Roseola infantum and subsequent epilepsy: A nationwide 20‐year retrospective cohort study

OBJECTIVE: This study was undertaken to evaluate whether roseola infantum is associated with an increased risk of subsequent epilepsy. METHODS: We conducted a nationwide retrospective cohort study using the Korean National Health Insurance Service database from January 2002 to December 2021. Children with roseola, identified using International Classification of Diseases, 10th Revision (ICD-10) code B08.2, were matched 1:1 by age and sex with children without roseola. Participants were followed from the date of roseola diagnosis, or the corresponding index date for controls, until incident epilepsy, death, or the end of the study period. The primary epilepsy definition required at least two medical encounters with ICD-10 code G40.x listed among the top five discharge diagnoses and cumulative antiseizure medication prescriptions for 180 days or longer. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for prespecified baseline and time-varying covariates. Sensitivity analyses used a more inclusive epilepsy definition. RESULTS: The cohort included 1 595 494 children: 797 747 with roseola and 797 747 matched controls. The mean age at cohort entry was 1.15 years, and 51.0% were male. During a mean follow-up of 10.5 years, roseola was associated with an increased risk of subsequent epilepsy (adjusted HR = 2.00, 95% CI = 1.91-2.09). The association was consistent across prespecified subgroups, with adjusted HRs ranging from 1.66 to 3.60. Postindex febrile convulsion showed the strongest independent association with epilepsy (adjusted HR = 12.31, 95% CI = 11.82-12.83). In sensitivity analyses using the inclusive epilepsy definition, roseola remained associated with increased epilepsy risk (adjusted HR = 1.52, 95% CI = 1.48-1.57). SIGNIFICANCE: In this nationwide cohort study, roseola infantum was associated with an increased risk of subsequent epilepsy. These findings demonstrate a population-level association between roseola infantum and epilepsy and warrant prospective studies with virologic confirmation and detailed epilepsy phenotyping.