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.