Antenatal Steroids and Cardiometabolic Risk

产前类固醇和心脏代谢风险

• 批准号: 8712519
• 负责人: JAMES C. ROSE
• 金额: $ 51.19万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-20 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8712519
• 关键词: 14 year old; 19 year old; Adolescent; Adolescent and Young Adult; Adrenal Cortex Hormones; Albumins; Angiotensin II; Angiotensins; Autonomic nervous system; Baroreflex; Blood Pressure; Cardiovascular system; Caring; Chronic Disease; Data; Diet; Disease; Equilibrium; Event; Excretory function; Exposure to; Fetus; Gestational Age; Glucose Intolerance; Goals; Growth; Health; Human; Hypertension; Individual; Infant; Instruction; Insulin Resistance; Intervention; Kidney; Leptin; Life; Long-Term Effects; Metabolic; Metabolic Diseases; Monitor; Natriuresis; Neonatal; Neonatal Mortality; Nephrons; OGTT; Obesity; Outcome; Peptidyl-Dipeptidase A; Physical activity; Physiological; Population; Pregnancy; Pregnant Women; Premature Birth; Prevention strategy; Principal Investigator; Renin-Angiotensin System; Rest; Risk; Risk Factors; Rosa; Sheep; Sodium; Steroids; Stress; Testing; United States; Very Low Birth Weight Infant; adipokines; adiponectin; body system; cohort; design; disorder risk; heart rate variability; improved; indexing; insight; insulin sensitivity; neonatal morbidity; peer; postnatal; prenatal; prenatal exposure; pressure; programs; resistin; response; treatment strategy; urinary; young adult

Antenatal corticosteroid (ANCS) treatment is recommended for all pregnant women expected to deliver between 24 and 34 weeks gestation, and over 100,000 fetuses are exposed to ANCS in the United States each year. ANCS significantly decreases neonatal mortality and morbidity, but has been associated with elevated blood pressure, insulin resistance, and reduced renal funcfion in adolescents and young adults. Our data indicate that 14 year olds who were born with very low birth weight (<1500g) and were exposed to ANCS show physiological differences that might predispose them to elevated blood pressure later in life. Specifically, the ANCS-exposed adolescents had lower levels of urinary Angiotensin Converting Enzyme 2, higher rafios of urinary Angiotensin II (Ang 11) to Angiotensin (1-7), lower urinary sodium levels, and higher urinary albumin levels. Thesefindingsin humans correspond to our colleagues'findingsthat ANCS-exposed sheep have reduced nephron number and sodium excretion, alterations in the renin-angiotensin system (RAS) favoring increased Ang 11 tone, increased blood pressure, insulin resistance, and increased leptin. ANCS-exposed sheep also have alterations in the central RAS that were associated with decreased heart rate variability and baroreflex sensitivity, and these alterations preceded the blood pressure elevation. In addifion, the effects of ANCS in sheep are exacerbated by obesity, which has important implications for our cohort in which > 34% are ovenweight. In the current application, we propose to study our human cohort at age 19 years, to assess the relationship of ANCS exposure to the following: 1) autonomic balance as reflected in heart rate variability and baroreflex sensitivity, 2) renal sodium handling, as indicated by stress-induced pressure natriuresis, 3) insulin sensitivity as assessed by oral glucose tolerance testing, 4) levels of circulating adipokines (leptin, adiponecfin, and resistin), and 5) blood pressure. We hypothesize that young adults who had very low birth weight and were exposed to ANCS will have decreased baroreflex sensitivity, decreased ability to excrete sodium, decreased insulin sensitivity, increased leptin levels, and increased blood pressure, and that these findings will be associated with alterations in the RAS that promote increased Ang II tone. We will collect data on known modifiable correlates, such as physical activity, adiposity, and diet. Our studies may identify a population at increased risk for cardiometabolic disease and inform approaches for monitoring and eariy intervention that will improve health outcomes of ANCS-exposed individuals as they mature. RELEVANCE (See instructions): Corticosteroids are commonly given to pregnant women with threatened preterm delivery to improve the survival of the infant. Exposure to antenatal steroids may have adverse long-term consequences. These studies will investigate the long-term effects of antenatal steroid exposure on cardiovascular and metabolic risk factors with a goal of prevenfing and treafing hypertension and metabolic disease in individuals born with very low birth weight and exposed prenatally to steroids.

建议所有预期提供的孕妇对产前皮质类固醇（ANC）治疗 在24至34周之间，在美国，超过100,000个胎儿暴露于ANC 每年。 ANC大大降低了新生儿死亡率和发病率，但与 青少年和年轻人的血压，胰岛素耐药性升高以及肾脏降低。 我们的数据表明，出生体重很低（<1500g）并暴露的14岁年轻人 ANC显示出生理差异，可能会使它们倾向于以后的血压升高。 具体而言，暴露于ANC的青少年的尿血管紧张素较低，转化酶2，， 尿血管紧张素II（ANG 11）的较高rafios（1-7），较低的尿钠水平和较高 尿白蛋白水平。这些人类中的依恋对应于我们的同事的aenc暴露 绵羊减少了肾单位数量和钠排泄，肾素 - 血管紧张素系统的改变 （RAS）有利于增加ANG 11音调，血压升高，胰岛素抵抗和瘦素增加。 暴露于ANC的绵羊也有与心脏减少有关的中央RAS的改变 速率变异性和压力反射灵敏度，这些变化在血压升高之前。在 添加的羊中ANC的影响会因肥胖而加剧，这对我们的肥胖具有重要意义 > 34％的烤箱。 在当前的应用中，我们建议在19岁时研究我们的人类队列，以评估 ANC接触以下的关系：1）心率变异性反映的自主平衡 2）压力诱导的压力纳特里雷SIS的肾脏敏感性，2）肾脏钠处理 通过口服葡萄糖耐量测试评估的胰岛素敏感性，4）循环脂肪因子水平（瘦素， 脂肪霉素和抵抗蛋白）和5）血压。 我们假设，出生体重很低并且暴露于ANC的年轻人将拥有 降低压力反射灵敏度，排泄钠的能力降低，胰岛素敏感性降低， 瘦素水平升高，血压升高，并且这些发现将与 RAS的变化促进了ANG II音调的增加。我们将收集有关已知可修改的数据 相关，例如体育锻炼，肥胖和饮食。我们的研究可能确定人口增加 心脏代谢疾病的风险，并告知监测和耳道干预的方法 改善ANC暴露个人成熟时的健康结果。 相关性（请参阅说明）： 皮质类固醇通常给予威胁性早产的孕妇以改善 婴儿的生存。暴露于产前类固醇可能会带来不利的长期后果。这些 研究将研究产前类固醇暴露对心血管和代谢的长期影响 危险因素具有预防和疾病的高血压和代谢性疾病的目标 出生体重非常低，并在产前暴露于类固醇。