EMA Assessment of Biobehavioral Processes in Human Pregnancy

描述(由申请人提供)：在美国，不良的出生结局(妊娠长度缩短/胎儿发育受损)被认为是母婴健康中最严重的问题。在动物和人类身上的大量经验证据表明，怀孕期间高水平的母亲心理社会压力是这些不利结果的独立风险因素。然而，将这些知识从人群水平转化到个人水平以进行风险评估和干预受到以下事实的限制：通常使用的自我报告、回顾应激反应的测量在预测不良出生结果方面的敏感性和特异性较低。压力和分娩结局文献的两个主要缺陷涉及(A)评估母亲心理社会压力的传统方法的局限性，以及(B)未能评估和解释生物应激反应的个体差异。生态瞬时评估(EMA)采样方法的最新进展现在提供了评估自然环境中心理、行为和生物过程的动态相互作用的机会，以弥补这篇文献中的缺点和知识空白。我们建议将这些方法引入并调整到行为围产学研究领域。我们的具体目标是：1)估计母体心理社会应激对a)母体-胎盘-胎儿(MPF)荷尔蒙参数和b)分娩结局的影响的程度；2)估计母体生物应激反应对a)MPF荷尔蒙参数和b)分娩结果的影响的程度；以及3)确定母体应激的影响的程度是否受应激发生的孕期调节。完整的前瞻性数据将在至少120名孕妇的样本中收集，这些孕妇在怀孕早期、中期和晚期进行了三次为期4天的评估。将使用电子日记(PDA)收集受试者心理状态和其他背景信息的15个测量/天。将收集产妇心率、呼吸和体力活动的连续动态测量，以及每天过程中的七个唾液样本，以指示自主神经和内分泌活动。在每次门诊结束时，将采集孕妇血液样本，以测定强积金内分泌介质(CRH，E3)。这些数据将被合并到时间同步数据集中；时间不变和时变变量将通过包括特定于受试者的自回归模型的方法来计算；将使用广义估计方程(GEE)和具有固定和随机影响的多水平混合模型(分层线性模型；HLM)来使用多变量和纵向回归分析来检验具体的目标和假设。我们建议的科学意义在于理解心理生物学机制，这些机制可能是个体对应激相关不良出生结果易感性的决定因素，而这项研究的公共卫生意义在于开发和评估新的措施和方法，这些措施和方法将增加生物心理社会风险评估的特异性和敏感性，并为制定和评估综合干预策略提供经验基础，以降低不良出生结果的不可接受的高发生率。我们的研究结果也将为国家儿童研究(NCS)拟议的心理生物压力评估方案提供参考。 公共卫生相关性：这项建议解决了可以说是我国母婴健康中最重要的公共卫生问题--与妊娠缩短/早产和胎儿生长减少/出生体重降低有关的不良妊娠和分娩结果。一些动物和人类的证据令人信服地表明，孕妇在怀孕期间与心理社会应激相关的过程是不良分娩结果以及随后的儿童和成人健康结果的一个重要的、潜在的可改变的风险因素。然而，尽管多年来的实证研究和发现，关于产前应激影响的性质、机制和时机的关键问题仍然有待回答。我们认为，将产前应激结果从人群转化为个人水平的关键第一步是找到方法，确定哪个亚群(S)的孕妇(在什么情况/背景下，以及在怀孕的哪个时间/阶段)特别容易受到产前应激的有害影响。我们提出，基于心理、行为和生物状态的实时、动态、重复采样(即生态瞬时评估(EMA))的较新的创新技术和方法可以成功地实现这一目标。这项研究的科学意义在于，它将澄清心理生物学机制，这些机制可能是个体对应激相关不良生育结果易感性的决定因素。对公共健康的影响是，它将提高生物、心理和社会风险评估的敏感性和特异性，并为制定和评估综合干预战略提供经验基础，以预防或管理妊娠应激，减少其对母亲及其未出生婴儿的不利健康后果。我们建议的研究的目标、方法和结果与NIH对临床转化研究的重视以及系统生物学向未来的新P4医学(预测性、预防性、个性化、参与性)发展的愿望是一致的。

DESCRIPTION (provided by applicant): Adverse birth outcomes (reduced length of gestation/ impaired fetal growth) are recognized as the most significant problem in maternal-child health in the United States. A substantial body of empirical evidence in animals and humans suggests that high levels of maternal psychosocial stress in pregnancy constitute an independent risk factor for these adverse outcomes. However, the translation of this knowledge from the population to individual level for risk assessment and intervention is limited by the fact that the commonly-used self-report, retrospective recall measures of stress have low sensitivity and specificity in predicting adverse birth outcomes. Two major weaknesses of the stress and birth outcome literature relate to (a) limitations in the traditional approach to assess maternal psychosocial stress, and (b) the failure to assess and account for individual differences in biological stress responsivity. Recent advances in ecological momentary assessment (EMA) sampling methods now afford the opportunity of assessing the dynamic interplay of psychological, behavioral and biological processes in natural settings to address shortcomings and knowledge gaps in this literature. We propose to import and adapt these methods into the area of behavioral perinatology research. Our specific aims are: 1) To estimate the magnitude of the effect of maternal psychosocial stress on a) maternal-placental-fetal (MPF) hormonal parameters, and b) birth outcomes; 2) To estimate the magnitude of the effect of maternal biological stress reactivity on a) MPF hormonal parameters, and b) birth outcomes; and 3) To determine whether the magnitude of the effect of maternal stress is modulated by the stage in gestation of occurrence of stress. Complete prospective data will be collected in a sample of at least 120 pregnant women over three 4-day assessments in early, mid and late gestation. Electronic diaries (PDAs) will be used to collect 15 measures/day of subjects' psychological state and other contextual information. Continuous ambulatory measures of maternal heart rate, respiration and physical activity, as well as seven saliva samples over the course of each day, will be collected for indicators of autonomic and endocrine activity. At the end of each ambulatory session, a maternal blood sample will be collected for measures of MPF endocrine mediators (CRH, E3). These data will be merged in time-synchronized datasets; time-invariant and time-variant variables will be computed by methods including subject-specific auto-regression models, and multivariate and longitudinal regression analysis will be employed to test the specific aims and hypotheses using generalizing estimating equations (GEE) and multi-level mixed models with fixed and random effects (hierarchical linear models; HLM). The scientific significance of our proposal pertains to understanding psychobiological mechanisms that are likely determinants of individual vulnerability for stress-related adverse birth outcomes, whereas the public health significance of this research pertains to the development and assessment of new measures and methodologies that will increase the specificity and sensitivity of biopsychosocial risk assessment and provide an empirical basis for the development and evaluation of comprehensive intervention strategies to reduce the unacceptably high incidence of adverse birth outcomes. Findings from our study also will inform the proposed psychobiological stress assessment protocol of the National Children's Study (NCS). PUBLIC HEALTH RELEVANCE: This proposal addresses what is arguably the most important public health issue in maternal-child health in our nation - adverse pregnancy and birth outcomes related to shortened gestation/preterm birth and reduced fetal growth/low birth weight. Several lines of animal and human evidence converge to convincingly suggest that maternal psychosocial stress-related processes in pregnancy represent an important and potentially modifiable risk factor for adverse birth outcomes and subsequent child and adult health outcomes. However, despite many years of empirical research and findings, key questions still remain to be answered about the nature, mechanism and timing of effects of prenatal stress. We argue that the critical first step towards translating prenatal stress findings from the population to the individual level is to develop ways to identify which subgroup(s) of pregnant women (under what circumstances/ context, and at which time/stage in gestation) are particularly susceptible to the detrimental effects of prenatal stress. We propose that newer, innovative technologies and methods based on real-time, ambulatory, repeated sampling of psychological, behavioral and biological states (i.e., ecological momentary assessment (EMA)) can be adapted successfully to achieve this objective. The scientific significance of this research is that it will clarify psychobiological mechanisms that are likely determinants of individual vulnerability for stress-related adverse birth outcomes. The public health impact is that it will increase the sensitivity and specificity of biopsychosocial risk assessment and provide an empirical basis for the development and evaluation of comprehensive intervention strategies to prevent or manage stress in pregnancy and reduce its adverse health consequences in the mother and her unborn child. The objectives, approach, and outcomes of our proposed research are consistent with the emphasis placed by the NIH on clinical translational research and the aspiration in Systems Biology to progress towards the new P4 medicine (predictive, preventive, personalized, participatory) of the future.