Prenatal Programming of Infant Temperament

描述（由申请人提供）：本提案的目的是确定子宫内暴露于母体应激和母体糖皮质激素（GCs）对两岁儿童气质和下丘脑-垂体-肾上腺皮质（HPA）轴调节的影响。虽然已经确定，在动物模型中，产前暴露于母亲压力和GCs升高对健康和发育具有终生影响，但对人类儿童的持久影响尚不清楚。一个小的，但越来越多的文献开始表明，产前暴露于母亲的压力和压力激素对产后发育有持续的影响。产前母亲压力的主要后果之一是增加行为抑制或情绪，以应对后代的挑战。然而，这些研究往往受限于他们对怀孕期间压力的回顾性报告或父母对孩子行为的报告，因此，可能反映出焦虑的母亲看待孩子的方式的差异。该项目将提供机会，利用实验室观察措施，对100名两岁儿童进行前瞻性研究，研究产前暴露于母亲心理社会和内分泌压力指标的影响，随后从妊娠早期（第14周）到足月，再到产后，直到两岁。具体目的是：(i)评估产前产妇心理社会压力和产妇GCs对行为抑制气质发展的影响。行为抑制气质将通过标准化的实验室观察措施进行评估，其中观察儿童对一系列新挑战的行为和情感反应，（ii）评估产前母亲心理社会压力和母亲GCs对HPA轴调节的影响。唾液皮质醇水平将在基线测量，并响应标准化的实验室挑战，以评估HPA轴的完整性。儿童早期的行为抑制和压力反应增加可能是暴露于产前母亲压力的结果，并可预测焦虑症的发展。一些回顾性研究表明，成人生活中的许多疾病部分起源于产前时期。为了更好地理解这种关联背后的过程，需要进行前瞻性研究，比如这项研究。

DESCRIPTION (provided by applicant): The aim of this proposal is to determine the effects of intrauterine exposure to maternal stress and maternal glucocorticoids (GCs) on temperament and hypothalamic-pituitary-adrenocortical (HPA) axis regulation in two-year-old children. Although it is established that prenatal exposure to maternal stress and elevated GCs has life-long implications for health and development in animal models, the lasting impact on the human child is not known. A small, but growing literature is beginning to demonstrate that prenatal exposure to maternal stress and stress hormones has persisting influences on postnatal development. One of the primary consequences of prenatal maternal stress is an increase in behavioral inhibition or emotionality in response to challenge in the offspring. These studies, however, are often limited by their reliance on retrospective report of stress during pregnancy or parent report of child behavior and thus, may reflect differences in the ways that anxious mothers perceive their children. This project will provide the opportunity to examine prospectively and using laboratory observational measures the influence of prenatal exposure to maternal psychosocial and endocrine indicators of stress in 100 two-year-old children from pregnancies followed with serial measures from early gestation (week 14) through term and then postpartum until the age of two years. The specific aims are to: (i) Evaluate the impact of prenatal maternal psychosocial stress and maternal GCs on the development of behaviorally inhibited temperament. Behaviorally inhibited temperament will be assessed with a standardized laboratory observational measure in which children's behavioral and affective responses to a series of novel challenges is observed, (ii) Assess the influence of prenatal maternal psychosocial stress and maternal GCs on HPA axis regulation. Salivary cortisol levels will be measured at baseline and in response to a standardized laboratory challenge to evaluate the integrity of the HPA axis. Behavioral inhibition and increased stress reactivity early in childhood are likely consequences of exposure to prenatal maternal stress and are predictive of the development of anxiety disorders. A number of retrospective studies have indicated that many of the diseases of adult life have part of their origin in the prenatal period. Prospective studies, such as this one, are needed to better understand processes that might underlie this association.