Cardiovascular consequences of extreme prematurity

Despite the recent focus on the influence of early life events on future levels of blood pressure (BP) and cardiovascular (CV) risk, most studies have focused on low birth weight in predominantly term babies as a measure of intra-uterine growth restriction. Therefore, the influence of prematurity per se on CV function is still not well understood.
Alongside effects on later BP, extreme prematurity might also impact on the structure and function of the large elastic arteries. Elastin synthesis within the walls of the large arteries begins early in foetal development but is highest in the immediate perinatal period of a normal gestation. Thereafter, the rate of synthesis falls rapidly, and becomes slow or even quiescent during adulthood. It has been suggested that elastin synthesis might be impaired as a result of intra-uterine growth restriction. However, it is also plausible that birth at extremely low gestations and subsequent extrauterine development might affect elastin synthesis and development of the large arteries, potentially leading to permanent changes in their mechanical properties and, possibly, premature vascular ageing, with an increase in CV risk.
On this basis, data from the EPICure trial were used to examine whether the CV phenotype is associated with extreme prematurity. The EPICure trial involves a cohort of babies born at or less than 25 completed weeks who were assessed until the age of 11 years for neurocognitive, respiratory and other outcomes. For CV assessment, EPICure survivors (n=219) were compared with age and sex-matched classmates (n=153). A subset of the extremely preterm children (n=68) and classmates (n=90) underwent detailed haemodynamic investigations, including measurement of supine BP, aortic pulse wave velocity (a measure of aortic stiffness) and augmentation index (a measure of arterial pressure wave reflections).
Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P=0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P<0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P<0.001) and this persisted after the adjustment for confounding variables. However, aortic stiffness did not differ between groups (P=0.1).
This study shows that children born at or less than 25 completed weeks of gestation have increased arterial pressure wave reflections at 11 years of age compared with age and sex-matched classmates born at term. Differences in wave reflections strongly suggest the presence of abnormalities in the smaller, more muscular, preresistance and resistance vessels. In contrast, aortic stiffness was not different between those children born extremely preterm and those born at term. These data demonstrate that haemodynamic abnormalities are present in children born extremely preterm, which are not indicated by the examination of seated brachial BP alone. Therefore, children born at extremely low gestational ages may be at increased future CV risk as adults, although further follow-up investigations are required to confirm these findings.

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