Comparison of the pulmonary vasculature in newborns and stillborns with congenital diaphragmatic hernia

The purpose of this study was to compare structural changes in the pulmonary vasculature in newborns with congenital diaphragmatic hernia (CDH) complicated by persistent pulmonary hypertension (PPH) and stillborns with CDH. Victorian blue van Gieson (VVG) staining and immunostaining with anti-alpha smooth-muscle actin (ASMA) was performed on lung tissue obtained at autopsy from 23 newborns with CDH complicated by PPH, 7 stillborns with CDH, and 11 age-matched controls with sudden infant death syndrome (SIDS). The degrees of adventitial and medial thickness and area were measured in pulmonary arteries with an external diameter (ED) of <75 μm, 75–100 μm, 100–150 μm, 150–250 μm, 250–500 μm, and >500 μm by image analyzer and compared statistically. The degrees of adventitial and medial thickness and area were measured in pulmonary veins with an ED of <100 μm, 100–200 μm, and >200 μm by image analyzer and compared statistically. In order to determine whether the characteristic structural changes were size-related, each was related to ED. There was a significant increase in adventitial thickness and area in arteries of all sizes in both newborns and stillborns with CDH compared to SIDS patients (P < 0.05). The degree of medial thickness in newborns and stillborns with CDH was significantly increased compared to SIDS patients (P < 0.01). The degree of medial area was significantly increased for arteries with ED less than 100 μm (P < 0.05) in newborns and stillborns with CDH compared with SIDS patients. There was a significant increase in adventitial thickness and area in veins of all sizes in newborns with CDH compared to stillborns with CDH and SIDS (P < 0.05). The degree of adventitial thickness and area of pulmonary veins were similar in stillborns with CDH and SIDS. There were no significant differences in medial thickness of veins between the three groups. The presence of abnormally thick-walled pulmonary arteries in stillborns with CDH suggests that the intrapulmonary arteries in CDH may become excessively muscularized during fetal life, becoming unable to adapt normally at birth. The absence of structural changes in pulmonary veins in stillborns with CDH suggests that the pulmonary venous changes observed in newborns with CDH complicated by PPH occur after birth as a result of increases in transvascular pressure or a response to release of peptide growth factors.