Effects of Cholic Acid Infusion in Fetal Lambs

The effects of prolonged intravenous infusions of cholic acid into fetal lambs are described in this study. The ewes (n = 10, 11 fetuses) were operated on at 114 days of gestation (term = 150 days) by placing plastic catheters in maternal and fetal vessels and in the amniotic cavity. Gestational ages were confirmed after delivery by radiographic examination of the ossification centers of the fetal legs. Infusions of cholic acid (1.6 μmoles/min −1 ) started 8 to 10 days after surgery in 5 fetuses (including one twin). The remaining 6 fetuses (also including one twin) were infused with 5% dextrose in water. Total plasma bile acids at the beginning of the experiment were similar in both groups (23.8±6.6 vs. 24.3±5.7 μM). No significant changes in fetal heart rate, blood pressure, blood gases or pH were detected during the infusion. Meconium‐stained amniotic fluid was observed during the third day of infusion in all the fetuses infused with cholic acid and in one control fetus. Fetuses infused with cholic acid were delivered alive 19–26 days before term. The concentration of plasma bile acids in the experimental group at delivery was 829±305 μM, i.e. significantly higher than that of the control group (24.4±5.7 μM). Control fetuses (except one twin) were delivered at term. We concluded that cholic acid, even at the high dose infused, is neither lethal nor severely harmful for the fetus. Meconium passage of the fetuses infused with cholic acid, in our experiment, appeared to be related to the stimulatory effect of cholic acid on fetal colonic motility rather than to fetal hypoxia. The cause of premature labor in the ewes with fetuses infused with cholic acid is not evident from the results of the present experiments.