A Reproducible Fetal Lamb Model of Complex Gastroschisis with Temporal Characterization of Bowel Changes

Abstract

Objectives To determine whether a fetal lamb model reproducibly induces complex gastroschisis at term with its associated structural and functional bowel changes, and to compare its occurrence and associated bowel findings at different post-induction intervals. Methods Gastroschisis was surgically induced in fetal lambs at gestational day 75 by creating a standardized abdominal wall defect stabilized with a silicone ring. Fetuses were assessed at term or at mid-gestation (13-21 days after induction), using non-operated littermates as controls. The primary outcome was occurrence of complex gastroschisis (bowel stenosis, atresia, volvulus, perforation, or necrosis) in survivors. At mid-gestation, this was compared between early (13-16 days) and late (17-21 days) groups, using Fisher s exact test. Sample size for the primary outcome at term was determined a priori (alpha=0.05, 80% power). Mid-gestation sample size was determined using the same statistical assumptions, informed by an initial exploratory cohort. Secondary outcomes included prenatal and in vivo imaging, ex vivo bowel contractility, amniotic fluid composition, and histology. Results Gastroschisis was induced in 32 fetuses. In the term cohort (n=14), 50% survived (7/14); all survivors had complex gastroschisis, with impaired bowel motility, altered enteric neural contractile responses, and smooth muscle remodeling compared with controls. Among fetuses assessed at mid-gestation (n=18), two died in utero; complex gastroschisis occurred more frequently in the late (5/7, 71%) than in the early (1/9, 11%; p=0.04) group. Mid-gestation fetuses with gastroschisis had greater intra-abdominal bowel dilation on ultrasound and higher amniotic fluid digestive enzyme levels than controls, with the greatest dilation in fetuses with complex gastroschisis. Conclusions This fetal lamb model reproducibly induced complex gastroschisis with structural and functional bowel changes in surviving lambs at term. Complex gastroschisis occurred more frequently at 17-21 than at 13-16 days after induction. At mid-gestation, fetuses with gastroschisis showed greater bowel dilation and differences in amniotic fluid composition than controls, whereas structural and functional bowel changes were not detected.