Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies.

中文翻译：

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在家族富集风险队列中，胎粪雄激素与儿童早期 ASD 相关表型特征相关

产前暴露于升高的雄激素已被认为是自闭症谱系障碍 (ASD) 的危险因素。这一假设已通过测量羊水、脐带血、唾液和血液中的类固醇得到检验，结果不一。为了提供胎儿暴露量的正交测量，本研究使用胎便（新生儿的第一次粪便）来测量早期自闭症风险纵向调查（EARLI）中婴儿的产前雄激素暴露量。EARLI 是一个富含家族的风险队列，招募了已经生有患有自闭症谱系障碍 (ASD) 孩子的孕妇。在年幼的孩子中，我们研究了 12 个月和 36 个月时未结合胎粪 (u) 和主要雄激素睾酮 (T)、脱氢表雄酮 (DHEA) 和雄烯二酮 (A4) 总浓度 (t) 与 ASD 相关性状之间的关系年龄。12 个月时使用婴儿自闭症观察量表 (AOSI) 测量特征，36 个月时使用社会反应量表 (SRS) 总分测量特征。170 名儿童患有胎便和 AOSI，140 名儿童患有胎便和 SRS，137 名儿童患有胎便并同时患有 AOSI 和 SRS。每种对数转换雄激素和对数转换 SRS 评分之间的单独稳健线性回归揭示了儿童性别、先证者性别和睾酮浓度之间的三向相互作用。在调整后的分析中，tT、u-A4 和 u-DHEA (P ≤ 0.01) 与 AOSI 评分呈正相关，而 uT (P = 0.004) 和 u-DHEA (P = 0.007) 与 SRS 总分呈正相关在有女性先证者的女性中（n = 10）。此外，较高浓度的 uT (P = 0.01) 和 tT (P = 0.01) 预测男性先证者 (n = 63) 的男性 SRS 总分较高。局限性 由于我们探索了三向相互作用，这导致某些分析的样本量有限。这项研究来自一个丰富的风险队列，这可能会限制普遍性，并且这项研究使用 ASD 评估量表作为结果而不是诊断类别。此外，由于胎便研究的缺乏，本研究中胎便的新用途限制了将该队列的结果与其他队列的结果进行比较的能力。这项研究支持胎便用于内源性胎儿代谢研究的效用，并建议患有自闭症的年长兄弟姐妹的性别应被视为相关研究中的生物学变量。