Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures

• Published in: Pediatrics (Evanston) 2010-07, Vol.126 (1), p.e1-e8
• Main Authors: Klein, Nicola P, Fireman, Bruce, Yih, W Katherine, Lewis, Edwin, Kulldorff, Martin, Ray, Paula, Baxter, Roger, Hambidge, Simon, Nordin, James, Naleway, Allison, Belongia, Edward A, Lieu, Tracy, Baggs, James, Weintraub, Eric
• Format: Article
• Language: English
• Subjects: Age Distribution; Chicken pox; Chickenpox Vaccine - administration & dosage; Chickenpox Vaccine - adverse effects; Cohort Studies; Convulsions & seizures; Databases, Factual; Female; Follow-Up Studies; Humans; Immunization; Incidence; Infant; Male; Measles; Measles-Mumps-Rubella Vaccine - administration & dosage; Measles-Mumps-Rubella Vaccine - adverse effects; Mumps; Pediatrics; Retrospective Studies; Seizures, Febrile - chemically induced; Seizures, Febrile - epidemiology; Seizures, Febrile - physiopathology; Severity of Illness Index; Sex Distribution; Time Factors; Vaccination - adverse effects; Vaccination - methods; Vaccines; Vaccines, Combined - administration & dosage; Vaccines, Combined - adverse effects
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2010-0665

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. 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. 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). 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.