Major Finding: In the 7- to10-day postvaccination period, use of MMRV was associated with 4.3 additional febrile seizures per 10,000 doses, compared with separate administration of MMR and varicella vaccine.
Data Source: Vaccine Safety Datalink data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients in 2000–2008.
Disclosures: Study funding came from the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Dr. Baxter have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur. The other authors reported no conflicts of interest.
Children aged 12–23 months old are at increased risk of febrile seizures 7–10 days after vaccination with the combination measles-mumps-rubella-varicella vaccine, compared with separate administration of the measles-mumps-rubella vaccine and the varicella vaccine, according to surveillance data from the United States.
The use of the combination measles-mumps-rubella-varicella (MMRV) vaccine instead of separate measles-mumps-rubella and varicella (MMR+V) vaccines accounted for one additional febrile seizure for every 2,300 MMRV vaccines administered—a nearly twofold increased risk, Dr. Nicola P. Klein of Kaiser Permanente Vaccine Study Center, Oakland, Calif., and her colleagues reported.
The researchers issued their preliminary findings to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) in February 2008.
ACIP subsequently changed its recommendations from a stated preference for MMRV to no preference for either MMRV or separate MMR+V vaccination.
“We analyzed [more than] 459,000 12- to 23-month old children vaccinated with either MMRV or separate MMR and varicella vaccines and found the MMRV vaccine to be associated with increased fever and seizures 7–10 days after vaccination,” they wrote (Pediatrics 2010 June [doi:10.1542/peds.2010–0665]).
Researchers compared seizure risk following MMRV to that following MMR+V using regression analyses and by incorporating chart-reviewed febrile seizure cases.
They looked at Vaccine Safety Datalink (VSD) data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients from 2000 to 2008. VSD's surveillance system monitors for potential associations between specific vaccines and adverse events using weekly data and sequential statistical analysis, according to investigators.
In the 7–10 days post vaccination, the MMRV vaccination was associated with 4.3 additional seizures per 10,000 doses. It was not associated with significantly elevated seizure risks during any of the five intervals outside that period, Dr. Klein and her colleagues said.
“Our study results show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7–10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines,” the investigators reported.
“Providers who choose to use the combination vaccine should be aware of and clearly communicate this increased risk to the families and caregivers of their patients,” Dr. Klein and her colleagues said.