Investigators from the Centers for Disease Control and Prevention (CDC) Vaccine Safety Datalink (VSD) Working Group studied the risk of a first seizure, subsequent seizures, and neurodevelopmental disability following the administration of diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine by a retrospective review of the medical records of a cohort of over 600,000 children under the age of 7 years enrolled in 4 HMOs in Washington, Oregon, and California between 1991 and 1993. Children with myoclonus, epilepsy, convulsions, and convulsions in the newborn were identified by the HMOs’ automated data systems for hospitalizations and clinic visits and by random sampling of medical records. Simple febrile seizures were defined as short and generalized, and complex febrile seizures were defined as febrile seizures that occurred more than once in 24 hours and either lasted for at least 12 minutes or were accompanied by focal signs. Nonfebrile seizures due to prior infection or trauma were excluded. The background rate of febrile seizures during the first 2 years of life was used to calculate the risk attributable to immunization.
Following 340,386 DTP and 137,457 MMR vaccinations, 2281 first seizures were identified using the automated data as described above and a total of 1094 children were selected randomly for chart review. Of these 1094 children, 716 had confirmed first seizures during the study period. First seizures were febrile in 487 (460 simple, 27 complex), nonfebrile in 137, infantile spasms or neonatal in 36, and other causes in 56. Febrile seizures occurred within 30 days after DTP and MMR vaccines in 42 (5 on the same day as DTP) and 32, respectively. Febrile seizures were recorded in the absence of vaccination in 521 children. Nonfebrile seizures occurred within 30 days after DTP and MMR vaccines in 10 and 3 children, respectively.
DTP was associated with a significantly increased risk of febrile seizures only on the day of vaccination (RR 5.70; 95% CI, 1.98–16.42), the risk being highest for 0- to 12-month-olds (RR 9.27; 95% CI, 1.21–70.78). MMR was also associated with increased risk of febrile seizures, but 8 to 14 days after vaccination (RR 5.7; 95% CI, 1.44–5.55). The estimated numbers of febrile seizures attributable to DTP and MMR vaccination were 6 to 9 and 25 to 34 per 100,000 children, respectively. Five percent of the children with febrile seizures occurring after vaccination but not associated with it developed epilepsy at 2-year follow-up. Febrile seizures associated with vaccination did not carry a higher risk of subsequent epilepsy or neurodevelopmental disabilities (ADHD, learning disorders, retardation, infanti1e autism, or other emotional and behavior disorders) than non-vaccine-related febrile seizures.
The Vaccine Safety Datalink project, initiated by the CDC in 1991, is a large, population-based study of adverse events associated with childhood immunizations. Use of the automated...