Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

Abstract

Studies have reported increased risks of febrile seizures shortly after administration of whole-cell pertussis vaccine,^1,2 as would be expected since the whole-cell pertussis vaccine often causes fever. Whole-cell pertussis vaccine has also been associated with serious neurological illnesses characterized by seizures and intellectual impairment,^3,4 but recent studies indicate that the vaccination only triggers an earlier onset of severe epileptic encephalopathy in children with sodium channel gene mutations.^5-7 The acellular 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.^8-12 Previous randomized controlled trials did not reveal differences in the risk of seizures after acellular pertussis vaccination compared with whole-cell pertussis vaccination, but the trials were not powered to detect rare adverse effects.^8-11 A study from the United Kingdom found a 2-fold higher risk of seizures on the day of the diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination, and a study from the United States found a 30% higher risk of seizures on the day of the first DTaP vaccination.^13,14 However, these estimates did not reach statistical significance and the studies did not distinguish between afebrile and febrile seizures.^13,14 We examined the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination in a large nationwide, population-based cohort study in Denmark.