Long-term pulmonary vascular consequences of perinatal insults.

Development of the pulmonary circulation is a critical component of fetal lung development, and continues throughout infancy and childhood, marking an extended window of susceptibility to vascular maldevelopment and maladaptation. Perinatal vascular insults may result in abnormal vascular structure or function, including decreased angiogenic signaling and vascular endowment, impaired vasoreactivity through increased pulmonary artery endothelial dysfunction and remodeling, or enhanced genetic susceptibility to pulmonary vascular disease through epigenetic modifications or germline mutations. Although some infants develop early onset pulmonary hypertension, due to the unique adaptive capabilities of the immature host many do not have clinically evident early pulmonary vascular dysfunction. These individuals remain at increased risk for development of late-onset pulmonary hypertension, and may be particularly susceptible to secondary insults. This review will address the role of perinatal vascular insults in the development of late pulmonary vascular dysfunction with an effort to highlight areas of critical research need.