P2.P318: Revisiting an ovine model for in utero repair of gastroschisis

Background: Gastroschisis is a congenital abdominal wall defect resulting in fetal bowel herniation. Outcomes range in severity from prolonged bowel dysmotility to intestinal atresias, volvulus, and/or necrosis. We aim to optimize an ovine model of simple gastroschisis and hypothesize that in utero repair will decrease bowel inflammation and improve postnatal bowel motility.

Methods: Ovine gastroschisis defect creation was achieved with a 2 or 3cm abdominal wall defect, with securement of a ring at gestational age (GA) 76-80 days. Fetuses either underwent in utero gastroschisis repair at GA 101-105 or ex-utero intrapartum treatment (EXIT) at GA 139-142. After birth, lambs were administered barium contrast and monitored with twice daily abdominal x-rays.

Results: A total of fourteen fetuses underwent defect creation, with six surviving to delivery, four lambs undergoing in utero repair and two lambs repaired at EXIT. An initial seven fetuses underwent 3cm defect creation with five in utero mortalities due to ring dislodgement or intestinal atresia. The surviving two fetuses were repaired in utero, with one requiring patch repair due to significant loss of abdominal domain. One lamb was euthanized shortly after delivery due to lungs of prematurity, while the other lamb received barium contrast with passage of contrast to the rectum within 25 hours. However, the lamb died due to Klebsiella pneumonia prior to complete evacuation of contrast. We then optimized the model by utilizing a smaller 2cm defect with no incidences of ring dislodgement and survival of four out of seven fetuses. Of the three demises none appeared to be related to the defect or repair and were likely due to the stress of fetal surgery. For the surviving lambs, two of the 2cm defect lambs underwent in utero repair and had complete passage of barium contrast by days 3 and 4 (Fig. 1). In contrast, one lamb repaired at EXIT failed to pass barium at study endpoint (day 7) while one passed barium on day 3 (Fig. 1). Necropsy of animals that underwent in utero repair demonstrated partial dissolution of the rind and fewer intestinal adhesions compared to EXIT lambs (Fig. 2).

Conclusion: These studies successfully optimized an ovine model of simple gastroschisis. We report six surviving lambs, with four lambs undergoing in utero repair and two repaired at EXIT. Preliminary barium motility and necropsy data suggests in utero repair of gastroschisis may improve postnatal bowel motility and reduces intestinal adhesions. Ongoing studies will assess inflammatory markers in amniotic fluid with and without in utero repair by multiplex analysis, bowel thickness and histologic score, as well as immunohistochemistry quantification of Interstitial Cells of Cajal.