Vitamin D Status and Neonatal Respiratory Health: A Systematic Review and Meta-Analysis of Risk and Intervention Efficacy

CONTEXT: Vitamin D (VD) is integral to lung maturation and immune regulation, yet its association with neonatal respiratory diseases remains debated. OBJECTIVES: This study aimed to clarify the association between vitamin D (VD) status and neonatal respiratory diseases, to quantify the risk posed by VD deficiency (VDD), and to evaluate the therapeutic benefits of VD supplementation. DATA SOURCES: A comprehensive search was conducted in PubMed, Web of Science, EMBASE, and other major databases for studies published up to October 1, 2025. DATA EXTRACTION: Following the PRISMA guidelines, 2 reviewers independently screened the studies, extracted data, and assessed its quality. Observational studies and randomized controlled trials (RCTs) were included. DATA ANALYSIS: Thirty-one studies (23 observational, 8 RCTs) involving over 3000 neonates were analyzed using a random-effects meta-analysis. Neonates with respiratory disease exhibited significantly lower 25(OH)D levels (standardized mean difference, SMD = -0.66; 95% CI: -0.90 to -0.41). Vitamin D deficiency was associated with an increased risk of respiratory distress syndrome (RDS) (adjusted odds ratio [aOR] = 2.57; 95% CI: 1.55-4.24); however, this association was attenuated after adjusting for publication bias. Vitamin D supplementation effectively restored VD status (SMD = 2.80, 95% CI: 1.70-3.89) and may reduce morbidity, particularly with higher doses (800-1000 IU/day) or maternal administration. CONCLUSIONS: Vitamin D deficiency represents a significant risk marker, but its role as an independent causal factor may be overestimated. Supplementation, particularly with higher doses or maternal administration, is a feasible adjunct strategy, but high-quality RCTs are imperative for establishing definitive intervention protocols. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD420251152942.