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

Abstract

: 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.

Primary and secondary paediatric hypertension

“…Individuals formerly born preterm may develop arterial -- particularly isolated systolic -- hypertension more often than their counterparts born at term. Many factors affect this tendency, such as an incomplete nephrogenesis, which implies the presence of kidneys with a reduced nephrons number and consequent decrease in haematic filtration, augmented sodium absorption and activation of the rennin–angiotensin–aldosterone system, increased arterial stiffness as a consequence of an elastin deficiency previously detected in anatomic specimens of human immature aorta, and reduced endothelial nitric oxide excretion, owing to raised hematic levels of ADMA, a strong direct inhibitor of nitric oxide, which exerts a strong vasoconstrictor action 42,43 …”

Preterm Birth, Kidney Function and Cardiovascular Disease in Children and Adolescents

“…Studies propose that the disruption of normal vasculogenesis in preterm children leads to structural and functional alterations of the vessels and impairment of endothelium-dependent vasodilatation, which lead to endothelial dysfunction and arterial HTN [ 55 ]. Furthermore, the oxidative stress and chronic inflammation of the tissues due to preterm birth and epigenetic mechanisms may be responsible for the increased risk of developing cardiovascular disease in later life [ 56 ]. The studies’ findings about the association of pulse wave velocity (PWV), as a marker of arterial stiffness, and preterm birth, are rather conflicting ( Table 2 ) [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Perspective Urinary Biomarkers According to Pathogenetic Mechanisms of Acute Kidney Injury in Preterm-Born Children

“…Згідно сучасних даних наукової літератури, існує прямий зв'язок між перенесеним епізодом ГПН і формуванням хронічної хвороби нирок (ХХН) та гіпертонічної хвороби [14] у шкільному та підлітковому віці, особливо у ПНД з низькою масою тіла при народженні (НМТ). Мета-аналіз 32 рукописів, [19], сепсис, вроджені вади серцево-судинної системи та ін.…”

“…Згідно сучасних даних наукової літератури, існує прямий зв'язок між перенесеним епізодом ГПН і формуванням хронічної хвороби нирок (ХХН) та гіпертонічної хвороби [14] у шкільному та підлітковому віці, особливо у ПНД з низькою масою тіла при народженні (НМТ). Мета-аналіз 32 рукописів, які включали 46 249 немовлят, показав, що НМТ асоційована зі значним ризиком подальшого розвитку ХХН [15][16][17], зокрема, на 81% вищий ризик розвитку альбумінурії та на 79 % вищий ризик зниження ШКФ ≤60 мл/хв/1,73 м², при порівнянні з новонародженими з нормальною масою тіла при народженні.…”