Preconception stress exposure: Impact on pregnancy and offspring neurodevelopment

项目摘要 健康和疾病的发展起源模型，即早期生活环境具有广泛的 对以后健康的影响，主要应用于产前压力对后代的作用 结果。尽管有令人信服的新证据表明，脆弱的暴露窗口发生在怀孕之前， 关于孕前压力暴露对怀孕健康，胎儿环境， 或对后代神经发育的影响。响应RFA-OD-16-004“环境对儿童健康的影响” 结果（ECHO）儿科队列研究（UG 3/UH 3），我们建议检验这一假设， 环境压力暴露将通过母体神经系统的改变来预测后代神经发育的缺陷。 调节怀孕期间压力的能力。此外，我们认为，孕前营养状况将 减轻孕前压力暴露对后代结果的负面影响。拟定研究 匹兹堡女孩研究（PGS）是一项对2,450名城市生活的年轻女性进行的纵向研究， 多重压力暴露的时间和慢性程度（例如住房和家庭压力， 在过去的16年里， 成年早期大多数PGS参与者来自研究中代表性不足的人群： 非洲裔美国人和低收入环境中的妇女。孕前压力暴露的生物标志物 (i.e.免疫和心脏代谢功能）和营养（即，维生素D、脂肪酸、铁、蛋白质和叶酸） 将在成年早期进行评估。在奖励期内怀孕的PGS参与者（N 800)将完成三项压力调节的心理生理评估（例如， 皮质醇反应），并评估胎盘功能。后代的神经发育将 在6个月、15个月、24个月和36个月时采用多模式措施进行评估（例如，神经和行为测量 执行功能和应激反应）。第一个研究目的是阐明前瞻性协会 孕前压力暴露和后代神经发育缺陷之间的联系。第二个目标是 确定产前压力调节介导这种关联的程度。我们的UG 3可行性目标将 在PGS基础设施内进行，从而确保所建立的方法将转化为 无缝连接到拟议的研究中。我们的跨学科团队在建议的各个方面都有专业知识， 研究，包括长期的，富有成效的合作研究人员在大学， 匹兹堡和芝加哥，这些机构非常适合支持这项研究。实现 拟议研究的既定目标将有助于确定最佳儿童健康的先决条件。 此外，我们的前瞻性设计测量产前应激调节和后代神经发育， 通过提供一个独特的机会，在整个联合体范围内进行测试，将对ECHO的使命做出重大贡献 在一个种族多样的队列中前瞻性地假设。

PROJECT SUMMARY The Developmental Origins of Health and Disease model, that the early life environment has widespread consequences for later health, has been applied primarily to the role of prenatal stressors on offspring outcomes. Despite compelling new evidence that vulnerable exposure windows occur prior to conception, very little is known about the impact of preconception stress exposure on pregnancy health, the fetal environment, or on offspring neurodevelopment. In response to RFA-OD-16-004 ‘Environmental Influences on Child Health Outcomes (ECHO) Pediatric Cohorts’ (UG3/UH3), we propose to test the hypothesis that preconception environmental stress exposure will predict deficits in offspring neurodevelopment via alterations in maternal capacity to regulate stress during pregnancy. Furthermore, we contend that preconception nutrition status will attenuate the negative effects of preconception stress exposure on offspring outcomes. The proposed study will build on the Pittsburgh Girls Study (PGS), a longitudinal study of 2,450 urban-living young women for whom the timing and chronicity of multiple stress exposures (e.g. housing and family stress, exposure to violence) has been prospectively and robustly measured for the past 16 years spanning childhood through early adulthood. The majority of PGS participants are from populations that are under-represented in research: African-Americans and women from low-income environments. Biomarkers of preconception stress exposure (i.e. immune and cardiometabolic function) and nutrition (i.e., vitamin D, fatty acids, iron, protein and folic acid) will be assessed in early adulthood. PGS participants who become pregnant over the period of award (N ≈ 800) will complete three psychophysiological assessments of stress regulation (e.g. intensity and recovery of cortisol response) during pregnancy, and placental function will be assessed. Offspring neurodevelopment will be assessed at 6, 15, 24 and 36 months with multi-modal measures (e.g., neural and behavioral measures of executive function and stress reactivity). The first study aim is to elucidate the prospective associations between preconception stress exposure and deficits in offspring neurodevelopment. The second aim is to determine the extent to which prenatal stress regulation mediates this association. Our UG3 feasibility aims will be carried out within the PGS infrastructure, thereby ensuring that methods established will translate seamlessly to the proposed study. Our interdisciplinary team has expertise in every aspect of the proposed study and includes long-standing, productive collaborations between investigators at the Universities of Pittsburgh and Chicago, institutions that are extremely well-suited to support the proposed study. Achieving the stated aims of the proposed study will contribute to the identification of prerequisites for optimal child health. Furthermore, our prospective design for measuring prenatal stress regulation and offspring neurodevelopment will significantly contribute to the mission of ECHO by providing a unique opportunity to test consortium-wide hypotheses prospectively in a racially diverse cohort.