A history of multiple febrile seizures increases the risk of developing epilepsy and psychiatric disorders later in life, with children who had >3 seizures at highest cumulative risk, according to a study published in JAMA Pediatrics.1

Febrile seizures are reported to occur in 2% to 5% of children between the ages of 6 months and 5 years.2 Although usually benign, children who have >1 febrile seizure are considered at risk of developing long-term sequelae. The study sought to link recurrent febrile seizure to the development of epilepsy, psychiatric disorders, and premature mortality.

Researchers used data from the Danish Civil Registration System to identify children born in Denmark between January 1, 1977, and December 31, 2011. The investigators further identified children who had been hospitalized or received outpatient care with a diagnosis of febrile seizure between the ages of 3 months and 5 years and had no prior diagnosis of epilepsy, cerebral palsy, intracranial tumors, severe head trauma, or intracranial infections before the onset of seizures. Children were followed until the end of 2016, and patients were subdivided into those with ≥1, ≥2, or ≥3 febrile seizures.

Epilepsy was defined as any diagnosis of epilepsy as registered in the Danish National Patient Register. Psychiatric disorders were identified through the Psychiatric Central Research Register and diagnosed using the International Classification of Diseases (ICD;pre-1993, ICD-8 290-315; post-1993, ICD-10 F00-F99). The Civil Registration System was used to identify children who had died.

A total of 75,593 children were identified with a diagnosis of febrile. Seizures were more common in boys compared with girls (3.9% vs 3.3%, respectively), and the age of seizure occurrence peaked at 16.7 months. The cumulative risk for recurrent febrile seizures was 22.7% after the first febrile seizure, 35.6% after the second seizure, and 43.5% after the third. This recurrence risk was largely similar for boys and girls. The risk of having a recurrent febrile seizures was higher if the first febrile seizure occurred before 2 years of age: 26.4% compared with 11.8% in children with their first seizure >2 years of age.

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

The 30-year risk for admission with a psychiatric disorder was 17.2%. In comparison, in children with at least 1 febrile seizure, the corresponding risk was 21.4%, increasing to 25.0% in children with ≥2 febrile seizures and to 29.1% in children with 3 or more admissions for febrile seizures.

Mortality increased with the number of hospital admissions associated with febrile seizures; at birth, the 30-year cumulative risk of dying was 1.0%, followed by 1.2% after the first febrile seizure, 1.4% after the second, and 1.9% after the third. This risk was associated primarily with children who later developed epilepsy.

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“A history of recurrent febrile seizures appears to carry a high risk of epilepsy and psychiatric morbidity but may increase mortality only in individuals who later develop epilepsy,” the authors concluded. “Thus, parents and medical professionals should be aware of early signs and symptoms and psychiatric disorders in children with a history of febrile seizures, to ensure early detection and treatment of these disorders.”

References

1. Dreier JW, Li J, Sun Y1, Christensen J. Evaluation of long-term risk of epilepsy, psychiatric disorders, and mortality among children with recurrent febrile seizures: a national cohort study in Denmark [published online October 7, 2019]. JAMA Pediatr. doi:10.1001/jamapediatrics.2019.3343

2. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281-1286.