Immunological mechanisms and prevention strategies for febrile seizures in children.

Authors

Binbin Chen, Enfu Tao

Published in

Frontiers in immunology. Volume 17. Pages 1833132. Epub Jul 10, 2026.

Abstract

Febrile seizures (FS) affect 2-5% of children globally, causing significant caregiver anxiety and healthcare utilization. Emerging evidence implicates neuroinflammation and T-cell-mediated immunity in FS pathogenesis, suggesting potential targets for future investigation. This Review synthesizes current evidence on FS prevention, emphasizing a paradigm shift from universal pharmacological approaches toward risk-stratified, personalized strategies. The COVID-19 pandemic provided unique insights: non-pharmaceutical interventions reduced FS incidence by 54-70%, while the Omicron variant emerged as a novel trigger associated with complex FS features. Prevention is conceptualized within a three-level framework: primary prevention targets all children through vaccination (MMR, PCV13, COVID-19 vaccines) and infection control; secondary prevention focuses on high-risk children with prior FS, where risk stratification integrates clinical predictors (complex features, young age, low fever), biomarkers (hyponatremia, zinc/vitamin D deficiency, inflammatory indices), and pathogen-specific risks (influenza A, Omicron); tertiary prevention addresses complications and epileptogenesis in children with complex FS or genetic predisposition (SCN1A, PCDH19). Key immunological mechanisms include HMGB1-NLRP3 inflammasome activation, TRPV1-mediated Th17 differentiation, and IL-1β/IL-10 dysregulation. Antipyretics do not prevent FS recurrence during distant febrile episodes, while intermittent benzodiazepines (diazepam, intranasal midazolam) effectively reduce early recurrence in high-risk children (NNT = 6.8), albeit with adverse effects in up to 36%. Emerging frontiers include novel therapeutic targets (HMGB1 inhibitors, TRP channel modulators, TSP-1 pathway inhibitors) and non-pharmacological innovations (wearable sensors, chronotherapy). Crucially, caregiver education underpins all prevention levels, addressing high rates of parental anxiety (58.2%). This integrated framework guides clinical practice toward more individualized, risk-based management.

PMID:
42500652
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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