Serum Bile Acid Profiles in Patients With Intrahepatic Cholestasis of Pregnancy (BAPP)

The goal of this observational study is to learn if analyzing bile acid patterns can help predict dangerous complications in pregnant women with intrahepatic cholestasis of pregnancy (ICP), a liver condition that can affect the baby. The main questions it aims to answer are:

• Can measuring specific types of bile acids (particularly taurine-conjugated versus glycine-conjugated bile acids) in the mother's and baby's blood help predict the risk of stillbirth and other complications?
• Do these bile acid patterns activate specific receptors (TGR5) that might contribute to immune problems or heart rhythm abnormalities in the baby?
• How do bile acid patterns in the mother's stool relate to her gut bacteria and the severity of ICP?
• Can heart rate monitoring (CTG) combined with bile acid measurements better identify high-risk pregnancies? ICP is a pregnancy-related liver condition that causes bile acids to build up in the mother's bloodstream. This can lead to serious risks for the baby, including an increased chance of stillbirth, premature birth, and heart rhythm problems. Current monitoring methods (such as heart rate monitoring and ultrasound) often don't show warning signs before complications occur.

Participants will:

• Provide blood samples at each routine bile acid check during pregnancy and at delivery
• Provide stool samples for analyzing gut bacteria and bile acids
• Have their baby's umbilical cord blood collected at birth for bile acid analysis
• Undergo standard heart rate monitoring (CTG) of the baby
• Have ultrasound examination of the baby's heart (echocardiography) The study will compare three groups: pregnant women with ICP, healthy pregnant women, and healthy non-pregnant women. The researchers hope this information will help doctors better predict which pregnancies need more intensive monitoring and potentially prevent stillbirths and other complications in women with ICP.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholestasis of Pregnancy

• Study Type: Observational
• Enrollment (Estimated): 74

Contacts and Locations

• Study Contact: Name: Silke Große, Dr. rer. nat.; Phone Number: +493641 9-329293; Email: silke.grosse@med.uni-jena.de
• Study Contact Backup: Name: Janine Zöllkau, Dr. med.; Email: janine.zoellkau@med.uni-jena.de

Study Locations

• Germany
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Recruiting
      • Klinik für Geburtsmedizin, Universitätsklinikum Jena
      • Contact: Janine Zöllkau, Dr. med.; Email: janine.zoellkau@med.uni-jena.de
      • Contact: Silke Große, Dr.; Phone Number: +49 3641 9329293; Email: silke.grosse@med.uni-jena.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Group 1:

Participants in this group are pregnant women diagnosed with or suspected of having ICP who are being treated at the Clinic for Obstetrics, University Hospital Jena, as part of routine clinical care.

Group 2:

Participants in this group are healthy pregnant women without ICP who are receiving routine prenatal care at the Clinic for Obstetrics, University Hospital Jena.

Group 3:

Participants in this group are healthy, non-pregnant female volunteers participating in the study independently of the clinical care setting.

Description

Inclusion Criteria Group I:

• Minimum age of 18 years
• Written informed consent
• Pregnant patients with suspected ICP
• Pregnant patients with confirmed ICP
• Pregnant patients with elevated total bile acids (>14 µmol/ml)
• Pregnant patients with elevated liver enzymes
• Pregnant patients that suffer from itching with elevated transaminases

Inclusion Criteria Group II:

• Minimum age of 18 years
• Confirmed pregnancy
• Written informed consent
• Generally considered healthy in common usage (corresponding to ASA II of the American Society of Anesthesiologists classification)

Inclusion Criteria Group III:

• Minimum age of 18 years
• Female gender
• Pregnancy excluded
• Written informed consent
• Generally considered healthy in common usage (corresponding to ASA II of the American Society of Anesthesiologists classification)

Exclusion Criteria Group II and III:

• Age <18 years
• Inability to provide informed consent
• Signs of an acute illness (for control groups II and III)
• Known liver, biliary, or pancreatic diseases (for control groups II and III)
• ICP in personal or family medical history (for control groups II and III)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Pregnant ICP patients; Diagnosis or suspicion of an ICP according to Hagenbeck et al. 2021
Healthy pregnant controls; Healthy patients with a confirmed pregnancy
Healthy non-pregnant controls; Healthy woman which are not pregnant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bile acid profile	Qualitative and quantitative bile acid profile in serum of mother and infant (umbilical cord blood)	Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TGR-5 activity	TGR5 activation by immunosuppressive bile acids calculated according to published protocols (Leonhardt et al. 2021)	Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion
bile acid profile in stool	The bile acid profile in stool is an exploratory outcome measure that examines the composition and concentration of various bile acids in stool samples.	Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion
materno-fetal bile acid transfer rate (bile acid profile)	The maternal-fetal bile acid transfer rate describes the extent and efficiency with which bile acids pass from the mother through the placenta into the fetal circulation (placental permeability).	Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Other Outcome Measures

Outcome Measure	Time Frame
Correlation between bile acid profiles and TGR5 activation	Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Investigators: Study Chair: Tanja Groten, Prof. Dr. med., University Hospital Jena

Publications and helpful links

General Publications

• Wahlstrom A, Sayin SI, Marschall HU, Backhed F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016 Jul 12;24(1):41-50. doi: 10.1016/j.cmet.2016.05.005. Epub 2016 Jun 16.
• Hagenbeck C, Hamza A, Kehl S, Maul H, Lammert F, Keitel V, et al. Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd. 2021;81(8):922-39.
• Shao Y, Yao Z, Lu J, Li H, Wu W, Ding M. [Change of heart rate power spectrum and its association with sudden death in the fetuses of rats with intrahepatic cholestasis of pregnancy]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2007;24(6):1215-9.
• Vasavan T, Deepak S, Jayawardane IA, Lucchini M, Martin C, Geenes V, et al. Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations. J Hepatol. 2021;74(5):1087-96.
• Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet. 2006;93(1):53-4.
• Katsidzira L, Ocvirk S, Wilson A, Li J, Mahachi CB, Soni D, et al. Differences in Fecal Gut Microbiota, Short-Chain Fatty Acids and Bile Acids Link Colorectal Cancer Risk to Dietary Changes Associated with Urbanization Among Zimbabweans. Nutr Cancer. 2019;71(8):1313-24.
• Li X, Xie H, Chao JJ, Jia YH, Zuo J, An YP, et al. Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy. BMC Microbiol. 2023;23(1):282.
• Staley C, Weingarden AR, Khoruts A, Sadowsky MJ. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl Microbiol Biotechnol. 2017;101(1):47-64.
• Lin Z, Wu J, Wang J, Levesque CL, Ma X. Dietary Lactobacillus reuteri prevent from inflammation mediated apoptosis of liver via improving intestinal microbiota and bile acid metabolism. Food Chem. 2023;404(Pt B):134643.
• Martinez-Gili L, Pechlivanis A, McDonald JAK, Begum S, Badrock J, Dyson JK, et al. Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis. Gut Microbes. 2023;15(1):2208501.
• Zhang X, Han S, Jiang X, Duan S, Gao Y, Ding J, et al. Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection. Front Cell Infect Microbiol. 2023;13:1254016.
• Ryan PM, Stanton C, Caplice NM. Bile acids at the cross-roads of gut microbiome-host cardiometabolic interactions. Diabetol Metab Syndr. 2017;9:102.
• Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30(3):332-8.
• Klinke P, Kurtz, Silbernagel (Hrsg.). Physiologie. In: Klinke, editor. Physiologie: Thieme; 2010. p. 471, 5.
• Leonhardt J, Haider RS, Sponholz C, Leonhardt S, Drube J, Spengler K, et al. Circulating Bile Acids in Liver Failure Activate TGR5 and Induce Monocyte Dysfunction. Cell Mol Gastroenterol Hepatol. 2021;12(1):25-40.
• de Vries E, Bolier R, Goet J, Pares A, Verbeek J, de Vree M, et al. Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. Gastroenterology. 2021;160(3):734-43 e6.
• Poupon RE, Chretien Y, Poupon R, Paumgartner G. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology. 1993;17(4):599-604.
• Trottier J, Bialek A, Caron P, Straka RJ, Heathcote J, Milkiewicz P, et al. Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study. Dig Liver Dis. 2012;44(4):303-10.
• Horvatits T, Drolz A, Roedl K, Rutter K, Ferlitsch A, Fauler G, et al. Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis. Liver Int. 2017;37(2):224-31.
• Manna LB, Ovadia C, Lovgren-Sandblom A, Chambers J, Begum S, Seed P, et al. Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study. BJOG. 2019;126(13):1633-40.
• Sepúlveda WH, González C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol. 1991;42(3):211-5.
• Williamson C, Miragoli M, Sheikh Abdul Kadir S, Abu-Hayyeh S, Papacleovoulou G, Geenes V, et al. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58-61.
• Gorelik J, Shevchuk A, de Swiet M, Lab M, Korchev Y, Williamson C. Comparison of the arrhythmogenic effects of tauro- and glycoconjugates of cholic acid in an in vitro study of rat cardiomyocytes. BJOG: An International Journal of Obstetrics & Gynaecology. 2004;111(8):867-70.
• Geenes V, Lövgren-Sandblom A, Benthin L, Lawrance D, Chambers J, Gurung V, et al. The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. PLoS One. 2014;9(1):e83828.
• Joutsiniemi T, Ekblad U, Rosén KG, Timonen S. Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2019;45(2):306-12.
• Toprak V, Kafadar MT. Intrahepatic cholestasis of pregnancy: Is fetoplacental doppler ultrasound useful in the diagnosis and follow-up? 2021;12:87-91.
• Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467-74.
• Blencowe H, Cousens S, Jassir FB, Say L, Chou D, Mathers C, et al. National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health. 2016;4(2):e98-e108.
• Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, 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.
• Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009;15(17):2049-66.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Bile acid profile; Intrahepatic Cholestasis of pregnancy
• Additional Relevant MeSH Terms: Intrahepatic Cholestasis of Pregnancy
• Other Study ID Numbers: Reg.-Nr.: 2023-2917-Material

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data concerns a vulnerable population (pregnant individuals and their newborns), which is why personal information is treated with particular sensitivity.; The local data protection policy must be observed.; In scientific cooperation, a release is conceivable after careful review and in accordance with legal, ethical, and organizational requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No