Recurrent febrile seizures in children are associated with a
higher risk of psychiatric disorders and epilepsy in later life, new research
shows.
Danish investigators found the 30-year risk of epilepsy and
psychiatric disorders in children who had three or more febrile seizures was
15% and 30%, respectively. In comparison, the risk of mental illness and
epilepsy in unaffected individuals is 2% and 17%, respectively.
"These findings are very important since both epilepsy
and psychiatric disorders may have a major impact on the quality of life in
affected individuals and their families, and because these disorders are
associated with great societal costs," study investigator Julie Werenberg
Dreier, PhD, postdoc, National Center for Register-based Research, Aarhus
Univerity, Denmark, told Medscape Medical News.
The study also showed that mortality is increased in
patients with recurrent febrile seizures who go on to develop epilepsy.
The findings were presented here at the Congress of the
European Academy of Neurology (EAN) 2019.
Stepwise Increased Risk
Febrile seizures are relatively common in childhood,
affecting an estimated 3% to 4% of children. In general, such seizures are
considered benign. However, children who have one episode are likely to have
recurrent seizures.
Previous studies have not been large enough to investigate
the long-term consequences of recurrent febrile seizures, said Dreier. From the
relevant Danish registries, she and her research team identified a cohort of
2.1 million singleton children born between 1977 and 2011. Of these, 75,593
(3.6%) were diagnosed with a febrile seizure for the first time.
Using a graph to illustrate ages of first hospital admission
for febrile seizures, Dreier demonstrated that the incidence rapidly increases
starting at about 6 months of age, peaks at about age 16 months, then declines.
At about age 3 years, "90% of all the children with febrile seizures will
have presented," she said.
Investigators defined three subpopulations of children with
febrile seizures and no previous diagnosis of epilepsy, cerebral palsy,
intracranial tumors, severe head trauma or intracranial infections. These
subpopulations included children who had experienced at least one febrile
seizure; those who had experienced at least two; and those who experienced at
least three.
The risk of recurrence before age 5 years in children who
had one febrile seizure was 22.7%. This risk increased with each additional febrile
seizure.
From other national registries, the investigators collected
data on epilepsy and psychiatric disorders. They used competing risk regression
to estimate cumulative incidences, and Cox regression to arrive at hazard
ratios (HRs) for risk of onset of these disorders at various ages depending on
the number of febrile seizures.
The cumulative incidence of epilepsy over a 30-year
follow-up period started at 2% at birth. For every febrile seizure, there was a
stepwise increase in the risk of epilepsy, so for children with three or more
febrile seizures, the 30-year cumulative incidence was just over 15%.
The researchers found that children with one febrile seizure
had a sevenfold increased risk of an epilepsy diagnosis before 5 years of age
(HR, 7.11). However, if the child had three or more febrile seizures, the risk
was elevated 42-fold (HR, 42.06).
Looking at admissions for psychiatric disorders, the
researchers found that the 30-year risk at birth was about 17%. Here again,
there was a stepwise increase with each additional febrile seizure. In the
subgroup with three or more febrile seizures, the risk approached 30%.
Dreier noted that when looking at the broad spectrum of
psychiatric disorders associated with febrile seizures, the "most
pronounced" were psychotic disorders including schizophrenia.
The researchers wanted to know if the association between
febrile seizures and psychiatric disorders could be explained by comorbid
epilepsy. After adjusting for epilepsy, "the association was somewhat
attenuated but was still significant," said Dreier. "So epilepsy
can't explain the entire pattern that we see."
Researchers also collected mortality data from the national
death registry. They found increased mortality in children with recurrent
febrile seizures, but after adjusting for epilepsy, "this association
completely disappears," said Dreier.
"This suggests that there's only an increased mortality
in children with recurrent febrile seizures who later develop epilepsy,"
she said.
It is unclear whether the associations uncovered by the
study were directly related to the seizures themselves or were as a result of
some common underlying conditions, such as genetic susceptibility, said Dreier.
Interesting Research
Commenting on the study following the presentation, session
co-chair Marte-Helene Bjørk, PhD, associate professor, University of Bergen,
Norway, described the study as "very elegant and interesting."
She speculated that the increased risk of psychiatric
disorders may be an effect of febrile seizures on the temporal lobe.
"It could be a direct effect of the seizures, but it's
also possible that it might be some genetic confounding that could increase the
risk of febrile seizures as well as the risk of psychiatric disorders,"
said Dreier.
The second session co-chair, Hanna Cock, MD, professor of
epilepsy and medical education, St. George's University Hospital, London,
United Kingdom, said parental anxiety may also play a role in the association
of febrile seizures with psychiatric disorders.
"There is so much evidence that the social background
and parenting in those early months and years is a huge predictor of future
psychiatric outcomes," said Cock.
She also wondered if these data may have implications for
counseling of families regarding psychiatric risk associated with febrile
seizures.
O3219
Long-term consequences of recurrent febrile seizures. J. Dreier1, Y. Sun1, J. Christensen2
1Aarhus University, Aarhus, Denmark, 2Viby, Denmark
Background and aims: We studied the long-term effect of recurrent febrile seizures on the risk of subsequent
epilepsy, mental illnesses, and death.
Methods: We carried out a register-based cohort study of all singleton children born in Denmark between 1977 and 2011 (N=2,103,232). Hospital contacts with febrile seizures between 3 months and 5 years of age of all cohort members were identified using the Danish National Patient Register. We used competing risks regression and Cox regression to estimate the cumulative and relative risk of febrile
seizures, recurrent febrile seizures, epilepsy, mental illnesses, and death.
Results: A total of 75,593 children (3.6%) were diagnosed with a first febrile seizure between 1977 and 2016. The risk of recurrent febrile seizures was 22.7% after the first
febrile seizure, 35.6% after the second febrile seizure, and 43.5% after the third febrile seizure. The risk of epilepsy increased progressively with the number of admissions with febrile seizures. The 30-year cumulative risk of epilepsy was 2.2% at birth compared with 15.8% after the third febrile
seizure, while the corresponding estimates for risk of mental illnesses were 17.2% and 29.1%, respectively. Mortality was increased among children with recurrent febrile seizures, although this risk was driven by children who
later developed epilepsy.
Conclusion: A history of recurrent febrile seizures was associated with a high risk of epilepsy and mental illness, but increased mortality was found only in individuals who later developed epilepsy.
Disclosure: This study was supported by the Novo Nordisk Foundation (grant number: NNF16OC0019126), the Central Denmark Region, and the Danish Epilepsy Associationsk associated with febrile seizures.
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