Skip to main content

Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy (ICP), Versus Pregnant and Nonpregnant Controls in Asian Indian Women and a Proposed Scoring to Optimize Management in ICP

Abstract

Objectives

This prospective clinical trial was conducted to assess serum bile acids (BA) levels in women with intrahepatic cholestasis of pregnancy (ICP) compared to both pregnant and non-pregnant controls; and evaluate perinatal outcome in relation to bile acid levels. A scoring is proposed based on biochemical markers to optimize management in ICP cases.

Materials and Methods

Serum bile-acids(BA) were assessed in 71 intrahepatic-cholestasis of pregnancy(ICP) cases (group-I), versus 50 pregnant (group-II) and 35 non-pregnant (group-III) controls. Ursodeoxycholic acid (UDCA) was administered in ICP group. Baseline bilirubin (SB), aminotransferases (AT), alkaline-phosphatase were sent in groups I & II. Investigations were repeated in group-I after 4 weeks. Perinatal complications were noted.

Results

Mean BA in group-I was 75.92 ± 39.9 µmol/L which reduced to 41.3 ± 15.4 µmol/L(45.6%, p < 0.001) with UDCA. Mean BA was 29.2 ± 5.7 and 5.9 ± 1.8 µmol/L in group-II and group-III. UDCA significantly reduced itching-score. Rate of fetal distress linearly increased with the increasing baseline levels of serum BA, AT and SB: from 2.5 to 100% at BA < 40 and ≥ 200 µmol/L, (p = 0.008); from 16.1 to 100% at AT < 100 and ≥ 500 IU/mL(p = 0.016); and from 6.8 to 100% at SB < 0.8 and > 5 mg/dL (p = 0.001); respectively. Their baseline levels were divided into 5 groups in correlation to fetal distress. Serum BA < 40, 40–80, 80–120, 120–200, ≥ 200 µmol/L; AT < 100,100–200,200–500, ≥ 500 IU/mL; and SB < 0.8, 0.8–1.0, 1.1–2, 2.1–5 and > 5 mg/dL. Nutan ICP scoring was proposed with a score 0 to 4 given to each parameter and score-based management protocol was suggested for fetal surveillance and delivery.

Conclusions

SBA are higher in Asian Indian pregnant women. Levels > 30 µmol/L can be taken as a cut off for diagnosing ICP in Asian-Indian women. Adopting higher cut-offs for this geographic part will avoid over-diagnosing ICP and iatrogenic early termination of pregnancy. Suggested scoring will help clinicians in optimizing the time of delivery on an individualized basis.

This is a preview of subscription content, access via your institution.

References

  1. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009;15:2049–66.

    Article  Google Scholar 

  2. Smith DD, Rood KM. Intrahepatic cholestasis of pregnancy. Clin Obstet Gynecol. 2020;63(1):134–51.

    Article  Google Scholar 

  3. Piechota J, Jelski W. 2020 Intrahepatic cholestasis in pregnancy: review of the literature. J Clin Med. 6:9(5):E1361.

  4. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467–74.

    Article  Google Scholar 

  5. Castaño G, Lucangioli S, Sookoian S, Mesquida M, Lemberg A, Di Scala M, et al. Bile acid profiles by capillary electrophoresis in intrahepatic cholestasis of pregnancy. Clin Sci (Lond). 2006;110(4):459–65.

    Article  Google Scholar 

  6. Palma J, Reyes H, Ribalta J, Hernández I, Sandoval L, Almuna R, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol. 1997;27(6):1022–8.

    CAS  Article  Google Scholar 

  7. Kenyon AP, Tribe RM, Nelson-Piercy C, Girling JC, Williamson C, Seed PT, et al. Pruritus in pregnancy: a study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis. Obstet Med. 2010;3:25–9.

    CAS  Article  Google Scholar 

  8. Reyes H, Gonzalez MC, Ribalta J, Aburto H, Matus C, Schramm G, et al. Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med. 1978;88(4):487–93.

    CAS  Article  Google Scholar 

  9. Sharma N, Panda S, Singh AS. Obstetric outcome during an era of active management for obstetrics cholestasis. J Obstet Gynecol India. 2016;66:38–41.

    Article  Google Scholar 

  10. Hafeez M, Ansari A, Parveen S, Salamat A, Aijaz A. Frequency of intrahepatic cholestasis of pregnancy in Punjab Pakistan: a single centre study. J Pak Med Assoc. 2016;66(2):203–6.

    PubMed  Google Scholar 

  11. 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-:1482–91.

  12. Zhao CQ, Shao Y, Wu WX. Study on clinical grading of intrahepatic cholestasis of pregnancy. J Pract Obstet Gynecol. 1999;15(4):199–200.

    Google Scholar 

  13. Chen J, Deng W, Wang J, Shao Y, Ou M, Ding M. Primary bile acids as potential biomarkers for the clinical grading of intrahepatic cholestasis of pregnancy. Int J Gynaecol Obstet. 2013;122(1):5–8.

    CAS  Article  Google Scholar 

  14. Rook M, Vargas J, Caughey A, Bacchetti P, Rosenthal P, Bull L. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort. PLoS ONE. 2012;7(3):e28343.

    CAS  Article  Google Scholar 

  15. Brouwers L, Koster MP, Page-Christiaens GC, Kemperman H, Boon J, Evers IM, et al. Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. Am J Obstet Gynecol. 2015;212(1):100.e1-7.

    CAS  Article  Google Scholar 

  16. Kawakita T, Parikh LI, Ramsey PS, Huang CC, Zeymo A, Fernandez M, et al. Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2015;213(4):570.e1-8.

    Article  Google Scholar 

  17. Bacq Y, Sentilhes L, Reyes HB, Glantz A, Kondrackiene J, Binder T, et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology. 2012;143(6):1492–501.

    CAS  Article  Google Scholar 

  18. Kong X, Kong Y, Zhang F, Wang T, Yan J. Medicine (Baltimore). Evaluating the Effectiveness and Safety of Ursodeoxycholic Acid in Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-Analysis. (A Prisma-Compliant Study). 2016;95(40):e4949.

  19. Cui D, Zhong Y, Zhang L, Du H. Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: A meta-analysis. J Obstet Gynaecol Res. 2017;43(9):1411-20.

  20. Di Mascio D, Quist-Nelson J, Riegel M, George B, Saccone G, Brun R, et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. J Matern Fetal Neonatal Med. 2019;1–9.

  21. Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, et al. Association of adverse perinatal outcomes intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019;393(10174):899–909.

    Article  Google Scholar 

  22. Grand’Maison S, Durand M, Mahone M. The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies. J Obstet Gynaecol Can. 2014;36(7):632–41.

    Article  Google Scholar 

  23. Chappell LC, Bell JL, Smith A, Linsell L, Juszczak E, Dixon PH, PITCHES study group, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849–60.

    CAS  Article  Google Scholar 

  24. Williamson C, Miragoli M, Sheikh Abdul Kadir S, et al. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58–61.

    Article  Google Scholar 

  25. Puljic A, Kim E, Page J, Esakoff T, Shaffer B, LaCoursiere DY, et al. Am J Obstet Gynecol. 2015;212(5):667.e1-5.

    Article  Google Scholar 

Download references

Acknowledgements

The project was funded by intramural grant of the institute, All India Institute of Medical Sciences, New Delhi

Funding

Intramural grant from All India Institute of Medical Sciences, New Delhi, India.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed in the patient management and follow-up. NA conceptualized the study. RM and VS were responsible for the acquisition of clinical data, and obtaining informed consent. NA, VK and RM were responsible for manuscript writing. NA, AK and AS had overall supervision. NA and VK were responsible for manuscript’s critical editing.

Corresponding author

Correspondence to Nutan Agarwal.

Ethics declarations

Conflict of interest

None of the authors have any potential conflict of interest.

Ethical statement

Study was conducted after obtaining approval from the Institute’s Ethics Committee.

Human Participants and/or Animals

All parts of Declaration of Helsinki have been applied.

Additional information

Publisher's Note

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

Nutan Agarwal is an Ex-Professor in Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India. Reeta Mahey is an Additional Professor, Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi. Vidushi Kulshrestha is an Associate Professor at Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi. Alka Kriplani is an Ex-Professor in Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India. Anoop Saraya is a Professor in Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Vikas Sachdev is a Senior Technician in Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Agarwal, N., Mahey, R., Kulshrestha, V. et al. Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy (ICP), Versus Pregnant and Nonpregnant Controls in Asian Indian Women and a Proposed Scoring to Optimize Management in ICP. J Obstet Gynecol India 72, 218–224 (2022). https://doi.org/10.1007/s13224-021-01501-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13224-021-01501-1

Keywords

  • Intrahepatic cholestasis of pregnancy
  • Serum bile acid
  • Ursodeoxycholic acid
  • Scoring for ICP