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对儿童的身体和神经心理发育产生长期影响，其方式与编程机制一致。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）翻译显示产前压力的性别依赖性影响的大量动物文献，和B）考虑最近人类发现的机制，将产前母体压力与性二态性身体结果（肛门生殖器距离）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。我们提出了一个前瞻性的纵向研究，在第一个三个月开始测试的假设，产前母亲的压力可能会改变性别依赖的发展在婴儿期通过胎儿肾上腺雄激素途径。我们将招募一组240名孕妇，从怀孕的前三个月开始跟踪她们，并定期收集行为和生物学数据，直到孩子15个月大，使用在之前的队列研究中成功应用的招募和保留程序。研究设计包括这一日益发展的研究领域的几项重要创新，包括a）从多个来源取样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深入调查; c）对婴儿生理和神经心理结果进行多项评估，其中早期出现的性别差异已得到可靠记录。该项目的具体目标是：1）调查孕妇心理压力和压力激素皮质醇与胎儿和胎盘激素活性生物标志物的关系，在每个怀孕三个月; 2）使用我们建立的NCS协议，从出生时的胎盘和脐带血中识别产前压力相关的压力和性类固醇激素途径的改变的证据; 3）整合母体和胎盘生物标志物，以预测出生时、9个月和15个月时的性别依赖性身体、神经认知和社会行为测量。这一系列的研究将补充和扩展现有的工作，阐明产妇压力传达给胎儿的生物学机制，提高我们对健康和疾病性别差异的病因学的理解。

 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.