Fetal Programming of Early Development

胎儿早期发育规划

• 批准号: 7153332
• 负责人: CURT ALAN SANDMAN
• 金额: $ 50.38万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7153332
• 关键词: attention; behavior test; brain morphology; child behavior; child physical development; clinical research; cognition; corticotropin releasing factor; cortisol; early experience; embryo /fetus; emotions; executive function; human subject; hypothalamic pituitary adrenal axis; intelligence tests; interview; longitudinal human study; magnetic resonance imaging; memory; middle childhood (6-11); outcomes research; placenta; prenatal stress; questionnaires; time resolved data

DESCRIPTION (provided by applicant): The focus of this application is on the developmental consequences for children exposed to stress during gestation. One of the major placental stress signals in pregnant primates is the peptide corticotrophin-releasing hormone (CRH). This peptide plays a key role in the maturation of the fetal hypothalamic-pituitary-adrenal (HPA) axis and it synchronizes events that underlie fetal growth and maturation. Placental CRH is responsive to all the major biological signals of stress in the maternal and fetal compartments. Stress-related alterations in the normal pattern of placental CRH production during pregnancy have major implications for childhood development. Extensive research supports the conclusion that placental CRH is the stress index consistently associated with birth outcomes, however placental CRH has not been used to predict neurodevelopmental outcomes. The focus on placental CRH capitalizes on a direct index of fetal experience and avoids the assumption that maternal stress results in a coherent and consistent maternal physiological profile that is transmitted to the fetus. We propose to assess 600 children (between the ages of 6-0 and 7-11 years) for whom we have extensive histories of prenatal stress exposure and birth phenotypes with measures of (a) emotional regulation; (b) cognition; (c) anatomy of brain structures (using structural magnetic resonance imaging (MRI); and (d) regulation of the HPA stress axis. Influences of prenatal CRH on emotional regulation (Aim 1) will be evaluated by examining the relation between levels of CRH with measures of parent and self-report of temperament. Programming effects of early exposure to CRH on cognition (Aim 2) will be evaluated by examining the relation between levels of placental CRH and performance on standardized measures of intelligence and novel measures of attention, memory and executive function. The effects of prenatal exposure to CRH on the volume of the hippocampus, amygdala and prefrontal cortex (Aim 3) will be evaluated in a subgroup of 80 children in the upper and lower quintile of third trimester CRH level. Prenatal influences of CRH on HPA reactivity (Aim 4) will be evaluated by assessing salivary cortisol at rest and after mild stress. These studies in children are the first to examine the role of prenatal CRH on human development.

描述（由申请人提供）：本申请的重点是妊娠期间暴露于压力的儿童的发育后果。在妊娠灵长类动物中，主要的胎盘应激信号之一是肽促肾上腺皮质激素释放激素（CRH）。该肽在胎儿下丘脑-垂体-肾上腺（HPA）轴的成熟中起关键作用，并参与胎儿生长和成熟的基础事件。胎盘CRH对母体和胎儿室中所有主要的应激生物信号都有反应。妊娠期间胎盘CRH正常产生模式的应激相关改变对儿童发育有重要影响。大量研究支持胎盘CRH是与出生结局一致相关的应激指数的结论，然而胎盘CRH尚未用于预测神经发育结局。对胎盘CRH的关注利用了胎儿经历的直接指数，并避免了母体应激导致传递给胎儿的连贯一致的母体生理特征的假设。我们建议评估600名儿童（年龄在6-0岁和7-11岁之间），我们对他们有广泛的产前压力暴露史和出生表型，测量（a）情绪调节;（B）认知;（c）大脑结构解剖（使用结构磁共振成像（MRI））;和（d）调节HPA应力轴。产前CRH对情绪调节的影响（目的1）将通过检查CRH水平与父母和气质自我报告的测量之间的关系来评估。将通过检查胎盘CRH水平与智力标准化测量和注意力、记忆力和执行功能新测量的表现之间的关系，评估早期暴露于CRH对认知的编程效应（目的2）。产前暴露于CRH对海马体，杏仁核和前额皮质（目标3）的体积的影响将在一个亚组的80名儿童在上和下五分位数的孕晚期CRH水平进行评估。通过评估静息时和轻度应激后的唾液皮质醇，评价CRH对HPA反应性的产前影响（目的4）。这些儿童研究是第一次检查产前CRH对人类发育的作用。