Prenatal Events-Postnatal Consequences

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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.