Abstract
Background: Vitamin D deficiency is highly prevalent among children in South Asia and is increasingly recognized as an immunologically relevant condition, not limited to bone health. In paediatric populations exposed to frequent respiratory and gastrointestinal pathogens, sustained low vitamin D status may influence inflammatory tone, antimicrobial defense, and long-term resistance to recurrent infections.
Objective: To investigate the longitudinal relationship between vitamin D deficiency and immune system function in children, and to evaluate whether deficiency is associated with greater infection burden and adverse clinical outcomes in a tertiary hospital cohort from Sindh, Pakistan.
Methods: A prospective longitudinal cohort design was implemented in a tertiary-care hospital in Sindh. Children aged 6 months to 12 years were enrolled and followed for 12 months with planned assessments at baseline, 3, 6, and 12 months. Serum 25-hydroxyvitamin D [25(OH)D] was measured at baseline and repeated during follow-up to classify deficiency (<20 ng/mL), insufficiency (20–29 ng/mL), and sufficiency (≥30 ng/mL). Immune profiling included inflammatory cytokines (IL-6, TNF-α), immune-regulatory markers (IL-10), Th1-related activity (IFN-γ), and an antimicrobial peptide surrogate (LL-37), alongside routine haematological indices. Clinical outcomes included the incidence and recurrence of acute respiratory infections and acute gastroenteritis, plus hospitalization events. Multivariable models were planned to adjust for age, sex, season, nutritional status, and baseline vulnerability indicators.
Results: Vitamin D deficiency constituted the largest baseline exposure group. Children classified as deficient demonstrated a pattern consistent with higher inflammatory activation (higher IL-6 and TNF-α) and reduced antimicrobial readiness (lower LL-37) compared with sufficient peers, with partial narrowing of biomarker differences at mid-follow-up in those whose vitamin D status improved. Clinically, deficient children experienced a higher burden of respiratory infections across follow-up and a higher proportion of hospitalization events, suggesting reduced disease resistance in this subgroup.
Conclusion: In this tertiary-care paediatric cohort from Sindh, vitamin D deficiency was common and aligned with immune marker patterns suggestive of heightened inflammation and weaker antimicrobial defense, alongside greater infection burden. These findings support integrating vitamin D assessment into paediatric risk evaluation for recurrent infections and justify pragmatic interventional trials targeting persistently deficient, high-risk children.