Hyperglycemia and Adverse Pregnancy Outcome Study-Cardiovascular Health of HAPO Offspring (HAPO CVH)

高血糖与不良妊娠结局研究-HAPO后代的心血管健康（HAPO CVH）

• 批准号: 10586908
• 负责人: Wendy J Brickman
• 金额: $ 194.17万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586908
• 关键词: Acceleration; Adult Children; Age; Aging; American Heart Association; Arterial Injury; Behavior; Birth; Blood; Blood Cells; Blood Pressure; Body mass index; Cardiovascular Diseases; Carotid Arteries; Child; Childhood; Clinical; Cohort Studies; Country; DNA; DNA Methylation; Data; Development; Early identification; Environment; Epigenetic Process; Event; Fasting; Follow-Up Studies; Future; Gestational Diabetes; Health; Health Status; Hyperglycemia; Hypertension; Intergenerational transfer; International; Intervention; Intervention Studies; Investigation; Life; Life Cycle Stages; Life Style; Lipids; Measures; Mediating; Medical Records; Metabolic; Mothers; National Heart, Lung, and Blood Institute; OGTT; Obesity; Outcome; Outcome Study; Pathway interactions; Phenotype; Postpartum Period; Pregnancy; Pregnant Women; Prevention; Resolution; Risk; Role; Site; Standardization; Texture; Time; Ultrasonography; Umbilical Cord Blood; Visit; Woman; Work; adverse pregnancy outcome; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; cardiovascular health; carotid intima-media thickness; critical period; effectiveness evaluation; epigenome; follow-up; health assessment; high risk; in utero; insight; intergenerational; intimal medial thickening; intrauterine environment; maternal obesity; maternal outcome; mortality; neonatal outcome; newborn adiposity; novel; offspring; premature; primary outcome; prospective; recruit; ultrasound; young adult

Project Summary Halting the intergenerational transfer of cardiovascular disease (CVD) risk is a priority for NHLBI and the American Heart Association (AHA). Yet, limited understanding around the timing, pathways, and mechanisms underlying the observed associations between maternal gestational health and offspring cardiovascular health (CVH) remains a significant barrier to developing targeted, timely interventions. We propose to leverage the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort to substantially advance understanding of the in utero origins of offspring CVH and CVD, as measured during the critical period of young adulthood. The original HAPO study recruited ~25,500 women in 2000-2006 to prospectively and uniformly examine the association of gestational glycemia, uncomplicated by treatment, with maternal and neonatal outcomes. Eleven years later, 4,832 offspring returned to study effects of GDM on offspring adiposity and glycemia. We hypothesize that there are significant independent associations of maternal adiposity, glycemia, BP, and lipids at ~28 weeks gestation with CVH and arterial injury among offspring at age 18-25 years, and that DNA methylation (DNAm) will be associated with upstream intrauterine exposures and downstream CVH and arterial injury. HAPO CVH will include a comprehensive CVH assessment of 1,000 HAPO FUS offspring from 4 HAPO centers. We will measure BP, adiposity, lipids, glycemia, and lifestyle behaviors, characterize total CVH with AHA’s ‘Life’s Simple 7’ framework, and obtain carotid ultrasonography to identify the earliest changes of subclinical CVD. We will also analyze existing cord blood DNAm data and will acquire new epigenome-wide association data from young adult DNA using the Illumina 850K chip. We will achieve our objectives through the following specific aims: Specific Aim 1: Define associations of the in utero cardiometabolic milieu at ~28 weeks’ gestation with offspring CVH and subclinical CVD in young adulthood. Hypothesis 1a: Poorer maternal gestational metabolic health is associated with poorer offspring CVH (Co-primary outcome) in young adulthood. Hypothesis 1b: Poorer maternal gestational metabolic health is associated with higher carotid IMT (Co-primary outcome), lower carotid distensibility, and unfavorable carotid artery grayscale features in young adulthood. Hypothesis 1c: Poorer maternal gestational metabolic health is associated with worsening of cardiovascular health from childhood to young adulthood. Specific Aim 2: Examine the role of epigenetic mechanisms in the association of upstream intrauterine cardiometabolic exposures and downstream CVH and subclinical CVD. Hypothesis 2a: Poorer maternal gestational metabolic health is associated with differential DNAm in aging-related pathways (measured as accelerated epigenetic aging) in cord blood and young-adult offspring. Hypothesis 2b : Poorer maternal gestational metabolic health is associated with differential DNAm in specific cardiometabolic pathways in young- adult offspring blood cells, and this differential DNAm partly statistically mediates the association of adverse intrauterine exposures with later CVH status and carotid arterial injury in young adulthood

项目摘要 停止心血管疾病（CVD）风险的代际转移是NHLBI和NHLBI的优先事项。 美国心脏协会（AHA）。然而，对时间、途径和机制的了解有限， 母亲妊娠期健康和后代心血管健康之间的关系 (CVH)仍然是制定有针对性的及时干预措施的一个重大障碍。我们建议利用 高血压和不良妊娠结局（HAPO）研究队列，以大大提高认识 胎儿CVH和CVD的宫内起源，在成年早期的关键时期进行测量。的 最初的HAPO研究在2000年至2006年招募了约25，500名女性，前瞻性地统一检查 妊娠合并症，治疗无并发症，与母亲和新生儿结局的关系。十一 20年后，4，832名后代返回研究GDM对后代肥胖和肥胖的影响。我们假设 孕28周时，母体肥胖、BMI、BP和血脂之间存在显著的独立相关性， 18-25岁的子代中存在CVH和动脉损伤， 将与上游宫内暴露和下游CVH和动脉损伤相关。公司简介 将包括对来自4个HAPO中心的1,000名HAPO FUS后代进行全面的CVH评估。我们将 测量血压、肥胖、血脂、血压和生活方式行为，用AHA的“生活简单”来描述总CVH 7'框架，并获得颈动脉超声检查以识别亚临床心血管疾病的最早变化。我们还将 分析现有的脐带血DNAm数据，并将从年轻成人中获得新的表观基因组关联数据 使用Illumina 850 K芯片的DNA。我们将通过以下具体目标实现我们的目标：具体 目的1：确定妊娠~28周子宫内心脏代谢环境与子代CVH的关系 和亚临床心血管疾病。假设1a：产妇妊娠期代谢健康状况 与青年期较差的后代CVH（共同主要结局）相关。假设1b：可能性 母亲妊娠期代谢健康与颈动脉IMT（共同主要结局）较高、颈动脉IMT（共同主要结局）较低、 扩张性和不利的颈动脉灰度特征。假设1c：可能性 母亲妊娠期代谢健康与从儿童到成年的心血管健康恶化有关。 年轻的成年具体目标2：检查表观遗传机制在上游基因相关性中的作用。 宫内心脏代谢暴露和下游CVH和亚临床CVD。假设2a：可能性 母体妊娠期代谢健康与衰老相关途径中的差异DNAm相关（测量 加速表观遗传老化）。假设2b：产妇死亡率 妊娠期代谢健康与年轻人特定心脏代谢途径中的差异DNAm相关， 成年后代的血细胞，这种差异DNA m部分统计介导的关联不利 宫内暴露伴晚发CVH状态和青年期颈动脉损伤