Association between Serum Vitamin D Levels and Febrile Seizures in Children: A Prospective Case–Control Study

Abstract Background: The association between vitamin D status and febrile seizures remains controversial, partly attributable to the differences in control group selection and inadequate confounder adjustment. Materials and Methods: This prospective case–control study evaluated the association between serum 25-hydroxyvitamin D [25(OH)D] levels and febrile seizures in children, accounting for key determinants of vitamin D status, including sun exposure. A total of 205 children aged 6 months to 6 years were enrolled: 41 with febrile seizures, 82 febrile controls without seizures, and 82 healthy controls. Serum 25(OH)D was measured by high-performance liquid chromatography with ultraviolet detection during the afebrile period (10–14 days post-presentation). Sun exposure was assessed using a structured questionnaire. A parsimonious multivariable logistic regression model including vitamin D, serum sodium, and sun exposure score was constructed among febrile children. Results: Mean 25(OH)D levels were 25 ± 10, 28 ± 14, and 33 ± 14 ng/mL in the febrile-seizure, febrile-control, and healthy control groups, respectively ( P = 0.004). No significant difference was observed between febrile children with and without seizures in the unadjusted analysis. In multivariable analysis, lower vitamin D was independently associated with febrile seizures (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.91–0.99, P = 0.036). Serum sodium was the strongest predictor (OR: 0.63, 95% CI: 0.52–0.76, P < 0.001). This association was attenuated and lost significance after excluding sun exposure (OR: 0.96, P = 0.162), suggesting model dependency. Conclusion: No association between vitamin D and febrile seizures was observed in unadjusted comparisons. The adjusted association was not robust across sensitivity analyses and should be considered exploratory. Serum sodium emerged as the most robust independent predictor, highlighting the importance of electrolyte monitoring during febrile illness.