Abstract
Pulmonary hypertension (PH) is associated with significant morbidities and high mortality in preterm infants, yet mechanisms contributing to the pathogenesis of PH, the impact of early pulmonary vascular disease (PVD) on the risk for BPD, the role for PH-targeted drug therapies, and long-term pulmonary vascular sequelae remain poorly understood. PVD is not a homogeneous disease, rather, PVD in the setting of prematurity includes various phenotypes as based on underlying pathophysiology, the severity of associated PH, the timing of disease onset, its contribution to hemodynamic and respiratory status, late outcomes, and other features. As with term newborns, severe hypoxemia with acute respiratory failure (HRF) in preterm infants can be due to marked elevation of pulmonary artery pressure with extrapulmonary shunt, traditionally referred to as persistent pulmonary hypertension of the newborn (PPHN). Transient and less severe levels of PH can also be observed during the early transition after birth without evidence of severe HRF, representing physiologic PH or delayed pulmonary vascular transition in preterm infants. Importantly, echocardiographic evidence of early PH has been strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), late PH, and chronic respiratory disease during infancy and early childhood. Late PH beyond the first postnatal months in preterm in neonates with established BPD is further associated with poor outcomes, especially as related to BPD severity. In addition, echocardiographic signs of PVD can further persist throughout childhood and may lead to chronic PH of variable severity and cardiac maldevelopment in prematurely born young adults. This review discusses the importance of characterizing diverse pulmonary vascular phenotypes in preterm infants to better guide clinical care and research, and to enhance the development of more precise therapeutic strategies to optimize early and late outcomes of preterm infants.