Background: Preterm birth (< 37 weeks of gestation) occurs in approximately 10% of births worldwide; the majority of preterm births are moderately preterm (between 32 and 36 weeks gestation). We hypothesized that when birth occurs before term the major conduit arteries would be structurally and functionally immature and thus ill-prepared for the hemodynamic transition that necessarily occurs at birth. Utilising a preclinical sheep model, our aims were to compare the structure and function of the thoracic aorta and common carotid arteries of moderately preterm (0.9 of gestation) and term-born lambs in the immediate period after birth, and to determine whether there was upregulation of vascular injury-associated genes following moderate preterm birth. Methods: Time-mated ewes were induced to vaginally deliver lambs either preterm (132 ± 1 days of gestation; n=11 females and n=10 males) or at term (147 ± 1 days of gestation; n=10 females and n=5 males). At 2 days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries and right and left common carotid arteries was conducted in anaesthetised lambs. The lambs were then euthanized and segments of the thoracic aorta and left common carotid artery were either snap frozen for later real-time PCR analyses or immersion- fixed in 10% buffered formalin for histological quantification of collagen, smooth muscle and elastin within the medial layer. Results: Overall there were few differences in vascular structure, wall composition and blood flow measurements of large conduit arteries at postnatal day 2 between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males; p=0.048), narrowing of the carotid arteries (p=0.004) and a reduction in peak aortic systolic blood flow (p=0.049); all of which have the potential to impact on cardiovascular function if they persist longterm. In addition, there was significantly increased mRNA expression of the cell adhesion marker P-selectin in the thoracic aortic wall (p=0.001) and the pro-inflammatory marker IL-1β in the left carotid artery (p=0.04) in preterm lambs, suggestive of postnatal vascular injury. Conclusions: The findings suggest that offspring born moderately preterm may be at increased risk of cardiovascular impairment later in life.
Black, M., Lombardo, P.
, Nguyen, V., Flores, T., Sutherland, M.
, Nitsos, I., ... Polglase, G. R.
(2019). Structural, Functional and Gene Expression Analyses of the Aorta and Carotid Arteries in Newborn Term and Moderately Preterm Lambs
. FASEB Journal
(Suppl. 1), [208.5].