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.

对于所有预计分娩的孕妇，建议进行产前皮质类固醇(ANCS)治疗 在美国，在怀孕24到34周之间，超过100,000个胎儿暴露在ANCs中 每年。ANCS显著降低新生儿死亡率和发病率，但与 青少年和年轻人的血压升高、胰岛素抵抗和肾功能下降。 我们的数据表明，出生时体重非常低(1500克)的14岁儿童暴露于 ANC表现出的生理差异可能使他们在以后的生活中容易患上高血压。 具体地说，接触ANCs的青少年尿血管紧张素转换酶2水平较低， 尿血管紧张素II(Ang 11)与血管紧张素(1-7)的比值较高，尿钠水平较低， 尿白蛋白水平。在人类中的这些发现与我们的同事发现的ANC接触到的是一致的 绵羊肾单位数量减少，钠排泄减少，肾素-血管紧张素系统发生变化 (RAS)倾向于血管紧张素11升高、血压升高、胰岛素抵抗和瘦素升高。 暴露于ANCS的绵羊中央RAS也发生了变化，这与心脏功能减退有关 心率变异性和压力反射敏感性，这些改变在血压升高之前。在……里面 此外，肥胖加剧了绵羊ANC的影响，这对我们的 其中34%的人体重超标。 在目前的应用中，我们建议研究我们19岁的人类队列，以评估 ANCs暴露与下列因素的关系：1)心率变异性所反映的自主神经平衡 压力感受性反射敏感性，2)肾钠处理，如应激性压力钠尿所示，3) 通过口服葡萄糖耐量试验评估胰岛素敏感性，4)循环脂肪因子(瘦素， 脂联素和抵抗素)，以及5)血压。 我们假设，出生体重非常低并暴露于ANC的年轻人将会有 压力反射敏感性降低，排钠能力降低，胰岛素敏感性降低， 瘦素水平升高和血压升高，这些发现将与 促进Ang II音调增加的RAS的变化。我们将收集已知可修改的数据 相关因素，如体力活动、肥胖和饮食。我们的研究可能会发现种群数量在增加 心脏代谢性疾病的风险，并告知监测和早期干预的方法 改善暴露于ANCs的人成熟后的健康状况。 相关性(请参阅说明)： 皮质类固醇通常用于有先兆早产的孕妇，以改善 婴儿的存活率。孕期接触类固醇可能会产生不良的长期后果。这些 研究将调查产前接触类固醇对心血管和代谢的长期影响 以预防和治疗高血压和代谢性疾病为目标的出生个体危险因素 出生体重很低，产前接触过类固醇。