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Intrahepatic Cholestasis of Pregnancy: Toward Improving Perinatal Outcome

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Abstract

Intrahepatic cholestasis of pregnancy (ICP) is associated with poor perinatal outcomes in some women such as preterm delivery and fetal demise. Ursodeoxycholic acid (UDCA) is the main therapeutic agent for ICP, but recent evidence failed to show an impact on most perinatal outcomes. Our objective is to summarize the latest evidence in the management of ICP, with a focus on perinatal outcome. We propose a practical approach that combines pharmacotherapy with biochemical and fetal testing, as well as delivery planning.

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References

  1. Marschall HU, WikströmShemer E, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology. 2013;58(4):1385–91. https://doi.org/10.1002/hep.26444.

    Article  PubMed  Google Scholar 

  2. Lee RH, Goodwin TM, Greenspoon J, Incerpi M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol. 2006;26(9):527–32. https://doi.org/10.1038/sj.jp.7211545.

    Article  CAS  PubMed  Google Scholar 

  3. Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health 4:35–37, 1999. Germain A, Carvajal JA, Glasinovic JC, et al.: Intrahepatic cholestasis of pregnancy. An intriguing pregnancy specific disorder. J Soc Gynecol Invest. 2002;9:10–4.

    Google Scholar 

  4. Reyes H. Intrahepatic cholestasis. A puzzling disorder of pregnancy [review]. J Gastroenterol Hepatol. 1997;12:211–6.

    Article  CAS  PubMed  Google Scholar 

  5. Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014;124(1):120–33. https://doi.org/10.1097/AOG.0000000000000346.

    Article  PubMed  Google Scholar 

  6. Berg B, Helm G, Petersohn I, et al. Cholestasis of pregnancy. Clinical and laboratory studies. Acta Obstet Gynecol Scand. 1986;65:107–13.

    Article  CAS  PubMed  Google Scholar 

  7. van Mil SW, Milona A, Dixon PH, et al. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. Gastroenterology. 2007;133:507–16.

    Article  PubMed  Google Scholar 

  8. Walker IA, Nelson-Piercy C, Williamson C. Role of bile acid measurement in pregnancy. Ann Clin Biochem. 2002;39(Pt 2):105–13. https://doi.org/10.1258/0004563021901856.

    Article  CAS  PubMed  Google Scholar 

  9. Laatikainen T, Ikonen E. Serum bile acids in cholestasis of pregnancy. Obstet Gynecol. 1977;50:313–8.

    CAS  PubMed  Google Scholar 

  10. Laatikainen T, Tulenheimo A. Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy. Int J Gynaecol Obstet. 1984;22:91–4.

    Article  CAS  PubMed  Google Scholar 

  11. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40:467–74.

    Article  PubMed  Google Scholar 

  12. 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 [published correction appears in Lancet. 2019 Mar 16;393(10176):1100]. Lancet. 2019;393(10174):899–909. https://doi.org/10.1016/S0140-6736(18)31877-4.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomized controlled trial. The Lancet. 2019;394:849–60.

    Article  CAS  Google Scholar 

  14. Ovadia C, Sajous J, Seed PT, et al. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2021;S2468–1253(21):00074–81. https://doi.org/10.1016/S2468-1253(21)00074-1.

    Article  Google Scholar 

  15. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318–28.

    Article  CAS  PubMed  Google Scholar 

  16. Palma J, Reyes H, Ribalta J, Hernández I, Sandoval L, Almuna R, Liepins J, Lira F, Sedano M, Silva O. ToháD, Silva JJ: Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol. 1997;27(6):1022.

    Article  CAS  PubMed  Google Scholar 

  17. Bacq Y, Sentilhes L, Reyes HB, Glantz A, Kondrackiene J, Binder T, Nicastri PL, Locatelli A, Floreani A, Hernandez I, Di Martino V. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology. 2012;143(6):1492.

    Article  CAS  PubMed  Google Scholar 

  18. Burrows RF, Clavisi O, Burrows E. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2001;(4):CD000493. https://doi.org/10.1002/14651858.CD000493.

  19. Gurung V, Middleton P, Milan SJ, Hague W, Thornton JG. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013;6:CD000493.

    Google Scholar 

  20. Obstetric Cholestasis (Green-top Guideline No. 43) https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg43/.

  21. Shen Y, Zhou J, Zhang S, et al. Is it necessary to perform the pharmacological interventions for intrahepatic cholestasis of pregnancy? A Bayesian network meta-analysis. Clin Drug Investig. 2019;39:15–26.

    Article  CAS  PubMed  Google Scholar 

  22. Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev. 2020;7:CD000493. https://doi.org/10.1002/14651858.CD000493.pub3.

    Article  PubMed  Google Scholar 

  23. Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG, PITCH Study Consortium. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ. 2012;344:e3799.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Lee RH, Mara Greenberg, Metz TD, Pettker CM. Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am J Obstet Gynecol. 2021;224(2):B2–B9. https://doi.org/10.1016/j.ajog.2020.11.002.

  25. Fleminger J, Seed PT, Smith A, Juszczak E, Dixon PH, Chambers J, Dorling J, Williamson C, Thornton JG, Chappell LC. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial. BJOG. 2021;128(6):1066–75. https://doi.org/10.1111/1471-0528.16567.

  26. Sentilhes L, Verspyck E, Pia P, Marpeau L. Fetal death in a patient with intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2006;107(2 Pt 2):458–60.

    Article  PubMed  Google Scholar 

  27. Laatikainen T, Tulenheimo A. Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy. Int J Gynaecol Obstet. 1984;22(2):91–4.

    Article  CAS  PubMed  Google Scholar 

  28. Lee RH, Incerpi MH, Miller DA, Pathak B, Goodwin TM. Sudden fetal death in intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2009;113(2 Pt 2):528–31.

    Article  PubMed  Google Scholar 

  29. Di Mascio D, Quist-Nelson J, Riegel M, George B, Saccone G, Brun R, Haslinger C, Herrera C, Kawakita T, Lee RH, Benedetti Panici P, Berghella V. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. J Matern Fetal Neonatal Med. 2019;19:1–9.

    Google Scholar 

  30. Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology. 2014;59(4):1482–91.

    Article  PubMed  Google Scholar 

  31. Lo JO, Shaffer BL, Allen AJ, Little SE, Cheng YW, Caughey AB. Intrahepatic cholestasis of pregnancy and timing of delivery. J Matern Fetal Neonatal Med. 2015;28(18):2254–8.

    Article  PubMed  Google Scholar 

  32. Puljic A, Kim E, Page J, Esakoff T, Shaffer B, LaCoursiere DY, Caughey AB. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol. 2015;212(5):667.e1-5.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555-0587, USA

    Antonio F. Saad, Luis D. Pacheco & George R. Saade

  2. Division of Surgical Critical Care, Department of Anesthesiology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA

    Antonio F. Saad & Luis D. Pacheco

  3. Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UK

    Lucy Chappell

Authors
  1. Antonio F. Saad
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  2. Luis D. Pacheco
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  3. Lucy Chappell
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  4. George R. Saade
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Correspondence to Antonio F. Saad.

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Ursodeoxycholic acid improves some perinatal outcomes. We propose an updated practical approach to ICP combining pharmacotherapy with biochemical and fetal testing, as well as delivery planning.

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Saad, A.F., Pacheco, L.D., Chappell, L. et al. Intrahepatic Cholestasis of Pregnancy: Toward Improving Perinatal Outcome. Reprod. Sci. 29, 3100–3105 (2022). https://doi.org/10.1007/s43032-021-00740-x

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  • DOI: https://doi.org/10.1007/s43032-021-00740-x

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