Measles-Mumps-Rubella-Varicella Combination Vaccine and the Risk of Febrile Seizures

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Pediatrics (2010) 126 (1): e1–e8. https://doi.org/10.1542/peds.2010-0665

Measles-Mumps-Rubella-Varicella Combination Vaccine and the Risk of Febrile Seizures

Nicola P. Klein, MD, PhD; Bruce Fireman, MS; W. Katherine Yih, MPH, PhD; Edwin Lewis, MPH; Martin Kulldorff, PhD; Paula Ray, MPH; Roger Baxter, MD; Simon Hambidge, MD, PhD; James Nordin, MD, MPH; Allison Naleway, PhD; Edward A. Belongia, MD; Tracy Lieu, MD, MPH; James Baggs, PhD; Eric Weintraub, MPH; for the Vaccine Safety Datalink

Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612.

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.

  • July 1, 2010