Inflammation and Sodium Balance are Associated with Febrile Seizures: A Large Retrospective Case–Control Study of 600 Children

A bstract Background: Febrile seizures (FSs) are the most common convulsive events in childhood. Inflammatory and biochemical markers may reflect physiological susceptibility to seizures; however, evidence from large, well-characterized cohorts remains limited. This study aimed to compare inflammatory and biochemical biomarkers between children with FSs and febrile controls and to identify independent factors associated with FSs. Materials and Methods: In this retrospective case–control study, 300 children with FS and 300 age-matched febrile controls aged 6–60 months were evaluated. Complete blood count parameters were analyzed—including white blood cell count (WBC), neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), mean platelet volume (MPV), and platelet count—as well as acute-phase markers including C-reactive protein (CRP) and serum sodium levels. Receiver operating characteristic curve analysis and multivariable logistic regression were performed to assess diagnostic performance and identify independent associations. Results: Children with FS had significantly higher WBC, neutrophil counts, NLR, RDW, and MPV, and significantly lower lymphocyte counts, CRP, and serum sodium levels compared with febrile controls (all P < 0.05). NLR demonstrated the strongest discriminative performance (area under the curve = 0.88), with an optimal cutoff value of >2.2 (sensitivity 78%, specificity 84%). In multivariable analysis, NLR, serum sodium, and CRP remained independently associated with FSs. Mild hyponatremia (serum sodium <135 mmol/L) was observed more frequently in children with FSs compared with febrile controls (19% vs 4%), while no cases of moderate or severe hyponatremia were identified. Conclusion: Children with FSs exhibit a distinct inflammatory–electrolyte profile, with NLR showing the strongest association and potential utility as a supportive biomarker. Mild hyponatremia further characterizes seizure susceptibility; however, these findings should be interpreted as associative rather than causal and within the broader clinical context.