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.

建议所有预期分娩的孕妇使用皮质类固醇（ANCS）治疗 在妊娠24至34周之间，在美国有超过100，000名胎儿暴露于ANCS 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，14岁出生时体重很低（<1500 g）的儿童， ANCS显示出生理差异，可能使他们在以后的生活中易患高血压。 具体来说，接触过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， 尿白蛋白水平这些在人类中的发现与我们同事的发现一致， 绵羊肾单位数量减少，钠排泄减少， (RAS)有利于增加血管紧张素11紧张度、增加血压、胰岛素抵抗和增加瘦素。 暴露于ANCS的绵羊也有中央RAS的改变，这与心脏功能下降有关。 心率变异性和压力反射敏感性，这些改变先于血压升高。在 此外，ANCS在绵羊中的作用因肥胖而加剧，这对我们的研究具有重要意义。 其中> 34%是烘箱重量的队列。 在本申请中，我们提出研究我们的19岁的人类队列，以评估 ANCS暴露与以下因素的关系：1）心率变异性反映的自主平衡 和压力反射敏感性，2）肾钠处理，如应激诱导的压力钠尿，3） 通过口服葡萄糖耐量试验评估的胰岛素敏感性，4）循环脂肪因子（瘦素， adiponecfin和adiponecfin），和5）血压。 我们假设出生体重很低并暴露于ANCS的年轻人将有 降低的压力反射敏感性，降低的钠排泄能力，降低的胰岛素敏感性， 瘦素水平升高，血压升高，这些发现将与 RAS的改变促进Ang II张力的增加。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， 心脏代谢疾病的风险，并提供监测和早期干预的方法， 随着年龄的增长，ANCS暴露个体的健康结果得到改善。 相关性（参见说明）： 糖皮质激素通常用于先兆早产的孕妇，以改善 婴儿的生存。产前接触类固醇可能会产生不良的长期后果。这些 研究将调查产前类固醇暴露对心血管和代谢的长期影响， 风险因素，目的是预防和治疗高血压和代谢性疾病， 出生体重极低，产前接触过类固醇。