Perinatal risk factors for type 1 diabetes revisited: a population-based register study

Abstract

Aims/hypothesis: Single-centre studies and meta-analyses have found diverging results as to which early life factors affect the risk of type 1 diabetes during childhood. We wanted to use a large, nationwide, prospective database to further clarify and analyse the associations between perinatal factors and the subsequent risk for childhood-onset type 1 diabetes using a case–control design. Methods: The Swedish Childhood Diabetes Register was linked to the Swedish Medical Birth Register and National Patient Register, and 14,949 cases with type 1 diabetes onset at ages 0–14 years were compared with 55,712 matched controls born from the start of the Medical Birth Register in 1973 to 2013. After excluding confounders (i.e. children multiple births, those whose mother had maternal diabetes and those with a non-Nordic mother), we used conditional logistic regression analyses to determine risk factors for childhood-onset type 1 diabetes. We used WHO ICD codes for child and maternal diagnoses. Results: In multivariate analysis, there were small but statistically significant associations between higher birthweight z score (OR 1.08, 95% CI 1.06, 1.10), delivery by Caesarean section (OR 1.08, 95% CI 1.02, 1.15), premature rupture of membranes (OR 1.08, 95% CI 1.01, 1.16) and maternal urinary tract infection during pregnancy (OR 1.39, 95% CI 1.04, 1.86) and the subsequent risk of childhood-onset type 1 diabetes. Birth before 32 weeks of gestation was associated with a lower risk of childhood-onset type 1 diabetes compared with full-term infants (OR 0.54, 95% CI 0.38, 0.76), whereas birth between 32 and 36 weeks’ gestation was associated with a higher risk (OR 1.24, 95% CI 1.14, 1.35). In subgroup analyses (birth years 1992–2013), maternal obesity was independently associated with subsequent type 1 diabetes in the children (OR 1.27, 95% CI 1.15, 1.41) and rendered the association with Caesarean section non-significant. In contrast to previous studies, we found no association of childhood-onset type 1 diabetes with maternal–child blood-group incompatibility, maternal pre-eclampsia, perinatal infections or treatment of the newborn with phototherapy for neonatal jaundice. The proportion of children with neonatal jaundice was significantly higher in the 1973–1982 birth cohort compared with later cohorts. Conclusions/interpretation: Perinatal factors make small but statistically significant contributions to the overall risk of childhood-onset type 1 diabetes. Some of these risk factors, such as maternal obesity, may be amendable with improved antenatal care. Better perinatal practices may have affected some previously noted risk factors over time.