Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination

Vaccine. 2014 Feb 3;32(6):645-50. doi: 10.1016/j.vaccine.2013.12.011. Epub 2013 Dec 25.


Background: In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad(®) compared to separately administered MMR and V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™.

Methods: We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad(®) study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups.

Results: In the main risk period 5-12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3-12.7; MMR], 3.5 [0.7-19.0; MMR+V], and 4.1 [1.5-11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4-3.9; MMR], 1.5 [0.8-2.9; MMR+V] and 2.4 [1.5-3.9; MMR and MMR+V].

Conclusions: This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad(®) suggesting a class effect for these quadrivalent vaccines.

Keywords: Febrile convulsion; First dose; MMR; MMRV; Vaccination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chickenpox Vaccine / administration & dosage
  • Chickenpox Vaccine / adverse effects*
  • Child, Preschool
  • Cohort Studies
  • Female
  • Germany / epidemiology
  • Humans
  • Infant
  • Male
  • Measles-Mumps-Rubella Vaccine / administration & dosage
  • Measles-Mumps-Rubella Vaccine / adverse effects*
  • Seizures, Febrile / chemically induced*
  • Seizures, Febrile / epidemiology
  • Vaccination / adverse effects*
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects


  • Chickenpox Vaccine
  • Measles-Mumps-Rubella Vaccine
  • Vaccines, Combined
  • measles, mumps, rubella, varicella vaccine