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Cited by 170Epilepsy research and treatmentPharmacovigilance and Adverse Drug ReactionsVirology and Viral Diseases

MMR Vaccination and Febrile Seizures: Evaluation of Susceptible Subgroups and Long-term Prognosis

Vestergaard, Mogens, Hviid, Anders, Madsen, Kreesten Meldgaard, Wohlfahrt, Jan, Thorsen, Poul, Schendel, Diana, Melbye, Mads, Olsen, Jørn·2004·JAMA
DOI 10.1001/jama.292.3.351
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Abstract

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 subsequent epilepsy. 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 different etiology.

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  • A significant risk of association between MMR exposure and febrile seizures during the two previous weeks was found in a person-time cohort of 537,171 children aged three months to five years (RR 1.10; 95% CI 1.05 to 1.15).

    “A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age.”

    From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Vestergaard 2004

  • In the Danish birth cohorts 1991 to 1998 (n = 537,171), the risk of febrile seizure was significantly higher among MMR-vaccinated children than among unvaccinated children (RR 1.10; 95% CI 1.05 to 1.15).

    “Globally, the risk of febrile seizure was significantly higher among the vaccinated (RR 1.10; 95% CI 1.05 to 1.15).”

    From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Vestergaard 2004

  • After MMR vaccination, the relative risk of febrile seizure was highest within two weeks (RR 2.75; 95% CI 2.55 to 2.97), did not differ significantly in weeks three to six, became slightly less than one in weeks seven to 52, and was not different from unvaccinated after week 53.

    “When different time frames after vaccination are considered, the RR was at the highest point within two weeks after immunisation (RR 2.75; 95% CI 2.55 to 2.97), did not differ significantly in weeks three to six and became slightly less than one in weeks seven, eight, nine to 26 and 27 to 52.The RR was not different to the unvaccinated after week 53.”

    From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Vestergaard 2004

  • A significant risk association was found only for recurrent febrile seizure episodes in children immunised with MMR within 14 days before the first episode (RR 1.19; 95% CI 1.10 to 1.41, adjusted for age, calendar period, age at first febrile seizure and current vaccination status).

    “A significant risk association was found only for recurrent febrile seizure episodes in children who were immunised with MMR within 14 days before the first episode (RR 1.19; 95% CI 1.10 to 1.41, adjusted for age, calendar period, age at first febrile seizure and current vaccination status).”

    From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Vestergaard 2004

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Authors
Vestergaard, M., Hviid, A., Madsen, K. M., Wohlfahrt, J., Thorsen, P., Schendel, D., Melbye, M., & Olsen, J.
Affiliations
Aarhus University (DK)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2004-07-21
Volume
292
Issue
3
Pages
351
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.292.3.351
OpenAlex
W2144921754
Cited by
170
References
26
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 13
FWCI
5.43
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
MMR vaccination, febrile seizures, MMR vaccine, vaccine adverse events, recurrent febrile seizures, epilepsy, family history of seizures, perinatal factors, socioeconomic status, incidence rate ratio, risk difference, children, Denmark
MeSH terms
Child, Preschool, Seizures, Febrile, Denmark, Humans, Infant, Prognosis, Registries, Risk, Cohort Studies, Measles-Mumps-Rubella Vaccine

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