母亲妊娠糖尿病与子代孤独症谱系障碍发生风险的关联分析

Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring

摘要:

目的 探讨母亲妊娠糖尿病暴露与子代孤独症谱系障碍（autism spectrum disorder，ASD）发生的关联。方法 采用病例对照研究方法，招募221例ASD儿童与400例健康儿童纳入研究。采用问卷调查及访谈形式收集儿童一般情况、家庭社会经济学特征、母亲孕产史、母亲孕期疾病暴露等情况，采用多因素logistic回归分析探讨母亲妊娠糖尿病暴露与子代ASD发生的关联，并探讨子代性别和妊娠糖尿病暴露对子代ASD的发生是否存在交互作用。结果 ASD组母亲妊娠糖尿病患病比例显著高于对照组（16.3% vs 9.4%，P=0.014）。校正性别、胎龄情况、出生方式、产次、母亲文化程度等变量后，母亲妊娠糖尿病暴露是子代ASD发生的危险因素（OR=2.18，95%CI：1.04~4.54，P=0.038）；在校正以上变量的基础上，进一步校正孕早期复合维生素服用、孕前3个月叶酸服用和辅助生殖等变量后，结果趋势未发生改变，但未见统计学意义（OR=1.94，95%CI：0.74~5.11，P=0.183）。妊娠糖尿病暴露与子代性别对子代ASD的发生存在交互作用（P<0.001）；性别分层分析显示，仅在妊娠糖尿病母亲的男性子代中ASD发病风险显著增加（OR=3.67，95%CI：1.16~11.65，P=0.027）。结论 母亲妊娠糖尿病暴露可能增加子代ASD的发生风险；妊娠糖尿病暴露和子代性别对子代ASD的发生存在交互作用。

Abstract:

Objective To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring.Methods A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored.Results The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027).Conclusions Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.