UC Davis

BACKGROUND: Gastroschisis is a congenital abdominal wall defect resulting in fetal bowel evisceration, causing significant postnatal morbidity, including prolonged bowel dysmotility and increased susceptibility to life-threatening infections. This study aims to optimize an ovine model of gastroschisis by evaluating defect size to improve fetal survival and assess the impact of in utero repair (IUR) on postnatal outcomes. METHODS: Ovine gastroschisis defect creation was achieved with a 2 or 3 cm abdominal wall defect at gestational age (GA) 76-82 days. Fetuses underwent repair either in utero at GA 101-107 or at birth via ex utero intrapartum treatment (EXIT) at GA 139-143. Postnatal outcomes included weight gain and bowel motility. Bowel histology, qRT-PCR of intestinal cytokines, and amniotic fluid cytokine analyses were performed. RESULTS: Initial defect size increase (1.5-3 cm) resulted in high rates of ring dislodgement (71%) and associated complications, which significantly improved with a 2 cm defect. Six lambs survived to delivery (four IUR and two EXIT). IUR lambs demonstrated significantly higher weight gain compared to EXIT lambs (p = 0.007) and faster barium clearance (64-84 h vs. 89- >168 h). Histologic intestinal damage was reduced in IUR animals vs. EXIT. IL-6 and IL-17A expression were increased in IUR intestine, while IFN-γ was increased in EXIT bowel. Amniotic fluid cytokine analysis demonstrated variability. CONCLUSIONS: We describe an optimized model of ovine simple gastroschisis with in utero repair. Postnatal outcomes suggest IUR may enhance bowel motility, reduce intestinal damage, and modulate inflammatory responses more effectively than EXIT repair.