributes to immune regulation in early life, but its relationship with neonatal sepsis remains uncertain. We examined the association between early neonatal vitamin D status and neonatal sepsis and used Mendelian randomization (MR) as a complementary genetic approach. This retrospective cohort included 366 hospitalized neonates born between 2018 and 2023 whose serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured within 72 h after birth and before vitamin D supplementation. Term neonates ( n = 235) constituted the prespecified primary analysis cohort. Multivariable logistic regression assessed the association between neonatal 25(OH)D and sepsis. Two-sample MR using genome-wide association study summary data was performed as a complementary analysis. The median neonatal 25(OH)D concentration was 37.7 nmol/L; 28.4% of neonates were deficient and 49.5% were insufficient. Among term neonates, each 10-nmol/L increase in 25(OH)D was associated with lower odds of neonatal sepsis (adjusted odds ratio 0.70, 95% confidence interval 0.54–0.90; p = 0.006). Genetically predicted higher 25(OH)D was nominally associated with lower odds of streptococcal septicemia (odds ratio 0.96, 95% confidence interval 0.924–0.996; p = 0.029). In this selected cohort of hospitalized neonates with clinician-directed 25(OH)D testing, lower concentrations measured shortly after birth were associated with higher odds of sepsis among term infants. The exploratory MR estimate for streptococcal septicemia was directionally consistent but nominal and did not establish causality. Prospective multicenter validation is required.