O2137: A Novel Model of Esophageal Atresia in the Fetal Lamb

Background: Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a common congenital anomaly, occurring in 1 in 3,500 live births. The standard of care treatment for long-gap esophageal atresia is postnatal esophageal lengthening and surgical repair, often months after birth. Here we present the first reported fetal animal model of pure esophageal atresia, which will enable further research on prenatal and postnatal esophageal lengthening techniques and devices.

Methods: Six fetal lambs underwent esophageal defect creation in mid-gestation at 115-123 days gestational age (GA). Each pregnant ewe underwent midline laparotomy and hysterotomy, with partial delivery of the lamb fetus. Fetuses underwent partial esophagectomy by either a cervical (n = 2) or thoracic approach (n =4). The resected segment of esophagus was either 2 cm in length for the short-gap atresia model, or 3.5-4 cm for a long-gap atresia. The distal esophagus was suture-ligated with 2-0 silk suture, and the end of the proximal pouch was closed in a rounded flap configuration with interrupted 5-0 Prolene stitches. Following the procedure, the fetus was returned to the uterus and allowed to gestate until term. One lamb with the thoracic model of long-gap atresia additionally underwent placement of internal traction sutures at the time of defect creation in order to stimulate tension-accelerated natural growth. The lambs were delivered by caesarean section at near-term (135-141 days GA) and humanely euthanized for necropsy and tissue analysis.

Results: All six lambs were born alive, with no evidence of polyhydramnios or growth restriction. In each lamb, the measured gap between proximal and distal esophagus was equal to the length of resection. In short-gap (2 cm) animals, the mobilized esophageal ends could be brought to overlap. In long-gap (3.5-4 cm) animals, the mobilized ends could be approximated. The proximal pouch was distensible and water-tight. In the animal where internal traction sutures had been placed, the 4 cm gap had been completely reduced and the proximal and distal ends of the esophagus were in contact, without excessive scarring or gross tissue abnormality. Histologic analysis of EA-model proximal and distal esophagus demonstrated normal esophageal tissue architecture.

Conclusion: This is the first reported prenatal animal model of pure esophageal atresia. Both short- and long-gap esophageal atresia can be modeled safely in the ovine fetus without inducing polyhydramnios, preterm labor, or fetal demise. This model will enable in-vivo study of prenatal esophageal development and novel techniques for esophageal lengthening.