FDA researchers detected a safety signal for seizures in children ages 2-4 following mRNA COVID-19 vaccination, according to a study published Wednesday in JAMA.

By Brenda Baletti, Ph.D.

The U.S. Food and Drug Administration (FDA) detected a safety signal for seizures in young children following mRNA COVID-19 vaccination, according to a study published Wednesday in JAMA Network Open.

Researchers analyzing near-real-time monitoring data on vaccinated children identified this new safety signal in children ages 2-4 who received the original Pfizer vaccine (BNT162b2) and children ages 2-5 who received the original Moderna vaccine (mRNA-1273).

The researchers also identified a safety signal for myocarditis or pericarditis following the Pfizer vaccine in adolescents ages 12-17. That signal had been previously identified.

A preprint study published last month, also funded by the FDA, found children ages 2-5 who received the COVID-19 mRNA vaccine were 2.5 times more likely to have a febrile seizure within a day of being vaccinated than they were to have one between eight and 63 days following vaccination.

The authors of the preprint, who analyzed the same data as the authors of the new JAMA study, also found a higher risk of febrile seizures among children ages 2-4 on the first day following the Pfizer vaccine than in the 8-63 days following vaccination. However, that increased risk was not statistically significant, the researchers reported.

Meanwhile, a government-funded report released earlier this month confirmed a causal link between mRNA COVID-19 vaccines and myocarditis — but rejected a causal link between the vaccines and a host of other adverse effects. The committee reviewed studies on adverse events related to COVID-19 vaccines in children under 18 but said it found insufficient evidence to make conclusions specific to children.

Most seizures occurred within three days of vaccination

The authors of the new JAMA study analyzed data on over 4 million children from three health claims databases run by Optum, Carelon Research, and CVS Health, supplemented with vaccination information from state and local systems.

The health claims databases are part of the FDA’s Biologics Effectiveness and Safety System, a drug safety monitoring system designed to monitor the emergence of safety signals after vaccination.

A safety signal is a sign that an adverse event may be caused by vaccination, but further research is required to verify a link.

The researchers looked into 21 prespecified health outcomes after vaccination before early 2023 among children ages 6 months to 17 years. They selected the outcomes — such as Guillain-Barré syndrome, encephalitis, seizures, myocarditis and pericarditis — based on serious events that followed other vaccines or that could be related to the new mRNA platforms or adjuvants.

For the 15 conditions that had sufficient historical data, the researchers compared the rates of each outcome following vaccination with annual historical rates from before the vaccine was available in 2019, 2020 or both.

Overall, the researchers identified 72 cases of seizures among children ages 2-4 or 5 years old. Most happened within three days of the shot and a majority of the seizures were febrile. They found the same signal in all three databases analyzed.

They also found the signal for myocarditis and pericarditis in children ages 12-17 in all three databases. Because that signal is already known, they did not investigate it further.

The researchers noted that the statistical signal for seizure in children was not previously reported in active surveillance studies of the vaccines, but said there are reports in the Vaccine Adverse Event Reporting System (VAERS) database, which is a passive reporting system.

In VAERS, eight seizures were identified after approximately 1 million mRNA vaccinations through August 2022 in children ages 6 months to 5 years. Six of those were afebrile, meaning they weren’t caused by a fever.

In Pfizer’s clinical trials among young children, there were also five cases of seizures. The company reported that only one of those was considered “possibly related to the vaccine.”

Strengths of the JAMA study included the large and geographically diverse population covered by the databases, the study authors said. Limitations included a lack of control for confounding variables.

The study included only data on safety monitoring from the monovalent COVID-19 vaccines. It did not evaluate the bivalent boosters.

The researchers’ conclusions downplayed the significance of the signal.

“The new statistical signal for seizure observed in our study should be interpreted with caution and further investigated in a more robust epidemiologic study,” they wrote.

Febrile seizures in young children, they said, may not be related to vaccination. They also said the signal changed or disappeared when they used different years’ data for background comparison.

“The FDA concludes that the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks of COVID-19 infection,” they added.

Corresponding author Patricia C. Lloyd, Ph.D., at the FDA, did not respond to The Defender’s request for comment.

Mainstream health news websites like MedPage Today also downplayed the significance of the signal.

MedPage quoted Dr. Michael Smith, division chief of Pediatric Infectious Diseases at Duke University School of Medicine in Durham, North Carolina, who said he found the overall results of the analysis reassuring.

“Yes, [the study authors] found myocarditis and pericarditis, which is known. They found a potential increase of seizures after these vaccines that is undergoing further analysis,” Smith said. “But for all of the other [safety] outcomes that they looked at, there was no association at all. This points to the overall safety of the vaccine[s].”

CDC finds vaccine doesn’t provide long-term protection for children, recommends boosters

Several days before the FDA reported the safety signal for seizures in young children, the CDC released a new study showing the protection offered by the vaccine against severe illness and hospitalization in children plummeted quickly after vaccination.

The study found that among children who had received two or more doses of the original monovalent vaccine, the vaccine was initially 52% effective against hospitalization. After four months effectiveness dropped to 19%.

Protection against “critical illness” similarly dropped from 57% to 25% after four months.

The authors concluded that based on the findings, children and adolescents should get boosters to remain up to date with their shots.

The researchers analyzed data on the monovalent COVID-19 vaccines given from Dec. 19, 2021 — when the vaccines were first authorized for children ages 5 and up — through Oct. 29, 2023.

They reported that too few children and adolescents had received the bivalent or updated monovalent vaccines to separately evaluate their effectiveness.

The study was published in the CDC’s Morbidity and Mortality Weekly Report on April 18. Several researchers on the study reported receiving research support from Pfizer or owning Pfizer stocks. One reported research support from Moderna.

The Defender asked one of the report’s authors, Laura D. Zambrano, Ph.D., if given the low rates of effectiveness and the recent findings on safety signals from the FDA, the authors might change their booster recommendations. Zambrano did not respond by press time.

The CDC continues to recommend children ages 6 months and up be vaccinated against COVID-19 and remain up to date with their vaccines.

As of April 13, 2024, 14% of children are reported to be up to date with the 2023-24 COVID-19 vaccine and 8.1% of children had a parent who said they intended to vaccinate their child.