natriuretic-peptide--brain and Cholestasis--Intrahepatic

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of stillbirth. This study aimed to assess the relationship between bile acid concentrations and fetal cardiac dysfunction in patients with ICP who were or were not treated with ursodeoxycholic acid (UDCA).. Bile acid profiles and NT-proBNP, a marker of ventricular dysfunction, were assayed in umbilical venous serum from 15 controls and 76 ICP cases (36 untreated, 40 UDCA-treated). Fetal electrocardiogram traces were obtained from 43 controls and 48 ICP cases (26 untreated, 22 UDCA-treated). PR interval length and heart rate variability (HRV) parameters were measured in 2 behavioral states (quiet and active sleep).. In untreated ICP, fetal total serum bile acid (TSBA) concentrations (r = 0.49, p = 0.019), hydrophobicity index (r = 0.20, p = 0.039), glycocholate concentrations (r = 0.56, p = 0.007) and taurocholate concentrations (r = 0.44, p = 0.039) positively correlated with fetal NT-proBNP. Maternal TSBA (r = 0.40, p = 0.026) and alanine aminotransferase (r = 0.40, p = 0.046) also positively correlated with fetal NT-proBNP. There were no significant correlations between maternal or fetal serum bile acid concentrations and fetal HRV parameters or NT-proBNP concentrations in the UDCA-treated cohort. Fetal PR interval length positively correlated with maternal TSBA in untreated (r = 0.46, p = 0.027) and UDCA-treated ICP (r = 0.54, p = 0.026). Measures of HRV in active sleep and quiet sleep were significantly higher in untreated ICP cases than controls. HRV values in UDCA-treated cases did not differ from controls.. Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype.. The risk of stillbirth in intrahepatic cholestasis of pregnancy (ICP) is linked to the level of bile acids in the mother which are thought to disrupt the baby's heart rhythm. We found that babies of women with untreated ICP have abnormally functioning hearts compared to those without ICP, and the degree of abnormality is closely linked to the level of harmful bile acids in the mother and baby's blood. Babies of women with ICP who received treatment with the drug UDCA do not have the same level of abnormality in their hearts, suggesting that UDCA could be a beneficial treatment in some ICP cases, although further clinical trials are needed to confirm this.

Topics: Adult; Alanine Transaminase; Bile Acids and Salts; Biomarkers; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Correlation of Data; Electrocardiography; Female; Fetal Blood; Fetal Heart; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications; Risk Assessment; Stillbirth; Treatment Outcome; Ursodeoxycholic Acid; Ventricular Dysfunction

To investigate changes in fetal myocardial deformation in intrahepatic cholestasis of pregnancy.. Patients with intrahepatic cholestasis of pregnancy were divided into 2 groups according to the total maternal serum bile acid concentration: mild cholestasis (10-40 μmol/L) and severe cholestasis (>40 μmol/L). Fetal echocardiography and velocity vector imaging were performed on women with cholestasis and control patients. The left ventricular global longitudinal strain and strain rate were measured. Clinical characteristics, maternal serum bile acid levels, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in umbilical vein blood were compared between groups. The relationships among fetal myocardial deformation, maternal total bile acids, and cord NT-proBNP were analyzed.. Twenty women with mild cholestasis, 20 with severe cholestasis, and 40 control patients were enrolled. There were no significant differences in maternal and gestational ages between the case and control groups. Maternal bile acids and NT-proBNP were significantly higher in fetuses of mothers with cholestasis than control fetuses. The left ventricular longitudinal strain (-10.56% ± 1.83% versus -18.36% ± 1.11%; P < .01), systolic strain rate (-1.63 ± 0.18 versus -2.04 ± 0.18 secondsz(-1); P < .01), and diastolic strain rate (1.37 ± 0.18 versus 1.83 ± 0.14 seconds(-1); P < .01) were significantly decreased in fetuses with severe cholestasis compared with control fetuses. There were positive correlations between fetal myocardial deformation and maternal total bile acids (r = 0.705, 0.643, and 0.690, respectively; P < .01) and between myocardial deformation and NT-proBNP (r = 0.672, 0.643, and 0.647; P < .01).. Fetal myocardial deformation is impaired in severe intrahepatic cholestasis of pregnancy. Further investigation is needed to determine whether fetal echocardiography and velocity vector imaging can help predict which fetuses of mothers with cholestasis are likely to have poor outcomes.

Topics: Apgar Score; Bile Acids and Salts; Cholestasis, Intrahepatic; Diastole; Echocardiography; Female; Fetal Blood; Fetal Diseases; Fetal Heart; Heart Ventricles; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications; Systole; Ultrasonography, Prenatal; Ventricular Dysfunction, Left