Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01–1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04–1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55–0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. The relative racial and ethnic homogeneity of Utah’s population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.

中文翻译：

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与自闭症相关的妊娠中期母体血清中性别特异性和性别无关的类固醇相关生物标志物

产前暴露于与炎症和类固醇失调相关的母体代谢状况此前已被认为与自闭症风险增加有关。类固醇相关的母体血清生物标志物也为患有自闭症的后代提供了对子宫内类固醇环境的深入了解。本研究探讨了后代自闭症与怀孕中期孕早期母体类固醇相关血清生物标志物之间的联系，这些生物标志物因产前代谢综合征（PNMS）暴露而丰富。比较患有自闭症 (N = 68) 和不患有自闭症 (N = 68) 后代的妊娠早期中期妊娠母体类固醇相关血清生物标志物（即雌二醇、游离睾酮、总睾酮和性激素结合球蛋白）。多重逻辑回归分析按性别和妊娠持续时间进行分层。对由自闭症状态和 PNMS 暴露定义的组进行了单向 ANCOVA 和事后测试。雌二醇增加仅在男性（AOR = 1.13 每 100 pg/ml，95% CI 1.01–1.27，p = 0.036）和足月妊娠中与自闭症显着相关（AOR = 1.17 每 100 pg/ml，95% CI 1.04– 1.32，p = 0.010）。总体而言，按性别和足月妊娠状态分层时，自闭症状态与性激素结合球蛋白下降显着相关（AOR = 0.65 每 50 nmol/L，95% CI 0.55–0.78，p < 0.001）。性激素结合球蛋白与自闭症之间的负相关与 PNMS 暴露无关。犹他州人口的相对种族和民族同质性限制了研究结果的普遍性。尽管在参与者亚组中总体性激素结合球蛋白浓度和雌二醇浓度上发现了自闭症状态的显着差异，但 PNMS 暴露的差异未能达到统计显着性，这可能反映了统计功效不足。仅男性的母体血清雌二醇升高和两性的母体血清性激素结合球蛋白降低都与自闭症风险增加相关。值得进一步研究以确定类固醇、代谢和炎症过程如何相互作用以影响妊娠中期早期的神经发育。