Prenatal stress exposures and fetal inflammation during mid-gestation

摘要 心理社会压力的母亲经历(例如，有压力的生活事件、感知到的压力、工作压力、糟糕的社交 支持)与早产和孕期炎症的风险增加有关 被认为是一条关键的机械途径。流行病学研究已经观察到 心理社会应激源和母体炎症水平。同样，炎症性生物标志物，以 妊娠中期和晚期的孕妇样本与早产有关。然而， 心理社会压力和母体炎症如何在早中期影响胎儿炎症 怀孕的情况仍不清楚。这是有问题的，因为大多数研究依赖于母体样本作为 孕中期胎儿健康状况。这种知识差距之所以持续存在，很大程度上是由于后勤和道德方面的原因。 在妊娠中期获取胎儿组织样本的挑战。弥合这一知识鸿沟具有重要意义 用于改善怀孕期间的胎儿健康，因为怀孕早期母亲炎症水平升高 可能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。有色人种和低社会经济地位的个人经历了 这是多种心理社会应激源造成的最大负担，并受到结构性歧视的不成比例的影响。 因此，我们将利用一组独特的接受选择性终止妊娠的孕妇。 2010至2016年间在加利福尼亚州旧金山的第二个三个月期间。这一研究人群是按种族划分的， 种族和人口结构多样化，主要服务于公共卫生领域的低收入有色人种妇女 保险公司。我们将首次在114年测量由24个炎症生物标志物组成的综合小组 之前储存了孕妇和脐带血清和胎盘样本。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 (PlGF)在母体血清中。我们的研究，利用HARD从一个关键的时间段获得生物制品 期间，将首次研究心理社会应激与胎儿炎症之间的关系 怀孕中期。我们将确定丰度的差异，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和母亲之间的关系。 并使用因子分析为每个基质创建炎症评分(目标2)。我们还将 使用结构方程模型评估脐带血清中测量的炎症是否受和 与母体和胎盘炎症水平有关(目标3)。重要的是，我们的研究结果将 对历史上被边缘化的人群在一段时间内的健康影响提供重要的见解 很难研究。了解孕中期胎儿炎症的起源及其与 母体炎症可能会为未来的研究提供信息，这些研究必须依赖母体措施作为胎儿的替代品 炎症和阐明在生物学相关的时间段的干预机会，以促进胎儿生长。

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.