title: The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid.
abstract: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Geenes
authors.affiliation: Departments of Clinical Chemistry and Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anita
authors.initials: A
authors.lastname: Lövgren-Sandblom
authors.affiliation: Departments of Clinical Chemistry and Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lisbet
authors.initials: L
authors.lastname: Benthin
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Dominic
authors.initials: D
authors.lastname: Lawrance
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chambers
authors.affiliation: School of Human Development, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Vinita
authors.initials: V
authors.lastname: Gurung
authors.affiliation: School of Human Development, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: Thornton
authors.affiliation: Women's Health Academic Centre, King's College London and King's Health Partners, London, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Chappell
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Erum
authors.initials: E
authors.lastname: Khan
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom ; Women's Health Academic Centre, King's College London and King's Health Partners, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Dixon
authors.affiliation: Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom ; Women's Health Academic Centre, King's College London and King's Health Partners, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Williamson
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood*; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic / Q000097:blood* / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005998:Glycine / Q000097:blood; D006801:Humans; D013058:Mass Spectrometry; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy*; D013654:Taurine / Q000097:blood; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D013654:Taurine; D014580:Ursodeoxycholic Acid; D005998:Glycine