Preterm birth and long-term risk of cardiovascular disease in mothers and offspring

母亲和后代的早产和心血管疾病的长期风险

基本信息

批准号：
9592417
负责人：
Casey Crump
金额：
$ 68.22万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9592417
关键词：
Address Adult Adult Children African Age Aortic Diseases Birth Cardiovascular Diagnostic Techniques Cardiovascular Diseases Cerebrovascular Disorders Clinical Cohort Analysis Conflict (Psychology)Country Data Databases Diabetes Mellitus Dose Environmental Risk Factor Family Relationship Family history of Fetal Growth Retardation Genetic Gestational Age Guidelines Heart failure Hypertension Incidence Individual Inflammation Inpatients Intervention Link Long-Term Care Medical Metabolic syndrome Methodology Mothers Myocardial Ischemia Outcome Outpatients Oxidative Stress Patient Care Peripheral Vascular Diseases Placental Insufficiency Population Pre-Eclampsia Premature Birth Premature Infant Public Health Registries Relative Risks Reporting Research Risk Risk Assessment Sample Size Siblings Sleep Apnea Syndromes Smoking Socioeconomic Status Subgroup Survivors Sweden Time trend Translating United States National Institutes of Health Woman cardiovascular disorder risk cardiovascular risk factor cohort congenital heart disorder cost cost efficient design disorder risk disparity reduction fetal follow-up high risk innovation low socioeconomic status offspring population health response screening working group

项目摘要

Currently about 1 of every 10 births in the US occurs preterm (gestational age <37 completed weeks), and because of advances in treatment, >95% of preterm infants survive to adulthood. Recent research has shown that both the mothers and offspring of preterm birth (PTB) have higher long-term risks of metabolic syndrome, a major risk factor for cardiovascular disease (CVD). Mothers who deliver preterm may also have higher long- term CVD incidence; however, the reported risks of CVD in adult offspring of PTB have been conflicting. A recent Trans-NIH Working Group highlighted a pressing need for studies that: (1) stratify long-term CVD risks by PTB subtype (e.g., spontaneous vs. indicated due to maternal/fetal conditions) to help elucidate underlying mechanisms and tailor long-term patient care; (2) allow longer follow-up into mid-adulthood or later when disease risks remain poorly understood; and (3) include large sample sizes to allow examination of long-term outcomes with high statistical power. We hypothesize that: (1) PTB is associated with higher long-term risks of CVD (i.e., ischemic heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, aortic disease) among mothers and adult offspring, with increasing dose-response relationships by earlier gestational age; and (2) These associations exist for all major types of PTB, but are stronger for those related to placental insufficiency (e.g., preeclampsia or diabetes), which is associated with oxidative stress and inflammation, leading to structural microvascular changes. To address these hypotheses, we propose to conduct the first comprehensive examination of PTB and its subtypes in relation to CVD risks among mothers and their adult offspring. We will assemble and analyze national databases containing all ~2.3 million births to ~1.2 million mothers in Sweden during 1973-1995 and all inpatient and outpatient diagnoses of CVD through 2015. Our specific aims are to: (1) Examine PTB and its subtypes in relation to long-term risks of CVD and CVD-related outcomes (hypertension, diabetes, sleep apnea) in mothers and adult offspring; (2) determine if there are sociodemographic subgroups that are more susceptible to PTB effects on long-term risks; and (3) explore potential confounding effects of unmeasured familial (genetic and shared environmental) factors on PTB-CVD associations using co-relative analyses. The proposed research is significant because PTB is common and unprecedented numbers of survivors are now reaching adulthood (~400,000/year in the US); thus even modestly increased long-term risks translate into a large population health burden. It is innovative because it will provide the first comprehensive examination of PTB and its subtypes in relation to CVD risks, and use a co-relative design to disentangle familial confounding. It is highly cost-efficient because we will assemble these data from national registries that are unavailable or prohibitively costly to collect in the US. The results will have major impacts by establishing the long-term CVD risks associated with PTB and its subtypes among mothers and adult offspring, and informing clinical guidelines for better risk assessment and long-term care.

目前，美国每 10 名新生儿中就有 1 名发生早产（胎龄 < 37 周），并且由于治疗的进步，超过 95% 的早产儿能够存活到成年。最近的研究表明早产 (PTB) 的母亲和后代患代谢综合征的长期风险较高，心血管疾病（CVD）的主要危险因素。早产的母亲也可能有更高的长期妊娠率。术语CVD发生率；然而，关于 PTB 成年后代发生 CVD 风险的报道是相互矛盾的。一个最近的跨 NIH 工作组强调迫切需要进行以下研究：(1) 对长期 CVD 风险进行分层按 PTB 亚型（例如，自发性与由于母体/胎儿状况而指示的），以帮助阐明潜在的机制并定制长期患者护理； (2) 允许更长时间的随访至中年或更晚对疾病风险仍知之甚少； (3) 包括大样本量，以便检查长期情况具有高统计功效的结果。我们假设：（1）PTB 与较高的长期风险相关 CVD（即缺血性心脏病、脑血管疾病、心力衰竭、周围血管疾病、主动脉疾病疾病）在母亲和成年后代中，随着妊娠早期的剂量反应关系的增加年龄; (2) 所有主要类型的 PTB 都存在这些关联，但与胎盘相关的关联更强功能不全（例如先兆子痫或糖尿病），与氧化应激和炎症有关，导致微血管结构改变。为了解决这些假设，我们建议进行第一个全面检查 PTB 及其亚型与母亲及其成人 CVD 风险的关系后代。我们将收集和分析包含约 230 万至约 120 万出生人口的国家数据库 1973 年至 1995 年期间瑞典的母亲以及截至 2015 年所有住院和门诊诊断的 CVD。具体目标是： (1) 检查 PTB 及其亚型与 CVD 和 CVD 相关长期风险的关系母亲和成年后代的结局（高血压、糖尿病、睡眠呼吸暂停）； (2)判断是否有更容易受到 PTB 对长期风险影响的社会人口亚群体； (3)探索未测量的家族（遗传和共同环境）因素对 PTB-CVD 的潜在混杂影响使用相关分析进行关联。拟议的研究意义重大，因为 PTB 很常见并且现在，数量空前的幸存者已步入成年（美国每年约 400,000 人）；因此甚至长期风险的适度增加会转化为巨大的人口健康负担。它之所以具有创新性，是因为它将首次对 PTB 及其亚型与 CVD 风险的关系进行全面检查，并使用相互关联的设计可以消除家庭的混乱。这是非常具有成本效益的，因为我们将组装这些来自国家登记处的数据在美国无法获得或收集成本高昂。结果通过确定与 PTB 及其亚型相关的长期 CVD 风险，将产生重大影响母亲和成年后代，并为更好的风险评估和长期护理提供临床指南。