Evaluation of Febrile Seizure Risk Following Ancestral Monovalent COVID-19 mRNA Vaccination Among U.S. Children Aged 2-5 Years

ObjectiveTo evaluate febrile seizure risk following monovalent COVID-19 mRNA vaccination among children aged 2-5 years. MethodsThe primary analysis evaluated children who had a febrile seizure outcome in the 0-1 days following COVID-19 vaccination. A self-controlled case series analysis was performed in three commercial insurance databases to compare the risk of seizure in the risk interval (0-1 days) to a control interval (8-63 days). The exposure of interest was receipt of dose 1 and/or dose 2 of monovalent COVID-19 mRNA vaccinations. The primary outcome was febrile seizure (0-1 day risk interval). A conditional Poisson regression model was used to compare outcome rates in risk and control intervals and estimate incidence rate ratios (IRR) and 95% confidence intervals (CIs). Meta-analyses were used to pool results across databases. ResultsThe primary meta-analysis found a statistically significant increased incidence of febrile seizure, in the 0-1 days following mRNA-1273 vaccination compared to the control interval (IRR: 2.52, 95% CI: 1.35 to 4.69, risk difference (RD)/100,000 doses = 3.22 (95%CI -0.31 to 6.75)). For the BNT162b2 vaccination, the IRR was elevated but not statistically significant (IRR: 1.41, 95%CI: 0.48 to 4.11, RD/100,000 doses = -0.25 (95%CI -2.75 to 2.24). ConclusionsAmong children aged 2-5 years, the analysis showed a small elevated incidence rate ratio of febrile seizures in the 0-1 days following the mRNA-1273 vaccination. Based on the current body of scientific evidence, the safety profile of the monovalent mRNA vaccines remains favorable for use in young children. Article SummaryIn this self-controlled case series study, researchers evaluated whether there is an elevated risk of febrile seizure immediately following monovalent COVID-19 mRNA vaccination. Whats Known on This SubjectThe United States Food and Drug Administration previously noted a potential safety concern for seizure in children aged 2-5 years receiving the ancestral monovalent COVID-19 mRNA vaccines. What This Study AddsIn this self-controlled case series that included participants aged 2-5 years from three commercial insurance databases, the incidence rate ratio of febrile seizures was significantly elevated in the 0-1 days following mRNA-1273 administration. Absolute risk was small.