A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. 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 ( = 118 autism with ID, = 249 autism without ID, = 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. 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. 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.

中文翻译：

---

妊娠早期母体类固醇激素水平和后代自闭症：基于人群的巢式病例对照研究


有人提出产前类固醇激素在自闭症病因学中的作用，但证据是相互矛盾的。在这里，我们检查了妊娠前三个月（平均 = 10.1 周）的母体雌二醇、睾酮、17-羟基孕酮 (OHP) 和皮质醇的血清水平与诊断出患有或不患有智力障碍的自闭症的几率之间的关系（ ID）在后代中（= 118 患有 ID 的自闭症，= 249 没有 ID 的自闭症，= 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，根据样本采集的妊娠时间进行标准化，并使用限制三次样条逻辑回归模型进行分析，调整儿童性别和孕产妇健康、人口和社会经济因素。我们观察到母体雌二醇、17-OHP 和皮质醇与自闭症之间存在显着的非线性关联，这种关联随着同时发生的 ID 的存在而变化。与平均水平相比，较低水平的雌二醇与较高的患 ID 的自闭症几率相关（浓度低于平均值 1 SD 的几率= 1.66；95% CI，1.24–2.11），而较高的皮质醇水平与较低的几率相关（高于平均值 1 SD 的比值比 = 0.55；95% CI，0.36–0.88）。相比之下，较高的 17-OHP 与无 ID 的自闭症几率增加相关（高于平均值 1 SD 的几率 = 1.49；95% CI，1.11–1.99）。我们没有观察到与孩子性别相互作用的证据。这些发现支持了这样的观点，即妊娠早期母体类固醇激素环境可能导致自闭症，但也强调了生命早期类固醇暴露与自闭症之间的复杂关系。