Evidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk. In this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance. PFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p = 0.042; FDR qvalue = 0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR = 0.100; 95% CI 0.016, 0.630; p = 0.014; FDR qvalue = 0.098). Testosterone level in AF weakly associated with ASD risk (adjusted OR = 1.002; 95% CI 1.000, 1.004; p = 0.05). However, after multiple comparison correction, the association was not significant (FDR qvalue = 0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity. The presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS. The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD.

中文翻译：

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自闭症谱系障碍，内分泌干扰化合物和羊水中的重金属：病例对照研究

有证据表明，某些非遗传因素（例如暴露于环境污染物中）与神经发育障碍（例如自闭症谱系障碍（ASD））有关。研究报告说，内分泌干扰化合物（EDC），包括多氯联苯，有机氯农药，全氟烷基物质（PFAS）和某些金属，对胎儿神经发育有不利影响。这项研究的目的是测量EDCs和金属的羊水（AF）水平，以及由AF诱导的受体活性，并研究产前暴露于EDCs和重金属与ASD风险之间的可能联系。在这项病例对照研究中，我们纳入了75例ASD病例和135个频率匹配的对照的AF样本，并测量了内源性激素，PFAS和包括重金属在内的元素的水平。还确定了内源激素和EDC对雌激素（ER），雄激素（AR），芳基烃（AhR）和甲状腺激素样活性受体的联合作用，并表示为受体配体当量。我们使用无条件逻辑回归分析评估了化学药品，性激素和受体活性的AF水平与ASD风险的关联。为了控制多个比较，使用了错误发现率（FDR），q值小于0.25被指定为统计显着性。在AF样品中可检测到PFAS和金属。ASD病例的PFAS AF水平明显低于对照组，全氟辛烷磺酸（PFOS）的校正比值比（OR）为0.410（95％CI 0.174，0.967; p = 0.042; FDR q值= 0.437）。主要成分包括PFAS同类物，铜，铁，雌激素活性与ASD风险呈显着负相关（校正OR = 0.100； 95％CI 0.016，0.630； p = 0.014； FDR q值= 0.098）。AF中的睾丸激素水平与ASD风险弱相关（校正OR = 1.002; 95％CI 1.000，1.004; p = 0.05）。但是，经过多次比较校正后，关联性并不显着（FDR qvalue = 0.437）。没有观察到房颤诱发的受体反应性和自闭症风险之间的显着关联。调整后的OR为2.176（95％CI 0.115，41.153），用于组合的雄激素活性与组合的雌激素活性之比。AF中PFAS和重金属的存在表明它们可以穿过胎盘。房颤中的PFAS同源物水平与ASD风险之间的负相关关系可能与PFAS的雌激素活性和抗雄激素活性弱有关。