Risk of hypertension following perinatal adversity: IUGR and prematurity

Abstract

Consistent with the paradigm shifting observations of David Barker and colleagues that revealed a powerful relationship between decreased weight through 2 years of age and adult disease, intrauterine growth restriction (IUGR) and preterm birth are independent risk factors for the development of subsequent hypertension. Animal models have been indispensable in defining the mechanisms responsible for these associations and the potential targets for therapeutic intervention. Among the modifiable risk factors, micronutrient deficiency, physical immobility, exaggerated stress hormone exposure and deficient trophic hormone production are leading candidates for targeted therapies. With the strong inverse relationship seen between gestational age at delivery and the risk of hypertension in adulthood trumping all other major cardiovascular risk factors, improvements in neonatal care are required. Unfortunately, therapeutic breakthroughs have not kept pace with rapidly improving perinatal survival, and groundbreaking bench-to-bedside studies are urgently needed to mitigate and ultimately prevent the tsunami of prematurity-related adult cardiovascular disease that may be on the horizon. This review highlights our current understanding of the developmental origins of hypertension and draws attention to the importance of increasing the availability of lactation consultants, nutritionists, pharmacists and physical therapists as critical allies in the battle that IUGR or premature infants are waging not just for survival but also for their future cardiometabolic health.

Postnatal β2 adrenergic treatment improves insulin sensitivity in lambs with IUGR but not persistent defects in pancreatic islets or skeletal muscle

“…The direct adrenergic mechanism may be in response to ADRβ2 activation and ADRβ1 inhibition to lower cardiomyocyte apoptosis via phosphoinositide 3 kinase and AKT pathways (Communal et al 1999;Chesley et al 2000;Gu et al 2000;Zaugg et al 2000;Zhu et al 2001). In humans, IUGR is associated with greater risk for cardiovascular pathologies including hypertension, tachycardia and irregular cardiac growth (Brodszki et al 2005;Crispi et al 2010;Zanardo et al 2011;Spence et al 2012;Bjarnegard et al 2013;Gaillard et al 2013;Chatmethakul & Roghair, 2019). From this experiment, we show that heart rates were faster in IUGR lambs irrespective of the postnatal treatment and that the hearts from IUGR lambs were less responsive to the ADRβ1 agonist dobutamine.…”

“…Deficiencies in insulin secretion and insulin sensitivity manifest early in children that were born small-for-gestational-age (SGA) and eventually progress into more pronounced metabolic pathologies that characterize the metabolic syndrome (Barker et al 1993bHofman et al 1997;Li et al 2001;Bazaes et al 2004;McMillen et al 2006McMillen et al , 2008Eriksson, 2019). Recapitulating the causal link between fetal growth restriction and lifelong metabolic disorders in numerous experimental models across a variety of species has implicated adaptive developmental programming in response to placental insufficiency as the underlying mechanism (Simmons et al 2001;Ford et al 2007;Owens et al 2007b;Jimenez-Chillaron et al 2009;Gatford et al 2010;Wallace et al 2018;Chatmethakul & Roghair, 2019).…”

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

“…Preterm birth and intrauterine growth restriction represent risk factors not only for the survival of newborns, but also for their future cardiometabolic health. Unfortunately, new therapeutic discoveries have not been developed at the same speed as rapidly improving perinatal survival [ 66 ].…”

Correlation between extremes birth weight and current metabolic status in overweight pubertal patients / Correlação entre extremos de peso ao nascimento e avaliação metabólica atual em pacientes púberes com excesso de peso

“…So, the presence of an adverse intrauterine and/or neonatal environment significantly increases the risk of obesity, insulin resistance and leptin deficiency with major implications for metabolic regulation. Therefore, low birth weight itself should be considered a marker, rather than a cause of later diseases, with the varying etiologies of low birth weight encompassing relatively benign normal genetic variation and more life-threatening events including intrauterine growth restriction and preterm delivery (23) . In this group, adolescents with LBW did not present worsening of the metabolic profile than the other groups.…”