cb‐Beyerlein 2017.

Study characteristics
Methods	Cohort study ‐ Germany
Participants	Between 1989 and 2000, a total of 1650 offspring of patients with T1D were recruited for the BABYDIAB study and were followed for 23,856 patient‐years. Between 2000 and 2006, 791 additional offspring or siblings of patients with T1D were screened in the context of the BABYDIET study and were followed by using the BABYDIAB protocol for 6358 patient‐years.
Interventions	MMR vaccination Vaccines recommended by the German Standing Committee on Vaccination (STIKO), which include diphtheria, hepatitis B, Hib, pertussis, poliomyelitis, tetanus, measles, mumps, rubella, meningococcal, pneumococcal, varicella, TBE, and influenza. Several vaccinations were typically given as a 3‐fold compound (MMR: measles, mumps, rubella) or a 5/6‐fold compound (diphtheria, Hib, pertussis, poliomyelitis, tetanus, and since 2001 additionally hepatitis B).
Outcomes	Type 1 diabetes (T1D) is one of the most common chronic diseases in childhood, with worldwide increasing incidence. The disease is preceded by a pre‐clinical period of islet autoimmunity, which most commonly develops in early infancy. Factors that induce a strong immune response in early life thus might be relevant for the development of T1D‐associated islet autoimmunity. Islet autoantibodies were measured in venous blood samples from scheduled visits. Children in the BABYDIAB study had scheduled visits at birth and at age 9 months, and at 2, 5, 8, 11, 14, 17, and 20 years of age, whereas children in the BABYDIET study had 3‐monthly visits from birth until the age of 3 years, and yearly until the age of 12 years. Measurement of islet autoantibodies in these studies has been described elsewhere. Islet autoimmunity was defined as the development of persistent autoantibodies to 1 or more of the antigens insulin, GAD65, IA‐2, or Zn‐T8, with sample values above the 99th percentile of published population control children classified as positive. In case of single positive antibodies against insulin or GAD65, affinity and epitope reactivity was determined, and children with low‐affinity antibodies (< 109 L/mol) were not classified as islet autoantibody positive, as these isolated antibody signals are not T1D specific and are not associated with increased T1D risk. Persistence was defined as positive in at least 2 consecutive samples. Islet autoantibody assays were evaluated according to the Diabetes Autoantibody Standardization Program.
Funding Source	Government
Notes	Conclusions: there was no evidence that early vaccinations increase the risk of T1D‐associated islet autoimmunity development.
Risk of bias
Bias	Authors' judgement	Support for judgement
PCS/RCS ‐ exposed cohort selection	Low risk	Adequate ‐ vaccination record
PCS/RCS ‐ non‐exposed cohort selection	Low risk	Adequate ‐ drawn from the same community
PCS/RCS ‐ comparability	Low risk	Adequate ‐ multivariate model
PCS/RCS ‐ assessment of outcome	Low risk	Adequate ‐ Diabetes Autoantibody Standardization Program
Summary Risk of Bias assessment	Low risk	Plausible bias is unlikely to have seriously altered the results.