Skip to main content
SpringerLink
Log in

Perinatal outcomes of intrahepatic cholestasis of pregnancy in twin versus singleton pregnancies: is plurality associated with adverse outcomes?

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To determine the rate of obstetric and neonatal complications associated with intrahepatic cholestasis of pregnancy in twin versus singleton gestations.

Methods

A retrospective cohort study including patients diagnosed with intrahepatic cholestasis of pregnancy at a single tertiary center between 2011 and 2016. Women were allocated into two groups: twin pregnancies (n = 56) and singleton pregnancies (n = 186). Obstetric and neonatal outcomes were compared between the two groups.

Results

Intrahepatic cholestasis of pregnancy was diagnosed earlier in gestation in twin compared to singleton pregnancies (33.1 ± 2.8 vs. 35.1 ± 3.0 weeks, respectively; adjusted P < 0.001). Maternal serum levels of fasting total bile acids were significantly higher in twin pregnancies compared to singletons [27 (IQR 16–44) vs. 16 (IQR 10–26) µmol/L, respectively; P = 0.01]. None of the pregnancies in our cohort was complicated by fetal death. Apgar score at 5 min and umbilical artery and vein PH at delivery were comparable between the two groups.

Conclusions

Intrahepatic cholestasis of pregnancy in twin pregnancies appears to be more severe compared to singletons, as reflected by an earlier presentation and higher levels of maternal serum total bile acids. Large prospective studies are required to customize a management strategy specific for women with twin pregnancies and intrahepatic cholestasis of pregnancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Geenes V, Williamson C (2009) Intrahepatic cholestasis of pregnancy. World J Gastroenterol 15(17):2049–2066

    Article  Google Scholar 

  2. Wikström Shemer E, Marschall HU, Ludvigsson JF, Stephansson O (2013) Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG 120(6):717–723. https://doi.org/10.1111/1471-0528.12174

    Article  PubMed  Google Scholar 

  3. Laifer SA, Stiller RJ, Siddiqui DS, Dunston-Boone G, Whetham JC (2001) Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy. J Matern Fetal Med 10(2):131–135

    Article  CAS  Google Scholar 

  4. Abedin P, Weaver JB, Egginton E (1999) Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health 4(1–2):35–37. https://doi.org/10.1080/13557859998173

    Article  CAS  PubMed  Google Scholar 

  5. Reyes H, Gonzalez MC, Ribalta J, Aburto H, Matus C, Schramm G, Katz R, Medina E (1978) Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med 88(4):487–493

    Article  CAS  Google Scholar 

  6. Savander M, Ropponen A, Avela K, Weerasekera N, Cormand B, Hirvioja ML, Riikonen S, Ylikorkala O, Lehesjoki AE, Williamson C, Aittomäki K (2003) Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy. Gut 52(7):1025–1029

    Article  CAS  Google Scholar 

  7. Lammert F, Marschall HU, Glantz A, Matern S (2000) Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 33(6):1012–1021

    Article  CAS  Google Scholar 

  8. Bacq Y, Sapey T, Bréchot MC, Pierre F, Fignon A, Dubois F (1997) Intrahepatic cholestasis of pregnancy: a prospective French study. Hepatology 26(2):358–364. https://doi.org/10.1002/hep.510260216

    Article  CAS  PubMed  Google Scholar 

  9. Reyes H, Simon FR (1993) Intrahepatic cholestasis of pregnancy: an estrogen-related disease. Semin Liver Dis 13(3):289–301. https://doi.org/10.1055/s-2007-1007357

    Article  CAS  PubMed  Google Scholar 

  10. Heikkinen J, Mäentausta O, Ylöstalo P, Jänne O (1981) Changes in serum bile acid concentrations during normal pregnancy, in patients with intrahepatic cholestasis of pregnancy and in pregnant women with itching. Br J Obstet Gynaecol 88(3):240–245

    Article  CAS  Google Scholar 

  11. Lunzer M, Barnes P, Byth K, O'Halloran M (1986) Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis. Gastroenterology 91(4):825–829

    Article  CAS  Google Scholar 

  12. Rioseco AJ, Ivankovic MB, Manzur A, Hamed F, Kato SR, Parer JT, Germain AM (1994) Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. Am J Obstet Gynecol 170(3):890–895

    Article  CAS  Google Scholar 

  13. Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C (2014) Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology 59(4):1482–1491. https://doi.org/10.1002/hep.26617

    Article  PubMed  PubMed Central  Google Scholar 

  14. Estiú MC, Frailuna MA, Otero C, Dericco M, Williamson C, Marin JJG, Macias RIR (2017) Relationship between early onset severe intrahepatic cholestasis of pregnancy and higher risk of meconium-stained fluid. PLoS ONE 12(4):e0176504. https://doi.org/10.1371/journal.pone.0176504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zecca E, De Luca D, Baroni S, Vento G, Tiberi E, Romagnoli C (2008) Bile acid-induced lung injury in newborn infants: a bronchoalveolar lavage fluid study. Pediatrics 121(1):e146–149. https://doi.org/10.1542/peds.2007-1220

    Article  PubMed  Google Scholar 

  16. Zecca E, De Luca D, Marras M, Caruso A, Bernardini T, Romagnoli C (2006) Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics 117(5):1669–1672. https://doi.org/10.1542/peds.2005-1801

    Article  PubMed  Google Scholar 

  17. Williamson C, Hems LM, Goulis DG, Walker I, Chambers J, Donaldson O, Swiet M, Johnston DG (2004) Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG 111(7):676–681. https://doi.org/10.1111/j.1471-0528.2004.00167.x

    Article  PubMed  Google Scholar 

  18. Glantz A, Marschall HU, Mattsson LA (2004) Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology 40(2):467–474. https://doi.org/10.1002/hep.20336

    Article  PubMed  Google Scholar 

  19. Raz Y, Lavie A, Vered Y, Goldiner I, Skornick-Rapaport A, Landsberg Asher Y, Maslovitz S, Levin I, Lessing JB, Kuperminc MJ, Rimon E (2015) Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. Am J Obstet Gynecol 213(3):395.e391–398. https://doi.org/10.1016/j.ajog.2015.05.011

    Article  Google Scholar 

  20. Marathe JA, Lim WH, Metz MP, Scheil W, Dekker GA, Hague WM (2017) A retrospective cohort review of intrahepatic cholestasis of pregnancy in a South Australian population. Eur J Obstet Gynecol Reprod Biol 218:33–38. https://doi.org/10.1016/j.ejogrb.2017.09.012

    Article  PubMed  Google Scholar 

  21. Liu X, Landon MB, Chen Y, Cheng W (2016) Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies. J Matern Fetal Neonatal Med 29(13):2176–2181. https://doi.org/10.3109/14767058.2015.1079612

    Article  PubMed  Google Scholar 

  22. Brouwers L, Koster MP, Page-Christiaens GC, Kemperman H, Boon J, Evers IM, Bogte A, Oudijk MA (2015) Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. Am J Obstet Gynecol 212(1):100.e101–107. https://doi.org/10.1016/j.ajog.2014.07.026

    Article  CAS  Google Scholar 

  23. Lee RH, Kwok KM, Ingles S, Wilson ML, Mullin P, Incerpi M, Pathak B, Goodwin TM (2008) Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy. Am J Perinatol 25(6):341–345. https://doi.org/10.1055/s-2008-1078756

    Article  PubMed  Google Scholar 

  24. Bacq Y, Sentilhes L, Reyes HB, Glantz A, Kondrackiene J, Binder T, Nicastri PL, Locatelli A, Floreani A, Hernandez I, Di Martino V (2012) Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology 143(6):1492–1501. https://doi.org/10.1053/j.gastro.2012.08.004

    Article  CAS  PubMed  Google Scholar 

  25. Henderson CE, Shah RR, Gottimukkala S, Ferreira KK, Hamaoui A, Mercado R (2014) Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol 211(3):189–196. https://doi.org/10.1016/j.ajog.2014.03.058

    Article  PubMed  Google Scholar 

  26. Shaw D, Frohlich J, Wittmann BA, Willms M (1982) A prospective study of 18 patients with cholestasis of pregnancy. Am J Obstet Gynecol 142(6 Pt 1):621–625

    Article  CAS  Google Scholar 

  27. Gonzalez MC, Reyes H, Arrese M, Figueroa D, Lorca B, Andresen M, Segovia N, Molina C, Arce S (1989) Intrahepatic cholestasis of pregnancy in twin pregnancies. J Hepatol 9(1):84–90

    Article  CAS  Google Scholar 

  28. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES (2005) Birth weight standards in the live-born population in Israel. Isr Med Assoc J 7(5):311–314

    PubMed  Google Scholar 

  29. Germain AM, Kato S, Carvajal JA, Valenzuela GJ, Valdes GL, Glasinovic JC (2003) Bile acids increase response and expression of human myometrial oxytocin receptor. Am J Obstet Gynecol 189(2):577–582

    Article  CAS  Google Scholar 

  30. Israel EJ, Guzman ML, Campos GA (1986) Maximal response to oxytocin of the isolated myometrium from pregnant patients with intrahepatic cholestasis. Acta Obstet Gynecol Scand 65(6):581–582

    Article  CAS  Google Scholar 

  31. Campos GA, Castillo RJ, Toro FG (1988) Effect of bile acids on the myometral contractility of the isolated pregnant uterus. Rev Chil Obstet Ginecol 53(4):229–233

    CAS  PubMed  Google Scholar 

  32. Campos GA, Guerra FA, Israel EJ (1986) Effects of cholic acid infusion in fetal lambs. Acta Obstet Gynecol Scand 65(1):23–26

    Article  CAS  Google Scholar 

  33. Williamson C, Miragoli M, Sheikh Abdul Kadir S, Abu-Hayyeh S, Papacleovoulou G, Geenes V, Gorelik J (2011) Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis 29(1):58–61. https://doi.org/10.1159/000324130

    Article  CAS  PubMed  Google Scholar 

  34. Sepúlveda WH, González C, Cruz MA, Rudolph MI (1991) Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol 42(3):211–215

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel

    Linoy Batsry, Keren Zloto, Anat Kalter, Micha Baum, Shali Mazaki-Tovi & Yoav Yinon

  2. Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Linoy Batsry, Keren Zloto, Anat Kalter, Micha Baum, Shali Mazaki-Tovi & Yoav Yinon

Authors
  1. Linoy Batsry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keren Zloto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anat Kalter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Micha Baum
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shali Mazaki-Tovi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoav Yinon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LB: data collection and management, data analysis, manuscript writing, and editing. KZ: data collection. AK: data collection. MB: data collection. SMT: project development and manuscript editing. YY: project development, data analysis, and manuscript editing.

Corresponding author

Correspondence to Linoy Batsry.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The study was approved by the ethics committee of Sheba medical center, which waived informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Batsry, L., Zloto, K., Kalter, A. et al. Perinatal outcomes of intrahepatic cholestasis of pregnancy in twin versus singleton pregnancies: is plurality associated with adverse outcomes?. Arch Gynecol Obstet 300, 881–887 (2019). https://doi.org/10.1007/s00404-019-05247-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-019-05247-0

Keywords

Search

Navigation