title: Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination.
abstract: 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.
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany. Electronic address: schink@bips.uni-bremen.de.
authors.forename: Tania
authors.initials: T
authors.lastname: Schink
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany. Electronic address: holstiege@bips.uni-bremen.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Holstiege
authors.affiliation: Center for Children and Adolescent Medicine of the Johannes Gutenberg-Universität, Langenbeckstraße 1, 55131 Mainz, Germany. Electronic address: frank.kowalzik@unimedizin-mainz.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Kowalzik
authors.affiliation: Center for Children and Adolescent Medicine of the Johannes Gutenberg-Universität, Langenbeckstraße 1, 55131 Mainz, Germany. Electronic address: Fred.Zepp@unimedizin-mainz.de.
authors.forename: Fred
authors.initials: F
authors.lastname: Zepp
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany. Electronic address: garbe@bips.uni-bremen.de.
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
mesh_terms: D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D003294:Seizures, Febrile / Q000139:chemically induced* / Q000453:epidemiology; D014611:Vaccination / Q000009:adverse effects*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019433:Chickenpox Vaccine; D022542:Measles-Mumps-Rubella Vaccine; D017778:Vaccines, Combined; C050102:measles, mumps, rubella, varicella vaccine
keywords: Febrile convulsion; First dose; MMR; MMRV; Vaccination