Risk of death is not increased in children with simple febrile seizures

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• Vestergaard M, Giørtz Pedersen M, Østergaard JR, Bøcker Pedersen C, Olsen J, Christensen J. Death in children with febrile seizures: a population-based cohort study. Lancet 2008;372:457-63
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Vestergaard M, Giørtz Pedersen M, Østergaard JR, Bøcker Pedersen C, Olsen J, Christensen J. Death in children with febrile seizures: a population-based cohort study. Lancet 2008;372:457-63 

Question Among children with febrile seizures, is there an increased risk of death?

Design Population-based cohort study with a nested case-control study.

Setting Denmark.

Participants A total of 1 675 643 children born between January 1, 1977, and December 31, 2004. The case-control portion of the study included 8172 children who died and 40 860 individually-matched control subjects.

Intervention Children were followed up from 3 months of age until death, emigration, or August 31, 2005.

Outcomes Overall and cause-specific death after first febrile seizures, estimated with survival analyses.

Main Results Of the children who died, there were 232 deaths among 55 215 children with a history of febrile seizures. The mortality rate ratio was 80% higher during the first year (adjusted mortality rate ratio 1.80 [95% CI 1.31-2.40]) and 90% higher during the second year (1.89 [1.27-2.70]) after the first febrile seizure; thereafter it was close to that noted for the general population. A total of 132 of 100 000 children (95% CI 102-163) died within 2 years of a febrile seizure compared with 67 (57-76) deaths per 100 000 children without a history of this disorder. In the nested case-control study, children with simple (≤15 minutes and no recurrence within 24 hours) febrile seizures had a mortality rate similar to that of the background population (adjusted mortality rate ratio 1.09 [95% CI 0.72-1.64]), whereas the mortality rate was increased for those with complex (>15 minutes or recurrence within 24 hours) febrile seizures (1.99 [1.24-3.21]). This finding was partly explained by preexisting neurologic abnormalities and subsequent epilepsy.

Conclusions The long-term mortality rate is not increased in children with febrile seizures, but there seems to be a small excess mortality rate during the 2 years after complex febrile seizures. Parents should be reassured that death after febrile seizures is very rare, even in children at high risk.

Commentary Despite the general acceptance that children with febrile seizures have a good prognosis, the hypothesis persists that febrile seizures are linked to sudden death through a common infectious or environmental agent, anatomic abnormality, or genetic susceptibility to fever. The shared susceptibility hypothesis has found little support, however, from large epidemiologic studies that showed sudden infant death syndrome (SIDS) and febrile seizures occur in different populations. SIDS is more frequent in African-American children, for example, whereas this higher risk is not mirrored in febrile seizures. SIDS and febrile seizures do not seem to occur together in families. In this study, Vestergaard et al tested the hypothesis that febrile seizures are associated with an increased risk of death by examining mortality data from nationwide registries in Denmark. The investigators found that in children who had febrile seizures, there was an increased risk of death in the 2 years after the first febrile seizure, but that the absolute risk was still very low. In a nested case control study, they reviewed medical records to obtain more clinical information than is available in registry data. They found that the increased risk of death after febrile seizure was seen only in children with complex febrile seizures and in those with underlying neurologic abnormalities. This well-conducted study again seems to refute, for children with simple febrile seizures, the idea of a shared cause between febrile seizures and sudden death. The study nevertheless suggests there may be a subset of children—notably those with complex features and underlying neurologic abnormalities—which might warrant closer attention and follow-up.