Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group

To explore whether perinatal factors are associated with the development of childhood type 1 diabetes.

We studied hospital records from 892 cases of childhood type 1 diabetes compared with 2,291 population-based control subjects in seven study centers in Europe.

In a pooled analysis incorporating stratification by center, we confirmed the previous findings that older maternal age, maternal preeclampsia, neonatal respiratory disease, and jaundice caused by blood group incompatibility are significant risk factors for type 1 diabetes, whereas being a firstborn child, having a low birth weight, or having a short birth length were protective. Cesarean section delivery and neonatal infectious diseases were not significantly associated with the risk of type 1 diabetes in this study. The strongest association was found for blood group incompatibility (AB0 and Rh factor) with an odds ratio (OR) of 2.96 (95% CI 1.88-4.65). AB0 incompatibility (OR = 3.92) was a more common and also a stronger risk factor than Rh incompatibility (OR = 1.62). The effect of AB0 blood group incompatibility was independent of treatment effects in logistical regression analysis.

Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.