Induction of Fetal Diuresis with Intraamniotic Furosemide Injection Reduces Intestinal Damage in a Rat Model of Gastroschisis

Abstract

Contact with amniotic fluid causes intestinal damage (ID) in fetuses with gastroschisis. Intraamniotic meconium has been shown to be responsible for ID, and ID has been shown to correlate with intraamniotic meconium concentrations. ID can be prevented by lowering the intraamniotic meconium concentration. A new method to lower intraamniotic meconium concentration might consist in the induction of fetal diuresis with intraamniotic diuretic injection. This hypothesis was tested in a rat model. There were 4 experimental groups. Rat fetuses without any manipulation. Fetuses were harvested by cesarean section for examination at E21.5 (Term). SHAM GROUP: On E18.5, the hind limb of the rat fetuses were exteriorized by hysterotomy and replaced in the uterus. GASTROSCHISIS GROUP: Gastroschisis was surgically created in rat fetuses on E18.5, under a dissection microscope (16×). GASTROSCHISIS+FUROSEMIDE GROUP: After surgical creation of gastroschisis on E18.5, intraamniotic furosemide (5 mg/kg) was administered to the fetuses on E20. All fetuses were harvested on E21.5. There was no significant difference between intestinal serosal thicknesses of the control and sham groups. The serosal thickness was significantly higher in the gastroschisis group compared to the control group. In the gastroschisis+furosemide group, the intestinal serosal thickness was found significantly decreased compared with the gastroschisis group. Intraamniotic furosemide injection caused a substantial decrease in ID encountered in gastroschisis. The induction of fetal diuresis with intraamniotic furosemide injection seems promising as a prenatal treatment modality.