{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:58:50Z","timestamp":1788998330131,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Intrahepatic cholestasis of pregnancy (ICP) is the most common, reversible, and closely related to pregnancy condition characterized by elevated levels of bile acids (BAs) in blood serum and an increased risk of adverse perinatal outcomes. Due to the complex interactions between the mother and the fetus in metabolism and transplacental BAs transport, ICP is classified as a fetal-maternal disease. The disease is usually mild in pregnant women, but it can be fatal to the fetus, leading to numerous complications, including intrauterine death. The pathophysiology of the disease is based on inflammatory mechanisms caused by elevated BA levels. Although ICP cannot be completely prevented, its early diagnosis and prompt management significantly reduce the risk of fetal complications, the most serious of which is unexpected intrauterine death. It is worth emphasizing that all diagnostics and management of ICP during pregnancy are based on BA levels. Therefore, it is important to standardize the criteria for diagnosis, as well as recommendations for management depending on the level of BAs, which undoubtedly determines the impact on the fetus. The purpose of this review is to present the potential and importance of BAs in the detection and rules of medical procedure in ICP.<\/jats:p>","DOI":"10.3390\/diagnostics12112746","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T02:03:58Z","timestamp":1668045838000},"page":"2746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Bile Acids in Intrahepatic Cholestasis of Pregnancy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-5995","authenticated-orcid":false,"given":"Maciej","family":"Majsterek","sequence":"first","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Wierzchowska-Opoka","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Makosz","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-1383","authenticated-orcid":false,"given":"Lena","family":"Kreczy\u0144ska","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-0409","authenticated-orcid":false,"given":"\u017baneta","family":"Kimber-Trojnar","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017cena","family":"Leszczy\u0144ska-Gorzelak","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.placenta.2021.09.014","article-title":"Current understanding of autophagy in intrahepatic cholestasis of pregnancy","volume":"115","author":"Shan","year":"2021","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jhep.2015.11.030","article-title":"Pregnancy and liver disease","volume":"64","author":"Westbrook","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Piechota, J., and Jelski, W. (2020). Intrahepatic Cholestasis in Pregnancy: Review of the Literature. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051361"},{"key":"ref_4","first-page":"26","article-title":"Treatment of obstetric cholestasis with polyunsaturated phosphatidylcholine and ursodeoxycholic acid","volume":"82","author":"Marciniak","year":"2011","journal-title":"Ginekol. Pol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Panaitescu, A.M., Popescu, M.R., Ciobanu, A.M., Gica, N., and Cimpoca-Raptis, B.A. (2021). Pregnancy Complications Can Foreshadow Future Disease\u2014Long-Term Outcomes of a Complicated Pregnancy. Medicina, 57.","DOI":"10.3390\/medicina57121320"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6679322","DOI":"10.1155\/2021\/6679322","article-title":"Molecular Pathogenesis of Intrahepatic Cholestasis of Pregnancy","volume":"2021","author":"Xiao","year":"2021","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.3748\/wjg.14.5781","article-title":"Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems","volume":"14","author":"Kondrackiene","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Stulic, M., Culafic, D., Boricic, I., Stojkovic Lalosevic, M., Pejic, N., Jankovic, G., Milovanovic, T., Culafic-Vojinovic, V., Vlaisavljevic, Z., and Culafic, M. (2019). Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester. Medicina, 55.","DOI":"10.3390\/medicina55080454"},{"key":"ref_9","unstructured":"Huang, S., Liu, Y., Guo, N., Liu, X., Li, G., and Du, Q. (2022). Serum profiles of inflammatory cytokines associated with intrahepatic cholestasis of pregnancy. J. Matern. Fetal Neonatal Med., 1\u201310."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Varlas, V.N., Boh\u00eel\u021bea, R., Gheorghe, G., Bostan, G., Angelescu, G.A., Penes, O.N., Bors, R.G., Clo\u021bea, E., Bacalbasa, N., and Diaconu, C.C. (2021). State of the Art in Hepatic Dysfunction in Pregnancy. Healthcare, 9.","DOI":"10.3390\/healthcare9111481"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"889646","DOI":"10.3389\/fimmu.2022.889646","article-title":"Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota","volume":"13","author":"Lin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1093\/jmcb\/mjw025","article-title":"Bile acids evoke placental inflammation by activating Gpbar1\/NF-\u03baB pathway in intrahepatic cholestasis of pregnancy","volume":"8","author":"Zhang","year":"2016","journal-title":"J. Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.gastha.2022.08.011","article-title":"A rare case of recurrent intrahepatic cholestasis of pregnancy with prolonged postpartum hepatic inflammation despite normalization of bile acid levels","volume":"2","author":"Shah","year":"2023","journal-title":"Gastro Hep Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/jog.12902","article-title":"Role of inflammation in intrahepatic cholestasis of pregnancy","volume":"42","author":"Biberoglu","year":"2016","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00281-021-00869-6","article-title":"Role of bile acids in inflammatory liver diseases","volume":"43","author":"Evangelakos","year":"2021","journal-title":"Semin. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Holtmann, T.M., Inzaugarat, M.E., Knorr, J., Geisler, L., Schulz, M., Bieghs, V., Frissen, M., Feldstein, A.E., Tacke, F., and Trautwein, C. (2021). Bile Acids Activate NLRP3 Inflammasome, Promoting Murine Liver Inflammation or Fibrosis in a Cell Type-Specific Manner. Cells, 10.","DOI":"10.3390\/cells10102618"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kawase, A., Hatanaka, M., Matsuda, N., Shimada, H., and Iwaki, M. (2022). Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158573"},{"key":"ref_18","first-page":"e10540","article-title":"Never Too Soon: An Unusual Case of Intrahepatic Cholestasis of Pregnancy at Five Weeks Gestation","volume":"12","author":"Wongjarupong","year":"2020","journal-title":"Cureus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e244254","DOI":"10.1136\/bcr-2021-244254","article-title":"Rare case of obstetric cholestasis presenting in the first trimester following in vitro fertilisation","volume":"14","author":"Koh","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_20","first-page":"4980610","article-title":"Unexplained First Trimester Intrahepatic Cholestasis of Pregnancy: A Case Report and Literature Review","volume":"2019","author":"Salame","year":"2019","journal-title":"Case Rep. Obstet. Gynecol."},{"key":"ref_21","first-page":"38","article-title":"Severe First Trimester Recurrent Intrahepatic Cholestasis of Pregnancy: A Case Report and Literature Review","volume":"6","author":"Hubschmann","year":"2016","journal-title":"AJP Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/01443615.2017.1286302","article-title":"Two cases of first onset intrahepatic cholestasis of pregnancy associated with moderate ovarian hyperstimulation syndrome after IVF treatment and review of the literature","volume":"37","author":"Mutlu","year":"2017","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106399","DOI":"10.1016\/j.prostaglandins.2019.106399","article-title":"Role of sphingolipids in the pathogenesis of intrahepatic cholestasis","volume":"147","author":"Pierzynski","year":"2020","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_24","first-page":"CD012546","article-title":"Total serum bile acids or serum bile acid profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy","volume":"7","author":"Manzotti","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yurtcu, N., Caliskan, C.S., Guvey, H., Celik, S., Hatirnaz, S., and Tinelli, A. (2022). Predictive and Diagnostic Value of Serum Adipokines in Pregnant Women with Intrahepatic Cholestasis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19042254"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3109\/00016348609158363","article-title":"Cholestasis of pregnancy. Clinical and laboratory studies","volume":"65","author":"Berg","year":"1986","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0301-2115(98)00086-4","article-title":"Relevance of serum bile acid profile in the diagnosis of intrahepatic cholestasis of pregnancy in an high incidence area: Portugal","volume":"80","author":"Brites","year":"1998","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1055\/a-1386-3912","article-title":"Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine-Section on Maternal Disorders","volume":"81","author":"Hagenbeck","year":"2021","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_29","first-page":"189","article-title":"Pregnancy outcome with intrahepatic cholestasis","volume":"94","author":"Heinonen","year":"1999","journal-title":"Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/hep.26444","article-title":"Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: A population-based cohort study","volume":"58","author":"Marschall","year":"2013","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0168-8278(89)90079-2","article-title":"Intrahepatic cholestasis of pregnancy in twin pregnancies","volume":"9","author":"Gonzalez","year":"1989","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1093\/humrep\/17.11.2897","article-title":"The course of pregnancy and delivery and the use of maternal healthcare services after standard IVF in Northern Finland 1990","volume":"17","author":"Koivurova","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cld.2015.08.010","article-title":"New Insights on Intrahepatic Cholestasis of Pregnancy","volume":"20","author":"Floreani","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_34","first-page":"S203","article-title":"The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy","volume":"64","author":"Hill","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: Results of aggregate and individual patient data meta-analyses","volume":"393","author":"Ovadia","year":"2019","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102013","DOI":"10.1016\/j.clinre.2022.102013","article-title":"Effects of elevated bile acid levels on fetal myocardium in intrahepatic cholestasis of pregnancy, a retrospective study from a neonatal perspective","volume":"46","author":"Wang","year":"2022","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5603\/GP.2019.0039","article-title":"Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy","volume":"90","year":"2019","journal-title":"Ginekol. Pol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1080\/14767058.2019.1685965","article-title":"Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: A systematic review","volume":"34","author":"Riegel","year":"2021","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/jog.15283","article-title":"Fetal cardiac dysfunction in pregnancies affected by intrahepatic cholestasis of pregnancy: A cohort study","volume":"48","author":"Rodriguez","year":"2022","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517.e1","DOI":"10.1016\/j.ajog.2022.06.013","article-title":"Beyond stillbirth: Association of intrahepatic cholestasis of pregnancy severity and adverse outcomes","volume":"227","author":"Sarker","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_41","first-page":"16","article-title":"Unfolding newer concepts in placental pathology of obstetric cholestasis-a cause for prematurity","volume":"14","author":"Devalla","year":"2022","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/jmwh.13362","article-title":"Navigating Uncertainty: A Case Study of Intrahepatic Cholestasis of Pregnancy","volume":"67","author":"Blumenfeld","year":"2022","journal-title":"J. Midwifery Womens Health"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1111\/1471-0528.17174","article-title":"Intrahepatic cholestasis of pregnancy-Time to redefine the reference range of total serum bile acids: A cross-sectional study","volume":"129","author":"Huri","year":"2022","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Seyed Khoei, N., Anton, G., Peters, A., Freisling, H., and Wagner, K.-H. (2020). The Association between Serum Bilirubin Levels and Colorectal Cancer Risk: Results from the Prospective Cooperative Health Research in the Region of Augsburg (KORA) Study in Germany. Antioxidants, 9.","DOI":"10.3390\/antiox9100908"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shulpekova, Y., Shirokova, E., Zharkova, M., Tkachenko, P., Tikhonov, I., Stepanov, A., Sinitsyna, A., Izotov, A., Butkova, T., and Shulpekova, N. (2022). A Recent Ten-Year Perspective: Bile Acid Metabolism and Signaling. Molecules, 27.","DOI":"10.3390\/molecules27061983"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1097\/AOG.0000000000004160","article-title":"Effect of Fasting on Total Bile Acid Levels in Pregnancy","volume":"136","author":"Smith","year":"2020","journal-title":"Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/GRF.0000000000000495","article-title":"Intrahepatic Cholestasis of Pregnancy","volume":"63","author":"Smith","year":"2020","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1055\/s-0028-1103158","article-title":"Bile acid ratio in diagnosis of intrahepatic cholestasis of pregnancy","volume":"26","author":"Huang","year":"2009","journal-title":"Am. J. Perinatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1055\/s-0035-1555128","article-title":"Bile acid determination after standardized glucose load in pregnant women","volume":"5","author":"Adams","year":"2015","journal-title":"Am. J. Perinatol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Haange, S.-B., Till, A., Bergh, P.-O., Fauler, G., Gigl, M., L\u00f6fgren-Sandblom, A., Schaap, F.G., Clavel, T., Trautwein, C., and Fenske, W. (2022). Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility. Metabolites, 12.","DOI":"10.3390\/metabo12070583"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, B., Kuipers, F., de Boer, J.F., and Kuivenhoven, J.A. (2022). Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles. J. Clin. Med., 11.","DOI":"10.3390\/jcm11010004"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Grant, S.M., and DeMorrow, S. (2020). Bile Acid Signaling in Neurodegenerative and Neurological Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21175982"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.livres.2020.05.001","article-title":"Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis","volume":"4","author":"Chiang","year":"2020","journal-title":"Liver Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tagawa, R., Kobayashi, M., Sakurai, M., Yoshida, M., Kaneko, H., Mizunoe, Y., Nozaki, Y., Okita, N., Sudo, Y., and Higami, Y. (2022). Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031793"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13293-019-0265-3","article-title":"The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis","volume":"10","author":"Phelps","year":"2019","journal-title":"Biol. Sex Differ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/cphy.c120023","article-title":"Bile acid metabolism and signaling","volume":"3","author":"Chiang","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jhep.2021.02.011","article-title":"Bile formation and secretion: An update","volume":"75","author":"Boyer","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Durn\u00edk, R., \u0160indlerov\u00e1, L., Babica, P., and Jur\u010dek, O. (2022). Bile Acids Transporters of Enterohepatic Circulation for Targeted Drug Delivery. Molecules, 27.","DOI":"10.3390\/molecules27092961"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.2174\/0929867324666170619104801","article-title":"Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones","volume":"26","author":"Wang","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1152\/physiol.00028.2020","article-title":"Bile Acids, Their Receptors, and the Gut Microbiota","volume":"36","author":"Poland","year":"2021","journal-title":"Physiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"An, C., Chon, H., Ku, W., Eom, S., Seok, M., Kim, S., Lee, J., Kim, D., Lee, S., and Koo, H. (2022). Bile Acids: Major Regulator of the Gut Microbiome. Microorganisms, 10.","DOI":"10.3390\/microorganisms10091792"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.chom.2022.02.004","article-title":"Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis","volume":"30","author":"Cai","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gr\u00fcner, N., and Mattner, J. (2021). Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver\u2013Gut Axis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031397"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000450983","article-title":"Bile Acid Uptake Transporters as Targets for Therapy","volume":"35","author":"Slijepcevic","year":"2017","journal-title":"Dig. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3389\/fnins.2017.00617","article-title":"Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System","volume":"11","author":"Mertens","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Shulpekova, Y., Zharkova, M., Tkachenko, P., Tikhonov, I., Stepanov, A., Synitsyna, A., Izotov, A., Butkova, T., Shulpekova, N., and Lapina, N. (2022). The Role of Bile Acids in the Human Body and in the Development of Diseases. Molecules, 27.","DOI":"10.3390\/molecules27113401"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00018-022-04278-2","article-title":"The role of bile acids in carcinogenesis","volume":"79","author":"Rozman","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"di Gregorio, M.C., Cautela, J., and Galantini, L. (2021). Physiology and Physical Chemistry of Bile Acids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041780"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Caliceti, C., Punzo, A., Silla, A., Simoni, P., Roda, G., and Hrelia, S. (2022). New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer. Nutrients, 14.","DOI":"10.3390\/nu14142964"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.3389\/fphar.2018.01382","article-title":"Pharmacological Applications of Bile Acids and Their Derivatives in the Treatment of Metabolic Syndrome","volume":"9","author":"Stanimirov","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1136\/gutjnl-2021-324305","article-title":"Novel therapeutic targets for cholestatic and fatty liver disease","volume":"71","author":"Trauner","year":"2022","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12848","DOI":"10.1111\/jcmm.15881","article-title":"A novel role for farnesoid X receptor in the bile acid-mediated intestinal glucose homeostasis","volume":"24","author":"Zhao","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbadis.2017.10.003","article-title":"Farnesoid X receptor: A \"homeostat\" for hepatic nutrient metabolism","volume":"1864","author":"Massafra","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fmed.2020.00544","article-title":"Bile Acids and FXR: Novel Targets for Liver Diseases","volume":"7","author":"Stofan","year":"2020","journal-title":"Front. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"853501","DOI":"10.1155\/2011\/853501","article-title":"TGR5: A novel target for weight maintenance and glucose metabolism","volume":"2011","author":"Chen","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Mart\u00ednez, O., Garc\u00eda-Montero, C., S\u00e1ez, M.A., \u00c1lvarez-Mon, M.A., Torres-Carranza, D., \u00c1lvarez-Mon, M., Bujan, J., Garc\u00eda-Honduvilla, N., and Bravo, C. (2022). The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease. Cells, 11.","DOI":"10.3390\/cells11030568"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wojczakowski, W., Kimber-Trojnar, \u017b., Dziwisz, F., S\u0142odzi\u0144ska, M., S\u0142odzi\u0144ski, H., and Leszczy\u0144ska-Gorzelak, B. (2021). Preeclampsia and Cardiovascular Risk for Offspring. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143154"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ya\u00f1ez, M.J., and Leiva, A. (2022). Human Placental Intracellular Cholesterol Transport: A Focus on Lysosomal and Mitochondrial Dysfunction and Oxidative Stress. Antioxidants, 11.","DOI":"10.3390\/antiox11030500"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Nikolov, A., and Popovski, N. (2021). Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030480"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wang, P., Song, Y., Zhong, H., Lin, S., Zhang, X., Li, J., Che, L., Feng, B., Lin, Y., and Xu, S. (2019). Transcriptome Profiling of Placenta through Pregnancy Reveals Dysregulation of Bile Acids Transport and Detoxification Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174099"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e243","DOI":"10.1002\/hsr2.243","article-title":"Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis","volume":"4","author":"Gagnon","year":"2021","journal-title":"Health Sci. Rep."},{"key":"ref_83","first-page":"165","article-title":"Cholestaza ci\u0119\u017carnych-choroba niedoceniona. Przegl\u0105d pi\u015bmiennictwa","volume":"3","year":"2010","journal-title":"Perinatol. Neonatol. Ginekol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1530\/EJE-20-1101","article-title":"ENDOCRINOLOGY in PREGNANCY: Metabolic impact of bile acids in gestation","volume":"184","author":"Fan","year":"2021","journal-title":"Eur. J. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.00028.2017","article-title":"Pregnancy and bile acid disorders","volume":"313","author":"Pataia","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ontsouka, E., Epstein, A., Kallol, S., Zaugg, J., Baumann, M., Schneider, H., and Albrecht, C. (2021). Placental Expression of Bile Acid Transporters in Intrahepatic Cholestasis of Pregnancy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910434"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.mam.2017.05.003","article-title":"Bile acids and gestation","volume":"56","author":"McIlvride","year":"2017","journal-title":"Mol. Aspects Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1021\/acs.chemrev.0c00659","article-title":"Structure and Function of Hepatobiliary ATP Binding Cassette Transporters","volume":"121","author":"Kroll","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1471-0528.1981.tb00975.x","article-title":"Changes in serum bile acid concentrations during normal pregnancy, in patients with intrahepatic cholestasis of pregnancy and in pregnant women with itching","volume":"88","author":"Heikkinen","year":"1981","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/0016-5085(86)90682-7","article-title":"Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis","volume":"91","author":"Lunzer","year":"1986","journal-title":"Gastroenterology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"166269","DOI":"10.1016\/j.bbadis.2021.166269","article-title":"Recognition of asymptomatic hypercholanemia of pregnancy: Different clinical features, fetal outcomes and bile acids metabolism from intrahepatic cholestasis of pregnancy","volume":"1868","author":"He","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1042\/cs1020587","article-title":"Relationship between asymptomatic hypercholanaemia of pregnancy and progesterone metabolism","volume":"102","author":"Pascual","year":"2002","journal-title":"Clin. Sci."},{"key":"ref_93","first-page":"CD000493","article-title":"Pharmacological interventions for treating intrahepatic cholestasis of pregnancy","volume":"7","author":"Walker","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ejogrb.2018.10.041","article-title":"Intrahepatic cholestasis of pregnancy: Review of six national and regional guidelines","volume":"231","author":"Bicocca","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/hep.26617","article-title":"Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population-based case-control study","volume":"59","author":"Geenes","year":"2014","journal-title":"Hepatology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/OGX.0000000000000524","article-title":"Intrahepatic cholestasis of pregnancy: A review of diagnosis and management","volume":"73","author":"Wood","year":"2018","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"569","DOI":"10.5604\/01.3001.0010.0294","article-title":"Sensitivity and specificity of biochemical tests for diagnosis of intrahepatic cholestasis of pregnancy","volume":"16","author":"Jurate","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Girling, J., Knight, C.L., and Chappell, L. (2022). Royal College of Obstetricians and Gynaecologists. Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022. BJOG Int. J. Obstet. Gynaecol.","DOI":"10.1111\/1471-0528.17206"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Society for Maternal-Fetal Medicine (SMFM), Lee, R.H., Greenberg, M., Metz, T.D., and Pettker, C.M. (2021). Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am. J. Obstet. Gynecol., 224, B2\u2013B9.","DOI":"10.1016\/j.ajog.2020.11.002"},{"key":"ref_100","unstructured":"(2022, November 04). South Australian Perinatal Practice Guideline. Intrahepatic Cholestasis of Pregnancy, Available online: https:\/\/www.sahealth.sa.gov.au\/wps\/wcm\/connect\/f91fbf004ee530b2a5ebadd150ce4f37\/Intrahepatic+cholestasis+of+pregnancy_PPG_v4_0.pdf?MOD=AJPERES&CACHEID=ROOTWORKSPACE-f91fbf004ee530b2a5ebadd150ce4f37-ocQJ9qe."},{"key":"ref_101","first-page":"713","article-title":"Clinical practice guidelines of the Team of Experts of the Polish Gynecological Society: Management of the intrahepatic cholestasis of pregnancy","volume":"83","author":"Oleszczuk","year":"2012","journal-title":"Ginekol. Pol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"757","DOI":"10.14218\/JCTH.2022.00147","article-title":"Guidelines for the Management of Cholestatic Liver Diseases (2021)","volume":"10","author":"Lu","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0022-4731(73)90039-3","article-title":"Excertion of progesterone metabolites in urine and bile of pregnant women with intrahepatic cholestasis","volume":"4","author":"Laatikainen","year":"1973","journal-title":"J. Steroid Biochem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1053\/he.2000.5921","article-title":"Effect of maternal cholestasis on bile acid transfer across the rat placenta-maternal liver tandem","volume":"31","author":"Macias","year":"2000","journal-title":"Hepatology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0168-8278(98)80234-1","article-title":"Beneficial effect of ursodeoxycholic acid on alterations induced by cholestasis of pregnancy in bile acid transport across the human placenta","volume":"28","author":"Serrano","year":"1998","journal-title":"J. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/00042737-200303000-00016","article-title":"Bile acid stress in the mother and baby unit","volume":"15","author":"Howard","year":"2003","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"10361","DOI":"10.1038\/s41598-020-67301-1","article-title":"Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy","volume":"10","author":"Papacleovoulou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.clinre.2019.07.006","article-title":"Fetal coenzyme Q10 deficiency in intrahepatic cholestasis of pregnancy","volume":"44","author":"Martinefski","year":"2020","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_109","first-page":"581","article-title":"Serum bile acids in the early diagnosis of intrahepatic cholestasis of pregnancy","volume":"61","author":"Heikkinen","year":"1983","journal-title":"Obstet. Gynecol."},{"key":"ref_110","unstructured":"UpToDate (2022, November 04). Intrahepatic Cholestasis of Pregnancy. Available online: https:\/\/www.uptodate.com\/contents\/intrahepatic-cholestasis-of-pregnancy?search=cholestasis%20in%20pregnancy&source=search_result&selectedTitle=1~64&usage_type=default&display_rank=1#H21."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/AOG.0000000000000346","article-title":"Intrahepatic cholestasis of pregnancy","volume":"124","author":"Williamson","year":"2014","journal-title":"Obstet. Gynecol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/11\/2746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:13:32Z","timestamp":1760145212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/11\/2746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":111,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["diagnostics12112746"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12112746","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]}}}