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Vestergaard M, Hviid A, Madsen KM, et al. MMR Vaccination and Febrile Seizures: Evaluation of Susceptible Subgroups and Long-term Prognosis. JAMA. 2004;292(3):351–357. doi:10.1001/jama.292.3.351
Author Affiliations: The Danish Epidemiology Science Centre, Department of Epidemiology and Social Medicine, Aarhus University, Aarhus (Drs Vestergaard, Madsen, and Olsen), The Danish Epidemiology Science Centre, Department of Epidemiology Research, Statens Serum Institut, Copenhagen (Dr Melbye and Mr Hviid and Ms Wohlfahrt), and North Atlantic Neuro-Epidemiology Alliances, Department of Epidemiology and Social Medicine, Aarhus (Drs Thorsen and Schendel), Denmark; and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Schendel).
Context The rate of febrile seizures increases following measles, mumps, and
rubella (MMR) vaccination but it is unknown whether the rate varies according
to personal or family history of seizures, perinatal factors, or socioeconomic
status. Furthermore, little is known about the long-term outcome of febrile
seizures following vaccination.
Objectives To estimate incidence rate ratios (RRs) and risk differences of febrile
seizures following MMR vaccination within subgroups of children and to evaluate
the clinical outcome of febrile seizures following vaccination.
Design, Setting, and Participants A population-based cohort study of all children born in Denmark between
January 1, 1991, and December 31, 1998, who were alive at 3 months; 537 171
children were followed up until December 31, 1999, by using data from the
Danish Civil Registration System and 4 other national registries.
Main Outcome Measures Incidence of first febrile seizure, recurrent febrile seizures, and
Results A total of 439 251 children (82%) received MMR vaccination and
17 986 children developed febrile seizures at least once; 973 of these
febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile
seizures increased during the 2 weeks following MMR vaccination (2.75; 95%
confidence interval [CI], 2.55-2.97), and thereafter was close to the observed
RR for nonvaccinated children. The RR did not vary significantly in the subgroups
of children that had been defined by their family history of seizures, perinatal
factors, or socioeconomic status. At 15 to 17 months, the risk difference
of febrile seizures within 2 weeks following MMR vaccination was 1.56 per
1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40)
for siblings of children with a history of febrile seizures, and 19.47 per
1000 (95% CI, 16.05-23.55) for children with a personal history of febrile
seizures. Children with febrile seizures following MMR vaccinations had a
slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41)
but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with
children who were nonvaccinated at the time of their first febrile seizure.
Conclusions MMR vaccination was associated with a transient increased rate of febrile
seizures but the risk difference was small even in high-risk children. The
long-term rate of epilepsy was not increased in children who had febrile seizures
following vaccination compared with children who had febrile seizures of a
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