Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation.

AIMS/HYPOTHESIS: To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. METHOD: Seven centres in Europe with access to population-based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors. Control children were chosen at random in each centre either from population registers or from schools and policlinics. Data on maternal and neonatal infections, common childhood infections and vaccinations were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a questionnaire or interview. RESULTS: Infections early in the child's life noted in the hospital record were found to be associated with an increased risk of diabetes, although the odds ratio of 1.61 (95% confidence limits 1.11, 2.33) was significant only after adjustment for confounding variables. None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes. Pre-school day-care attendance, a proxy measure for total infectious disease exposure in early childhood, was found, however, to be inversely associated with diabetes, with a pooled odds ratio of 0.59 (95% confidence limits 0.46, 0.76) after adjustment for confounding variables. CONCLUSION/INTERPRETATION: It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system.