# Febrile Seizures and Subsequent Autism Spectrum Disorder: A Nationwide Population-Based Cohort Study

## TL;DR

Febrile seizures alone do not increase autism risk, but children with seizures and other neurodevelopmental issues may need closer monitoring.

## Contribution

This study clarifies that febrile seizures are not directly linked to autism but may indicate underlying neurodevelopmental vulnerability.

## Key findings

- Febrile seizures were not independently associated with ASD risk after adjusting for comorbidities.
- Neurodevelopmental conditions like ADHD and epilepsy were strongly linked to ASD risk.
- Developmental surveillance should focus on children with neurodevelopmental disorders, not just febrile seizures.

## Abstract

What are the main findings?
•Febrile seizures were not independently associated with ASD risk after adjustment in a nationwide cohort.•The elevated autism risk was associated with coexisting neurodevelopmental comorbidities rather than febrile seizures alone.

Febrile seizures were not independently associated with ASD risk after adjustment in a nationwide cohort.

The elevated autism risk was associated with coexisting neurodevelopmental comorbidities rather than febrile seizures alone.

What are the implications of the main findings?
•Febrile seizures may serve as an early clinical marker of underlying neurodevelopmental vulnerability rather than a direct cause of autism spectrum disorder.•Children with febrile seizures and neurodevelopmental comorbidities may warrant enhanced long-term developmental surveillance.

Febrile seizures may serve as an early clinical marker of underlying neurodevelopmental vulnerability rather than a direct cause of autism spectrum disorder.

Children with febrile seizures and neurodevelopmental comorbidities may warrant enhanced long-term developmental surveillance.

Objectives: To access the effects of febrile seizures from coexisting neurodevelopmental conditions that are commonly associated with autism spectrum disorder. We examined whether febrile seizures are independently associated with ASD after considering neurodevelopmental comorbidities and seizure-related clinical characteristics. Methods: We conducted a nationwide population-based matched cohort study using Taiwan’s National Health Insurance Research Database. The study included 948 children with FS and 3804 age- and sex-matched controls without FS. Participants were followed longitudinally for incident ASD. Associations were evaluated using Cox proportional hazards models with additional analyses restricted to the FS cohort. Neurodevelopmental comorbidities assessed included attention-deficit/hyperactivity disorder (ADHD), epilepsy, and Tourette syndrome/tic disorder. Results: Among 4752 children followed for more than 10 years, 43 (0.9%) developed ASD. FS were not independently associated with ASD in adjusted Cox regression models. In contrast, ADHD, epilepsy, and Tourette syndrome/tic disorder were strongly and consistently associated with ASD across analytic models. Conclusions: Febrile seizures were not independently associated with autism spectrum disorder. Instead, ASD risk was largely explained by coexisting neurodevelopmental comorbidities, consistent with a shared neurodevelopmental susceptibility framework. These findings suggest that developmental surveillance should prioritize children with neurodevelopmental disorders rather than those with febrile seizures alone.