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Ahmadi S, Sahraei Z. Vitamin D and Pneumonia in Children: Immunological Mechanisms, Clinical Outcomes, and Current Evidence. Pharm Biomed Res 2026; 12 (2) :73-86
URL: http://pbr.mazums.ac.ir/article-1-736-en.html

Background: Vitamin D plays a notable role in regulating both innate and adaptive immunity. It supports the production of antimicrobial peptides, promotes autophagy, and helps control inflammatory signaling. These functions suggest that vitamin D may contribute to respiratory defense. However, the relationship between vitamin D levels and childhood pneumonia remains unclear and has shown inconsistent results in different studies. 
Objectives: To explore the biological mechanisms of vitamin D in respiratory immunity, evaluate the association between serum 25(OH)D levels and childhood pneumonia risk/severity, assess trial results in deficient versus replete populations, and identify sources of inconsistency across studies.
Methods: This narrative review includes observational and interventional studies from several regions, such as South Asia, the Middle East, and Africa. We included studies that reported serum 25(OH)D levels, markers of pneumonia severity, and clinical outcomes in children. Special attention was given to mechanistic evidence, dose-response patterns, and differences in findings between vitamin D deficient and vitamin D adequate populations. 
Results: Observational studies show that children with pneumonia have lower vitamin D levels than healthy controls. Deficiency is associated with greater susceptibility, longer hospital stays, hypoxemia, and a higher risk of complications like sepsis. A dose-response relationship has been observed, where higher 25(OH)D levels are associated with less severe disease. However, randomized controlled trials have produced mixed results. Benefits, such as reduced recurrence and modest recovery improvements, are mainly seen in vitamin D deficient populations, with little to no effect in replete groups. These inconsistencies likely stem from differences in study design and a lack of detailed clinical endpoints. 
Conclusion: Observational studies associate low vitamin D with worse pneumonia outcomes in children, but randomized control trials show inconsistent results. Potential benefits (reduced recurrence, modest clinical improvement) appear mainly in deficient children, yet causality remains unproven due to heterogeneity in study design, deficiency definitions, and outcome measures. The lack of standardized pediatric vitamin D cutoffs (ranging from <12 to <20 ng/mL) limits clinical application. Rigorous prospective trials with uniform metrics are needed to establish causality and identify which deficient children benefit most.