EMA Assessment of Biobehavioral Processes in Human Pregnancy

描述（由申请人提供）：不良的出生结果（妊娠长度缩短/胎儿生长受损）被认为是美国母婴健康中最重要的问题。动物和人类的大量经验证据表明，怀孕期间母亲的高水平社会心理压力是这些不良后果的独立危险因素。然而，由于通常使用的自我报告、回顾性回忆应激措施在预测不良出生结局方面的敏感性和特异性较低，因此将这些知识从人群转化为个体水平进行风险评估和干预受到了限制。压力和分娩结果文献的两个主要弱点涉及(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，以解决本文献中的缺点和知识空白。我们建议将这些方法引入并应用于行为围产学研究领域。我们的具体目标是：1)估计母亲心理社会压力对a)母亲-胎盘-胎儿（MPF）激素参数和b)分娩结局的影响程度；2)估计母亲生物应激反应对a) MPF激素参数和b)分娩结局的影响程度；(3)探讨应激的影响程度是否受应激发生的妊娠阶段的调节。完整的前瞻性数据将在至少120名孕妇的样本中收集，在妊娠早期、中期和晚期进行3次为期4天的评估。使用电子日记（pda）每天收集15次受试者的心理状态和其他情境信息。将在每天的过程中收集产妇心率、呼吸和身体活动的连续动态测量，以及七个唾液样本，以作为自主神经和内分泌活动的指标。在每次门诊结束时，将采集产妇血液样本，用于MPF内分泌介质（CRH, E3）的测量。这些数据将合并成时间同步的数据集；定常变量和时变变量将通过特定主题的自回归模型计算，多变量和纵向回归分析将采用广义估计方程（GEE）和具有固定和随机效应的多级混合模型（层次线性模型；HLM）来检验特定目标和假设。我们的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易受压力相关不良出生结果影响的决定因素，鉴于本研究的公共卫生意义在于开发和评估新的措施和方法，这些措施和方法将提高生物心理社会风险评估的特异性和敏感性，并为开发和评估综合干预策略提供经验基础，以降低不可接受的不良出生结果的高发生率。我们的研究结果也将为国家儿童研究（NCS）提出的心理生物学压力评估方案提供信息。

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).