Prenatal Events-Postnatal Consequences

描述（由申请人提供）：本申请是作为我们的NICHD资助的计划项目资助（PPG）的竞争补充提交的，“产前事件-产后后果”，调查产前类固醇暴露对血压和血压调节相关系统的影响。拟议的补充项目将与项目4（临床项目）一起实施，该项目正在研究一个由200名早产极低出生体重（VLBW）青少年组成的队列，产前接触率为50%。虽然一些研究表明，低出生体重和早产与高血压风险增加之间存在显著相关性，但尚未充分研究可能的潜在机制。作为PPG资助的一部分，我们正在检查这些早产VLBW青少年中可能存在的产前类固醇暴露导致的肾素-血管紧张素系统（RAS）、交感肾上腺系统和HPA轴的改变。然而，这些机制中的许多尚未在足月出生的儿童中进行研究，因此无法确定早产的影响。因此，本补充申请的主要目的是招募和研究一组正常出生体重（NBW）的足月出生青少年，与我们的早产VLBW青少年队列进行比较，以确定早产可能对涉及血压调节的系统的发育和表达的影响，与产前类固醇暴露无关。其意义在于，自1990年以来早产增加了20%（自2000年以来增加了9%），成年后患高血压以及心血管和代谢疾病的风险增加。此外，有证据表明，青少年一般人群的血压水平不断上升，其中一些可能反映了肥胖和久坐不动的生活方式的增加趋势。所获得的数据将提高我们对早产后果的理解，并深入了解早产和足月出生青少年血压调节的潜在机制。这些知识最终将为确定早期干预策略提供基础，以预防高血压及其相关的心血管和肾脏后遗症的发展。相关性（参见说明）：所获得的数据将提高我们对早产后果的理解，并深入了解早产和足月出生青少年血压调节的潜在机制。这些知识最终将为确定早期干预策略提供基础，以预防高血压及其相关的心血管和肾脏后遗症的发展。

DESCRIPTION (provided by applicant): This application is being submitted as a competing supplement to our NICHD-funded Program Project Grant (PPG), "Prenatal Events-Postnatal Consequences," investigating the effects of antenatal steroid exposure on blood pressure and systems associated with blood pressure regulation. The proposed supplemental project will be carried out in conjunction with Project 4, the clinical project, which is studying a cohort of 200 adolescents born prematurely with very low birth weight (VLBW) with a 50% antenatal exposure rate. While a number of studies demonstrate significant associations between low birth weight and prematurity with increased risk for developing hypertension, the possible underlying mechanisms have not been fully examined. As part of the funded PPG, we are examining alterations in the renin-angiotensin system (RAS), the sympathoadrenal system and HPA axis which may exist as a consequence of antenatal steroid exposure in these prematurely-born VLBW adolescents. However, many of these mechanisms have not been studied in children born full-term, and thus the impact of prematurity can not be determined. Consequently, the primary aim of this supplemental application is to recruit and study a group of adolescents born full-term with normal birth weight (NBW) to compare with our cohort of preterm VLBW adolescents to determine the effects that prematurity may have on the development and expression of systems involved with blood pressure regulation, independent of antenatal steroid exposure. The significance lies in the 20% increase in preterm birth since 1990 (9% since 2000) and the greater risk of developing hypertension, as well as cardiovascular and metabolic diseases, in adulthood in this population. Furthermore, there is evidence of increasing blood pressure levels in the general population of adolescents some of which may reflect increasing trends in obesity and sedentary lifestyles. The data obtained will improve our understanding of the consequences of premature birth, and provide insight into the underlying mechanisms of blood pressure regulation in both premature and term-born adolescents. This knowledge will ultimately provide the basis for identifying early intervention strategies to prevent the development of hypertension and its associated cardiovascular and renal sequelae. RELEVANCE (See instructions): The data obtained will improve our understanding of the consequences of premature birth, and provide insight into the underlying mechanisms of blood pressure regulation in both premature and term-born adolescents. This knowledge will ultimately provide the basis for identifying early intervention strategies to prevent the development of hypertension and its associated cardiovascular and renal sequelae.