title: Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data.
abstract: Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth.
  
  
  
  A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination.
  
  
  
  Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]).
  
  
  
  We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyerlein
authors.affiliation: Department of Mathematics of the Technische Universität München, Munich, Germany.
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Strobl
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Winkler
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Carpus
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Knopff
authors.affiliation: Kassenärztliche Vereinigung Bayerns (Bavarian Association of Statutory Health Insurance Physicians), Munich, Germany.
authors.forename: Ewan
authors.initials: E
authors.lastname: Donnachie
authors.affiliation: Department of Mathematics of the Technische Universität München, Munich, Germany; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Donna P
authors.initials: DP
authors.lastname: Ankerst
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany. Electronic address: anette-g.ziegler@helmholtz-muenchen.de.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D000367:Age Factors; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014611:Vaccination / Q000009:adverse effects*; D014612:Vaccines / Q000009:adverse effects / Q000276:immunology
chemical_list: D014612:Vaccines
keywords: Islet autoimmunity; Type 1 diabetes; Vaccinations