Placental contributions to disparities in offspring cardiovascular health across the life course

胎盘对后代整个生命过程心血管健康差异的贡献

基本信息

批准号：
10664146
负责人：
Alexa Ann Freedman
金额：
$ 13.06万
依托单位：
NORTHSHORE UNIVERSITY HEALTHSYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-15 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10664146
关键词：
Address Adolescence Adult Award Birth Black race Blood Pressure Blood Vessels Body mass index Cardiovascular Diseases Cardiovascular system Cause of Death Characteristics Child Childhood Chronic Disease Clinical Coronary heart disease Creativeness Data Data Collection Data Sources Development Disparity Disparity population Early Intervention Epidemiologist Evaluation Fetal Development Fetal Growth Functional disorder Funding Generations Goals Health Histologic Hypertension Image Analysis Infant Inflammatory Intervention Knowledge Left ventricular structure Lesion Life Cycle Stages Longitudinal Studies Longterm Follow-up Maternal-Fetal Exchange Measures Mediating Mediator Medical Waste Mentors Mentorship Monitor Morality Morbidity - disease rate Organ Outcome Parents Pathogenesis Perinatal Perinatal Epidemiology Pilot Projects Placenta Play Positioning Attribute Pregnancy Premature Birth Prevalence Process Reporting Research Risk Risk Factors Role Serum Siblings Small for Gestational Age Infant Stress Structure Techniques Thick Training Twin Multiple Birth United Kingdom United States Work adverse pregnancy outcome arterial stiffness cardiovascular disorder risk cardiovascular health career cohort design disease disparity disparity reduction experience follow-up health disparity improved in utero insight intergenerational metabolic profile mortality neonate novel offspring perinatal intervention perinatal period population based premature racial disparity risk stratification social disparities socioeconomic disadvantage socioeconomic disparity stillbirth transmission process young adult

项目摘要

PROJECT SUMMARY/ABSTRACT There are significant and persistent racial and socioeconomic disparities in cardiovascular disease (CVD) in the United States. Growing evidence indicates that the perinatal period is a critical window for intergenerational transmission of CVD disparities. Infants born preterm or small for gestational age are at greater risk of CVD morbidity and mortality in adulthood. Further, disparities in preterm birth and small for gestational age infant mirror those observed in CVD. As the organ at the maternal-fetal interface responsible for regulating fetal development, the placenta is the key to understanding intergenerational transmission of disparities. Consistent with this view, studies have reported that reduced placental size is associated with offspring CVD, though placental size is a crude measure of function. Techniques to improve assessment of placental function include histologic evaluation for vascular and inflammatory lesions and image analysis to evaluate vascular structure. Studies leveraging these robust placental measures have important scientific and clinical implications. Scientifically, they yield deeper mechanistic insights about the gestational origins of CVD risk, which can inform development of gestational interventions. Clinically, they have the potential to mitigate CVD disparities by improving risk stratification and informing treatment approaches. Accordingly, the goal of this proposal is to understand the placental mechanisms underlying racial and socioeconomic disparities in offspring cardiovascular health across the life course. Evaluating placental measures in relation to offspring cardiovascular health will be accomplished by initiating pediatric cardiovascular follow up in offspring from the Stress Pregnancy and Health study (SPAH; N=150). In addition, two complementary cohorts with routine placental data collection and longitudinal follow up will be leveraged: the Collaborative Perinatal Project (CPP; N=43,837) and the Avon Longitudinal Study of Parents and Children (ALSPAC; N=799). These cohorts will be used to address three aims. Aim 1: To determine whether placental dysfunction impacts CVD risk factor disparities in childhood by (a) evaluating placental lesions and vascular structure and (b) leveraging a sibling comparison design to control for parental and environmental confounding. Aim 2: To determine whether placental lesions are associated with disparities in cardiovascular structure, function, and CVD risk factors in adolescence and young adulthood. Aim 3: To determine whether placental lesions are associated with disparities in offspring premature CVD mortality in adulthood. As a perinatal epidemiologist, this award will help me extend my expertise to evaluating offspring cardiovascular outcomes. Through the process of conducting this research, I will obtain mentorship and training in leading longitudinal studies, comprehensive placental evaluation, and cardiovascular health across the life course. Collectively, this research and training will equip me with the expertise necessary to develop a unique research career investigating placental contributions to disparities in offspring cardiovascular health across the life course.

项目概要/摘要心血管疾病（CVD）方面存在显着且持续的种族和社会经济差异美国。越来越多的证据表明，围产期是代际交往的关键窗口期。 CVD 差异的传递。早产儿或小于胎龄的婴儿患心血管疾病的风险更大成年期的发病率和死亡率。此外，早产和小于胎龄儿的差异反映 CVD 中观察到的结果。作为母胎界面上负责调节胎儿的器官发育中，胎盘是理解代际传递差异的关键。持续的根据这一观点，研究报告称胎盘尺寸减小与后代 CVD 相关，但胎盘大小是功能的粗略衡量标准。改善胎盘功能评估的技术包括血管和炎症病变的组织学评估以及评估血管结构的图像分析。利用这些强有力的胎盘测量的研究具有重要的科学和临床意义。从科学上讲，它们对 CVD 风险的妊娠起源产生了更深入的机制见解，这可以为您提供信息妊娠干预措施的发展。临床上，它们有可能通过以下方式减少 CVD 差异：改善风险分层并告知治疗方法。因此，本提案的目标是了解后代种族和社会经济差异背后的胎盘机制整个生命过程中的心血管健康。评估与后代相关的胎盘措施心血管健康将通过对后代进行儿科心血管随访来实现压力怀孕与健康研究（SPAH；N=150）。此外，两个具有常规功能的互补队列将利用胎盘数据收集和纵向随访：围产期合作项目（CPP； N=43,837）和雅芳家长与儿童纵向研究（ALSPAC；N=799）。这些群体将是用于实现三个目标。目标 1：确定胎盘功能障碍是否影响 CVD 危险因素通过（a）评估胎盘病变和血管结构以及（b）利用兄弟姐妹来消除儿童时期的差异比较设计来控制父母和环境的混杂因素。目标 2：确定是否胎盘病变与心血管结构、功能和 CVD 危险因素的差异相关青春期和青年期。目标 3：确定胎盘病变是否与后代成年后过早心血管疾病死亡率的差异。作为围产期流行病学家，该奖项将有助于我将我的专业知识扩展到评估后代心血管结局。通过进行的过程这项研究，我将获得领导纵向研究、综合胎盘研究的指导和培训评估和整个生命过程中的心血管健康。总的来说，这项研究和培训将装备我拥有发展独特的研究生涯所需的专业知识，调查胎盘对后代心血管健康在整个生命过程中的差异。