METHODS: Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child\'s sex and maternal health, demographic, and socioeconomic factors.
RESULTS: We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24-2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36-0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11-1.99). We observed no evidence for interaction with sex of the child.
CONCLUSIONS: These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism.
方法:这里,我们检查了母体雌二醇的血清水平,睾丸激素,17-羟基孕酮(OHP),和皮质醇从妊娠的前三个月(平均=10.1周)与诊断自闭症的几率相关,有或没有共同发生的智力障碍(ID)在后代(n=118自闭症与ID,n=249没有ID的自闭症,n=477对照)。使用高灵敏度液相色谱串联质谱法测量母体激素水平,根据样本收集的妊娠时间进行标准化,并利用调整儿童性别和孕产妇健康的有限三次样条逻辑回归模型进行分析,人口统计学,和社会经济因素。
结果:我们观察到母体雌二醇之间的显着非线性关联,17-OHP,和患有自闭症的皮质醇,随着共存ID的存在而变化。与平均水平相比,较低的雌二醇水平与较高的ID自闭症几率相关(低于平均值1SD的浓度比值比=1.66;95%CI,1.24-2.11),而较高的皮质醇水平与较低的赔率相关(高于平均值1SD的赔率=0.55;95%CI,0.36-0.88)。相比之下,较高的17-OHP与无ID自闭症的几率增加相关(高于平均值1SD的比值比=1.49;95%CI,1.11~1.99).我们没有观察到与孩子性别互动的证据。
结论:这些发现支持以下观点:孕早期母体类固醇激素环境可能导致自闭症,但也强调了早期类固醇暴露与自闭症之间的复杂关系。