Potential Role of Febrile Seizures and Other Risk Factors Associated With Sudden Deaths in Children

Abstract

Key Points Question Are febrile seizures associated with increased risk of sudden deaths in young children, and could febrile seizures contribute to some deaths? Findings In this case series of 391 children from 18 countries, febrile seizure rates were increased among both sudden explained and sudden unexplained deaths compared with the general population, suggesting that seizures contributed to some of these deaths. No sudden deaths occurred in more than 3100 life-years among siblings of children with sudden unexplained death. Meaning Patients with febrile seizures are at increased risk for sudden death, but the risk is small; identifying clinical features or biomarkers of high risk is essential to develop and assess preventive strategies.

Evaluation of Concordance Between Original Death Certifications and an Expert Panel Process in the Determination of Sudden Unexplained Death in Childhood

“…We confirmed the predominant extrinsic factor was decedents found prone/faced down, consistent with functional impairment of reflexive autonomic, motor, and arousal responses, which in some cases may be because of the postictal state. 2 , 13 , 14 …”

“… 3 African American children have a more than 2-fold risk of SUDC compared with non-Hispanic White, Asian, or Pacific Islander children. 2 …”

Sudden Unexplained Death in Childhood: A Neuropathology Review

“…Not all SUDC cases with FS history are associated with hippocampal changes suggesting other mechanisms are likely relevant in some instances (12,16). FS history might represent an independent marker for SUDC, with the caveat that not all FS are clinically obvious, and FS are probably underreported (2,17). The estimated FS prevalence of ∼1-2% in the general pediatric population, and a low overall SUDC annual incidence, suggests additional factors modulate risk of SUDC in susceptible children, although data are limited regarding specific genetic variants influencing risk.…”

“…The strong association between hippocampal alterations and FS history has prompted speculation that the mechanism of SUDC could be a terminal seizure-like event, reminiscent of sudden unexpected death in epilepsy (SUDEP) (2,12). A key unanswered question, however, is the biologic relevance of GCL alterations as it remains unclear whether these changes are a cause or a consequence of seizures.…”

“… Sudden Unexplained Death in Childhood (SUDC) is the unexpected death of a child over age 12 months that remains unexplained after a thorough case investigation, including review of the child's medical history, circumstances of death, a complete autopsy and ancillary testing ( 1 ). First defined in 2005, SUDC cases are more often male, with death occurring during a sleep period, being found prone, peak winter incidence, associated with febrile seizure history in ~28% of cases and mild pathologic changes insufficient to explain the death ( 1 , 2 ). There has been little progress in understanding the causes of SUDC and no progress in prevention.…”