Effects of Cholic Acid Infusion in Fetal Lambs

Abstract

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 mumoles/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 microM). 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 microM, i.e. significantly higher than that of the control group (24.4 +/- 5.7 microM). 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of postprandial bile acids in prediction of perinatal outcome in intrahepatic cholestasis of pregnancy

“…High maternal bile acid levels are shown to stimulate fetal colonic motility resulting in meconium passage into the amniotic fluid in animal models. 19 We observed significantly higher MSA in the ICP group compared to controls (17.5% vs 3.7%) but failed to demonstrate a significant difference between the severe and mild cases of ICP (25.8% vs 7.4%). Only the gestational age at diagnosis was found to be associated with MSA in the logistic regression model.…”

Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates

“…It is, however, also known from animal models that high maternal bile acid levels stimulate fetal colonic motility, causing the fetus to void meconium. 17 In our material, the probability of meconium passage and green staining of placenta and membranes increased gradually in relation to elevated bile acid levels in an almost linear fashion, calculated with simple logistic regression. In the stratified groups, the frequencies of meconium passage were 21% in the no ICP group and 22% in the mild ICP group, suggesting that ICP with bile acid levels below 40 mol/L does not affect the colonic motility of the fetus.…”

La cholestase intrahépatique gravidique

“…Lors de la cholestase intrahépatique gravidique, il existe une augmentation du taux d'acides biliaires dans le liquide amniotique [35], le sang foetal [36] et le liquide méconial [37]. Or différentes études animales et expérimentales ont démontré que les acides biliaires pouvaient être responsables d'effets délétères pour le foetus : ils induisent une vasoconstriction des veines de la plaque choriale du placenta [38]; majorent le risque de passage de méconium dans le liquide amniotique chez le foetus de brebis [39] lui-même responsable de vasoconstriction aiguë des veines du cordon ombilical [40]; altèrent l'activité contractile des cardiomyocytes chez le rat suggérant qu'une augmentation des acides biliaires dans le sang foetal pourraient entraîner une MFIU brutale par arythmie cardiaque [41]. De plus, le transport des acides biliaires du foetus vers la mère au niveau du placenta est diminué lors d'une cholestase intrahépatique gravidique, responsable d'une accumulation potentielle toxique d'acides biliaires dans le sang foetal [42].…”