title: Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.
abstract: OBJECTIVE
  In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine.
  
  
  METHODS
  Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses.
  
  
  RESULTS
  MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6).
  
  
  CONCLUSIONS
  Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.
authors.affiliation: Kaiser Permanente Vaccine Study Center, Oakland, CA 94612, USA. nicola.klein@kp.org
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Bruce
authors.initials: B
authors.lastname: Fireman
authors.forename: W Katherine
authors.initials: WK
authors.lastname: Yih
authors.forename: Edwin
authors.initials: E
authors.lastname: Lewis
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: Paula
authors.initials: P
authors.lastname: Ray
authors.forename: Roger
authors.initials: R
authors.lastname: Baxter
authors.forename: Simon
authors.initials: S
authors.lastname: Hambidge
authors.forename: James
authors.initials: J
authors.lastname: Nordin
authors.forename: Allison
authors.initials: A
authors.lastname: Naleway
authors.forename: Edward A
authors.initials: EA
authors.lastname: Belongia
authors.forename: Tracy
authors.initials: T
authors.lastname: Lieu
authors.forename: James
authors.initials: J
authors.lastname: Baggs
authors.forename: Eric
authors.initials: E
authors.lastname: Weintraub
mesh_terms: D017677:Age Distribution; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D003294:Seizures, Febrile / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D012720:Severity of Illness Index; D017678:Sex Distribution; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019433:Chickenpox Vaccine; D022542:Measles-Mumps-Rubella Vaccine; D017778:Vaccines, Combined; C050102:measles, mumps, rubella, varicella vaccine