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

• 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
• 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

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个出生中约有1个发生早产（胎龄<37个完成的几周），并且 由于治疗的进步，> 95％的早产儿存活到成年。最近的研究表明 母亲和早产的后代（PTB）都有代谢综合征的长期风险， 心血管疾病（CVD）的主要危险因素。交付早产的母亲也可能有更高的长期 术语CVD发病率；但是，据报道，PTB的成人后代中CVD的风险一直存在冲突。一个 最近的Trans-NIH工作组强调了对研究的紧迫需求：（1）分层CVD风险 通过PTB亚型（例如，自发性与由于母亲/胎儿条件的指示），以帮助阐明基础 机制和量身定制的长期患者护理； （2）允许更长的后续行动到后期或以后 疾病的风险仍然不足以理解； （3）包括大型样本量以允许长期检查 具有高统计能力的结果。我们假设：（1）PTB与较高的长期风险有关 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）在母亲和成人后代，随着早期妊娠的剂量反应关系增加 年龄; （2）所有主要类型的PTB都存在这些关联，但与胎盘有关 与氧化应激和炎症有关的功能不全（例如，先兆子痫或糖尿病） 导致结构微血管变化。为了解决这些假设，我们建议进行第一个 对PTB及其与CVD风险有关的PTB及其亚型的全面检查 后代。我们将组装和分析包含所有约230万分至120万的国家数据库 1973年至1995年，瑞典的母亲，以及2015年CVD的所有住院和门诊诊断。 具体目的是：（1）检查与CVD和CVD相关的长期风险有关的PTB及其亚型 母亲和成人后代的结局（高血压，糖尿病，睡眠呼吸暂停）； （2）确定是否有 社会人口统计学亚组对PTB对长期风险的影响更容易受到影响； （3）探索 未测量家族性（遗传和共享环境）因素对PTB-CVD的潜在混杂作用 使用共生分析的关联。拟议的研究很重要，因为PTB很常见，并且 空前的幸存者数量已达到成年（美国约400,000个）；这样甚至 长期的长期风险适度转化为人口巨大的健康负担。这是创新的，因为它 将对PTB及其子类型进行首次全面检查，并使用CVD风险，并使用 共生设计，以消除家族性混淆。这是高度成本效益的，因为我们将组装 这些数据来自国家注册管理局，这些数据在美国收集不可用或昂贵。结果 通过建立与PTB及其亚型相关的长期CVD风险来产生重大影响 母亲和成人后代，并为临床指南提供更好的风险评估和长期护理。