Cardiovascular malformations in congenital diaphragmatic hernia: Human andexperimental studies

Background/Purpose: Cardiovascular malformations (CVM) associated with cong enital diaphragmatic hernia (CDH) account in part for the high mortality ca used by this defect. The aim of this study is to examine the nature of thes e malformations in a large series of autopsies and to assess if similar def ects are also present in rat fetuses with experimental CDH. Methods: The incidence of CVM and their nature were examined in the autopsy records of 136 stillborns and neonates with CDH admitted to our institutio n in the last 30 years. Experimental CDH was induced in rat fetuses by givi ng 100 mg of nitrofen to their mothers on gestational day 9.5, and the fetu ses were harvested on day 21 (near full term). The presence of CDH and the anatomy of the heart and great vessels were studied under dissecting micros cope after formalin fixation. Unexposed fetuses were used as controls. Results: Thirty-three newborns with CDH (24%) had CVM, either isolated or a ssociated with other defects, and 7 had heart hypoplasia. Most CVM (ventric ular septal defect, tetralogy of Fallot, transposition of the great vessels , double-outlet right ventricle) involved the outflow tract. In our animal experiments, no malformations were found in 21 control pups. Conversely, 80 of 130 nitrofen-exposed fetuses (61%) had CDH, and 59 of them (74%) had CV M. A significant association (Fisher's Exact test, P<.01) was found between CDH and CVM because only 25 of the 50 exposed animals without CDH (50%) ha d CVM. Again, most defects involved the outflow tract and were similar to t hose seen in human CDH (tetralogy of Fallot, persistent truncus, ventricula r septa[ defect, double-outlet right ventricle, aberrant right subclavian a rtery, agenetic ductus, and interrupted aortic arch). Animals with CDH had significantly decreased heart weight to fetal weight ratio in comparison wi th controls and with those without CDH. Conclusions: The similar nature of the cardiovascular defects found in babi es succumbing to CDH and in nitrofen-exposed rats suggests that a similar d isturbance of the regional organogenesis related to the neural crest might be involved in both settings, and further validates the use of this animal model for clarifying the cellular and molecular pathogenetic mechanisms. J Pediatr Surg 34:1352-1358. Copyright (C) 1999 by W.B. Saunders Company.