Placental fetal vascular malperfusion in congenital diaphragmatic hernia

The success of in-utero or intrapartum treatment for congenital diaphragmatic hernia (CDH) can be impacted by poor placental function; however, this relationship has not yet been studied. To analyze placental histomorphology in CDH, the frequencies of 24 independent clinical and 48 placental phenotypes were compared. Slides from 103 CDH placentas (group 1) and 133 clinical umbilical cord (UC) compromise/anatomical UC abnormality placentas without CDH (group 2) were subjected to hematoxylin/eosin staining and CD34 immunostaining and then examined. CD34 immunostaining was performed to identify clustered distal villi with endothelial fragmentation of recent fetal vascular malperfusion (FVM). Cesarean delivery and ex utero intrapartum treatment were more common in group 1, but group 2 showed a higher frequency of statistically significant increases in other clinical phenotypes. The frequencies of large vessels and distal villous FVMs (clustered endothelial fragmentation by CD34 immunostaining, stromal vascular karyorrhexis, avascular, or mineralized villi) did not differ between the groups, but low-grade distal villous FVMs were statistically significantly more common in group 1 than in group 2, while high-grade distal villous FVMs were significantly more common in group 2 than group 1. Large vessel and distal villous FVMs were manyfold more common in both the CDH and UC compromise groups than in the general population. However, CDH placentas were more likely to show low-grade distal villous FVMs and less likely to show high-grade distal villous FVMs in UC compromise placentas. FVM of CDH may therefore be caused by a similar pathomechanism as that of UC compromise, resulting in impaired placental fetal blood outflow.