The risk for febrile seizure (FS) in children under 2 years of age after vaccination is small and should be weighed against the potential benefit of timely vaccination, according to a new studypublished online June 6 in Pediatrics.

“Our results suggest that the risk of FS is increased after certain combinations of vaccines, but the absolute risk of FS after these combinations is small,” write lead author Jonathan Duffy, MD, MPH, from the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues.

The researchers reviewed data from 1,915,108 vaccination events obtained from the Vaccine Safety Datalink, a collaboration between the CDC and several health care organizations, to evaluate the risk for FS after administration of influenza vaccine, alone or in combination with other vaccines.

To control for other factors, the authors used a self-controlled risk interval method to analyze the data, with the risk interval defined as the day of vaccination and day after it (days 0 – 1). They defined the control period as days 14 to 20 after vaccination. The control interval was designed to represent “a time period during which neither inactivated nor live-attenuated vaccines induce fever and the risk of FS is at baseline.”

Overall they identified 333 chart-confirmed FS cases among children aged 6 to 23 months during the influenza seasons between 2006 and 2011. Of those, 103 FS cases occurred in the risk interval period and 230 fell into the control period.

Included children were 6 to 23 months of age and were stratified into 2 groups: the risk interval group (n = 103), composed of children who experienced a FS within 1 day after receiving at least 1 vaccine of any type, and the control interval group, consisting of children with an FS 14 to 20 days after vaccination (n = 230).

The researchers found that simultaneous administration of a pneumococcal conjugate vaccine (PCV) along with a trivalent inactivated influenza vaccine (IIV3), or a vaccine to prevent diphtheria/tetanus/acellular pertussis (DTaP), increased the absolute risk for FS by 30 per 100,000 children vaccinated when compared with the risk for FS if vaccines were administered on separate days.

The study authors also found that, after adjustment for the receipt of concomitant vaccines, only the 7-valent pneumococcal vaccine was associated with an independent increased risk for FS (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.00 – 3.91). The influenza vaccine (IIV3) had no independent risk (IRR, 0.46; 95% CI, 0.21 – 1.02); however, risk was increased when IIV3 was given with PCV (IRR, 3.50; 95% CI, 1.13 – 10.85) or a DTaP-containing vaccine (IRR, 3.50; 95% CI, 1.52 – 8.07). The researchers note, however, that the risk for FS may vary annually on the basis of differences in vaccine formulation.

The authors defined FS “as a seizure with a recorded temperature ≥ 38°C (100.4°F) or a caregiver-reported fever within 24 hours, or a clinician’s diagnosis of FS, excluding patients with intracranial infection, metabolic disturbance, or a history of a febrile seizure.”

In a commentary that accompanies the study, Mark H. Sawyer, MD, and colleagues, from the American Academy of Pediatrics Committee on Infectious Diseases, note that these findings mean that “one could expect to see at most 1 child who experiences a febrile seizure every 5 to 10 years due to administration of these vaccines together in the first 2 years of life.”

The authors acknowledge study limitations, such as the inability to study every unique vaccine combination and the low overall number of FS cases. They note, however, that by pooling data over several influenza seasons, two-way and three-way interactions between IIV3 and other vaccines can be evaluated.

The study authors and commentators acknowledge the risk for FS when these vaccines are administered together; however, they agree that the benefit of timely vaccination in this age group far outweighs the risk. “The benefits of giving these vaccines simultaneously include decreased office visits associated with painful vaccines, decreased episodes of vaccine-associated fussiness, and, most important, the assurance that children will be fully immunized and protected from infections that carry real morbidity and mortality,” write Dr. Sawyer and colleagues.