MATERNAL STRESS AND FETAL/INFANT DEVELOPMENT

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。最近的证据表明，人类胎儿暴露在对健康具有永久性影响的深刻影响中(Barker，1998；Nathanielsz，1999)。母体压力会引发一系列事件，改变人类胎儿的正常发育过程。暴露在高压力信号下的人类胎儿在子宫内的学习受到损害(Sandman等人，1999a；1999b)，早产和低出生体重的风险增加了三倍(Wadhwa等人，1993；1998)。此外，多达一半的早产儿或小儿生有运动、感觉或认知障碍(McCarton等人，1996年)。这项为期五年的计划的主要目的是确定产前母体应激和母体神经内分泌反应对胎儿行为的影响，并在200名多民族妇女中评估胎儿行为和婴儿发育之间的关系。具体目标是：(A)确定影响胎儿行为的主要应激因素。怀孕期间将对压力进行五次测量(访谈和问卷调查)。胎儿的行为和发育将通过传统的胎儿生长测量和胎儿行为状态、运动(休息和挑战)、反应性和胎心率(FHR)习惯化的测量来量化。(B)确定母亲应激相关(HPA)轴活动和失调对胎儿和婴儿行为以及婴儿HPA活动的影响。由于母体应激改变了胎鼠大脑中的多肽受体和脑多肽水平(Takahashi等人，1992；波兰等人，1999；Insel等人，1990；Sanchez等人，1993；Fride等人，1985)，并且由于它影响人类胎儿行为和出生结果，因此将从每次产前和出生后访问时获取的血液中分析母体多肽水平。母亲应激肽对婴儿行为和HPA活性的影响将在3个月、6个月、12个月和24个月时确定。(C)描述胎儿行为和婴儿行为之间的关系。胎儿中枢神经系统活动(习惯化)的灵敏测量将与静止和挑战后胎儿行为的当代测量相结合，以描述胎儿的成熟。这些措施将被输入预测婴儿神经运动发育的模型中。婴儿的行为将通过贝利发育量表、神经运动状态检查以及基础和昼夜节律测量的下丘脑-垂体-肾上腺(HPA)活动来评估。(D)确定参与调节HPA途径的基因的变异性，HPA途径将应激、分娩和发育联系在一起。该项目旨在通过检查应激的时间和持续时间，通过调查与产前应激有关的生物机制，特别是HPA和胎盘轴，以及通过对婴儿产前应激的发育后果进行纵向研究，来确定对胎儿有害的母亲应激状况。该项目的中心目标是描述孕妇在怀孕期间的压力状况。参考资料：Barker DJP。(1998)《母亲、婴儿和晚年的健康》(第二版)。爱丁堡：丘吉尔·利文斯通。Fride E等人的研究成果。(1985)在冲突情况下，产前应激损害母亲的行为，并减少海马苯二氮卓类受体。《生命科学》，36,2103-9。陈晓华，等.(1990)产前应激对大脑阿片受体有长期影响。大脑研究，551，93-7。麦卡顿CM，华莱士IF，Divon M，Vaughan HG。(1996)早产儿、小于胎龄儿到6岁的认知和神经发育：出生体重和胎龄的比较。儿科，98,1167-78。Nathanielsz PW.(1999)子宫中的生命：健康和疾病的起源。纽约州伊萨卡：普罗米修斯出版社。波兰再。(1999)在围产期应激的成年雄性大鼠中，H-MRS测量的大脑N-乙酰天冬氨酸浓度降低：初步观察和对神经发育障碍的推测意义。《精神病学研究杂志》，33，41-51。Sanchez医学博士等人。(1993)在大鼠出生后发育过程中，B-内啡肽对出生前应激的反应。大脑发育研究，74,142-5。黄晓明，黄晓明，等人的研究.(1999a)母亲促肾上腺皮质激素释放激素与人类胎儿的习惯化。发育心理生物学，34,163-73。黄晓明，张晓华，李晓波，等.(1999 B)人类妊娠中促肾上腺皮质激素释放激素(CRH)与胎儿反应。《纽约科学院年鉴》，第897期，第66-75页。高桥LK，特纳JG，卡林NH。(1992)产前应激改变成年大鼠的脑儿茶酚胺能活动，并增强应激诱导的行为。大脑研究，574,131-7。Wadhwa P，Sandman C，Porto M等人。(1993)产前应激与婴儿出生体重和出生时胎龄的关系：一项前瞻性调查。《美国妇产科杂志》，69,858-65。Wadhwa P，Porto M，Garite TJ等人。(1998)妊娠早期的母亲促肾上腺皮质激素释放激素水平预测人类妊娠的长度。《美国妇产科杂志》，179,1079-85。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent evidence indicates that the human fetus is exposed to profound influences that have permanent implications for health (Barker, 1998; Nathanielsz, 1999). Maternal stress initiates a cascade of events that alter normal developmental processes in the human fetus. Human fetuses exposed to elevated stress signals have impaired learning in utero (Sandman et al., 1999a; 1999b) and are at three-fold increased risk for preterm birth and low birth weight (Wadhwa et al., 1993; 1998). Moreover, as many as one-half of the infants born early or small, have motor, sensory, or cognitive handicaps (McCarton et al., 1996). The primary aim of this five-year proposal is to determine the influence of prenatal maternal stress and maternal neuroendocrine responses on fetal behavior and to assess the relationship between fetal behavior and infant development in a multiethnic sample of 200 women. The specific aims are to: (a) Identify the primary stress factors that influence fetal behavior. Stress will be measured (interviews and questionnaires) five times during pregnancy. Fetal behavior and development will be quantified by conventional measures of fetal growth and by measures of fetal behavioral state, movement (at rest and challenge), reactivity and habituation of fetal heart rate (FHR). (b) Determine the influence of maternal stress-related (HPA) axis activity and disregulation on fetal and infant behavior and infant HPA activity. Because maternal stress alters peptide receptors and brain peptide levels in the fetal rat brain (Takahashi et al., 1992; Poland et al., 1999; Insel et al., 1990; Sanchez et al., 1993; Fride et al., 1985) and because it influences human fetal behavior and birth outcomes, maternal peptide levels will be assayed from blood obtained at each prenatal and postnatal visit. The influence of maternal stress peptides on infant behavior and HPA activity will be determined at three, six, twelve, and twenty-four months. (c) Describe the relationshipo between fetal behavior and infant behavior. A sensitive measure of fetal CNS activity (habituation) will be integrated with contemporary measures of fetal behavior at rest and after challenge, to describe fetal maturation. These measures will be entered into models to predict infant neuromotor development. Infant behavior will be assessed with the Bayley Scales of Development, the Neuromotor Status Examination, and by basal and circadian measures of hypothalamic-pituitary-adrenal (HPA) activity. (d) To identify variability in genes involved in the regulation of the HPA pathway that links stress, parturition, and development. This project is designed to identify maternal stressful conditions that are harmful to the fetus by examination of the timing and duration of stress, by investigation of biological mechanisms related to prenatal stress, specifically the HPA and placental axis and by longitudinal studies of developmental consequences of prenatal stress in the infant. The central objective of this project is to characterize maternal stress conditions over the course of the pregnancy. References Barker DJP. (1998) Mothers, Babies, and Health Later in Life (Second edition). Edinburgh: Churchill Livingstone. Fride E, et al. (1985) Prenatal stress impairs maternal behavior in a conflict situation and reduces hippocampal benzodiaxepine receptors. Life Science, 36, 2103-9. Insel T, Kinsley CH, Mann PE, et al. (1990) Prenatal stress has long-term effects on brain opiate receptors. Brain Research, 551, 93-7. McCarton CM, Wallace IF, Divon M, Vaughan HG. (1996) Cognitive and neurological development of the premature, small for gestational age infant through age 6: Comparison by birth weight and gestational age. Pediatrics, 98, 1167-78. Nathanielsz PW. (1999) Life in the Womb: The Origin of Health and Disease. Ithaca, NY: Promethean Press. Poland RE. (1999) Brain N-acetyl aspartate concentration measured by H MRS are reduced in adult male rats subjected to perinatal stress: preliminary observations and bypothetical implications for neurodevelopmental disorders. Journal of Psychiatric Research, 33, 41-51. Sanchez MD, et al. (1993) The B-endorphin response to prenatal stress during postnatal development in the rat. Developmental Brain Research, 74, 142-5. Sandman CA, Wadhwa P, Chicz-DeMet A, et al. (1999a) Maternal corticotropin-releasing hormone and habituation in the human fetus. Developmental Psychobiology, 34, 163-73. Sandman CA, Wadhwa P, Glynn L, et al. (1999b) Corticotrophin-releasing hormone (CRH) and fetal responses in human pregnancy. New York Academy of Sciences Annals, 897, 66-75. Takahashi LK, Turner JG, Kalin NH. (1992) Prenatal stress alters brain catecholaminergic activity and potentiates stress-induced behavior in adult rats. Brain Research, 574, 131-7. Wadhwa P, Sandman C, Porto M, et al. (1993) The association between prenatal stress and infant birth weight and gestational age at birth: A prospective investigation. American Journal of Obstetrics and Gynecology, 69, 858-65. Wadhwa P, Porto M, Garite TJ, et al. (1998) Maternal Corticotropin-releasing hormone levels in early third trimester predict length of gestation in human pregnancy. American Journal of Obstetrics & Gynecology, 179, 1079-85.