Childhood Febrile Seizures Linked to Epilepsy, Psych Disorders

Ricki Lewis, PhD

October 08, 2019

Recurrent febrile seizures in children are associated with an elevated risk for epilepsy and psychiatric disorders, with increased mortality among

individuals who developed epilepsy, according to results of a study published online yesterday in JAMA Pediatrics.

Febrile seizures affect 2% to 3% percent of children between the ages of 3 months and 5 years. Children who are young at the first incident; have short- duration, low-grade fever when the seizure begins; and/or have a family history of febrile seizures are likely to experience subsequent seizures.

Small-scale studies have associated recurrent seizures with developing epilepsy and certain psychiatric disorders, such as schizophrenia, mood disorders, and personality disorders. But long-term effects of recurrent seizures have not been studied in large populations.

Julie Werenberg Dreier, PhD, Aarhus University, Denmark, and colleagues addressed the concern with a population-based cohort study of the 2,103,232 singleton children born from 1977 through 2011, using data from the Danish Civil Registration System. They calculated the risk of recurrent febrile seizures and checked patient registries to determine whether the seizures were associated with development of epilepsy, psychiatric disorders, and death over the long term.

The youngest children were 3 months old. Each child had at least 5 years of follow-up.

Of the children, 75,593 (3.6%) were diagnosed with a first febrile seizure between 1977 and 2016. The events were more common in boys (3.9%) than in girls (3.3%), but the risks of recurrent febrile seizures, epilepsy, psychiatric disorders, and death were similar in boys and girls.

The risk of additional febrile seizures increased with number: 3.6% at birth, 22.7% after the first febrile seizure, 35.6% after the second febrile seizure, and 43.5% after the third febrile seizure.

Age 2 years appeared to be a critical point, with the risk of recurrent febrile seizures higher when the earlier ones were before this age.

Recurrence risk was 26.4% if the first febrile seizure was before age 2 years, but only 11.8% if the first seizure was after age 2 years. Recurrence risk shot up to 61.3% for children who had three hospital admissions with febrile seizures before age 2 years.

Epilepsy risk increased with the number of febrile seizures and hospital admissions. The 30-year cumulative incidence of epilepsy was 2.2% at birth, 6.4% after the first febrile seizure, 10.8% after the second febrile seizure, and rose to 15.8% after the third seizure.

Risk of psychiatric disorders also increased over time with the number of febrile seizures, from 17.2% at birth to 29.1% after the third febrile seizure.

Mortality increased among children with recurrent febrile seizures, from 1% at birth to 1.9% after the third febrile seizure. Children who later developed epilepsy were at higher risk for mortality.

The researchers conclude that because a history of recurrent febrile seizures is associated with elevated risk for epilepsy and psychiatric illness, and an increase in mortality in children who develop epilepsy, that "parents and medical professionals should be aware of early signs and symptoms of epilepsy and psychiatric disorders in children with a history of febrile seizures, and especially in children with recurrent febrile seizures, to ensure early detection and treatment of these disorders."

A limitation of the study is the changing criteria for inclusion in the consulted registries, which results in a somewhat apples-and-oranges situation.

Specifically, in 1995, the civil registry in Denmark began to include outpatient and emergency department cases of febrile seizures, after which the epilepsy risk fell, perhaps reflecting inclusion of more minor cases. Psychiatric registries also began to include outpatient data, and then psychiatric diagnoses increased. Overall admissions for febrile seizures increased in Denmark over time compared to the United States and some other nations, but not if solely inpatient diagnoses are considered.

The authors previously reported the results July 1 at the Congress of the European Academy of Neurology (EAN) 2019.

The researchers have disclosed no relevant financial relationships.

JAMA Pediatr.  Published October 7, 2019. Full text

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