We hypothesize that exposure to antenatal glucocorticoids (ANCS) in very low birth weight (VLBW;1501g) infantsis associated with elevated blood pressure at 14 years of age. ANCS are frequently given to mothers who are expectedto deliver prematurely to improve survival of premature infants. However, ANCS have been associated with elevatedblood pressure at 14 years of age. Childhood blood pressure is correlated with blood pressure in adulthood, and thelatter influences the risk of cardiovascular morbidity. Among VLBW babies, both the survival rate and the rate ofexposure to ANCS are high; thus, the proposed research is pertinent to a significant public health concern.Supporting the proposed link between ANCS and elevated blood pressure in adulthood, animals studies indicate thatANCS alter the developing kidney and brain, possibly by decreasing the activity of the renin-angiotensin system(RAS). These alterations lead to lifelong changes in kidney structure and function and altered cardiovascular control,predisposing the adult to hypertension.The subjects for the proposed study are VLBW children who were singleton births, born 1992-1995, cared for in ourintensive care nurseries, and followed in our out-patient neonatal follow up clinic through one year adjusted age. Inthis sample the frequency of ANCS exposure is 47%. We propose measurements of the following: 1) resting bloodpressure, height, and weight, at 3 visits in the year after the child's fourteenth birthday, 2) ambulatory blood pressure, 3)blood pressure response to exercise and cold stress, 4) heart rate variability, 5) salivary cortisol, 6) level of fitness andphysical activity, 7) body composition using DXA scans, 8) microalbuminuria, 9) elements of the RAS in the urine andblood, and 10) estimated glomerular filtration rate. Data on perinatal exposures and growth through one year adjustedage will be obtained from medical records and a computerized database. Multivariate analyses will be used to estimatethe difference in blood pressure between children exposed to ANCS and those not exposed to ANCS, adjusting forpotential confounders and a number of known correlates of blood pressure.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD047584-04
Application #
7714585
Study Section
Special Emphasis Panel (ZHD1-DSR-A (JR))
Project Start
2008-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
4
Fiscal Year
2008
Total Cost
$253,632
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
South, Andrew M; Nixon, Patricia A; Chappell, Mark C et al. (2018) Obesity is Associated with Higher Blood Pressure and Higher Levels of Angiotensin II but Lower Angiotensin-(1-7) in Adolescents Born Preterm. J Pediatr :
South, Andrew M; Nixon, Patricia A; Chappell, Mark C et al. (2018) Association between preterm birth and the renin-angiotensin system in adolescence: influence of sex and obesity. J Hypertens 36:2092-2101
Chappell, Mark C; Al Zayadneh, Ebaa M (2017) Angiotensin-(1-7) and the Regulation of Anti-Fibrotic Signaling Pathways. J Cell Signal 2:
Washburn, Lisa K; Nixon, Patricia A; Snively, Beverly M et al. (2017) Antenatal corticosteroids and cardiometabolic outcomes in adolescents born with very low birth weight. Pediatr Res 82:697-703
Massmann, G Angela; Zhang, Jie; Seong, Won Joon et al. (2017) Sex-dependent effects of antenatal glucocorticoids on insulin sensitivity in adult sheep: role of the adipose tissue renin angiotensin system. Am J Physiol Regul Integr Comp Physiol 312:R1029-R1038
Sigmund, Curt D; Diz, Debra I; Chappell, Mark C (2017) No Brain Renin-Angiotensin System: Déjà vu All Over Again? Hypertension 69:1007-1010
South, Andrew M; Nixon, Patricia A; Chappell, Mark C et al. (2017) Antenatal corticosteroids and the renin-angiotensin-aldosterone system in adolescents born preterm. Pediatr Res 81:88-93
Su, Yixin; Bi, Jianli; Pulgar, Victor M et al. (2017) Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells. Am J Physiol Renal Physiol 312:F1056-F1062
Wilson, Bryan A; Chappell, Mark C (2017) Assessment of the Renin-Angiotensin System in Cellular Organelle: New Arenas for Study in the Mitochondria. Methods Mol Biol 1614:99-121
Nixon, Patricia A; Washburn, Lisa K; Michael O'Shea, Thomas et al. (2017) Antenatal steroid exposure and heart rate variability in adolescents born with very low birth weight. Pediatr Res 81:57-62

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