Vitamin D Roles Across Developmental Stages in Pediatric Pneumonia: Linking Genetics, Microbiome, Maternal Status and Immunity.

BACKGROUND: Pneumonia remains a leading cause of morbidity and mortality among children globally, especially in low- and middle-income countries, where poor nutrition and limited access to healthcare increase vulnerability. Vitamin D deficiency is common among children and has emerged as a significant risk factor associated with respiratory infections. This review aims to synthesize current evidence on the role of vitamin D across developmental stages in pediatric pneumonia. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar to identify relevant studies on vitamin D and pediatric pneumonia. Peer-reviewed articles, including observational studies, randomized controlled trials, and reviews, were screened. Evidence was synthesized from immunology, genetics, maternal health, and microbiome research to provide an integrated perspective on vitamin D-mediated immune responses and clinical outcomes. RESULTS: Mechanistically, vitamin D enhances host defense by inducing antimicrobial peptides such as cathelicidin and β-defensins. It improves macrophage phagocytic function, modulates Toll-like receptor signaling, and preserves airway epithelial barrier integrity. Vitamin D also modulates adaptive immunity by suppressing pro-inflammatory Th1 and Th17 responses while promoting regulatory T-cell activity and anti-inflammatory cytokine production. Epidemiological studies consistently show an association between low serum 25-hydroxyvitamin D levels and increased risk and severity of pneumonia, although results from supplementation trials remain heterogeneous. Recent evidence highlights additional modifiers of vitamin D-mediated immunity, including maternal vitamin D status, vitamin D receptor (VDR) genetic polymorphisms, early-life immune programming, and respiratory microbiome interactions, which may explain variability in clinical outcomes across populations and developmental stages. CONCLUSION: Overall, this review provides a comprehensive framework linking vitamin D biology with immune system development in children and their risk of pneumonia. It emphasizes the importance of age-specific supplementation strategies and well-designed mechanistic and clinical studies to improve prevention and management.