Antenatal Steroids and Cardiometabolic Risk

产前类固醇和心脏代谢风险

• 批准号: 8381685
• 负责人: JAMES C. ROSE
• 金额: $ 47.8万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8381685
• 关键词: 14 year old; 19 year old; Adolescent; 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.

建议所有预计分娩的孕妇进行产前皮质类固醇 (ANCS) 治疗 妊娠 24 至 34 周期间，美国有超过 100,000 名胎儿接触 ANCS 每年。 ANCS 显着降低新生儿死亡率和发病率，但与 青少年和年轻人血压升高、胰岛素抵抗和肾功能下降。 我们的数据表明，出生时体重极低（<1500g）并暴露于环境中的 14 岁儿童 ANCS 显示出生理差异，可能会使他们在以后的生活中容易出现血压升高。 具体来说，接触 ANCS 的青少年尿液中血管紧张素转换酶 2 的水平较低， 尿血管紧张素 II (Ang 11) 与血管紧张素 (1-7) 的比率较高，尿钠水平较低，尿钠水平较高 尿白蛋白水平。这些在人类身上的发现与我们同事的 ANCS 暴露的发现相对应 绵羊的肾单位数量和钠排泄减少，肾素-血管紧张素系统发生变化 (RAS) 有利于 Ang 11 张力增加、血压升高、胰岛素抵抗和瘦素增加。 暴露于 ANCS 的绵羊中央 RAS 也发生改变，这与心脏功能下降有关 心率变异性和压力反射敏感性，这些变化先于血压升高。在 此外，肥胖会加剧 ANCS 对绵羊的影响，这对我们的健康具有重要影响。 其中 > 34% 为体重的队列。 在当前的申请中，我们建议研究 19 岁的人类队列，以评估 ANCS 暴露与以下因素的关系： 1) 反映在心率变异性上的自主平衡 和压力感受反射敏感性，2) 肾钠处理，如应激诱导的压力钠排尿所示，3) 通过口服葡萄糖耐量测试评估胰岛素敏感性，4) 循环脂肪因子（瘦素、 脂联素和抵抗素），5）血压。 我们假设出生体重极低且接触过 ANCS 的年轻人将会患有 压力反射敏感性降低，钠排泄能力降低，胰岛素敏感性降低， 瘦素水平升高，血压升高，这些发现与 RAS 的改变促进 Ang II 张力增加。我们将收集已知可修改的数据 相关因素，例如体力活动、肥胖和饮食。我们的研究可能会发现人口在增加 心脏代谢疾病的风险，并提供监测和早期干预方法，这些方法将 改善暴露于 ANCS 的个体成熟后的健康状况。 相关性（参见说明）： 皮质类固醇通常用于有早产先兆的孕妇，以改善妊娠状况。 婴儿的生存。接触产前类固醇可能会产生长期不良后果。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 旨在预防和治疗出生个体高血压和代谢疾病的危险因素 出生体重极低并在产前接触类固醇。