MOTHERS AND BABIES HEALTH AND WELL-BEING STUDY

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。在美国，早产一直被描述为母婴健康中最严重的问题，因为它是导致先天死亡和发病的主要原因；在过去的40年里，它的患病率并没有下降；而且在大多数病例中，其病因尚不清楚(克雷西，1994)。在寻找其他危险因素的过程中，产前应激已被确定为一个感兴趣的变量。越来越多的人认识到，在怀孕期间经历心理和社会逆境的妇女，即使在调整了既定的生物医学和社会人口风险因素的影响之后，早产的风险也会增加(Wadhwa等人，1993；Wadhwa等人，1996；Wadhwa等人，1997；Wadhwa等人，1998a；Wadhwa等人，1998b；Wadhwa等人，在出版社a；Wadhwa等人，在出版社b；Wadhwa等人，在出版社c；Sandman等人，1999；Killingsworth-Rini等人，1999；Dunkel-Schetter等人，2000；Feldman等人，2000年；Glynn等人，2001；Culhane等人，正在出版)。这可能是由于所经历的压力的水平和类型的不同，但最有可能的是个体之间的差异。尽管持续时间、暴露频率和所经历的压力性质等参数在确定不良妊娠结局的风险方面很重要，但肯定不是所有产前压力水平高的妇女都会早产。显然，个体对压力的生理反应存在差异，这些反应的差异被认为在压力对生物结果(如妊娠长度)的影响中起着重要作用。本提案的目的是研究怀孕期间女性对轻微行为挑战的生物反应中的个体差异在与孕期长短相关的结果中的作用。我们的目标是更好地了解调节个体对压力的反应倾向的特定因素，以及这种反应如何影响所观察到的产前应激与不良妊娠结局之间的关系。行为挑战是心理社会挑战的标准操作，当个体经历心理社会压力时，它会唤起来自相同生理系统的反应。因此，接受这一温和挑战的受试者的反应代表了他们对心理社会压力的反应，然而，在受控环境下进行的挑战是短暂的，受试者的心理和生物反应很小。主要的研究假设是，怀孕期间母亲对行为挑战(即高反应性)的更大的生物学反应将显著预测更早的分娩。第二项研究假设母亲对挑战的生物反应性的影响将通过胎盘促肾上腺皮质激素释放激素(CRH)来调节；母亲对行为挑战的生物反应的幅度将随着妊娠的推进而降低；基线激素水平、生物医学(产科)风险状况和母亲的心理社会因素将与对挑战的生物反应性的测量显著相关。为了验证这些假设，一项为期三年的前瞻性纵向研究被提出，样本为200名单胎宫内妊娠妇女。这项研究样本将从自然早产的低生物医学(产科)风险和高生物医学(产科)风险的临床人群中选择，在怀孕10-12周之前招募，在怀孕的两个时间点进行测试，在分娩期间跟踪，并在产后进行一次测试。具体目标1：量化母亲对行为挑战范式的生理反应参数。具体目标2：量化母亲在怀孕期间对行为挑战的生理反应的变化。具体目标3：评估母亲对行为挑战的生理反应对妊娠结局的影响，与妊娠长度有关。具体目标4：量化胎盘促肾上腺皮质激素释放激素(CRH)在妊娠过程中的活性。具体目标5：检查基线激素水平、生物医学(产科)风险和心理社会因素对母亲对行为挑战的生理反应的影响。具体目标6：研究心理社会环境、基线生理状态、对行为挑战的生理反应以及生物医学/社会人口学风险因素对与妊娠长度相关的妊娠结局的综合影响。

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. Prematurity has been described as the most significant problem in maternal-child health in the United States because it is the leading cause of inhant mortality and morbidity; its prevalence has not decreased over the last 40 years; and its etiology is unknown in a majority of cases (Creasy, 1994). In the emerging search for additional risk factors, prenatal stress has been identified as a variable of interest. There is a growing recognition, supported by the studies of the principal investigator (PI) and colleagues, that women who experience psychological and social adversity during pregnancy are at increased risk for preterm delivery, even after adjusting for the effects of established biomedical and sociodemographic risk factors (Wadhwa et al, 1993; Wadhwa et al, 1996; Wadhwa et al, 1997; Wadhwa et al, 1998a; Wadhwa et al, 1998b; Wadhwa et al, in press a; Wadhwa et al, in press b; Wadhwa et al, in press c; Sandman et al, 1999; Killingsworth-Rini et al, 1999; Dunkel-Schetter et al, 2000; Feldman et al, 2000; Glynn et al, 2001; Culhane et al, in press). This may be due to differences in the level and type of stress experienced, but mostly likely also varies across individuals. Although parameters such as the duration, frequency of exposure, and nature of the stress experienced are important in determining risks for adverse pregnancy outcomes, certainly not all women with high levels of prenatal stress deliver preterm. Clearly there are differences between individuals in their physiologic responsivity to stress, and the differences in these responses are belived to play a significant role in the impact of stress on biological outcomes such as gestational length. The objective of the present proposal is to examine the role of individual differences in women's biological responses to a mild behavioral challenge during pregnancy in outcomes related to the length of gestation. Our goal is to gain a better understanding of the specific factors that mediate an individual's propensity to respond to stress and how this response affects the observed relationshipo between prenatal stress and adverse pregnancy outcomes. The behavioral challenge is a standard operationalization of psychosocial challenge that evokes responses from the same physiologic systems that are involved when an individual experiences psychosocial stress. The responses of subjects undergoing this mild challenge are thus representative of their responses to psychosocial stress, yet the challenge, given in a controlled setting, is brief and the psychological and biological responses evoked in subjects is minimal. The primary study hypothesis is that greater maternal biological reactivity to a behavioral challenge (i.e., hyperreactivity) during pregnancy will significantly predict earlier delivery. Secondary study hypotheses are that the effects of maternal biological reactivity to challenge will be mediated via placental corticotropin-releasing hormone (CRH); that the magnitude of the maternal biological response to a behavioral challenge will decrease with advancing gestation; and that baseline hormonal levels, biomedical (obstetric) risk status, and maternal psychosocial factors will correlate significantly with measures of biological reactivity to challenge. To test these hypotheses, a prospective, longitudinal study is proposed over a three-year period in a sample of 200 women with a singleton intrauterine pregnancy. This study sample will be selected from clinical populations at low and high biomedical (obstetric) risk for pontaneous preterm birth, recruited before 10-12 weeks gestation, tested at two points in time in pregnancy, followed through delivery, and tested once in the post-partum period. Specific Aim 1: To quantify parameters of maternal physiological reactivity to a behavioral challenge paradigm. Specific Aim 2: To quantify changes in maternal physiological reactivity to a behavioral challenge over the course of gestation. Specific Aim 3: To assess the influence of maternal physiological reactivity to a behavioral challenge on pregnancy outcomes related to the length of gestation. Specific Aim 4: To quantify placental corticotropin-releasing hormone (CRH) activity over the course of gestation. Specific Aim 5: To examine the influence of baseline hormonal levels, biomedical (obstetric) risk and psychosocial factors on maternal physiological reactivity to a behavioral challenge. Specific Aim 6: To examine the combined effects of psychosocial environment, baseline physiological state, physiological reactivity to a behaviroal challenge, and biomedical/sociodemographic risk factors on pregnancy outcomes related to gestational length.