OBJECTIVE Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardiometabolic 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 preexisting 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 cardiometabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders. RESULTS A total of 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 (adjusted hazard ratio [aHR] 1.43 [95% CI 1.36–1.49]), ASD (aHR 1.94 [1.80–2.09]), diabetes (aHR 4.73 [4.34–5.16]), hypertension (aHR 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 with those unexposed. Among women with preexisting diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22 [95% CI 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 cardiometabolic outcomes in offspring, with differences seen across diabetes subtypes. Pregnancy glycemia was associated with cardiometabolic outcomes, but not neurobehavioral outcomes, and provides a potentially modifiable risk factor to decrease cardiometabolic outcomes in offspring.

中文翻译：

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怀孕期间患有糖尿病的母亲的后代的长期神经行为和代谢结果：加拿大安大略省的一项大型、基于人群的队列研究


目的 患有糖尿病的女性的后代患神经行为和心脏代谢疾病的风险增加，但关于妊娠期间血糖水平与这些长期后代结局之间的关系的证据很少。研究设计和方法 我们对 1991 年 4 月至 2018 年 3 月期间在安大略省的分娩进行了一项基于人群的队列研究。女性患有既往糖尿病、妊娠期糖尿病或没有糖尿病。我们应用 Cox 比例风险模型来检查后代患注意力缺陷多动障碍 (ADHD)、自闭症谱系障碍 (ASD) 和心脏代谢结果的风险，并评估妊娠 HbA1c 水平与结果风险之间的关联，并调整混杂因素。结果 总共对 3,407,961 对母婴进行了长达 29 年的随访。使用 Cox 比例风险模型，患有 1 型糖尿病的女性后代患 ADHD（调整后风险比 [aHR] 1.43 [95% CI 1.36–1.49]）、ASD（aHR 1.94 [1.80–2.09]）、糖尿病的风险最高(aHR 4.73 [4.34–5.16])、高血压 (aHR 2.32 [2.07–2.61]) 和心血管疾病 (CVD) (aHR 1.72 [1.56–1.90])，其次是患有 2 型糖尿病和妊娠糖尿病的女性的后代与那些未暴露的人。在患有糖尿病的女性中，妊娠 HbA1c 水平与后代糖尿病 (aHR 1.22 [95% CI 1.12–1.32])、高血压 (aHR 1.42 [1.29–1.57]) 和 CVD (aHR 1.20 [1.11–1.11]) 之间存在关联。 1.29]），但与神经行为结果没有统计学上的显着关联。结论 在子宫内暴露于母亲糖尿病与后代 ADHD、ASD 和心脏代谢结果的增加相关，不同糖尿病亚型之间存在差异。 妊娠血糖与心脏代谢结果相关，但与神经行为结果无关，并提供了一个潜在的可改变的危险因素，以减少后代的心脏代谢结果。