Skeletal malformations associated with esophageal atresia: Clinical and experimental studies

Background/Purpose: Patients with esophageal atresia (EA) often have skelet al malformations. The purpose of this study is to examine if similar defect s occur in rat fetuses prenatally exposed to Adriamycin, a chemical capable of causing EA in these animals. Methods: The charts of 443 babies with EA were reviewed to assess the incid ence and nature of these defects in them. Time-mated female rats were given either 2 mg/kg intraperitoneal Adriamycin (experimental group, n = 16) or no treatment (control group, n = 4) on gestational days 8 and 9, and the fe tuses were removed near term. Skeletal anatomy was studied after alcian blu e and alizarin red staining. Results: A total of 528 skeletal malformations, mainly abnormal segmentatio n and vertebral identity (extra or defective bodies or ribs), mishaped vert ebral bodies, and limb malformations like radial aplasia or hypoplasia were found in 245 babies (55%). Costal fusion and sternal anomalies were presen t in 17 and 4 babies, respectively. In the animal study, all control fetuse s were normal, whereas 83 of 134 experimental fetuses (62%) had EA accompan ied by other malformations. No segmentation or vertebral identity anomalies were seen, but butterfly, wedged, and asymmetric vertebral bodies were fou nd at various levels in all animals with EA and in about half of those with out it. Three fetuses had rib anomalies, and 3 more had sternal malformatio ns. Ossification of limbs was delayed in treated fetuses and short, thick, and crooked bones were seen in 4 of 31 fetuses with EA and in none of the A driamycin-exposed ones without EA. Conclusions: Adriamycin exposure induces in fetal rats, in addition to esop hageal, duodenal, and anorectal atresias, high proportions of vertebral mal formations and some limb defects of nature not identical but quite similar to that of babies with EA. This further validates this model for investigat ing the nature of the processes leading to EA and its associated malformati ons. J Pediatr Surg 34:1385-1392. Copyright (C) 1999 by W.B. Saunders Compa ny.