The role of host-microbial interactions in altering preterm birth risk among black women

摘要：在美国，黑人和非黑人妇女在围产期结局方面存在明显差异。 美国。即使在控制社会经济地位和医疗合并症的情况下，黑人女性也有 剖宫产率、严重孕产妇发病率(SMM)和总体孕产妇死亡率(MM)较高。在……里面 事实上，黑人女性在怀孕期间和怀孕后的死亡率是白人女性的三倍。虽然是种族问题 围产期结局的差异是多因素的，越来越多的证据表明，环境 暴露--贫困、心理社会因素、母亲不良童年经历(ACE)和压力赋予 严重的健康风险。例如，较高的ACE分数与一系列负面的体检和 妊娠外的心理社会后果，如心血管疾病、糖尿病、 癌症和抑郁症。同样，更高的ACE分数和更大的压力也与 不良妊娠结局。尽管有这些发现，但早期生命的生物学基础 经历和母亲的压力可能会导致MM和SMM仍然是一个谜。我们的提案将提供一个 综合和创新的方法来了解生物学，特别是免疫学和社会文化 影响SMM的因素。据了解，导致SMM和MM的因素和原因是 多面性。然而，在非产科人群中的研究揭示了重要的发现。第一，扰动 免疫功能中的关键生物事件会导致糖尿病、高血压和其他疾病 不利的血管表型。第二，心理社会压力源，特别是早期生活压力源，有助于 不利的健康后果，并牵涉到观察到的种族差异。有很大的知识差距，如 心理社会应激源如何可能导致孕产妇发病率和孕产妇死亡率显著增加 黑人妇女的发病率和死亡率。我们假设心理社会应激源改变了功能性 孕妇的免疫状况导致多种生物学效应，使妇女易患SMM和 在我们最近资助的续订RO1中，我们招收了800名孕妇，即每年200名。包含 这项研究的标准包括将女性自我报告为黑人种族。我们已经获得了心理社会 衡量标准，如不良童年事件(ACE)、感知压力(PSS)和邻里剥夺。为 在这一补充期间，我们建议招收120名孕妇，而不是预期的200名家长 R01在第一年，参加一个子研究，以确定母亲的压力可能如何扰乱免疫功能。我们 将在20-26周之间评估功能免疫图谱，以反映大多数产妇发病之前的一段时间 事件。我们将比较得分高和低的黑人女性的免疫状况 心理社会指标是我们的主要结果。因为次要结果将是探索性的，并将调查 功能性免疫模式与母体发病率和重度母体发病率的关系 120个女人。对于SMM和MM，所有120名患者的医疗记录将被仔细评判。

Abstract: There are stark disparities in perinatal outcomes between Black and non-Black women in the United States. Even when controlling for socioeconomic status and medical comorbidities, Black women have a higher rate of cesarean delivery, severe maternal morbidity (SMM) and overall maternal mortality (MM). In fact, Black women die at three times the rate of white women during and following pregnancy. While racial disparities in perinatal outcomes are multifactorial, there is increasing evidence that environmental exposures—poverty, psychosocial factors, maternal adverse childhood experiences (ACE) and stress confer significant health risk. For example, higher ACE scores have been linked to a host of negative physical and psychosocial outcomes outside of pregnancy such as increased risk for cardiovascular disease, diabetes, cancers, and depression. Similarly, higher ACE scores and higher stress have also been associated with adverse pregnancy outcomes. Despite these findings, the biological underpinnings as to how early life experiences and maternal stress may lead to MM and SMM remain a mystery. Our proposal will provide an integrated and innovative approach to understand biological, specifically immunological, and sociocultural factors that contribute to SMM. It is understood that the factors and causes leading to SMM and MM are multifaceted. Yet, research in non-obstetrical populations have revealed important findings. First, perturbations in immune function are key biological events contributing to disease states such as diabetes, hypertension and adverse vascular phenotypes. Second, psychosocial stressors, specifically early life stressors, contribute to adverse health outcomes and are implicated in observed racial disparities. There are large knowledge gaps as to how psychosocial stressors may contribute to maternal morbidity and to the significant increases in maternal morbidity and mortality among black women. We hypothesize that psychosocial stressors alter the functional immune profile in pregnant women leading to diverse biological effects that predispose women to SMM and MM. In our recently funded renewal RO1, we are enrolling 800 pregnant women or 200 per year. Inclusion criteria for this study includes women to be self-reporting race as black. We are already obtaining psychosocial metrics, such as adverse childhood events (ACE), perceived stress (PSS) and neighborhood deprivation. For the period of this supplement, we propose to enroll 120 pregnant women, from the 200 expected in the parent R01 in year 1, to participate in a sub-study to determine how maternal stress may perturb immune function. We will assess functional immune profiles between 20-26 weeks to reflect a period prior to most maternal morbidity events. We will compare the immune profile between black women who have high and low scores on the psychosocial metrics as our primary outcome. As secondary outcome will be exploratory and will investigate the association of a functional immune profile with maternal morbidity and severe maternal morbidity in these 120 women. Medical records for all 120 patients will be carefully adjudicated for SMM and MM.