Understanding Prenatal Signals and Infant Development (UPSIDE)

 描述(由申请人提供)：许多研究的一致结果表明，怀孕期间的母亲压力可能会以符合编程机制的方式对儿童的身体和神经心理发育产生长期影响。然而，解释这些关联的生物学机制仍然不确定。特别缺少的是人类研究，a)翻译大量动物文献，表明产前应激对性别的影响，b)考虑人类最近发现的将产前应激与性-二态生理结果(肛门距离)和具有显著性别差异的神经发育障碍(学习困难、自闭症)联系起来的机制。我们提出了一项从妊娠早期开始的前瞻性纵向研究，以检验这一假设，即产前母体应激可能通过作用于胎儿肾上腺雄激素途径改变婴儿时期的性别依赖发育。为此，我们将招募240名孕妇，从怀孕前三个月开始跟踪她们，并使用先前队列研究中成功应用的招募和保留程序定期收集行为和生物数据，直到孩子15个月大。研究设计包括在这一不断增长的研究领域中的几项重要创新，包括a)从多个来源采集的关于应激激素和性类固醇激素的详细数据，b)使用与国家儿童研究(NCS)合作开发的方案对胎盘结构和功能进行密集询问，c)对婴儿生理和神经心理结果的多重评估，早期出现的性别差异已被可靠地记录下来。该项目的具体目标是：1)调查孕妇的心理应激和应激激素皮质醇与胎儿和胎盘激素活动的生物标记物的关系；2)使用我们建立的NCS方案，确定出生时胎盘和脐带血中与应激相关的应激和性类固醇激素途径改变的证据；3)在出生时、9个月和15个月时整合母体和胎盘生物标记物来预测性别依赖的身体、神经认知和社会行为措施。这一系列研究将补充和扩展现有的工作，澄清母亲应激传递给胎儿的生物学机制，并提高我们对健康和疾病中性别差异的病因的理解。

 DESCRIPTION (provided by applicant): Consistent findings across many studies demonstrate that maternal stress during pregnancy can have long-lasting effects on children's physical and neuropsychological development in a manner consistent with a programming mechanism. The biological mechanisms accounting for these associations remain uncertain, however. Particularly missing is human research that a) translates the sizable animal literature showing sex- dependent effects of prenatal stress and b) considers mechanisms underlying recent human findings linking prenatal maternal stress to sexually-dimorphic physical outcomes (anogenital distance) and neurodevelopmental disorders with significant sex differences (learning difficulties, autism). We propose a prospective longitudinal study starting in the first trimester to test the hypothesis that prenatal maternal stress may alter sex-dependent development in infancy by acting on fetal adrenal androgen pathways. We will do this by recruiting a cohort of 240 pregnant women, following them from the first trimester and regularly collecting behavioral and biological data until the child is 15 months of age using procedures for recruitment and retention successfully applied in prior cohort studies. The research design includes several important innovations in this growing field of study, including a) detailed data on stress hormones alongside sex steroid hormones sampled from multiple sources, b) intensive interrogation of placental structure and function using the protocols developed from the work with the National Children's Study (NCS); c) multiple assessments of infant physical and neuropsychological outcomes for which early emerging sex differences have been reliably documented. The specific aims of the project are to: 1) investigate maternal psychological stress and the stress hormone cortisol in relation to biomarkers of fetal and placental hormone activity, in each trimester of pregnancy; 2) identify evidence of prenatal stress-related alteratios in stress and sex steroid hormone pathways from the placenta and cord blood at birth using our established NCS protocols; 3) integrate maternal and placental biomarkers in predicting sex-dependent physical, neurocognitive, and social behavior measures at birth, 9 and 15 months. This line of research will complement and extend existing work by clarifying the biological mechanisms by which maternal stress is communicated to the fetus and improving our understanding of the etiology of sex differences in health and disease.