MMRV remains associated with increased risk for febrile seizures

The measles-mumps-rubella-varicella vaccine was associated with a nearly twofold increase in risk for febrile seizures in children aged 12 to 23 months during the 7 to 10 day period after vaccination, according to a in a recently published study.

In February 2008, the AAP submitted preliminary evidence to the Advisory Committee on Immunization Practices connecting the measles-mumps-rubella-varicella vaccine (MMRV, ProQuad, Merck) to an elevated risk for febrile seizures in children aged 12 to 23 months during the 1 to 2 weeks after immunization. Researchers from Kaiser Permanente and other sites recently revisited these findings and evaluated an expanded data pool using information taken from various sites in the Vaccine Safety Datalink (VSD) database.

Data from 2000 to 2008 on children who had received MMRV, separate measles-mumps-rubella (MMR, M-M-R II, Merck) and varicella (VAR, Varivax, Merck) vaccines or MMR or VAR only were included. To determine whether seizures were febrile, the researchers performed chart reviews on all seizures that occurred within 0 to 42 days after MMRV vaccination, 7 to 10 days after separately administered MMR and VAR vaccines and a random sample of those that happened during 0 to 6 and 11 to 42 days after receipt of separate MMR and VAR vaccines. Information on child or family history of seizures was also studied if available.

Between January 2006 and October 2008, 83,107 children were immunized with MMRV while 376,354 were vaccinated with separate MMR and VAR vaccines between January 2000 and October 2008. The 145,302 children who received MMR alone and the 107,744 who received VAR alone during the study period served as comparison groups.

Results showed that seizure incidence was elevated for all measles- containing vaccines during 7 to 10 days postimmunization, with the highest rates occurring among MMRV recipients. Children vaccinated with MMRV were also more likely to experience seizures during postvaccination days 8 to 10 (RR=7.6; P<.0001), while those immunized with separate MMR and VAR vaccines had a higher chance of having a seizure during postvaccination days 7 to 10 (RR=4.0; P<.0001), and children who only received MMR had an increased likelihood of experiencing a seizure 7 to 11 days after immunization (RR=3.7; P<.0001).

“During days 7 to 10, unadjusted rates for seizures were 84.6 seizures per 1000 person-years after MMRV vaccination, 42.2 seizures per 1000 person-years after MMR and varicella vaccination, and 26.4 seizures per 1,000 person-years after MMR vaccination alone,” the researchers wrote. “Unadjusted rates during days 7 to 10 were nearly 8 times higher for MMRV and 4 and 3.5 times higher for MMR and varicella and MMR vaccination alone, respectively.”

Risk for seizures was also higher after MMRV vaccination than after immunization with separate MMR and VAR vaccines during 7 to 10 days postvaccination (RR=1.98; 95% CI, 1.43-2.73). However, there was no significant association between MMRV and elevated seizure risk outside of the 7- to 10-day range, according to the researchers.

Calculations also indicated that MMRV was linked to 4.3 additional seizures per 10,000 doses (95% CI, 2.6-5.6) during 7 to 10 days postvaccination.

“The use of MMRV vaccine instead of separate MMR and varicella vaccines approximately doubles the risk for fever and febrile seizures, resulting in one additional febrile seizure for every 2,300 doses of MMRV vaccine administered instead of separate MMR and varicella vaccines,” wrote the researchers. “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.” – by Melissa Foster

Klein NP. Pediatrics. 2010; 126:e1-e8.

PERSPECTIVE

Paul Offit, MD
Paul Offit

Klein and coworkers found a slight increase in the incidence of febrile seizures in children receiving the combined measles-mumps-rubella-varicella vaccine (ProQuad) compared with those who had received the MMR and varicella vaccines separately. Only about four excess cases of febrile seizures per 10,000 doses of ProQuad were observed. This study is yet another testament to the thoroughness and care of the CDC in detecting and publishing even rare vaccine side effects post-licensure.

Paul Offit, MD
Infectious Diseases in Children Editorial Board

The measles-mumps-rubella-varicella vaccine was associated with a nearly twofold increase in risk for febrile seizures in children aged 12 to 23 months during the 7 to 10 day period after vaccination, according to a in a recently published study.

In February 2008, the AAP submitted preliminary evidence to the Advisory Committee on Immunization Practices connecting the measles-mumps-rubella-varicella vaccine (MMRV, ProQuad, Merck) to an elevated risk for febrile seizures in children aged 12 to 23 months during the 1 to 2 weeks after immunization. Researchers from Kaiser Permanente and other sites recently revisited these findings and evaluated an expanded data pool using information taken from various sites in the Vaccine Safety Datalink (VSD) database.

Data from 2000 to 2008 on children who had received MMRV, separate measles-mumps-rubella (MMR, M-M-R II, Merck) and varicella (VAR, Varivax, Merck) vaccines or MMR or VAR only were included. To determine whether seizures were febrile, the researchers performed chart reviews on all seizures that occurred within 0 to 42 days after MMRV vaccination, 7 to 10 days after separately administered MMR and VAR vaccines and a random sample of those that happened during 0 to 6 and 11 to 42 days after receipt of separate MMR and VAR vaccines. Information on child or family history of seizures was also studied if available.

Between January 2006 and October 2008, 83,107 children were immunized with MMRV while 376,354 were vaccinated with separate MMR and VAR vaccines between January 2000 and October 2008. The 145,302 children who received MMR alone and the 107,744 who received VAR alone during the study period served as comparison groups.

Results showed that seizure incidence was elevated for all measles- containing vaccines during 7 to 10 days postimmunization, with the highest rates occurring among MMRV recipients. Children vaccinated with MMRV were also more likely to experience seizures during postvaccination days 8 to 10 (RR=7.6; P<.0001), while those immunized with separate MMR and VAR vaccines had a higher chance of having a seizure during postvaccination days 7 to 10 (RR=4.0; P<.0001), and children who only received MMR had an increased likelihood of experiencing a seizure 7 to 11 days after immunization (RR=3.7; P<.0001).

“During days 7 to 10, unadjusted rates for seizures were 84.6 seizures per 1000 person-years after MMRV vaccination, 42.2 seizures per 1000 person-years after MMR and varicella vaccination, and 26.4 seizures per 1,000 person-years after MMR vaccination alone,” the researchers wrote. “Unadjusted rates during days 7 to 10 were nearly 8 times higher for MMRV and 4 and 3.5 times higher for MMR and varicella and MMR vaccination alone, respectively.”

Risk for seizures was also higher after MMRV vaccination than after immunization with separate MMR and VAR vaccines during 7 to 10 days postvaccination (RR=1.98; 95% CI, 1.43-2.73). However, there was no significant association between MMRV and elevated seizure risk outside of the 7- to 10-day range, according to the researchers.

Calculations also indicated that MMRV was linked to 4.3 additional seizures per 10,000 doses (95% CI, 2.6-5.6) during 7 to 10 days postvaccination.

“The use of MMRV vaccine instead of separate MMR and varicella vaccines approximately doubles the risk for fever and febrile seizures, resulting in one additional febrile seizure for every 2,300 doses of MMRV vaccine administered instead of separate MMR and varicella vaccines,” wrote the researchers. “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.” – by Melissa Foster

Klein NP. Pediatrics. 2010; 126:e1-e8.

PERSPECTIVE

Paul Offit, MD
Paul Offit

Klein and coworkers found a slight increase in the incidence of febrile seizures in children receiving the combined measles-mumps-rubella-varicella vaccine (ProQuad) compared with those who had received the MMR and varicella vaccines separately. Only about four excess cases of febrile seizures per 10,000 doses of ProQuad were observed. This study is yet another testament to the thoroughness and care of the CDC in detecting and publishing even rare vaccine side effects post-licensure.

Paul Offit, MD
Infectious Diseases in Children Editorial Board