Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

Abstract

Preterm-born individuals have elevated blood pressure. We tested the hypothesis that this associates with an enhanced antiangiogenic circulating profile and that this association is mediated by variations in capillary density. We studied 204 adults aged 25 years (range, 20–30 years), of which 102 had been followed up prospectively since very preterm birth (mean gestational age, 30.3±2.5 weeks) and 102 were born term to uncomplicated pregnancies. A panel of circulating biomarkers, including soluble endoglin and soluble fms-like tyrosine kinase-1, were compared between groups and related to perinatal history and adult cardiovascular risk. Associations with cardiovascular phenotype were studied in 90 individuals who had undergone detailed assessment of microvascular, macrovascular, and cardiac structure and function. Preterm-born individuals had elevations in soluble endoglin (5.64±1.03 versus 4.06±0.85 ng/mL; P <0.001) and soluble fms-like tyrosine kinase-1 (88.1±19.0 versus 73.0±15.3 pg/mL; P <0.001) compared with term-born individuals, proportional to elevations in resting and ambulatory blood pressure, as well as degree of prematurity ( P <0.05). Maternal hypertensive pregnancy disorder was associated with additional increases in soluble fms-like tyrosine kinase-1 ( P =0.002). Other circulating biomarkers, including those of inflammation and endothelial activation, were not related to blood pressure. There was a specific graded association between soluble endoglin and degree of functional and structural capillary rarefaction ( P =0.002 and P <0.001), and in multivariable analysis, there were capillary density–mediated associations between soluble endoglin and blood pressure. Preterm-born individuals exhibit an enhanced antiangiogenic state in adult life that is specifically related to elevations in blood pressure. The association seems to be mediated through capillary rarefaction and is independent of other cardiovascular structural and functional differences in the offspring.

Preterm birth: risk factor for early-onset chronic diseases

“…13,14 Recent comprehensive vascular phenotyping in people born preterm showed structural macrovascular changes -particularly a narrowing of the aorta -and microvascular dysfunction evident by early adulthood. 15 These long-term changes may, in part, be driven by coassociated perinatal factors such as maternal hypertension and post-…”

Endothelial Colony‐Forming Cells in Young Adults Born Preterm: A Novel Link Between Neonatal Complications and Adult Risks for Cardiovascular Disease

“…These findings suggest that ECFC may play a role in the maintenance of microvasculature and potentially stimulate angiogenesis postnatally. Interestingly, microvasculature rarefaction, considered as an important element in the pathogenesis of increased peripheral resistance and hypertension, was previously reported in young adults born prematurely 3, 4. This phenomenon was more marked among those with higher blood pressure and an enhanced antiangiogenic state.…”

“…Mounting evidence supports the adverse effect of preterm birth, and more so very preterm birth (<32 weeks gestational age), on cardiovascular health 1, 2. Individuals born preterm display both structural and functional cardiovascular alterations, which include higher blood pressure,2 microvasculature rarefaction,3, 4 increased vascular resistance,5 as well as changes in heart shape and function,6, 7, 8 which are independent harbingers of hypertension and cardiovascular disease 9, 10. Given that rates of preterm birth have increased along with improved survival, it is expected that the absolute number of adults born preterm, and therefore at risk of developing cardiovascular disease, will escalate in the future.…”

What a general paediatrician needs to know about early life programming

“…Human infants born after IUGR have reduced numbers of nephrons,42 increasing the risk of hypertension in adulthood. Prematurity has also been associated with a reduction in capillary density, thought to be related to an increased risk of hypertension 43. In animal models, antenatal glucocorticoid exposure leads to reduced nephron number and changes in cardiac noradrenergic innervation24 together with a reduction in pancreatic β-cell growth, a risk factor for type 2 diabetes 44.…”