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承受压力的儿童的发育后果。怀孕灵长类动物的主要胎盘应激信号之一是肽促肾上腺皮质激素释放激素（CRH）。这种肽在胎儿下丘脑-垂体-肾上腺 (HPA) 轴的成熟中起着关键作用，并且它同步胎儿生长和成熟的事件。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。怀孕期间胎盘 CRH 产生正常模式与压力相关的改变对儿童发育具有重大影响。大量研究支持这样的结论：胎盘 CRH 是与出生结果一致相关的压力指数，但胎盘 CRH 尚未用于预测神经发育结果。对胎盘 CRH 的关注利用了胎儿经历的直接指数，并避免了这样的假设：母体压力会导致连贯一致的母体生理特征传递给胎儿。我们建议对 600 名儿童（年龄在 6-0 岁至 7-11 岁之间）进行评估，我们对这些儿童有丰富的产前压力暴露史和出生表型，并采取以下措施：(a) 情绪调节； (b) 认知； (c) 大脑结构的解剖学（使用结构磁共振成像 (MRI)）；以及 (d) HPA 应激轴的调节。将通过检查 CRH 水平之间的关系来评估产前 CRH 对情绪调节（目标 1）的影响通过父母和自我报告的气质测量，将通过检查胎盘 CRH 水平与标准化智力测量和新颖测量的表现之间的关系来评估早期接触 CRH 对认知的编程影响（目标 2）。产前暴露于 CRH 对海马体、杏仁核和前额皮质体积（目标 3）的影响将在妊娠晚期 CRH 水平上五分位和下五分位的 80 名儿童中进行评估。产前 CRH 对 HPA 反应性的影响（目标 4）将通过评估静息时和轻度应激后的唾液皮质醇来评估。这些研究是首次针对儿童进行的研究。产前 CRH 对人类发育的作用。