Importance The United States Food and Drug Administration noted a potential safety concern for seizure in children aged 2-5 years receiving the ancestral monovalent COVID-19 mRNA vaccines.

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

Design, Setting, and Participants The 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).

Exposure Receipt of dose 1 and/or dose 2 of monovalent COVID-19 mRNA vaccinations.

Main Outcomes and Measures The primary outcome was febrile seizure (0-1 day risk interval).

Analysis 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.

Results 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, 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).

Conclusions and Relevance Among 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.

Question Among children aged 2-5 years, is the risk of febrile seizure elevated immediately following monovalent COVID-19 mRNA vaccination compared with a later period after vaccination?

Findings In 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.

Meaning The incidence of febrile seizures was elevated immediately following vaccination with the monovalent mRNA-1273 COVID-19 vaccine in children aged 2-5 years. Based on the current body of evidence, the safety profile of monovalent mRNA vaccines remains favorable for use in young children.

Both Drs Djibo and McMahill-Walraven are CVS Health employees

https://bestinitiative.org/wp-content/uploads/2023/07/BEST_Prelim_Seizure_Safety_Signal_Ages-2-5_2023.pdf

The US Food and Drug Administration provided funding for this study and contributed as follows: led the design of the study, interpretation of the results, writing of the manuscript, decision to submit, and made contributions to the coordination of data collection and analysis of the data.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

We conducted this study within the Biologics Effectiveness and Safety (BEST) Initiative. FDA Amendments Act of 2007 required that FDA develop a national electronic system for monitoring safety of FDA-regulated medical products. FDA built the Sentinel Initiative in response to the congressional requirement, and the BEST Initiative commenced as a Center for Biologics Evaluation and Research (CBER) component of Sentinel. The Office of Human Research Protection (OHRP) determined that the regulations OHRP administers (45 CFR part 46) do not apply to the activities that are included in the FDA's Sentinel Initiative.

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