Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations.
Adult
Alanine Transaminase
/ blood
Bile Acids and Salts
/ blood
Biomarkers
/ blood
Cholagogues and Choleretics
/ therapeutic use
Cholestasis, Intrahepatic
/ blood
Correlation of Data
Electrocardiography
/ methods
Female
Fetal Blood
Fetal Heart
/ physiopathology
Humans
Natriuretic Peptide, Brain
/ blood
Peptide Fragments
/ blood
Pregnancy
Pregnancy Complications
/ blood
Risk Assessment
Stillbirth
/ epidemiology
Treatment Outcome
Ursodeoxycholic Acid
/ therapeutic use
Ventricular Dysfunction
/ blood
Bile
Cholic acid
Female
Heart rate
Intrahepatic cholestasis of pregnancy
Pregnancy
Stillbirth
Ursodeoxycholic acid
Ventricular dysfunction
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
26
03
2020
revised:
22
11
2020
accepted:
24
11
2020
pubmed:
5
12
2020
medline:
1
2
2022
entrez:
4
12
2020
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 33276032
pii: S0168-8278(20)33825-3
doi: 10.1016/j.jhep.2020.11.038
pmc: PMC8062912
pii:
doi:
Substances chimiques
Bile Acids and Salts
0
Biomarkers
0
Cholagogues and Choleretics
0
Peptide Fragments
0
pro-brain natriuretic peptide (1-76)
0
Natriuretic Peptide, Brain
114471-18-0
Ursodeoxycholic Acid
724L30Y2QR
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1087-1096Subventions
Organisme : British Heart Foundation
ID : RG/17/13/33173
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 092993/Z/10/Z
Pays : United Kingdom
Organisme : Department of Health
ID : 12/164/16
Pays : United Kingdom
Organisme : Department of Health
ID : IS-BRC-1215-20006
Pays : United Kingdom
Organisme : Department of Health
ID : RP-2014-05-019
Pays : United Kingdom
Informations de copyright
Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest BHG has previously served as a director for Monica Healthcare Limited and has no commercial or financial connections in the company. CW and HUM are consultants with Mirum Pharmaceuticals and CW is a consultant for GlaxoSmithKline. The remaining authors have no conflicts of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.
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