Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD

Abstract

OBJECTIVES: Epilepsy, febrile seizures, and attention-deficit/hyperactivity disorder (ADHD) are disorders of the central nervous system and share common risk factors. Our goal was to examine the association in a nationwide cohort study with prospective follow-up and adjustment for selected confounders. We hypothesized that epilepsy and febrile seizures were associated with subsequent ADHD. METHODS:A population-based cohort of all children born in Denmark from 1990 through 2007 was followed up until 2012. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for ADHD were estimated by using Cox regression analysis, comparing children with epilepsy and febrile seizure with those without these disorders, adjusted for socioeconomic and perinatal risk factors, as well as family history of neurologic and psychiatric disorders. RESULTS:A total of 906 379 individuals were followed up for 22 years (∼10 million personyears of observation); 21 079 individuals developed ADHD. Children with epilepsy had a fully adjusted IRR of ADHD of 2.72 (95% CI, 2.53-2.91) compared with children without epilepsy. Similarly, in children with febrile seizure, the fully adjusted IRR of ADHD was 1.28 (95% CI, 1.20-1.35). In individuals with both epilepsy and febrile seizure, the fully adjusted IRR of ADHD was 3.22 (95% CI, 2.72-3.83). CONCLUSIONS:Our findings indicate a strong association between epilepsy in childhood and, to a lesser extent, febrile seizure and subsequent development of ADHD, even after adjusting for socioeconomic and perinatal risk factors, and family history of epilepsy, febrile seizures, or psychiatric disorders. Ms Bertelsen conceptualized and designed the study, conducted the initial analyses, and drafted the initial manuscript; Ms Larsen conducted the initial analyses and critically reviewed the manuscript; Dr Petersen supervised the initial analyses and critically reviewed the manuscript; Dr Christensen conceptualized and designed the study, helped draft the initial manuscript, and critically reviewed the manuscript; Dr Dalsgaard conceptualized and designed the study, helped draft the initial manuscript, and critically reviewed the manuscript; and all authors approved the fi nal manuscript as submitted. WHAT'S KNOWN ON THIS SUBJECT:Several studies have demonstrated an association between seizure disorders and attention-defi cit/hyperactivity disorder in childhood. Genetic and environmental risk factors infl uence this association, but former studies on this subject have been limited by retrospective designs and small sample sizes. WHAT THIS STUDY ADDS:This prospective population-based study found a strong association between childhood epilepsy and febrile seizures and subsequent attention-defi cit/hyperactivity disorder, even after adjusting for perinatal and socioeconomic risk factors, as well as family history of neurologic and psychiatric disorders.by guest on May 9, 2018 http://pediatrics.aappublications.org/ Downloaded from BERTELSEN et alThe population prevalence of epilepsy has been esti...

Cognitive functioning in a representative cohort of preschool children with febrile seizures

“…There are few population‐based studies exploring cognitive test results in children with FS. In the study by Bertelsen et al, a population‐based cohort of all children born in Denmark from 1990 through 2007 was followed. Children with FS had a 20%‐35% increased risk of ADHD compared with children without FS.…”

“…In a large register‐ and population‐based study from Denmark, the association between childhood epilepsy and FS on the one hand and subsequent attention‐deficit/hyperactivity disorder (ADHD) on the other was studied. Children with FS, (data on types of FS could not be analysed), were found to have a 20%‐35% increased risk of ADHD compared with children without FS …”

Analysis of Shared Heritability in Common Disorders of the Brain

“…In general, brain disorders (here excepting those caused by trauma, infection or cancer) show substantial heritability from twin and family studies (4). Epidemiological and twin studies have explored patterns of phenotypic overlaps(5–7), and substantial comorbidity has been reported for many pairs of disorders, including bipolar disorder-migraine(8), stroke-major depressive disorder(MDD)(9), epilepsy-autism spectrum disorders (ASD) and epilepsy-attention deficit hyperactivity disorder (ADHD)(10, 11). Furthermore, neurological and psychiatric research has shown that mutations in the same ion channel genes confer pleiotropic risk for multiple distinct brain phenotypes(12–14).…”

Medication treatment for attention‐deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy

“…Patients with epilepsy have a three‐ to five‐fold increased risk of attention‐deficit/hyperactivity disorder (ADHD) diagnosis, and 20%‐50% of children with epilepsy exhibit subclinical ADHD symptoms . Untreated, ADHD is associated with severe adverse outcomes, making effective treatment crucial.…”

“…ADHD, epilepsy, methylphenidate, neurodevelopmental disorders, pharmacoepidemiology, seizures, treatment 1 | INTRODUCTION Patients with epilepsy have a three-to five-fold increased risk of attention-deficit/hyperactivity disorder (ADHD) diagnosis, [1][2][3] and 20%-50% of children with epilepsy exhibit subclinical ADHD symptoms. 4 Untreated, ADHD is associated with severe adverse outcomes, [5][6][7][8] making effective treatment crucial.…”