Maternal Bile Acid Levels Research Articles

Effects of elevated bile acid levels on fetal myocardium in intrahepatic cholestasis of pregnancy, a retrospective study from a neonatal perspective

AimIntrahepatic cholestasis of pregnancy (ICP) is a liver disease which may lead to a sudden fetal death.Previous studies have suggested that the fetal accident may be related to their cardiac dysfunction.However,the relationship between fetal cardiac dysfunction and their maternal bile acid levels is not clear.This objective was to clarify the relationship from a neonatal perspective and to furtherly make clear the aftereffect by analyzing the cardiac parameters of the older neonates. MethodsIn this case-control study,patients and their neonates,managed between 10 September 2018 and 30 June 2021 at a Chinese university hospital center,were divided into severe ICP group,mild ICP group and control gestational group.The maternal bile acid levels and the cardiac paramerers of one-day-old neonates and five-day-old neonates were analyzed,respectively. ResultsThe specific-myocardial enzyme(CK-MB) and left ventricular fraction shortening(FS) of neonates showed significant difference between ICP group and control group, and were meaningfully correlated with maternal bile acid levels.However,There was no significant difference in cardiac injury parameters of older neonates between the ICP group and control group. ConclusionsThe elevated maternal bile acid levels can lead to fetal myocardial injury and the injury can be recovered after removel from high concentrations of bile acid.

Ursodeoxycholic acid reduces cholestatic hepatitis and maternal bile acid levels in intrahepatic cholestasis of pregnancy

Ursodeoxycholic acid reduces cholestatic hepatitis and maternal bile acid levels in intrahepatic cholestasis of pregnancy

Pregnancy outcomes in women with primary biliary cholangitis and primary sclerosing cholangitis: a retrospective cohort study.

To determine maternal, obstetric and neonatal outcomes in a cohort of women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Retrospective cohort study. Ten specialist centres managing pregnant women with liver disease. Women with a diagnosis of PBC and PSC and a pregnancy of ≥20 completed weeks of gestation. Retrospective case notes review. Adverse outcomes were defined as: maternal - development of ascites, variceal bleeding, encephalopathy and jaundice; obstetric events - gestational hypertension, pre-eclampsia and postpartum haemorrhage; and neonatal - stillbirth, preterm delivery and admission to neonatal unit. The relationship of alanine transferase (ALT) and bile acid levels with gestation at delivery was studied. The first recorded pregnancies of 34 women with PSC and 27 women with PBC were analysed. There were 60 live births and one intrapartum stillbirth that did not occur in the context of maternal cholestasis. The overall median gestation of delivery was 38weeks but the rate of preterm birth was 28% (17/61 deliveries), 76% (13/17) of which were spontaneous. Gestation at birth negatively correlated with maternal serum ALT concentration at booking (P=0.017) and serum bile acid concentration during pregnancy (P=0.016). There were no other significant correlations and maternal and neonatal outcomes were good. Pregnancy in PBC and PSC is well tolerated, but women should be counselled regarding the increased risk of preterm birth. Measurement of maternal ALT and bile acids may help identify women at risk of preterm delivery. Pregnancy in women with PBC and PSC is well tolerated; however, rates of preterm birth are high and are related to maternal bile acid levels.

Drug resistant fetal arrhythmia in obstetric cholestasis.

Obstetric cholestasis (OC) is a pregnancy specific liver disease characterized by increased levels of bile acid (BA) and pruritus. Raised maternal BA levels could be associated with intrauterine death, fetal distress, and preterm labor and also alter the rate and rhythm of cardiomyocyte contraction and may cause fetal arrhythmic events. We report a case of drug resistant fetal supraventricular tachycardia and concomitant OC. Conclusion. If there are maternal OC and concomitant fetal arrhythmia, possibility of the resistance to antiarrhythmic treatment should be kept in mind.

Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels

The primary aim of this study was to investigate the correlation between pregnancy outcome and bile acid (BA) levels in pregnancies that were affected by intrahepatic cholestasis of pregnancy (ICP). In addition, correlations between maternal and fetal BA levels were explored. We conducted a retrospective study that included women with pruritus and BA levels ≥10 μmol/L between January 2005 and August 2012 in 3 large hospitals in the Netherlands. The study group was divided in mild (10-39 μmol/L), moderate (40-99 μmol/L), and severe (≥100 μmol/L) ICP. Main outcome measures were spontaneous preterm birth, meconium-stained amniotic fluid, asphyxia, and perinatal death. Univariate and multivariate logistic regression analysis was used to study associations between BA levels and adverse outcome. A total of 215 women were included. Gestational age at diagnosis and gestational age at delivery were significantly lower in the severe, as compared with the mild, ICP group (P < .001). Spontaneous preterm birth (19.0%), meconium-stained fluid (47.6%), and perinatal death (9.5%) occurred significantly more often in cases with severe ICP. Higher BA levels were associated significantly with spontaneous preterm birth (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 1.03-1.28), meconium-stained amniotic fluid (aOR, 1.15; 95% CI, 1.06-1.25), and perinatal death (aOR, 1.26; 95% CI, 1.01-1.57). Maternal BA levels at diagnosis and at delivery were correlated positively with umbilical cord blood BA levels (P = .006 and .012, respectively). Severe ICP is associated with adverse pregnancy outcome. Levels of BA correlate between mother and fetus.

Hepatology highlights

Hepatology highlights

Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy is characterized by pruritus, elevated bile acids and liver enzymes, and occasionally jaundice. It has specific implications for maternal and perinatal outcomes. Symptomatic and therapeutic treatment with ursodeoxycholic acid is usually initiated. Bile acid levels in their initial and serial determination can assist with antepartum management. Preterm delivery, meconium-stained amniotic fluid, and respiratory distress commonly complicate these pregnancies. The difficulty in predicting and preventing unanticipated fetal death near term drives the obstetrician's desire to deliver infants before 38 weeks. The neonatologist in turn manages potential complications related to prematurity and the compounding negative effect of bile acids on respiratory function. The pathophysiology of elevated maternal bile acid levels on the fetal lung should prompt a high level of care and attention during the first hours after birth in all newborn infants born to women with intrahepatic cholestasis of pregnancy.

Intrahepatic Cholestasis of Pregnancy and Bile Acid Levels *

We thank Dr. Sentilhes and coworkers for their interest in the results from the observational part of the Swedish ICP study, in which we demonstrated that fetal risk correlated with maternal bile acid levels. We stratified a large patient material (n = 690) of pregnant women with pruritus into three groups: no ICP (serum bile acids <10μmol/L), mild ICP (10-39 μmol/L) and severe ICP (≥40μmol/L). Spontaneous preterm delivery; asphyxial events (operative delivery due to asphyxia, arterial umbilical pH <7.05, or Apgar score <7 at 5 minutes); and meconium staining of amniotic fluid, placenta, and membranes were found to be significantly increased in the group with severe ICP compared with the groups with no ICP and mild ICP. No differences in these variables were detected between the group with no ICP and the group with mild ICP. Furthermore, a higher frequency of intrauterine fetal death (IUFD) in prior pregnancies was reported by women in the group with severe ICP (4.1%) compared with the groups with no ICP (0.6%) and mild ICP (0.8%) (P < .001). The rates of IUFD in the group with no ICP and the group with mild ICP did not differ significantly from the overall IUFD rate in Sweden (0.4%). In their comments, our French colleagues referred to the fact that one of our IUFD cases had bile acid levels below 40 μmol/L (27 μmol/L). This case was a twin pregnancy, in which one fetus died and the other survived. At delivery, a tight knot on the umbilical cord of the dead twin was found. Fetuses in twin pregnancies are indeed exposed to a higher risk, and all cases of IUFD in ICP pregnancies are not necessarily related to the disease. A recent study by Williamson et al.1 investigated fetal outcome in women with ICP, and they reported high fetal complication rates. However, in this study several confounding factors were present. Their patient material was based on a questionnaire survey in women with ICP that were identified by a patient support group. As the authors themselves stated in the article, this fact may indicate that the material was enriched by pregnancies in which complications had occurred. It should be pointed out that induction of labor, especially before term, is associated with an increase of fetal and maternal risk in terms of prolonged labor, higher frequencies of emergency cesarean section, and fetal asphyxia. We agree that the slight increase in risk of respiratory distress syndrome in the neonate is not an important issue when deciding to induce labor. Nevertheless, it should be underlined that inductions of labor should be conducted only in cases in which benefits outweigh risks. Our study proved that fetuses in pregnant women with bile acid levels exceeding 40 μmol/L were exposed to an increased risk, and in this group it seems reasonable to propose active management (pharmacological treatment or induction of labor). Because we could not find any increase of fetal risk in our large study population of women with ICP and bile acid levels 10 to 39 μmol/L, we cannot find any evidence to support that these women would benefit from routine induction before term. To further address this issue, a randomized study between active and expectant management should be conducted in this specific group. Anna Glantz M.D.*, Hanns-Ulrich Marschall M.D. Ph.D.*, Lars-Åke Mattsson M.D., Ph.D.*, * Dept of Obstetrics/Gynaecology, Sahlgrenska University Hospital/East, Göteborg, Sweden.

Bile acid stress in the mother and baby unit.

Intrahepatic cholestasis of pregnancy (ICP) affects about 0.7% of deliveries in Britain. It is regarded as a benign condition for the mother but is associated with increased fetal mortality in late pregnancy and early delivery is advised. Ursodeoxycholic acid (UDCA) treatment is beneficial to the mother and does not appear to harm the fetus. ICP is often regarded as a disease of the maternal liver already made 'cholestatic' by high levels of circulating progesterone. We propose that ICP should be considered as a feto-maternal disease involving complex interactions between maternal and fetal bile acid metabolism across the placenta. During the late stages of gestation, when there is a rise in fetal and maternal bile acid levels, the placenta may fail to render potentially hepatotoxic bile acids water soluble and hence excretable. This might cause a vicious cycle leading to further cholestasis in the maternal liver already challenged by progesterone.

Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy

Cardiotocography (CTG) and serum total bile acid level were used in the perinatal surveillance of 117 pregnancies with intrahepatic cholestasis. Signs of fetal distress occurred more commonly in cholestasis pregnancies with high maternal bile acid levels. Despite careful monitoring one intrauterine fetal loss occurred without any warning signs in CTG. In this case the serum bile acid level was only moderately elevated. CTG seems to be suitable for detection of fetal distress in cholestasis pregnancies. Those with high maternal bile acid level should be subjected to a more intensive follow-up. Some fetal risk, however, seems to remain despite of the use of these methods.