Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort.
Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort.
复制标题
DOI：
10.1186/s13229-020-00395-6
复制
发表时间：
2020-11-23
期刊：
影响因子：
6.2
通讯作者：
Snyder NW
中科院分区：
文献类型：
--
作者：
Terloyeva D;Frey AJ;Park BY;Kauffman EM;Mathew L;Bostwick A;Varner EL;Lee BK;Croen LA;Fallin MD;Hertz-Picciotto I;Newschaffer CJ;Lyall K;Snyder NW
产前暴露于增加的雄激素已被认为是自闭症谱系障碍（ASD）的危险因素。这一假设已经通过测量羊水、脐带血、唾液和血液中的类固醇进行了检验，结果好坏参半。为了提供胎儿暴露的正交测量，本研究使用胎粪（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。EARLI是一个家庭富集风险队列，招募了已经有一个患有ASD诊断的孩子的孕妇。在年龄较小的儿童中，我们调查了胎粪未结合（u）和主要雄激素睾酮（T），脱氢表雄酮（DHEA）和雄烯二酮（A4）的总（t）浓度与12和36个月龄ASD相关性状之间的关系。在12个月时用婴儿自闭症观察量表（AOSI）测量特征，在36个月时用社会反应量表（SRS）总分测量特征。170例患儿有胎粪和AOSI，140例有胎粪和SRS，137例有胎粪和AOSI和SRS。 每个对数转换的雄激素和对数转换的SRS评分之间的单独的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。在校正分析中，在女性先证者（n = 10）中，t-T、u-A4和u-DHEA（P ≤ 0.01）与AOSI评分呈正相关，而u-T（P = 0.004）和u-DHEA（P = 0.007）与SRS总分呈正相关。此外，较高浓度的u-T（P = 0.01）和t-T（P = 0.01）预测较高的SRS总评分在男性先证者（n = 63）。 由于我们探索了三向相互作用，这导致一些分析的样本量有限。这项研究来自一个可能限制普遍性的高风险队列，并且这项研究使用ASD评估量表作为结局，而不是诊断类别。此外，由于缺乏胎粪研究，本研究中胎粪的新用途限制了将该队列的结果与其他队列进行比较的能力。这项研究支持胎粪的内源性胎儿代谢的研究，并建议自闭症的哥哥姐姐的性别应被视为一个生物学变量在相关研究的效用。
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.
登录
查看更多内容
影响因子：
4.9
作者：
Jamnadass ES;Keelan JA;Hollier LP;Hickey M;Maybery MT;Whitehouse AJ
通讯作者：
Whitehouse AJ
影响因子：
3.9
作者：
Constantino, JN;Davis, SA;Reich, W
通讯作者：
Reich, W
影响因子：
--
作者：
Lundstrom, Sebastian;Chang, Zheng;Lichtenstein, Paul
通讯作者：
Lichtenstein, Paul
影响因子：
7.6
作者：
Kung, Karson T. F.;Spencer, Debra;Hines, Melissa
通讯作者：
Hines, Melissa
影响因子：
3.9
作者：
Bryson, Susan E.;Zwaigenbaum, Lonnie;Brian, Jessica
通讯作者：
Brian, Jessica