Research Article
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Assessment of fetal cardiac function and epicardial fat thickness in intrahepatic cholestasis pregnancies

Year 2025, Volume: 8 Issue: 5, 946 - 951, 16.09.2025
https://doi.org/10.32322/jhsm.1758040

Abstract

Aims: This study is to evaluate fetal cardiac activity and epicardial fat thickness (EFT) in pregnant women with intrahepatic cholestasis (IHCP) and to investigate the relationship between these measurements and perinatal outcomes.
Methods: This prospective case-control study was conducted between May 2022 and October 2024 at a tertiary perinatology clinic. The study group comprised 38 women with IHCP, and the control group included 39 healthy pregnancies matched for gestational age and maternal characteristics. Fetal cardiac function was evaluated by echocardiographic parameters including the Myocardial Performance Index (MPI), isovolumic contraction time (ICT), ejection time (ET), and PR interval, and EFT was quantified in the four-chamber view. Doppler indices of the umbilical, middle cerebral, and uterine arteries, along with neonatal outcomes such as gestational age, birth weight, APGAR scores, and neonatal intensive care unit (NICU) admission, were recorded.
Results: In the IHCP cohort, bile acid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were significantly elevated (p<0.001). MPI, ICT, ET, and PR interval values were also increased, indicating subclinical effects on fetal cardiac function. No significant differences were detected in EFT between groups. Gestational age at birth was lower in the IHCP group (p=0.005), and NICU admission was clinically higher, though not statistically significant.
Conclusion: IHCP may impair fetal cardiac conduction and contractility, with these alterations positively associated with serum bile acid concentrations. EFT seems more closely linked to chronic metabolic stress than to acute conditions. Regular echocardiographic monitoring may aid in safeguarding fetal well-being.

Ethical Statement

Ethical approval was obtained by the institutional review board from XXX Hospital on 20.04.2022# 2022/56. The study complied with the ethical principles for medical research of the Declaration of Helsinki .

Supporting Institution

none

Project Number

20.04.2022# 2022/56

Thanks

none

References

  • Jamshidi Kerachi A, Shahlaee MA, Habibi P, Dehdari Ebrahimi N, Ala M, Sadeghi A. Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. BMC Med. 2025; 23(1):129. doi:10.1186/s12916-025-03935-0
  • Odabaş RK, Sökmen Y, Dünder E, Taşpınar A. The incidence of intrahepatic cholestasis of pregnancy and its maternal, fetal, and neonatal adverse outcomes: a systematic review and meta-analysis. J Midwife Womens Health. 2024;69(3):370-382. doi:10.1111/jmwh.13640
  • Hobson SR, Cohen ER, Gandhi S, et al. Guideline no. 452: diagnosis and management of intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Can. 2024;46(8):102618. doi:10.1016/j.jogc.2024.102618
  • Demir M, Sertel E. The role of aspartate aminotransferase/Platelet Ratio Index score in predicting intrahepatic cholestasis of pregnancy and its relationship with total bile acid level: a case-control study from a tertiary center. Gynecol Obstet Reprod Med. 2024;30(3):167-173. doi:10.21613/GORM.2023.1527
  • Palmer KR, Xiaohua L, Mol BW. Management of intrahepatic cholestasis in pregnancy. Lancet. 2019;393(10174):853-854. doi:10.1016/S0140-6736(18)32323-7
  • Arthuis C, Diguisto C, Lorphelin H, et al. Perinatal outcomes of intrahepatic cholestasis during pregnancy: an 8-year case-control study. PLoS One. 2020;15(2):e0228213. doi:10.1371/journal.pone.0228213
  • Wang J, Lun W, Shi W. Effects of elevated bile acid levels on fetal myocardium in intrahepatic cholestasis of pregnancy, a retrospective study from a neonatal perspective. Clin Res Hepatol Gastroenterol. 2022; 46(8):102013. doi:10.1016/j.clinre.2022.102013
  • Lee RH, Mara Greenberg, Metz TD, Pettker CM. Society for Maternal-Fetal Medicine consult series #53: intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2021;224(2):B2-B9. doi: 10.1016/j.ajog.2020.11.002
  • Williamson C, Miragoli M, Sheikh Abdul Kadir S, et al. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58-61. doi:10.1159/000324130
  • Oliveira M, Dias JP, Guedes-Martins L. Fetal cardiac function: Myocardial Performance Index. Curr Cardiol Rev. 2022;18(4):20-31. doi: 10.2174/1573403X18666211227145856
  • Bligard KH, Doering M, Porat S, Rosenbloom JI. Reference ranges for left Modified Myocardial Performance Index: systematic review and meta-analysis. Fetal Diagn Ther. 2024;51(2):159-167. doi:10.1159/000535602
  • Ozturk M, Agaoglu Z, Ozturk FH, et al. Evaluation of fetal myocardial performance index in gestational diabetes mellitus. Congenital Anomalies. 2023;63(5):164-169. doi:10.1111/cga.12531
  • Sever B, Bayraktar B, Adıyaman D, et al. Association of increased fetal epicardial fat thickness with maternal pregestational and gestational diabetes. J Mater Fetal Neonat Med. 2023;36(1):2183474. doi:10.1080/14767058.2023.2183474
  • Manjunath BST. Fetal epicardial fat thickness as a marker for gestational diabetes mellitus. IJSR. 2024;34-36. doi:10.36106/ijsr
  • Nyawo TA, Pheiffer C, Mazibuko-Mbeje SE, et al. Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases: oxidative stress and inflammation emerge as major therapeutic targets. Antioxidants. 2021; 10(11):1758. doi:10.3390/antiox10111758
  • Sakcak B, Farisoğulları N, Denizli R, et al. Evaluation of the Fetal Myocardial Performance Index and epicardial fat thickness in pregnant women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2023;36(1):2192322. doi:10.1080/14767058.2023.2192322
  • Majsterek M, Wierzchowska-Opoka M, Makosz I, Kreczyńska L, Kimber-Trojnar Ż, Leszczyńska-Gorzelak B. Bile acids in intrahepatic cholestasis of pregnancy. Diagnostics (Basel). 2022;12(11):2746. doi:10. 3390/diagnostics12112746
  • Ozgen L, Ozgen G, Karasin SS, Bayram F. Fibrinogen levels and total serum bile acids in intrahepatic cholestasis of pregnancy. J Coll Physicians Surg Pak. 2022;32(11):1404-1409. doi:10.29271/jcpsp.2022.11.1404
  • Yakut K, Öcal DF, Sanhal Yaşar C, Halıcı Öztürk F, Şanlı C, Çelen Ş. Fetal epicardial fat thickness in fetal growth restriction; effects on fetal heart function and relationship with the severity of disease. J Matern Fetal Neonatal Med. 2022;35(25):6946-6952. doi:10.1080/14767058.2021. 1931676
  • Dayanan R, Bulan DD, Ozkan MA, Ozkan HD, Caglar AT. Fetal pulmonary-artery Doppler dynamics in preeclampsia: acceleration time, ejection time, PAT/ET ratio, and prediction of adverse neonatal pulmonary outcome. J Ultrasound Med. 2025;44(10):1903-1912. doi:10. 1002/jum.70031
  • Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One. 2010;5(3):e9689. doi:10.1371/journal.pone.0009689
  • Schultz F, Hasan A, Alvarez-Laviada A, et al. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts. Prog Biophys Mol Biol. 2016; 120(1-3):149-163. doi:10.1016/j.pbiomolbio.2016.01.003
  • Ibrahim E, Diakonov I, Arunthavarajah D, et al. Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5. Sci Rep. 2018;8(1):7110. doi:10.1038/s41598-018-25569-4
  • Guerra M, Montaño I, Haye MT, Toro V, Maiz N. Fetal PR interval in pregnancies with intrahepatic cholestasis of pregnancy: a case-control study. Am J Perinatol. 2024;41(S 01):e2964-e2969. doi:10.1055/ a-2184-0242
  • Rodríguez M, Moreno J, Márquez R, et al. Increased PR interval in fetuses of patients with intrahepatic cholestasis of pregnancy. Fetal Diagn Ther. 2016;40(4):298-302. doi:10.1159/000444297
  • Eyisoy ÖG, Demirci O, Taşdemir Ü, Özdemir M, Öcal A, Kahramanoğlu Ö. Effect of maternal ursodeoxycholic acid treatment on fetal atrioventricular conduction in patients with intrahepatic cholestasis of pregnancy. Fetal Diagn Ther. 2024;51(6):617-623. doi:10.1159/000540261
  • Anwaier A, Li J, Liu W, Dong L, Ding Y, Yu Z. Influence of maternal diabetes during pregnancy on ultrasound-measured fetal epicardial fat thickness: a meta-analysis. Biomol Biomed. 2025;25(6):1245-1258. doi: 10.17305/bb.2025.11909
  • Sweeting A, Wong J, Murphy HR, Ross GP. A clinical update on gestational diabetes mellitus. Endocr Rev. 2022;43(5):763-793. doi:10. 1210/endrev/bnac003
  • Zhou Q, Yuan Y, Wang Y, et al. The severity of intrahepatic cholestasis during pregnancy increases risks of adverse outcomes beyond stillbirth: evidence from 15,826 patients. BMC Pregn Childbirth. 2024;24(1):476. doi:10.1186/s12884-024-06645-2
  • Ovadia C, Seed PT, Sklavounos A, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019;393(10174):899-909. doi:10.1016/S0140-6736(18)31877-4
  • You S. Bile acids and premature labor in intrahepatic cholestasis of pregnancy. University of Rhode Island; 2016.

İntrahepatik kolestazlı gebeliklerde fetal kardiyak fonksiyon ve epikardiyal yağ kalınlığının değerlendirilmesi

Year 2025, Volume: 8 Issue: 5, 946 - 951, 16.09.2025
https://doi.org/10.32322/jhsm.1758040

Abstract

Amaç: Bu çalışma, intrahepatik kolestaz (İHK) tanısı konulan gebelerde fetal kardiyak aktiviteyi ve epikardiyal yağ dokusu (EFT) kalınlığını değerlendirmeyi ve bu parametrelerin perinatal sonuçlarla olan ilişkisini araştırmayı amaçlamaktadır.
Yöntem: Bu prospektif olgu-kontrol çalışması, Mayıs 2022 ile Ekim 2024 tarihleri arasında bir üçüncü basamak perinatoloji kliniğinde gerçekleştirilmiştir. Çalışma grubunu İHK tanısı konulan 38 gebe oluştururken, kontrol grubunu gestasyonel yaş ve maternal özellikler açısından eşleştirilmiş 39 sağlıklı gebe oluşturmuştur. Fetal kardiyak fonksiyon, ekokardiyografik parametrelerle (MPI, ICT, ET, PR aralığı) değerlendirilmiş ve EFT dört boşluk görüntüsünde ölçülmüştür. Umbilikal arter, orta serebral arter ve uterin arter Doppler indeksleri ile birlikte yenidoğan sonuçları (doğum haftası, doğum ağırlığı, APGAR skorları ve YDYB kabulü) kaydedilmiştir.
Bulgular: İHK grubunda safra asidi, AST ve ALT düzeyleri anlamlı şekilde artmıştı (p<0.001). MPI, ICT, ET ve PR aralığı değerlerinde belirgin artış gözlenmiş olup, bu durum embriyonal kalp fonksiyonlarında subklinik etkilenmeyi düşündürmektedir. Gruplar arasında EFT düzeylerinde anlamlı bir fark saptanmamıştır. Doğum haftası İHK grubunda daha erken gerçekleşmiştir (p=0.005) ve yenidoğan yoğun bakım gereksinimi klinik olarak artmış olsa da istatistiksel olarak anlamlı bulunmamıştır.
Sonuç: İHK, fetal kardiyak iletim ve kontraksiyon mekanizmaları üzerinde olumsuz etkilere yol açabilir. Bu değişiklikler, serum safra asidi düzeyleriyle pozitif ilişki göstermektedir. EFT, akut durumlardan çok kronik metabolik stresle ilişkili görünmektedir. Zamanında yapılan ekokardiyografik takip, fetal iyilik halinin korunmasında faydalı olabilir.

Project Number

20.04.2022# 2022/56

References

  • Jamshidi Kerachi A, Shahlaee MA, Habibi P, Dehdari Ebrahimi N, Ala M, Sadeghi A. Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. BMC Med. 2025; 23(1):129. doi:10.1186/s12916-025-03935-0
  • Odabaş RK, Sökmen Y, Dünder E, Taşpınar A. The incidence of intrahepatic cholestasis of pregnancy and its maternal, fetal, and neonatal adverse outcomes: a systematic review and meta-analysis. J Midwife Womens Health. 2024;69(3):370-382. doi:10.1111/jmwh.13640
  • Hobson SR, Cohen ER, Gandhi S, et al. Guideline no. 452: diagnosis and management of intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Can. 2024;46(8):102618. doi:10.1016/j.jogc.2024.102618
  • Demir M, Sertel E. The role of aspartate aminotransferase/Platelet Ratio Index score in predicting intrahepatic cholestasis of pregnancy and its relationship with total bile acid level: a case-control study from a tertiary center. Gynecol Obstet Reprod Med. 2024;30(3):167-173. doi:10.21613/GORM.2023.1527
  • Palmer KR, Xiaohua L, Mol BW. Management of intrahepatic cholestasis in pregnancy. Lancet. 2019;393(10174):853-854. doi:10.1016/S0140-6736(18)32323-7
  • Arthuis C, Diguisto C, Lorphelin H, et al. Perinatal outcomes of intrahepatic cholestasis during pregnancy: an 8-year case-control study. PLoS One. 2020;15(2):e0228213. doi:10.1371/journal.pone.0228213
  • Wang J, Lun W, Shi W. Effects of elevated bile acid levels on fetal myocardium in intrahepatic cholestasis of pregnancy, a retrospective study from a neonatal perspective. Clin Res Hepatol Gastroenterol. 2022; 46(8):102013. doi:10.1016/j.clinre.2022.102013
  • Lee RH, Mara Greenberg, Metz TD, Pettker CM. Society for Maternal-Fetal Medicine consult series #53: intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2021;224(2):B2-B9. doi: 10.1016/j.ajog.2020.11.002
  • Williamson C, Miragoli M, Sheikh Abdul Kadir S, et al. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58-61. doi:10.1159/000324130
  • Oliveira M, Dias JP, Guedes-Martins L. Fetal cardiac function: Myocardial Performance Index. Curr Cardiol Rev. 2022;18(4):20-31. doi: 10.2174/1573403X18666211227145856
  • Bligard KH, Doering M, Porat S, Rosenbloom JI. Reference ranges for left Modified Myocardial Performance Index: systematic review and meta-analysis. Fetal Diagn Ther. 2024;51(2):159-167. doi:10.1159/000535602
  • Ozturk M, Agaoglu Z, Ozturk FH, et al. Evaluation of fetal myocardial performance index in gestational diabetes mellitus. Congenital Anomalies. 2023;63(5):164-169. doi:10.1111/cga.12531
  • Sever B, Bayraktar B, Adıyaman D, et al. Association of increased fetal epicardial fat thickness with maternal pregestational and gestational diabetes. J Mater Fetal Neonat Med. 2023;36(1):2183474. doi:10.1080/14767058.2023.2183474
  • Manjunath BST. Fetal epicardial fat thickness as a marker for gestational diabetes mellitus. IJSR. 2024;34-36. doi:10.36106/ijsr
  • Nyawo TA, Pheiffer C, Mazibuko-Mbeje SE, et al. Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases: oxidative stress and inflammation emerge as major therapeutic targets. Antioxidants. 2021; 10(11):1758. doi:10.3390/antiox10111758
  • Sakcak B, Farisoğulları N, Denizli R, et al. Evaluation of the Fetal Myocardial Performance Index and epicardial fat thickness in pregnant women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2023;36(1):2192322. doi:10.1080/14767058.2023.2192322
  • Majsterek M, Wierzchowska-Opoka M, Makosz I, Kreczyńska L, Kimber-Trojnar Ż, Leszczyńska-Gorzelak B. Bile acids in intrahepatic cholestasis of pregnancy. Diagnostics (Basel). 2022;12(11):2746. doi:10. 3390/diagnostics12112746
  • Ozgen L, Ozgen G, Karasin SS, Bayram F. Fibrinogen levels and total serum bile acids in intrahepatic cholestasis of pregnancy. J Coll Physicians Surg Pak. 2022;32(11):1404-1409. doi:10.29271/jcpsp.2022.11.1404
  • Yakut K, Öcal DF, Sanhal Yaşar C, Halıcı Öztürk F, Şanlı C, Çelen Ş. Fetal epicardial fat thickness in fetal growth restriction; effects on fetal heart function and relationship with the severity of disease. J Matern Fetal Neonatal Med. 2022;35(25):6946-6952. doi:10.1080/14767058.2021. 1931676
  • Dayanan R, Bulan DD, Ozkan MA, Ozkan HD, Caglar AT. Fetal pulmonary-artery Doppler dynamics in preeclampsia: acceleration time, ejection time, PAT/ET ratio, and prediction of adverse neonatal pulmonary outcome. J Ultrasound Med. 2025;44(10):1903-1912. doi:10. 1002/jum.70031
  • Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One. 2010;5(3):e9689. doi:10.1371/journal.pone.0009689
  • Schultz F, Hasan A, Alvarez-Laviada A, et al. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts. Prog Biophys Mol Biol. 2016; 120(1-3):149-163. doi:10.1016/j.pbiomolbio.2016.01.003
  • Ibrahim E, Diakonov I, Arunthavarajah D, et al. Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5. Sci Rep. 2018;8(1):7110. doi:10.1038/s41598-018-25569-4
  • Guerra M, Montaño I, Haye MT, Toro V, Maiz N. Fetal PR interval in pregnancies with intrahepatic cholestasis of pregnancy: a case-control study. Am J Perinatol. 2024;41(S 01):e2964-e2969. doi:10.1055/ a-2184-0242
  • Rodríguez M, Moreno J, Márquez R, et al. Increased PR interval in fetuses of patients with intrahepatic cholestasis of pregnancy. Fetal Diagn Ther. 2016;40(4):298-302. doi:10.1159/000444297
  • Eyisoy ÖG, Demirci O, Taşdemir Ü, Özdemir M, Öcal A, Kahramanoğlu Ö. Effect of maternal ursodeoxycholic acid treatment on fetal atrioventricular conduction in patients with intrahepatic cholestasis of pregnancy. Fetal Diagn Ther. 2024;51(6):617-623. doi:10.1159/000540261
  • Anwaier A, Li J, Liu W, Dong L, Ding Y, Yu Z. Influence of maternal diabetes during pregnancy on ultrasound-measured fetal epicardial fat thickness: a meta-analysis. Biomol Biomed. 2025;25(6):1245-1258. doi: 10.17305/bb.2025.11909
  • Sweeting A, Wong J, Murphy HR, Ross GP. A clinical update on gestational diabetes mellitus. Endocr Rev. 2022;43(5):763-793. doi:10. 1210/endrev/bnac003
  • Zhou Q, Yuan Y, Wang Y, et al. The severity of intrahepatic cholestasis during pregnancy increases risks of adverse outcomes beyond stillbirth: evidence from 15,826 patients. BMC Pregn Childbirth. 2024;24(1):476. doi:10.1186/s12884-024-06645-2
  • Ovadia C, Seed PT, Sklavounos A, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019;393(10174):899-909. doi:10.1016/S0140-6736(18)31877-4
  • You S. Bile acids and premature labor in intrahepatic cholestasis of pregnancy. University of Rhode Island; 2016.
There are 31 citations in total.

Details

Primary Language English
Subjects Gastroenterology and Hepatology, Obstetrics and Gynaecology
Journal Section Research Article
Authors

Neval Çayönü Kahraman 0000-0001-8832-0081

Zeynep Şeyhanlı 0000-0003-3924-3723

Gülşan Karabay 0000-0003-2567-2850

Özgür Arat 0000-0003-0445-1653

Kadriye Yakut Yücel 0000-0003-3182-4312

Şevki Çelen 0000-0001-7033-3474

Ali Turhan Çağlar 0000-0002-7022-3029

Yaprak Engin Üstün 0000-0002-1011-3848

Project Number 20.04.2022# 2022/56
Submission Date August 4, 2025
Acceptance Date September 5, 2025
Publication Date September 16, 2025
Published in Issue Year 2025 Volume: 8 Issue: 5

Cite

AMA Çayönü Kahraman N, Şeyhanlı Z, Karabay G, et al. Assessment of fetal cardiac function and epicardial fat thickness in intrahepatic cholestasis pregnancies. J Health Sci Med / JHSM. September 2025;8(5):946-951. doi:10.32322/jhsm.1758040

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