Abstract

Background: The U.S. Food and Drug Administration’s Biologics Effectiveness and Safety (BEST) Initiative detected a statistical signal for seizures/convulsions following exposure to BNT162b2 in individuals aged 2-4 years and mRNA-1273 in individuals aged 2-5 years. The crude association from initial safety monitoring does not imply causality; further evaluations were performed to assess post-vaccination risk of seizures.

Objectives: To evaluate febrile seizure risk following monovalent COVID-19 vaccination among children aged 2-5 years.

Methods: A self-controlled case series analysis was performed to compare the risk of febrile seizure in the risk interval following vaccination (0-1 days) to a control interval (8-63 days). The primary analysis included individuals aged 2-5 vaccinated with mRNA-1273 and individuals aged 2-4 vaccinated with BNT126b2 who had a febrile seizure outcome following COVID-19 vaccination from three commercial insurance databases (Optum, Carelon Research, CVS Health). Exposure was defined as receipt of dose 1 and/or dose 2 of COVID-19 ancestral monovalent mRNA vaccines. 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) in each database. From the conditional Poisson regression model, we derived the attributable risk (AR) per 100,000 vaccinations. Meta-analyses were used to pool results across databases.

Results: There were 10 febrile seizures observed in the risk window following 110,126 mRNA-1273 doses and 7 febrile seizures observed in the risk window following 163,733 BNT162b2 doses. The 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). For the BNT162b2 vaccination, the IRR was elevated but not statistically significant (IRR: 1.41, 95%CI: 0.48 to 4.11). We estimated an AR of 3.22 excess febrile seizure events per 100,000 mRNA-1273 vaccinations (95%CI -0.31 to 6.75), and no excess febrile seizure events following BNT162b2 vaccination (AR: 0.25 per 100,000 vaccinations 95%CI -2.75 to 2.24).

Conclusions: Among children aged 2-5 years who experienced febrile seizures following vaccination, the analysis showed an elevated IRR of febrile seizures in the 0-1 days following the mRNA-1273 vaccination; however, absolute risk was low. Based on the current body of scientific evidence, the safety profile of the ancestral monovalent COVID-19 mRNA vaccines remains favorable for use in young children.