Influence of early-life parental severe life events on the risk of type 1 diabetes in children: the DiPiS study

Stress and severe life events (SLEs) modify autoimmune disease susceptibility. Here, we aimed to establish if SLEs reported by parents during the first 2 years of life influence the risk of developing type 1 diabetes (T1D) using data from the prospective Diabetes Prediction in SkAne (DiPiS) study. Prospective questionnaire data recorded at 2 months (n = 23,187) and 2 years of age (n = 3784) from the DiPiS cohort of children were included in the analysis. SLEs were analyzed both by groups and as a combined variable. A Cox proportional hazards model was used to calculate hazard ratios (HRs) for T1D diagnosis for the total cohort and for the HLA-DQ2/8 high-risk population. Affected first-degree relatives, HLA-DQ risk group, paternal education level, and parents' country of birth were included as covariates. There was a significantly increased risk of T1D in children with SLEs occurring during the child's first 2 years of life for both the total cohort (HR 1.67; 95% CI 1.1, 2.7; p = 0.03) and the DQ2/8 cohort (HR 2.2; 95% CI 1.1, 4.2; p = 0.018). Subgroup analysis of events related to unemployment, divorce, or family conflict showed a significant hazard for these events occurring both during and after pregnancy in the DQ2/8 cohort (HR 2.17; 95% CI 1.1, 4.3; p = 0.03 and HR 4.98; 95% CI 2.3, 11; p < 0.001, respectively) and after pregnancy in the total cohort (multiple regression HR 2.07; 95% CI 1.01, 4.2; p = 0.047). Children of parents experiencing an SLE during the child's first 2 years of life were at increased risk of T1D. Further studies including those measuring immune and stress-related biomarkers are necessary to validate the findings.