EMA Assessment of Biobehavioral Processes in Human Pregnancy

描述（由申请人提供）：不良出生结局（妊娠期缩短/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心理社会压力构成了这些不良后果的独立风险因素。然而，这种知识的翻译从人口到个人水平的风险评估和干预是有限的事实，即常用的自我报告，回顾性回忆措施的压力预测不良出生结果的敏感性和特异性低。压力和出生结果文献的两个主要弱点涉及：（a）评估产妇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压力反应的个体差异。生态瞬时评估（EMA）抽样方法的最新进展，现在提供了机会，评估在自然环境中的心理，行为和生物过程的动态相互作用，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行为围产期学研究领域。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）激素参数和B）出生结果的影响的大小; 2）估计母体生物应激反应对a）MPF激素参数和B）出生结果的影响的大小;（3）确定母体应激效应的大小是否受应激发生的妊娠阶段的调节。将在妊娠早期、中期和晚期的3次4天评估中，从至少120名妊娠女性样本中收集完整的前瞻性数据。将使用电子日记（PDA）每天收集15项受试者的心理状态和其他背景信息。将收集母亲心率、呼吸和身体活动的持续动态测量以及每天7份唾液样本，以用于自主神经和内分泌活动的指标。在每次门诊结束时，将采集母体血液样本用于测量MPF内分泌介质（CRH，E3）。这些数据将合并到时间同步数据集中;将通过包括受试者特定自回归模型在内的方法计算时不变和时变变量，并将采用多变量和纵向回归分析，使用广义估计方程（GEE）和具有固定和随机效应的多水平混合模型（分层线性模型; 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涉及新措施和方法的开发和评估，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，并为开发和评估采取全面的干预战略，以降低不良生育结果的高发生率。从我们的研究结果也将通知拟议的心理生物压力评估协议的国家儿童研究（NCS）。

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).