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

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 aci...

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Autores principales: Vasavan, Tharni, Deepak, Sahil, Jayawardane, Indu Asanka, Lucchini, Maristella, Martin, Catherine, Geenes, Victoria, Yang, Joel, Lövgren-Sandblom, Anita, Seed, Paul Townsend, Chambers, Jenny, Stone, Sophia, Kurlak, Lesia, Dixon, Peter Hendy, Marschall, Hanns-Ulrich, Gorelik, Julia, Chappell, Lucy, Loughna, Pam, Thornton, Jim, Pipkin, Fiona Broughton, Hayes-Gill, Barrie, Fifer, William Paul, Williamson, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062912/
https://www.ncbi.nlm.nih.gov/pubmed/33276032
http://dx.doi.org/10.1016/j.jhep.2020.11.038
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author Vasavan, Tharni
Deepak, Sahil
Jayawardane, Indu Asanka
Lucchini, Maristella
Martin, Catherine
Geenes, Victoria
Yang, Joel
Lövgren-Sandblom, Anita
Seed, Paul Townsend
Chambers, Jenny
Stone, Sophia
Kurlak, Lesia
Dixon, Peter Hendy
Marschall, Hanns-Ulrich
Gorelik, Julia
Chappell, Lucy
Loughna, Pam
Thornton, Jim
Pipkin, Fiona Broughton
Hayes-Gill, Barrie
Fifer, William Paul
Williamson, Catherine
author_facet Vasavan, Tharni
Deepak, Sahil
Jayawardane, Indu Asanka
Lucchini, Maristella
Martin, Catherine
Geenes, Victoria
Yang, Joel
Lövgren-Sandblom, Anita
Seed, Paul Townsend
Chambers, Jenny
Stone, Sophia
Kurlak, Lesia
Dixon, Peter Hendy
Marschall, Hanns-Ulrich
Gorelik, Julia
Chappell, Lucy
Loughna, Pam
Thornton, Jim
Pipkin, Fiona Broughton
Hayes-Gill, Barrie
Fifer, William Paul
Williamson, Catherine
author_sort Vasavan, Tharni
collection PubMed
description 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.
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spelling pubmed-80629122021-05-01 Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations Vasavan, Tharni Deepak, Sahil Jayawardane, Indu Asanka Lucchini, Maristella Martin, Catherine Geenes, Victoria Yang, Joel Lövgren-Sandblom, Anita Seed, Paul Townsend Chambers, Jenny Stone, Sophia Kurlak, Lesia Dixon, Peter Hendy Marschall, Hanns-Ulrich Gorelik, Julia Chappell, Lucy Loughna, Pam Thornton, Jim Pipkin, Fiona Broughton Hayes-Gill, Barrie Fifer, William Paul Williamson, Catherine J Hepatol Research Article 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. Elsevier 2021-05 /pmc/articles/PMC8062912/ /pubmed/33276032 http://dx.doi.org/10.1016/j.jhep.2020.11.038 Text en © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Vasavan, Tharni
Deepak, Sahil
Jayawardane, Indu Asanka
Lucchini, Maristella
Martin, Catherine
Geenes, Victoria
Yang, Joel
Lövgren-Sandblom, Anita
Seed, Paul Townsend
Chambers, Jenny
Stone, Sophia
Kurlak, Lesia
Dixon, Peter Hendy
Marschall, Hanns-Ulrich
Gorelik, Julia
Chappell, Lucy
Loughna, Pam
Thornton, Jim
Pipkin, Fiona Broughton
Hayes-Gill, Barrie
Fifer, William Paul
Williamson, Catherine
Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title_full Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title_fullStr Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title_full_unstemmed Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title_short Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
title_sort fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062912/
https://www.ncbi.nlm.nih.gov/pubmed/33276032
http://dx.doi.org/10.1016/j.jhep.2020.11.038
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