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Current Hypertension Reviews


ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

Systematic Review Article

Factors Predisposing to Hypertension in Subjects Formerly Born Preterm: Renal Impairment, Arterial Stiffness, Endothelial Dysfunction or Something Else?

Author(s): Antonio Crisafulli , Pier P. Bassareo *, Sean Kelleher , Giuseppe Calcaterra and Giuseppe Mercuro

Volume 16 , Issue 2 , 2020

Page: [82 - 90] Pages: 9

DOI: 10.2174/1573402115666190627140523


Subjects formerly born preterm subsequently develop arterial - particularly isolated systolic- hypertension more frequently than their peers born at term.

Numerous factors may influence this predisposition, including an incomplete nephrogenesis, implying the presence of kidneys with a reduced number of nephrons and consequent reduction in haematic filtration, increased sodium absorption and activation of renin-angiotensin-aldosterone system, increased arterial rigidity produced by an elastin deficiency previously observed in anatomic specimens of human immature aorta, and reduced endothelial nitric oxide excretion, due to high blood levels of ADMA, a strong direct inhibitor of nitric oxide that exerts a vasoconstrictor effect.

Other possible factors (i.e. excretion of neuroendocrine compounds) may also be implicated. The aim of this paper was to review all possible mechanisms involved in the observed increase in blood pressure in individuals who had been born preterm and/or with intrauterine growth restriction. The outlook for new and promising laboratory techniques capable of identifying alterations in the metabolic pathways regulating blood pressure levels, such as metabolomics, is also provided.

Keywords: Prematurity, preterm birth, low birth weight, blood pressure, hypertension, perinatal programming.

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Luyckx VA. Preterm birth and its impact on renal health. Semin Nephrol 2017; 37(4): 311-9.
[ ] [PMID: 28711069]
Bassareo PP, Fanos V, Mercuro G. Response to ‘In adolescence, extreme prematurity is associated with significant changes in the microvasculature, elevated blood pressure and increased carotid intima-media thickness’. Arch Dis Child 2015; 100(5): 508-9.
[ ] [PMID: 25653223]
de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort MB. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension 2012; 59(2): 226-34.
[ ] [PMID: 22158643]
Mercuro G, Bassareo PP, Flore G, et al. Prematurity and low weight at birth as new conditions predisposing to an increased cardiovascular risk. Eur J Prev Cardiol 2013; 20(2): 357-67.
[ ] [PMID: 22345683]
Sipola-Leppänen M, Karvonen R, Tikanmäki M, et al. Ambulatory blood pressure and its variability in adults born preterm. Hypertension 2015; 65(3): 615-21.
[ ] [PMID: 25601930]
Steen E, Bonamy AK, Norman M, Hellström-Westas L. Preterm birth may be a larger risk factor for increased blood pressure than intrauterine growth restriction. Acta Paediatr 2015; 104(11): 1098-103.
[ ] [PMID: 26094552]
Juonala M, Cheung MM, Sabin MA, et al. Effect of birth weight on life-course blood pressure levels among children born premature: The cardiovascular risk in young finns study. J Hypertens 2015; 33(8): 1542-8.
[ ] [PMID: 26136063]
Richir MC, van Leeuwen PA, van den Berg A, et al. Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: A prospective pilot study. Pediatr Pulmonol 2008; 43(12): 1161-6.
[ ] [PMID: 18991340]
Hinchliffe SA, Lynch MR, Sargent PH, Howard CV, Van Velzen D. The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol 1992; 99(4): 296-301.
[ ] [PMID: 1581274]
Koeda Y, Nakamura M, Tanaka F, et al. Serum C-reactive protein levels and death and cardiovascular events in mild to moderate chronic kidney disease. Int Heart J 2011; 52(3): 180-4.
[ ] [PMID: 21646742]
Böger RH, Zoccali C. ADMA: A novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atheroscler Suppl 2003; 4(4): 23-8.
[ ] [PMID: 14664899]
Rinat C, Becker-Cohen R, Nir A, et al. A comprehensive study of cardiovascular risk factors, cardiac function and vascular disease in children with chronic renal failure. Nephrol Dial Transplant 2010; 25(3): 785-93.
[ ] [PMID: 19934091]
Ritz E. Hypertension: The kidney is the culprit even in the absence of kidney disease. Kidney Int 2007; 71(5): 371-2.
[ ] [PMID: 17315002]
Tulassay T, Vásárhelyi B. Birth weight and renal function. Curr Opin Nephrol Hypertens 2002; 11(3): 347-52.
[ ] [PMID: 11981267]
Kusano E. Mechanism by which chronic kidney disease causes cardiovascular disease and the measures to manage this phenomenon. Clin Exp Nephrol 2011; 15(5): 627-33.
[ ] [PMID: 21629994]
Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ. Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001; 322(7292): 949-53.
[ ] [PMID: 11312225]
South AM, Nixon PA, Chappell MC, et al. Renal function and blood pressure are altered in adolescents born preterm. Pediatr Nephrol 2019; 34(1): 137-44.
[ ] [PMID: 30112655]
Tauzin L. Alterations in viscoelastic properties following premature birth may lead to hypertension and cardiovascular disease development in later life. Acta Paediatr 2015; 104(1): 19-26.
[ ] [PMID: 25263973]
Rossi P, Tauzin L, Marchand E, Boussuges A, Gaudart J, Frances Y. Respective roles of preterm birth and fetal growth restriction in blood pressure and arterial stiffness in adolescence. J Adolesc Health 2011; 48(5): 520-2.
[ ] [PMID: 21501813]
Berry CL. The growth and development of large arteries. Exp Embryol Teratol 1974; 1(0): 34-64.
[PMID: 4464052]
Leung DY, Glagov S, Mathews MB. Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension. Circ Res 1977; 41(3): 316-23.
[ ] [PMID: 890887]
Bendeck MP, Keeley FW, Langille BL. Perinatal accumulation of arterial wall constituents: Relation to hemodynamic changes at birth. Am J Physiol 1994; 267(6 Pt 2): H2268-79.
[PMID: 7810727]
Resnick N, Gimbrone MA Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J 1995; 9(10): 874-82.
[ ] [PMID: 7615157]
Jensen DE, Rich CB, Terpstra AJ, Farmer SR, Foster JA. Transcriptional regulation of the elastin gene by insulin-like growth factor-I involves disruption of Sp1 binding. Evidence for the role of Rb in mediating Sp1 binding in aortic smooth muscle cells. J Biol Chem 1995; 270(12): 6555-63.
[ ] [PMID: 7896792]
Berry CL, Looker T, Germain J. Nucleic acid and scleroprotein content of the developing human aorta. J Pathol 1972; 108(4): 265-74.
[ ] [PMID: 4676620]
Berry CL, Looker T. An alteration in the chemical structure of the aortic wall induced by a finite period of growth inhibition. J Anat 1973; 114(Pt 1): 83-94.
[PMID: 4541392]
Martyn CN, Greenwald SE. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet 1997; 350(9082): 953-5.
[ ] [PMID: 9314885]
Chemla D, Hébert JL, Coirault C, et al. Total arterial compliance estimated by stroke volume-to-aortic pulse pressure ratio in humans. Am J Physiol 1998; 274(2): H500-5.
[PMID: 9486253]
Tauzin L, Rossi P, Giusano B, et al. Characteristics of arterial stiffness in very low birth weight premature infants. Pediatr Res 2006; 60(5): 592-6.
[ ] [PMID: 16988197]
Bonamy AK, Bendito A, Martin H, Andolf E, Sedin G, Norman M. Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res 2005; 58(5): 845-9.
[ ] [PMID: 16183828]
Roberts G, Lee KJ, Cheong JL, Doyle LW. Victorian Infant Collaborative Study Group. Higher ambulatory blood pressure at 18 years in adolescents born less than 28 weeks’ gestation in the 1990s compared with term controls. J Hypertens 2014; 32(3): 620-6.
[ ] [PMID: 24345783]
Tauzin L, Rossi P, Grosse C, et al. Increased systemic blood pressure and arterial stiffness in young adults born prematurely. J Dev Orig Health Dis 2014; 5(6): 448-52.
[ ] [PMID: 25154472]
Oren A, Vos LE, Bos WJ, et al. Gestational age and birth weight in relation to aortic stiffness in healthy young adults: Two separate mechanisms? Am J Hypertens 2003; 16(1): 76-9.
[ ] [PMID: 12517688]
Bassareo PP, Saba L, Puddu M, Fanos V, Mercuro G. Impaired central arterial elasticity in young adults born with intrauterine growth restriction. Int Angiol 2017; 36(4): 362-7.
[PMID: 25027598]
Tauzin L. Reply to letter by Bassareo regarding the article of Tauzin et al. ‘Increased systemic blood pressure and arterial stiffness in young adults born prematurely’. J Dev Orig Health Dis 2015; 6(2): 126.
[ ] [PMID: 26038782]
Franco MC, Christofalo DM, Sawaya AL, Ajzen SA, Sesso R. Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels. Hypertension 2006; 48(1): 45-50.
[ ] [PMID: 16682609]
Payne JA, Alexander BT, Khalil RA. Reduced endothelial vascular relaxation in growth-restricted offspring of pregnant rats with reduced uterine perfusion. Hypertension 2003; 42(4): 768-74.
[ ] [PMID: 12874089]
Bassareo PP, Fanos V, Puddu M, et al. Reduced brachial flow-mediated vasodilation in young adult ex extremely low birth weight preterm: A condition predictive of increased cardiovascular risk? J Matern Fetal Neonatal Med 2010; 23(Suppl. 3): 121-4.
[ ] [PMID: 20925458]
Koenigsberger M, Sauser R, Bény JL, Meister JJ. Role of the endothelium on arterial vasomotion. Biophys J 2005; 88(6): 3845-54.
[ ] [PMID: 15792979]
Bassareo PP, Puddu M, Flore G, et al. Could ADMA levels in young adults born preterm predict an early endothelial dysfunction? Int J Cardiol 2012; 159(3): 217-9.
[ ] [PMID: 21420186]
Sonmez A, Celebi G, Erdem G, et al. Plasma apelin and ADMA Levels in patients with essential hypertension. Clin Exp Hypertens 2010; 32(3): 179-83.
[ ] [PMID: 20504125]
Curgunlu A, Uzun H, Bavunoğlu I, Karter Y, Genç H, Vehid S. Increased circulating concentrations of asymmetric dimethylarginine (ADMA) in white coat hypertension. J Hum Hypertens 2005; 19(8): 629-33.
[ ] [PMID: 15829997]
Bassareo PP, Fanos V, Puddu M, Flore G, Mercuro G. Advanced intrauterine growth restriction is associated with reduced excretion of asymmetric dimethylarginine. Early Hum Dev 2014; 90(4): 173-6.
[ ] [PMID: 24503253]
Bertagnolli M, Xie LF, Paquette K, et al. Endothelial colony- forming cells in young adults born preterm: A novel link between neonatal complications and adult risks for cardiovascular disease. J Am Heart Assoc 2018; 7(14) e009720
[ ] [PMID: 29987124]
Bassareo PP, Fanos V, Noto A, et al. Clinical metabolomics and hematic ADMA predict the future onset of cardiorenal syndrome in young grown-up subjects who were born preterm. Clin Biochem 2014; 47(6): 423-6.
[ ] [PMID: 24316102]
Bassareo PP, Fanos V, Mussap M, et al. Urinary NGAL and hematic ADMA levels: An early sign of cardio-renal syndrome in young adults born preterm? J Matern Fetal Neonatal Med 2013; 26(Suppl. 2): 80-3.
[ ] [PMID: 24059560]
Nuyt AM, Alexander BT. Developmental programming and hypertension. Curr Opin Nephrol Hypertens 2009; 18(2): 144-52.
[ ] [PMID: 19434052]
Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA. Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res 2007; 61(5 Pt 2): 5R-10R.
[ ] [PMID: 17413851]
Johansson S, Norman M, Legnevall L, Dalmaz Y, Lagercrantz H, Vanpée M. Increased catecholamines and heart rate in children with low birth weight: Perinatal contributions to sympathoadrenal overactivity. J Intern Med 2007; 261(5): 480-7.
[ ] [PMID: 17444887]
Cohen G, Vella S, Jeffery H, Lagercrantz H, Katz-Salamon M. Cardiovascular stress hyperreactivity in babies of smokers and in babies born preterm. Circulation 2008; 118(18): 1848-53.
[ ] [PMID: 18852367]
Drake AJ, Tang JI, Nyirenda MJ. Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease. Clin Sci (Lond) 2007; 113(5): 219-32.
[ ] [PMID: 17663659]
Hellström A, Hård AL, Niklasson A, Svensson E, Jacobsson B. Abnormal retinal vascularisation in preterm children as a general vascular phenomenon. Lancet 1998; 352(9143): 1827.
[ ] [PMID: 9851388]
Lewandowski AJ, Davis EF, Yu G, et al. Elevated blood pressure in preterm-born offspring associates with a distinct antiangiogenic state and microvascular abnormalities in adult life. Hypertension 2015; 65(3): 607-14.
[ ] [PMID: 25534704]
Parkinson JR, Hyde MJ, Gale C, Santhakumaran S, Modi N. Preterm birth and the metabolic syndrome in adult life: A systematic review and meta-analysis. Pediatrics 2013; 131(4): e1240-63.
[ ] [PMID: 23509172]
Hovi P, Vohr B, Ment LR, et al. APIC Adults born preterm international collaboration. blood pressure in young adults born at very low birth weight: Adults born preterm international collaboration. Hypertension 2016; 68(4): 880-7.
[ ] [PMID: 27572149]
Bassareo PP, Abella R, Fanos V, Mercuro G. Biomarkers of corticosteroid-induced hypertrophic cardiomyopathy in preterm babies. Front Biosci (Elite Ed) 2010; 2: 1460-71.
[ ] [PMID: 20515817]
Raaijmakers A, Petit T, Gu Y, et al. Design and feasibility of “PREMATurity as predictor of children’s Cardiovascular-renal Health” (PREMATCH): A pilot study. Blood Press 2015; 24(5): 275-83.
[ ] [PMID: 26107770]
Falkner B. Maternal and gestational influences on childhood blood pressure. Pediatr Nephrol 2020; 35: 1409-8.
[ ] [PMID: 30790042]
Kumar RK, Singhal A, Vaidya U, Banerjee S, Anwar F, Rao S. Optimizing nutrition in preterm low birth weight infants-consensus summary. Front Nutr 2017; 4: 20.
[ ] [PMID: 28603716]
Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: Two cohorts after randomised trials. Lancet 2001; 357(9254): 413-9.
[ ] [PMID: 11273059]
Singhal A, Cole TJ, Fewtrell M, Deanfield J, Lucas A. Is slower early growth beneficial for long-term cardiovascular health? Circulation 2004; 109(9): 1108-13.
[ ] [PMID: 14993136]
Bassareo PP, Mercuro G. Stem cells and heart: An open future or a mirage? J Pediatr Neonat Individual Med 2016; 5(1) e050102
Bertagnolli M, Nuyt AM, Thébaud B, Luu TMM. Endothelial progenitor cells as prognostic markers of preterm birth-associated complications. Stem Cells Transl Med 2017; 6(1): 7-13.
[ ] [PMID: 28170188]
Pintus R, Bassareo PP, Dessì A, Deidda M, Mercuro G, Fanos V. Metabolomics and cardiology: Toward the path of perinatal programming and personalized medicine. BioMed Res Int 2017; 2017 6970631
[ ] [PMID: 28758121]
Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989; 298(6673): 564-7.
[ ] [PMID: 2495113]
Chatmethakul T, Roghair RD. Risk of hypertension following perinatal adversity: IUGR and prematurity. J Endocrinol 2019; 242(1): T21-32.

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