Associations between birthweight, gestational age at birth and subsequent type 1 diabetes in children under 12: a retrospective cohort study in England, 1998-2012

Abstract

Aims/hypothesis: With genetics thought to explain only 40-50% of the total risk of type 1 diabetes, environmental risk factors in early life have been proposed. Previous findings from studies of type 1 diabetes incidence by birthweight and gestational age at birth have been inconsistent. This study aimed to investigate the relationships between birthweight, gestational age at birth and subsequent type 1 diabetes in England.

Methods: Data were obtained from a population-based database comprising linked mother-infant pairs using English national Hospital Episode Statistics from 1998 to 2012. In total, 3,834,405 children, categorised by birthweight and gestational age at birth, were followed up through record linkage to compare their incidence of type 1 diabetes through calculation of multivariable-adjusted HRs.

Results: Out of 3,834,405 children, 2969 had a subsequent hospital diagnosis of type 1 diabetes in childhood. Children born preterm (<37 weeks) or early term (37-38 weeks) experienced significantly higher incidence of type 1 diabetes than full term children (39-40 weeks) (HR 1.19 [95% CI 1.03, 1.38] and 1.27 [95% CI 1.16, 1.39], respectively). Children born at higher than average birthweight (3500-3999 g or 4000-5499 g) after controlling for gestational age experienced higher incidence of type 1 diabetes than children born at medium birthweight (3000-3499 g) (HR 1.13 [95% CI 1.03, 1.23] and 1.16 [95% CI 1.02, 1.31], respectively), while children at low birthweight (<2500 g) experienced lower incidence (0.81 [95% CI 0.67, 0.98]), signifying a statistically significant trend (p trend 0.001).

Conclusions/interpretation: High birthweight for gestational age and low gestational age at birth are both independently associated with subsequent type 1 diabetes. These findings help contextualise the debate about the potential role of gestational and early life environmental risk factors in the pathogenesis of type 1 diabetes, including the potential roles of insulin sensitivity and gut microbiota.

Keywords: Birthweight; England/epidemiology; Gestational age; Hospital Episode Statistics; Large for gestational age; National Health Service; Preterm; Record linkage; Small for gestational age; Type 1 diabetes mellitus.

Fig. 1

Flowchart showing the derivation of the 3,834,405 mother–infant pairs used in the analysis after exclusions (excl.)

Fig. 2

Adjusted Cox proportional hazard ratios comparing incidence of type 1 diabetes in cohorts of children by BFGA in (a) quintiles and (b) deciles. p trend <0.0001 for both models. Error bars are 95% CI. Note: infant sex is already accounted for in the calculation of BFGA. The HRs were further adjusted in the Cox model for maternal type 1 diabetes, gestational diabetes, maternal obesity, maternal age, deprivation quintile and Caesarean section. Covariates were included in the model categorised as presented in Table 1