Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations

Autor: Catherine Martin, Barrie Hayes-Gill, Sahil Deepak, Jim G Thornton, Hanns-Ulrich Marschall, Anita Lövgren-Sandblom, Catherine Williamson, Joel S.C. Yang, William P. Fifer, Victoria Geenes, S Stone, Jenny Chambers, Pam Loughna, Fiona Broughton Pipkin, Julia Gorelik, Lucy C Chappell, Maristella Lucchini, Indu Asanka Jayawardane, Peter H. Dixon, Paul T. Seed, Tharni Vasavan, Lesia O. Kurlak
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cholagogues and Choleretics
Gastroenterology
chemistry.chemical_compound
Electrocardiography
0302 clinical medicine
Pregnancy
Intrahepatic cholestasis of pregnancy
Natriuretic Peptide
Brain
Ventricular Dysfunction
heart rate
Cholic acid
Bile
Correlation of Data
Bile acid
Ursodeoxycholic Acid
Alanine Transaminase
Stillbirth
Fetal Blood
Ursodeoxycholic acid
ursodeoxycholic acid
cholic acid
Treatment Outcome
female
030211 gastroenterology & hepatology
Female
stillbirth
Cholestasis of pregnancy
intrahepatic cholestasis of pregnancy
medicine.drug
Research Article
Adult
medicine.medical_specialty
medicine.drug_class
Heart rate
bile
Cholestasis
Intrahepatic
Risk Assessment
Bile Acids and Salts
03 medical and health sciences
Fetal Heart
Internal medicine
medicine
Humans
PR interval
Fetus
Hepatology
business.industry
ventricular dysfunction
medicine.disease
Peptide Fragments
Pregnancy Complications
030104 developmental biology
chemistry
business
Biomarkers
Zdroj: Vasavan, T, Deepak, S, Jayawardane, I A, Lucchini, M, Martin, C, Geenes, V, Yang, J, Lövgren-Sandblom, A, Seed, P T, Chambers, J, Stone, S, Kurlak, L, Dixon, P H, Marschall, H-U, Gorelik, J, Chappell, L, Loughna, P, Thornton, J, Pipkin, F B, Hayes-Gill, B, Fifer, W P & Williamson, C 2020, ' Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations ', Journal of Hepatology, vol. 0, no. 0, pp. 1-10 . https://doi.org/10.1016/j.jhep.2020.11.038
Journal of Hepatology
DOI: 10.1016/j.jhep.2020.11.038
Popis: Background & Aims 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). Methods 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). Results 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. Conclusions 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. Lay summary 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.
Graphical abstract
Highlights • ICP is associated with an abnormal fetal cardiac phenotype. • Phenotype includes increased PR interval, heart rate variability and NT-proBNP level. • Degree of abnormality is associated with fetal and maternal total serum bile acid levels. • NT-proBNP level in particular is associated with fetal bile acid hydrophobicity index. • UDCA treatment partially ameliorates this phenotype.
Databáze: OpenAIRE
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