Introduction: Past studies of DTP vaccination have shown an association with febrile, but not afebrile, seizures. However, these studies have had limited power to detect small effects and the possible relationship of MMR exposure and seizures has not been extensively studied. The Vaccine Safety Datalink is a population-based study of adverse events following childhood immunization in four health maintenance organizations, and follows approximately 2% of the nation's children <7 years old. We report the findings of a study of febrile and afebrile seizures following 340,386 DTP vaccinations and 137,457 MMR vaccinations among 679,942 children <7 years of age.

Methods: Tracking systems collected information on immunizations routinely administered at all medical sites within each HMO, including clinics, hospitals, and emergency departments. Medical outcomes betwen 1991 and 1993 were identified from automated data systems, and medical records were reviewed for children with ICD-9 codes indicative of possible seizure events. At one HMO, cases were ascertained through ancillary data sources (eg pharmacy files), while at two HMOs a sample of records were reviewed due to the large number of potential cases. Validated seizures were classified by type, including simple and complex febrile seizures and afebrile seizures. Seizures were further categorized according to whether it was an incident (first ever) or recurrent seizure. Cox proportional hazards analysis, adjusted for age, time, and HMO, assessed the association between immunization and incident seizures.

Results: There were 936 validated incident seizures, including 581 simple or complex febrile seizures and 234 afebrile seizures. DTP was associated with a a 5.6 fold elevated risk for febrile seizure on the day of vaccination (RR 5.6;95%CI 2.3,13.9). This risk dropped sharply and was not significantly elevated in the 1-7 days following vaccination. MMR was associated with an almost three-fold elevated risk (RR 2.9;95%CI 1.6,5.3) for febrile seizure in the 8-14 days following vaccination. This risk also dropped sharply, and did not persist in the 15-30 day period following vaccination. Neither DTP nor MMR was associated with a significantly increased risk for afebrile seizures.

Discussion: DTP is associated with a transiently elevated risk for febrile seizures in the period shortly after vaccination, while MMR is associated with a smaller, but elevated, risk for febrile seizures 8-14 days following vaccination. We did not find significant risks for afebrile seizures following either DTP or MMR vaccination.