Febrile seizures affect 2%–5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3‐ to 72‐month‐old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty‐six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure‐free controls. Study designs varied: 15 cohort, 2 cross‐sectional, 3 case–control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile‐seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case–control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow‐up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer‐term prospective studies are needed.

Over the past two decades, the U.S. Department of Defense (DoD) has invested unparalleled resources into developing effective treatments for military-related psychological health conditions. Systematic reviews, which are a key component in the knowledge translation process, function to translate the available research into evidence-based health care guidelines that promote optimal clinical care. Although a few government agencies, including the Department of Veterans Affairs (VA) and the Agency for Healthcare Research and Quality (AHRQ), have established evidence synthesis centers, there is no similar center within DoD that focuses exclusively on psychological health issues. Thus, the Southern California Evidence-Based Practice Center, which is affiliated with the RAND Corporation, has been awarded a multiyear contract to synthesize research on psychological health interventions important to military populations. This document is a systematic review. The review will be of interest to health policymakers and practitioners, as well as to patients experiencing transitions in mental health care. None of the authors has any conflict of interest to declare.The research reported here was completed in May 2021 and underwent security review by the sponsor and the Defense Office of Prepublication and Security Review before public release.