Maternal type 1 diabetes, pre-term birth and risk of autism spectrum disorder–a prospective cohort study

Abstract

Abstract Background It has been suggested that maternal type 1 diabetes (T1D) increases the risk of autism spectrum disorder (ASD) in the offspring. However, it is unclear whether this risk is mediated by pre-term birth, affecting around one-third of pregnancies with T1D, and whether maternal levels of glycated haemoglobin (HbA1c) impact the risk. Methods A cohort of 1.4 million Swedish children born between 1998 and 2015, and their parents. Maternal T1D and HbA1c before or in early pregnancy, gestational and ASD diagnoses were obtained from Swedish national registers. Relative risk (RR) and 95% CIs of ASD were estimated by hazard ratios (HRs) from Cox regression or RR from log-binomial regression. Results Of 1 406 650 children, 8003 (0.6%) were born to mothers with T1D, 24 941 (1.8%) were diagnosed with ASD and 81 915 (5.8%) were born pre-term. The risk of ASD was increased in offspring of mothers with T1D was HR = 1.40 (1.21–1.61). The RR for each +5-mmol/mol excess HbA1c was estimated at HR = 1.03 (0.97–1.10). The T1D effect on ASD mediated through pre-term birth was estimated at RR = 1.06 (1.05 to 1.08), corresponding to 22% (16% to 41%) of the total effect. T1D in pregnancy was associated with increased ASD risk in the offspring. Twenty percent of the total effect was accounted for by pre-term birth. HbA1c was not associated with ASD risk, beyond the risk associated by the T1D diagnosis itself. Conclusion Awareness of ASD in the offspring of mothers with T1D may be warranted, especially considering the additional effect of pre-term birth.