Elevated Blood Pressure in Offspring Born Premature to Hypertensive Pregnancy

Abstract

Abstract-Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Key Words: blood pressure Ⅲ preeclampsia Ⅲ endothelial function Ⅲ fetal programming Ⅲ prematurity D e novo onset hypertension affects 5% to 7% of all pregnancies 1 and is manifest as a spectrum of hypertensive complications ranging from gestational hypertension to severe preeclampsia. 2 Hypertensive pregnancy has 3,4 emerged as an independent risk factor for premature maternal cardiovascular disease, 1,5,6 and recently offspring of hypertensive pregnancies have also been found to be at greater risk of higher blood pressure in childhood 7-11 and stroke in later life. 12 Furthermore, the risk to the offspring is graded and greatest in those whose mothers had more severe hypertensive signs, such as early onset hypertension or preeclampsia. 12 Severe hypertensive pregnancy is commonly associated with premature delivery and intrauterine growth restriction. 13 Prematurity and growth restriction, in turn, have been independently linked with hypertension and cardiovascular complications in the offspring, 14 -16 and it is postulated that this is mediated through intrauterine conditions adversely affecting the development of the offspring vascular system. 17 Interestingly, despite both prematurity and intrauterine growth restriction leading to the same clinical sequelae of hypertension, the persistent underlying vascular phenotype appears to vary with, for example, only the term intrauterine growthrestricted offspring exhibiting endothelial dysfunction. 15,18 -20 Better understanding of the long-term changes in vascular pathophysiology related to different pregnancy complications may allow novel primary cardiovascular prevention strategies targeted at key aspects of vascular function. 21

Arterial stiffness: using simple surrogate measures to make sense of a biologically complex phenomenon

“…This hypothesis is consistent with what is known about the biological process of arterial stiffening 8 and clinical research that highlights regional changes in arterial stiffness 9 and selective derangement in parameters of vascular function in younger cohorts. 9,10 Arterial stiffness reflects a multifactorial interplay of structural and cellular changes in the vessel wall, and is not uniform within the arterial tree.…”

“…9,10 Arterial stiffness reflects a multifactorial interplay of structural and cellular changes in the vessel wall, and is not uniform within the arterial tree. 5 The structural proteins elastin and collagen are the primary mediators of arterial wall compliance and stability.…”

Does hypertensive disorder of pregnancy predict offspring blood pressure at 21 years? Evidence from a birth cohort study

“…23 Another recent study with similar findings suggests that endothelial dysfunction in the offspring is either persistent after the preeclampsia in pregnancy or there is a heritable predisposition to endothelial dysfunction in both mother and child. 24 The elevated BP in the off- spring of preeclampsia pregnancies may also simply reflect a familial aggregation of this phenotype. 8 This strong familial aggregation of BP among the offspring of mothers with hypertension of pregnancy suggests that perhaps there are possibility of additional specific hereditary factors and intrauterine environmental effects.…”

Preterm Birth and Hypertension Risk

“…To date, studies have reported increased aortic stiffness in children as early as 7 to 14 years of age that were born moderately or very preterm. [29][30][31] In addition, adolescents and young adults born preterm were found to have smaller aortic, carotid, and brachial artery luminal diameters compared with controls born at term 18,32,33 ; aortic growth was shown to be impaired from the early neonatal period after preterm birth. 34 Furthermore, in a sheep model of moderate preterm birth, evidence of vascular injury to the ascending aorta was observed in animals examined at 11 weeks postnatal age.…”

“…35 Carotid intima-media thickness, an early marker of atherosclerosis and nonatherosclerotic remodeling, has also been shown to be increased in relation to lumen diameter. 31,33 The effect of preterm birth on microvascular development has also been highlighted by studies showing reduced retinal vascular caliber and density (independently of retinopathy of prematurity), as well as reduced cutaneous capillary density in children and young adults born very preterm. 19,36 To date, studies assessing endothelial function have shown either no effect 18,19,31 or diminished brachial artery flowmediated dilatation 37 in children and young adults born preterm; whether changes will be apparent later in adult life remain to be evaluated.…”