Prenatal stress exposures and fetal inflammation during mid-gestation

妊娠中期的产前应激暴露和胎儿炎症

• 批准号: 10666896
• 负责人: Stephanie Marie Eick
• 金额: $ 25.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666896
• 关键词: Affect; Biological; Biological Markers; Blood; California; Child Health; Color; Communities; Corticotropin-Releasing Hormone; Data; Development; Discrimination; Disparity; Enzyme-Linked Immunosorbent Assay; Equation; Ethics; Ethnic Origin; Etiology; Exposure to; Factor Analysis; Fetal Development; Fetal Growth; Fetal Tissues; Fetal health; Fetus; Future; Health; Human; IL6 gene; IL8 gene; Immune system; Individual; Inflammation; Inflammation Mediators; Inflammatory; Interferons; Intervention; Investigation; Knowledge; Link; Low income; Measures; Mediating; Modeling; Mothers; Occupations; Outcome; PGF gene; Participant; Pathology; Pathway interactions; Patient Self-Report; Persons; Placenta; Positioning Attribute; Pregnancy; Pregnancy Complications; Premature Birth; Premature Labor; Proxy; Psychosocial Stress; Questionnaires; Race; Receptor Protein-Tyrosine Kinases; Risk; Role; Sampling; San Francisco; Scientific Advances and Accomplishments; Second Pregnancy Trimester; Serum; Shapes; Signaling Molecule; Social support; Stress; Stressful Event; Termination of pregnancy; Third Pregnancy Trimester; Time; Tissue Sample; Umbilical Cord Blood; Vascular Endothelial Growth Factor Receptor-1; Woman; adverse birth outcomes; adverse outcome; adverse pregnancy outcome; biological adaptation to stress; chemokine; clinical practice; cohort; critical period; cytokine; developmental disease; early pregnancy; epidemiology study; experience; fetal; healthy pregnancy; improved; insight; low socioeconomic status; marginalization; marginalized population; maternal serum; perceived stress; perinatal health; pregnancy health; pregnant; premature; prenatal; prenatal stress; psychosocial stressors; public health insurance; social disparities; social stressor; stressor; study population; women of color

ABSTRACT Maternal experiences of psychosocial stress (e.g., stressful life events, perceived stress, job strain, poor social support) are associated with an increased risk of preterm birth and inflammation during pregnancy has been implicated as a key mechanistic pathway. Epidemiologic studies have observed positive relationships between psychosocial stressors and maternal inflammation levels. Similarly, inflammatory biomarkers, measured in maternal samples during the second and third trimesters, have been associated with preterm birth. However, how psychosocial stress and maternal inflammation both influence fetal inflammation during early to mid- gestation remains unknown. This is problematic because most studies rely on maternal samples as proxies of fetal health during mid-pregnancy. This knowledge gap persists in large part due to logistical and ethical challenges in obtaining fetal tissue samples during mid-gestation. Closing this knowledge gap has implications for improving fetal health across pregnancy, as elevated levels of maternal inflammation during early pregnancy may lead to elevated levels of fetal inflammation later in gestation, which in turn can affect fetal development and child health outcomes. Communities of color and low socioeconomic status individuals experience the highest burden of multiple psychosocial stressors and are disproportionately affected by structural discrimination. Accordingly, we will utilize a unique cohort of pregnant people who underwent elective pregnancy terminations during the second trimester in San Francisco, CA between 2010 and 2016. This study population is racially, ethnically, and demographically diverse, serving primarily low-income women of color with public health insurance. We will, for the first time, measure a comprehensive panel of 24 inflammatory biomarkers in 114 previously banked maternal and cord sera and placenta samples. In parallel, we will quantify levels of corticotropin-releasing hormone (CRH), FMS-like tyrosine kinase receptor (FLT1), and placental growth factor (PlGF) in maternal sera. Our study, which leverages hard to obtain biospecimens from a critically important time period, will be the first to examine the relationship between psychosocial stress and fetal inflammation during mid-gestation. We will determine differences in abundances and assess correlations among biomarkers across the three matrices (Aim 1). Further, we will examine relationships between psychosocial stress and maternal and fetal inflammation and create inflammation scores for each matrix using factor analysis (Aim 2). We will also use structural equation modeling to assess whether inflammation measured in cord serum is influenced by and associated with maternal and placenta inflammation levels (Aim 3). Importantly, results from our study will provide important insights on the health effects of historically marginalized populations during a time period that is difficult to study. Understanding the origins of fetal inflammation during mid-gestation and its relationship with maternal inflammation can inform future studies that must rely on maternal measures as proxies for fetal inflammation and elucidate intervention opportunities at biologically relevant time periods to improve fetal growth.

抽象的 母亲经历社会心理压力（例如，压力性生活事件、感知到的压力、工作紧张、社交能力差） 支持）与早产风险增加和怀孕期间炎症有关 被认为是一个关键的机制途径。流行病学研究观察到两者之间呈正相关 社会心理压力源和产妇炎症水平。同样，炎症生物标志物，测量 妊娠中期和晚期的母亲样本与早产有关。然而， 心理社会压力和母体炎症如何影响早中期胎儿炎症 妊娠情况仍未知。这是有问题的，因为大多数研究依赖母体样本作为 怀孕中期胎儿的健康。这种知识差距在很大程度上是由于后勤和道德方面的原因而持续存在的 妊娠中期获取胎儿组织样本的挑战。缩小这一知识差距具有重要意义 改善整个怀孕期间的胎儿健康，因为怀孕早期母体炎症水平升高 可能会导致妊娠后期胎儿炎症水平升高，进而影响胎儿发育 和儿童健康结果。有色人种社区和社会经济地位较低的个人会经历 多重社会心理压力源的负担最重，并且受到结构性歧视的影响尤为严重。 因此，我们将利用一组接受选择性妊娠终止的独特孕妇 2010 年至 2016 年期间在加利福尼亚州旧金山的妊娠中期。该研究人群按种族划分， 种族和人口结构多样化，主要为低收入有色人种女性提供公共卫生服务 保险。我们将首次在 114 个国家中测量 24 种炎症生物标志物的综合组 之前储存的母体血清和脐带血清以及胎盘样本。与此同时，我们将量化 促肾上腺皮质激素释放激素 (CRH)、FMS 样酪氨酸激酶受体 (FLT1) 和胎盘生长因子 母体血清中的 (PlGF)。我们的研究利用了在极其重要的时刻努力获取生物样本的优势 期间，将首先检查心理社会压力与胎儿炎症之间的关系 妊娠中期。我们将确定丰度差异并评估生物标志物之间的相关性 三个矩阵（目标 1）。此外，我们将研究心理社会压力与母亲之间的关系。 和胎儿炎症，并使用因子分析为每个矩阵创建炎症评分（目标 2）。我们也会 使用结构方程模型来评估脐带血清中测量的炎症是否受到以下因素的影响： 与母体和胎盘炎症水平相关（目标 3）。重要的是，我们的研究结果将 提供关于历史上边缘化人群在一段时间内对健康的影响的重要见解 很难学习。了解妊娠中期胎儿炎症的起源及其与 母体炎症可以为未来的研究提供信息，这些研究必须依赖母体测量作为胎儿的替代指标 炎症并阐明在生物学相关时间段进行干预以改善胎儿生长的机会。