Combination Vaccine Associated With Small Increased Risk of Febrile Seizure on Day of Vaccination

In a study that included nearly 400,000 children, receipt of the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine was associated with an increased risk of febrile seizures on the day of the first and the second vaccinations, but the absolute risk was low, according to a study in the Feb. 22/29 issue of JAMA. The risk of epilepsy was not higher among vaccinated vs. unvaccinated children.
 
Studies have reported increased risks of febrile seizures shortly after administration of whole-cell pertussis vaccine, as would be expected since the whole-cell pertussis vaccine often causes fever, according to background information in the article. The acellular [may contain cellular material but does not contain complete cells] pertussis vaccine has replaced the whole-cell pertussis vaccine in most countries because the efficacy of the acellular vaccine is comparable with the whole-cell vaccine and it has substantially fewer adverse effects, including fever. Whether there is an increased risk of febrile seizures with the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine was introduced in a combined vaccine in January 1997.
 
Yuelian Sun, PhD, of Aarhus University in Aarhus, Denmark, and colleagues examined the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. The study included 378,834 children who were born in Denmark between January 2003 and December 2008 and followed up through December 31, 2009. With the data, the researchers calculated the rate of febrile seizures within 0 to seven days (0, 1-3, and 4-7 days) after each vaccination and of epilepsy after the first vaccination.
 
Overall, of the children included in the study, 7,811 (2.1 percent) were diagnosed with febrile seizures before 18 months. Of these children, 17 were diagnosed within 0 to seven days after the first vaccination, 32 within 0 to seven days after the second vaccination, and 201 within 0 to seven days after the third vaccination. Analysis indicated that children did not have higher risks of febrile seizures during the 0 to seven days after the three vaccinations compared with a reference group of children who were not within 0 to seven days of vaccination. The researchers did find a higher risk of febrile seizures on the day of the first vaccination and on the day of the second vaccination, but not on the day of the third vaccination, compared with the reference group. On the day of vaccination, nine children were diagnosed with febrile seizures after the first, 12 children after the second, and 27 children after the third.
 
Within seven years of follow-up, 2,248 children were diagnosed with epilepsy, 131 unvaccinated children and 2,117 vaccinated children. Among 2,117 children diagnosed with epilepsy after vaccination, 813 were diagnosed between three and 15 months and 1,304 were diagnosed later in life, but only two children were diagnosed with epilepsy on the day of the first vaccination and one on the day of the second vaccination. Compared with the unvaccinated cohort, vaccinated children had a lower risk of epilepsy in the first 15 months of life but had a similar risk of epilepsy afterward, the authors write.
 
Although the relative risks of febrile seizures on the day of the two DTaP-IPV-Hib vaccinations were increased, the absolute risk of febrile seizures after DTaP-IPV-Hib vaccination was very low, and the prognosis of febrile seizures occurring shortly after vaccination was similar to the prognosis of febrile seizures occurring outside the risk period of vaccination.

Reference: JAMA. 2012;307[8]:823-831.