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Long-Term Neurobehavioral and Metabolic Outcomes in Offspring of Mothers with Diabetes During Pregnancy: A large, population-based cohort study in Ontario, Canada.

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posted on 2024-05-31, 19:36 authored by Denice S Feig, Azmina Artani, Ayesha Asaf, Ping Li, Gillian L Booth, Baiju R Shah

Objective

Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardio-metabolic disorders, but there is scant evidence regarding the association between glycemic level during pregnancy and these long-term offspring outcomes.

Research Design and Methods

We conducted a population-based, cohort study of deliveries in Ontario between April 1991, and March 2018. Women had pre-existing diabetes, gestational diabetes, or no diabetes. We applied a Cox-proportional hazard model to examine the risk of developing attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and cardio-metabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders.

Results

3,407,961 mother/infant pairs were followed up to 29 years. Using a Cox proportional hazard model, offspring of women with type 1 diabetes had the highest risk of ADHD (aHR 1.43(1.36-1.49), ASD (aHR 1.94(1.80-2.09), diabetes (aHR 4.73(4.34-5.16), hypertension (adj HR 2.32(2.07-2.61)), and cardiovascular disease (CVD) (aHR 1.72(1.56-1.90)), followed by offspring of women with type 2 diabetes and gestational diabetes compared to those unexposed. Among women with pre-existing diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22(1.12-1.32)), hypertension (aHR 1.42(1.29-1.57)), and CVD (aHR 1.20(1.11-1.29)) but no statistically significant association with neurobehavioral outcomes.

Conclusions

In-utero exposure to maternal diabetes was associated with an increase in ADHD, ASD and cardio-metabolic outcomes in offspring, with differences seen across diabetes sub-types. Pregnancy glycemia was associated with cardio-metabolic outcomes, but not neurobehavioral outcomes and provides a potentially modifiable risk factor to decrease cardio-metabolic outcomes in offspring.