Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
JAMA Netw Open. 2021 Oct 1;4(10):e2128005. doi: 10.1001/jamanetworkopen.2021.28005.
Maternal diabetes has been suggested as a risk factor for attention-deficit/hyperactivity disorder and autism in offspring, but evidence on its association with the full spectrum of psychiatric disorders remains lacking.
To investigate the associations between maternal diabetes diagnosed before or during pregnancy and 10 types of psychiatric disorders in offspring during the first 4 decades of life.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from several Danish nationwide medical and administrative registries in Denmark on all 2 413 335 live births from 1978 to 2016. Data were analyzed between October 1, 2019, and July 15, 2021.
Any maternal diabetes diagnosis during pregnancy (56 206 offspring [2.3%]) and 3 diabetes subtypes (pregestational type 1 diabetes, 22 614 offspring [1.0%]; pregestational type 2 diabetes, 6713 offspring [0.3%]; and gestational diabetes, 26 879 offspring [1.1%]).
Outcomes included 10 types of psychiatric disorders: any psychiatric disorder, substance use disorders, schizophrenia, mood disorders, anxiety disorders, eating disorders, personality disorders, intellectual disorders, developmental disorders, and behavioral disorders. Hazard ratios (HRs) and 95% CIs were computed using Cox proportional hazards regression models. Covariates included maternal and paternal history of any psychiatric disorder, offspring sex, calendar period of birth, singleton status, and several maternal characteristics during pregnancy (ie, age, parity, educational level, smoking, cohabitation, residence, and body mass index). Sibship design and competing risk analyses were also conducted.
A total of 2 413 335 individuals (1 239 148 male participants [51%]; age range, 1-39 years; median age, 19.0 years [IQR, 5.8-20.8 years]) were included in this study. During the 39-year follow-up time, 151 208 offspring (6.4%) received a diagnosis of a psychiatric disorder. Offspring born to mothers with any diabetes diagnosis during pregnancy were at increased risk of developing any psychiatric disorder (HR, 1.15; 95% CI, 1.10-1.20), schizophrenia (HR, 1.55; 95% CI, 1.15-2.08), anxiety disorders (HR, 1.22; 95% CI, 1.09-1.36), intellectual disabilities (HR, 1.29; 95% CI, 1.11-1.50), developmental disorders (HR, 1.16; 95% CI, 1.03-1.30), and behavioral disorders (HR, 1.17; 95% CI, 1.08-1.27) compared with offspring born to mothers without a diabetes diagnosis during pregnancy. No association was observed for substance use disorders, mood disorders, eating disorders, and personality disorders.
This study shows a pattern that suggests that prenatal exposure to maternal diabetes during pregnancy was associated with increased risk of psychiatric disorders overall and most specific psychiatric disorders in offspring in their first 4 decades of life.
重要性:有研究提示,母亲糖尿病是子女发生注意力缺陷/多动障碍和自闭症的一个风险因素,但有关其与全谱精神疾病之间关联的证据仍存在不足。
目的:本研究旨在调查在妊娠前或妊娠期间被诊断为糖尿病的母亲与子女在生命的前 40 年中发生的 10 种类型的精神疾病之间的关联。
设计、地点和参与者:本基于人群的队列研究使用了来自丹麦几个全国性医疗和行政登记处的数据,这些数据来自于 1978 年至 2016 年期间的 2413335 例活产儿。数据分析于 2019 年 10 月 1 日至 2021 年 7 月 15 日进行。
暴露:妊娠期间的任何母亲糖尿病诊断(56206 例后代[2.3%])和 3 种糖尿病亚型(妊娠前 1 型糖尿病,22614 例后代[1.0%];妊娠前 2 型糖尿病,6713 例后代[0.3%];和妊娠期糖尿病,26879 例后代[1.1%])。
主要结局和测量:结局包括 10 种类型的精神疾病:任何精神疾病、物质使用障碍、精神分裂症、心境障碍、焦虑障碍、饮食障碍、人格障碍、智力障碍、发育障碍和行为障碍。使用 Cox 比例风险回归模型计算危险比(HR)和 95%置信区间。协变量包括母亲和父亲任何精神疾病史、子女性别、出生年份、单胎状态以及妊娠期间的几个母亲特征(即年龄、产次、教育水平、吸烟、同居、居住和体重指数)。还进行了同胞设计和竞争风险分析。
结果:本研究共纳入 2413335 人(1239148 名男性参与者[51%];年龄范围 1-39 岁;中位数年龄 19.0 岁[IQR,5.8-20.8 岁])。在 39 年的随访期间,151208 例子女(6.4%)被诊断为精神疾病。与未在妊娠期间患有糖尿病的母亲所生的子女相比,妊娠期间患有任何糖尿病诊断的母亲的子女发生任何精神疾病(HR,1.15;95%CI,1.10-1.20)、精神分裂症(HR,1.55;95%CI,1.15-2.08)、焦虑障碍(HR,1.22;95%CI,1.09-1.36)、智力障碍(HR,1.29;95%CI,1.11-1.50)、发育障碍(HR,1.16;95%CI,1.03-1.30)和行为障碍(HR,1.17;95%CI,1.08-1.27)的风险增加。未观察到物质使用障碍、心境障碍、饮食障碍和人格障碍的相关性。
结论和相关性:本研究表明,产前暴露于母亲妊娠期间的糖尿病与后代在生命的前 40 年中整体发生精神疾病以及大多数特定精神疾病的风险增加有关。