Serum Bile Acid Profiles in Patients With Intrahepatic Cholestasis of Pregnancy

Обзор

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.

Первичные конечные точки

• bile acid profile [Срок оценки: Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion]

Вторичные конечные точки (3)

• TGR-5 activity [Срок оценки: Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion]
• bile acid profile in stool [Срок оценки: Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion]
• materno-fetal bile acid transfer rate (bile acid profile) [Срок оценки: Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion]

Критерии участия

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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Германия · 1 центр

• Klinik für Geburtsmedizin, Universitätsklinikum Jena — Jena

Публикации

• Hagenbeck C, Hamza A, Kehl S, Maul H, Lammert F, Keitel V, Hutten MC, Pecks U. Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd. 2021 Aug;81(8):922-939. doi: 10.1055/a-1386-3912. Epub 2021 Aug 9. PMID 34393256
• 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 Dec;24(6):1215-9. Chinese. PMID 18232463
• Vasavan T, Deepak S, Jayawardane IA, Lucchini M, Martin C, Geenes V, Yang J, Lovgren-Sandblom A, Seed PT, Chambers J, Stone S, Kurlak L, Dixon PH, Marschall HU, Gorelik J, Chappell L, Loughna P, Thornton J, Pipkin FB, Hayes-Gill B, Fifer WP, Williamson C. Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations. J Hepatol. 2021 M PMID 33276032
• Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet. 2006 Apr;93(1):53-4. doi: 10.1016/j.ijgo.2005.12.030. Epub 2006 Mar 9. No abstract available. PMID 16527280
• Katsidzira L, Ocvirk S, Wilson A, Li J, Mahachi CB, Soni D, DeLany J, Nicholson JK, Zoetendal EG, O'Keefe SJD. 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):1313-1324. doi: 10.1080/01635581.2019.1602659. Epub 2019 Apr 22. PMID 31007075
• Li X, Xie H, Chao JJ, Jia YH, Zuo J, An YP, Bao YR, Jiang X, Ying H. Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy. BMC Microbiol. 2023 Oct 3;23(1):282. doi: 10.1186/s12866-023-02983-x. PMID 37784030
• 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 Jan;101(1):47-64. doi: 10.1007/s00253-016-8006-6. Epub 2016 Nov 25. PMID 27888332
• 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. PMID 27320064

Идентификаторы

NCT: NCT07428226 · Reg.-Nr.: 2023-2917-Material

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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