Vascular Contributions to Cognitive Impairment after Adverse Pregnancy Outcomes: the nuMoM2b-Heart Health Study

血管对不良妊娠结果后认知障碍的影响：nuMoM2b-心脏健康研究

• 批准号: 10517965
• 负责人: Eliza C Miller
• 金额: $ 5.23万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2023-01-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10517965
• 关键词: Academic Medical Centers; Adverse event; Age; Aging; Ancillary Study; Back; Biological Markers; Brain imaging; Cardiac health; Cardiovascular system; Cerebral small vessel disease; Characteristics; Child; Cognition; Collection; Conceptions; Data; Dementia; Development; Discipline of obstetrics; Enrollment; Fetal Growth Retardation; Future; Goals; Hypertension; Impaired cognition; Intervention; Investments; Life; Mediating; Medical center; Monitor; Mothers; Neurocognitive; Nulliparity; Outcome Study; Participant; Persons; Phenotype; Placenta Diseases; Population; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Prevention strategy; Prospective cohort; Risk; Site; Universities; Vascular Cognitive Impairment; Virulence Factors; Visit; White Matter Hyperintensity; Woman; adverse pregnancy outcome; brain magnetic resonance imaging; cardiovascular risk factor; cerebrovascular; cohort; dementia risk; high risk; indexing; magnetic resonance imaging biomarker; predictive modeling; prospective; sex; vascular cognitive impairment and dementia; vascular risk factor

PROJECT SUMMARY/ABSTRACT Vascular contributions to cognitive impairment and dementia (VCID) are now recognized as a key pathogenic factor in dementia, and represent a promising target for intervention. Adverse pregnancy outcomes (APOs), such as preeclampsia, preterm delivery, and fetal growth restriction, are associated with future maternal cardiovascular and cerebrovascular risk. However, the impact of APOs on maternal VCID remains unexamined. Most existing women's cardiovascular and aging cohorts lack rigorously phenotyped, prospectively collected pregnancy data, and the impact of maternal factors that may predispose to both APOs and VCID is not well understood. From 2010-2013, the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) study enrolled a diverse cohort of 10,037 healthy women at 8 US academic medical centers, who were followed from early in conception through the delivery of their first child. Several years later, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study (nuMoM2b-HHS) brought back 4,475 nuMoM2b women for a second study wave, to characterize subsequent pregnancy outcomes and accumulation of cardiovascular risk factors following pregnancy. A third study wave of in-person visits will begin in early 2022. In this ancillary study, we propose to conduct neurocognitive assessments on all nuMoM2b-HHS participants during this third study wave. We will perform brain magnetic resonance imaging (MRI) on a sub-cohort of 250 women followed at the Columbia University Irving Medical Center study site, including all who experienced APOs in the index pregnancy. The overall goal of the study is to capitalize on this unique obstetric cohort to determine the impact of APOs on long term maternal VCID, through the following specific aims: (1) Investigate the impact of APOs on maternal cognition 10-15 years after delivery by comparing global cognition scores between women who experienced APOs and women who did not; (2) Determine the impact of APOs on MRI biomarkers of maternal VCID, including white matter hyperintensity volume and additional markers of cerebral small vessel disease. We hypothesize that the association of APOs with VCID markers will be partially mediated by development of new hypertension after the index pregnancy. As an exploratory aim, we will use deep pregnancy phenotyping, including maternal characteristics, biomarkers of ischemic placental disease and APOs, to create a VCID prediction model. This will be the first US study to use prospectively collected pregnancy data to investigate the impact of APOs, a sex-specific vascular risk factor, on VCID in women. Understanding the effects of APOs on early markers of VCID could help us identify women early in life who are at higher risk of dementia, and develop preventive strategies to thwart the progression of cognitive decline in this population. In addition, the collection of neurocognitive assessments on the entire nuMoM2b-HHS cohort during this study wave is an important investment, which will provide baseline data for future studies as these women continue to age.

项目摘要/摘要 血管对认知损害和痴呆的贡献(VCID)现在被认为是一种关键的致病因素 导致痴呆症的因素，是一个有希望的干预目标。不良妊娠结局(APO)， 如先兆子痫、早产和胎儿生长受限，与未来的母亲 心脑血管风险。然而，载脂蛋白对母体VCID的影响仍然存在 未经审查。大多数现有的女性心血管疾病和老年队列缺乏严格的表型， 前瞻性收集的妊娠数据，以及可能易患两种APO的母亲因素的影响 而VCID还没有被很好地理解。2010-2013年未经产妊娠结局监测研究 准妈妈(NuMoM2B)研究招募了10,037名健康女性的不同队列，这些女性来自美国8所大学医学院 中心，从受孕早期到第一个孩子的分娩都被跟踪。几年后， 未分娩妊娠结局研究：监测准妈妈心脏健康研究(nuMoM2B-HHS) 带回4475名nuMoM2B女性进行第二波研究，以确定后续怀孕的特征 妊娠后心血管危险因素的累积和结局。面对面学习的第三波浪潮 访问将于2022年初开始。在这项辅助研究中，我们建议对所有 NuMoM2B-HHS参与者在第三次研究浪潮中。我们将进行脑部磁共振成像 (核磁共振)对哥伦比亚大学欧文医学中心研究现场的250名女性进行了跟踪调查， 包括所有在指征妊娠中经历过APOS的患者。这项研究的总体目标是利用 这一独特的产科队列旨在通过以下途径确定APO对长期孕妇VCID的影响 具体目标如下：(1)通过以下方式调查APO对产后10-15年母亲认知的影响 比较经历过APOS的女性和没有经历过APOS的女性的全球认知得分； 确定载脂蛋白对母体VCID的MRI生物标志物的影响，包括白质高信号 脑部小血管病变的体积和附加标志物。我们假设APO的关联 VCID标志物将部分通过指标妊娠后新高血压的发生而起调节作用。 作为一个探索性的目标，我们将使用深度妊娠表型，包括母亲的特征，生物标志物 对缺血性胎盘疾病和APOS的预测，以创建VCID预测模型。这将是第一项美国研究 使用前瞻性收集的怀孕数据来调查APOS的影响，APOS是一种性别特有的血管风险 女性VCID的影响因素。了解载脂蛋白对VCID早期标志物的影响有助于我们识别 生命早期患痴呆症风险较高的妇女，并制定预防策略，以阻止 在这一人群中认知能力下降的进程。此外，关于神经认知评估的收集 在这一研究浪潮中，整个nuMoM2B-HHS队列是一项重要的投资，这将提供基线 随着这些女性继续变老，为未来的研究提供数据。