Preconception stress exposure: Impact on pregnancy and offspring neurodevelopment

孕前压力暴露：对妊娠和后代神经发育的影响

• 批准号: 10004737
• 负责人: ALISON E HIPWELL
• 金额: $ 229.66万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004737
• 关键词: African American; Age; Attention; Attenuated; Award; Biological Markers; Biometry; C-reactive protein; CRH gene; Chicago; Child; Child Health; Childbirth; Childhood; Chronic; Collaborations; Conceptions; Data; Development; Disease; Disease model; Ensure; Environment; Exposure to; Family; Fatty Acids; Folic Acid; Fostering; Future; Growth and Development function; Health; Housing; Hydrocortisone; Immune; Impairment; Individual Differences; Infrastructure; Institution; Iron; Knowledge; Life; Link; Longitudinal Studies; Low income; Measures; Mediating; Methodology; Methods; Mission; Modeling; Nutritional; Nutritional status; Outcome; Oxidoreductase; Participant; Pediatric cohort; Phase; Placenta; Population; Population Heterogeneity; Pregnancy; Prenatal Nutrition; Prevention; Proteins; Psychophysiology; Public Assistance; Public Health; Recovery; Regulation; Research; Research Personnel; Risk; Role; Sampling; Short-Term Memory; Specific qualifier value; Steroids; Stress; Testing; Tissues; Translating; Triglycerides; Underrepresented Populations; Universities; Venous blood sampling; Vitamin D; Woman; Work; base; behavior measurement; biological systems; cardiometabolism; cohort; design; emerging adult; executive function; fetal; girls; healthy pregnancy; hypothalamic-pituitary-adrenal axis; improved; maternal stress; multimodality; neurodevelopment; nutrition; offspring; pediatric health outcomes; postnatal period; pregnant; prenatal; prenatal health; prenatal stress; prospective; prospective test; psychosocial; racial diversity; relating to nervous system; resilience; response; stress reactivity; stressor; transmission process; violence exposure; young woman

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.

项目摘要 健康和疾病模型的发展起源，即早期生活环境的宽度 后来健康的后果主要用于产前压力源对后代的作用 结果。尽管有令人信服的新证据表明易受伤害的暴露窗口是在概念之前发生的，但 关于牙前对待压力暴露对妊娠健康的影响，胎儿环境，鲜明了解 或后代神经发育。为了回应RFA-OD-16-004'环境对儿童健康的影响 结果（Echo）小儿同伙（UG3/UH3），我们建议检验先入为主的假设 环境压力暴露将预测后代神经发育中的定义 怀孕期间调节压力的能力。此外，我们认为，先选的营养状况将 减轻牙王应力暴露对后代结果的负面影响。拟议的研究 将建立在匹兹堡女孩研究（PGS）的基础上，这是一项对2,450名城市生活年轻女性的纵向研究 多次压力暴露的时间和慢性（例如住房和家庭压力，暴露于 暴力）在过去的16年中一直被前瞻性，坚固地测量。 成年早期。大多数PGS参与者来自研究不足的人群： 来自低收入环境的非裔美国人和妇女。牙前性应力暴露的生物标志物 （即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） 将在成年初进行评估。在奖励期间怀孕的PGS参与者（n≈ 800）将完成应力调节的三项心理生理评估（例如，强度和恢复 皮质醇反应）在怀孕期间和占位术功能将被评估。后代神经发育会 通过多模式测量在6、15、24和36个月进行评估（例如，神经和行为测量 执行功能和压力反应性）。第一个研究的目的是阐明前瞻性关联 在孕前压力暴露和定义后代神经发育之间。第二个目标是 确定产前应力调节该关联的程度。我们的UG3可行性目标将 在PGS基础架构内进行，从而确保建立的方法将翻译 无缝地进行拟议的研究。我们的跨学科团队在提议的各个方面都有专业知识 研究并包括大学研究人员之间的长期产品合作 匹兹堡和芝加哥，非常适合支持该研究的机构。实现 拟议的研究的陈述目标将有助于确定最佳儿童健康的先决条件。 此外，我们测量产前压力调节和后代神经发育的前瞻性设计 通过提供一个独特的机会来测试财团，将为Echo的任务做出重大贡献 在大致多样化的队列中前瞻性地假设。