Plasma vascular endothelial growth factor A and placental growth factor: novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia

Pulmonary hypertension (PH) due to abnormal pulmonary vascular development is an important determinant of illness severity in congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor A (VEGFA) and placental growth factor (PLGF) may be important mediators of pulmonary vascular development in health and disease. This prospective study investigated the relationship between plasma VEGFA and PLGF and measures of pulmonary artery pressure, oxygenation, and cardiac function in CDH. A cohort of 10 infants with CDH consecutively admitted to a surgical neonatal intensive care unit (NICU) was recruited. Eighty serial plasma samples were obtained and analyzed by multiplex immunoassay to quantify VEGFA and PLGF. Concurrent assessment of pulmonary artery pressure (PAP) and cardiac function were made by echocardiography. Plasma VEGFA was higher and PLGF was lower in CDH compared with existing normative data. Combined plasma VEGFA: PLGF ratio correlated positively with measures of PAP, diastolic ventricular dysfunction, and oxygenation index. Nonsurvivors had higher VEGFA: PLGF ratio than survivors at days 3-4 of life and in the second week of life. These findings suggest that increased plasma VEGFA and reduced PLGF correlate with clinical severity of pulmonary vascular disease and may be associated with adverse outcome in CDH. This potential role for combined plasma VEGFA and PLGF in CDH as disease biomarkers, pathogenic mediators, and therapeutic targets merits further investigation.