{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:36Z","timestamp":1783660416273,"version":"3.55.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Febrile seizures (FS) affect 2\u20135% 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\u201370%, 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-1\u03b2\/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\u00a0=\u00a06.8), 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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1833132","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:24:02Z","timestamp":1783657442000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunological mechanisms and prevention strategies for febrile seizures in children"],"prefix":"10.3389","volume":"17","author":[{"given":"Binbin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Wenling Maternal and Child Health Care Hospital","place":["Wenling, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enfu","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Neonatal Intensive Care Unit, Wenling Maternal and Child Health Care Hospital","place":["Wenling, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4103\/jfcm.jfcm_10_24","article-title":"Characteristics of pediatric patients with febrile convulsions admitted to a tertiary care hospital in Riyadh, Saudi Arabia","volume":"32","author":"Abuhaimed","year":"2025","journal-title":"J Family Community Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h4240","article-title":"Febrile seizures","volume":"351","author":"Patel","year":"2015","journal-title":"BMJ"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.31729\/jnma.6322","article-title":"Febrile seizure in children attending a tertiary care centre in Western Nepal: a descriptive cross-sectional study","volume":"59","author":"Shrestha","year":"2021","journal-title":"JNMA J Nepal Med Assoc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/inf.0000000000003894","article-title":"Comparison of clinical characteristics of children infected with coronavirus disease 2019 between Omicron variant BA.5 and BA.1\/BA.2 in Japan","volume":"42","author":"Ikuse","year":"2023","journal-title":"Pediatr Infect Dis J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/irv.70045","article-title":"Inpatient burden of respiratory syncytial virus infection and influenza in children younger than 5\u2009years in Japan, 2011-2022: a database study","volume":"18","author":"Arashiro","year":"2024","journal-title":"Influenza Other Respir Viruses"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28925","article-title":"Changes in trends of pediatric \u03b2- and \u03b3-herpesvirus infections during the COVID-19 pandemic: a single-center observational study","volume":"95","author":"Kozawa","year":"2023","journal-title":"J Med Virol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2020.11.006","article-title":"Changes in pediatric seizure-related emergency department attendances during COVID-19 - 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