Bacillus Calmette‐Guérin (BCG) Vaccination in Infancy and Risk of Childhood Diabetes

Abstract

Background: A narrow time window in infancy may be relevant for the aetiology of immune-mediated type 1 diabetes. We investigated whether a non-specific immune stimulation in the first year of life, as resulting from Bacillus Calmette-Guérin (BCG) vaccination, was associated with childhood diabetes. Methods: Using data from a birth cohort assembled through linkage of administrative databases, 78 492 subjects born in 1974 were the object of the present analysis. Information was extracted from the birth, death, and BCG vaccination registries. Diabetes-related health services were obtained from administrative health databases (physician billing claims and hospitalisation data) until 1994. Subjects were classified as having diabetes according to two validated definitions: (1) ≥2 diabetes-related medical visits within 2 years or ≥1 hospitalisation for diabetes; and 2) ≥4 diabetes-related medical visits within 2 years. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI), adjusted for potential confounders. Results: Forty-four per cent of subjects were BCG vaccinated in the first year of life. According to the first and second definition, respectively, 293 (0.37%) and 230 (0.29%) subjects were classified as having diabetes. There was no association between BCG vaccination in the first year of life and risk of diabetes with either definition (HR def1 = 0.92, 95% CI 0.73, 1.17; HRdef2 = 1.04, 95% CI 0.80, 1.37), and results did not differ by sex. Conclusions: Given the potentially critical importance of the exposure window and paucity of studies addressing BCG vaccination timing in relation to diabetes risk, this question deserves further investigation.

The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders

“…Lastly, as BCG is able to induce trained immunity, it could be expected that BCG-vaccinated children are at higher risk to develop T1DM. However, in an observational trial no such correlation has been found ( 214 , 215 ). Interestingly, in a randomized controlled trial, BCG was suggested to have a beneficial effect on insulin production, as induction of TNF production resulted in reduced autoimmune phenotype of innate immune cells and induction of Tregs ( 216 , 217 ).…”

Environmental risk factors for type 1 diabetes

“…Clinical data have shown no association between BCG vaccination and type 1 diabetes or islet autoimmunity. A 20 year follow-up of the 1974 Canadian birth cohort, of which 45% were given BCG in the first year of life, showed no association with type 1 diabetes, 54 nor did case-control studies from Canada 55 and Sweden. 56 The German BABYDIAB study 57 reported no association between BCG vaccination and development of islet autoimmunity.…”

A Time‐varying Covariate Approach for Survival Analysis of Paediatric Outcomes

“…However, in some paediatric studies, where time‐varying exposures are measured, conventional survival model based on time‐fixed analysis is still widely adopted. Some example studies include identifying factors associated with breast‐feeding duration, assessing the relationship between vaccination and childhood diabetes, and determining neonatal factors affecting the development of childhood epilepsy . Time‐varying exposures are often treated as time‐fixed variables over the entire follow‐up period, which may lead to incorrect inferences …”