Vitamin D and Neonatal Sepsis: Current Evidence, Biological Mechanisms, and Future Directions—A Scoping Review

Objective: Neonatal sepsis is a major cause of morbidity and mortality. Vitamin D modulates immune responses and influences the risk and outcomes of neonatal sepsis. Therefore, we aimed to systematically outline the role of vitamin D in neonatal sepsis, including its effects on incidence, severity, treatment outcomes, and underlying mechanisms. Methods: A literature search was conducted in the MEDLINE and EMBASE databases with English language restrictions and no date limit. Eligible sources included experimental, observational, and descriptive studies as well as reviews addressing vitamin D status, supplementation, and mechanisms in neonatal sepsis. This review followed the PRISMA Extension for Scoping Reviews guidelines. Results: Forty-five studies were selected and analyzed. Vitamin D deficiency was globally prominent among neonates and may be correlated with an increased risk or severity of sepsis. Most studies were observational, primarily case-control or cross-sectional, and conducted in South Asia and the Middle East, with increasing research activity after 2018. The number of term infants was higher than that of preterm infants. Recently, innate immune mechanisms, including antimicrobial peptides and toll-like receptor signaling, were highlighted. However, comparisons across studies were limited by inconsistencies in design, vitamin D cut-offs, timing of blood sampling, and sepsis definitions. Only six studies included patients with culture-proven sepsis, whereas others included clinically suspected cases. Few studies assessed the long-term outcomes, immune maturation, or neurodevelopmental consequences. Conclusions: Vitamin D deficiency may be associated with neonatal sepsis; however, the findings remain inconsistent because of methodological variability. Therefore, high-quality, standardized, multicenter studies are needed. The review also identified substantial methodological heterogeneity regarding vitamin D assessment, sepsis definitions, and neonatal populations, which currently limits evidence-based clinical recommendations.