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1/1/2019

Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease.  While the incidence of ICP varies greatly among ethnic groups, in the United States incidence ranges from 0.32% in predominantly White populations to 5.6% in predominantly Latina populations.  Risk factors include multifetal gestations, a personal/ family history of ICP, in vitro fertilization, cholelithiasis, advanced maternal age, Hepatitis C, and additionally is known to exhibit seasonal patterns with increased incidence during winter months.

Although ICP is the most common liver disease of pregnancy, its cause and course are still poorly understood but known to lead to stagnation of bile flow and resultant retention of bile components. This causes bile salts to build up within the hepatocytes and increases the accumulation of bile acids in the blood, which is potentially toxic to the developing fetus as they cross the placenta in the fetal circulation and often lead to maternal symptoms of pruritis.

ICP is associated with preterm delivery, non-reassuring fetal status, meconium-staining, respiratory distress syndrome, and stillbirth, with a linear relationship between serum bile acid levels and the risk of fetal complications. Pregnancies complicated by ICP are additionally at an increased risk of preeclampsia and gestational diabetes. 

ICP classically presents in the third trimester with pruritis of the palms and soles, often worse at night.  Patients may have excoriations due to scratching, but typically do not have a rash.  Patients may also demonstrate dark urine, pale stools, and rarely, jaundice.

The diagnosis is confirmed by elevated total serum bile acids in the absence of an alternative diagnosis. The primary bile acids are cholic and chenodeoxycholic acid.  Although diagnostic thresholds may differ, “severe cholestasis” has been consistently defined in the literature as bile acids >40 µmol/L with more recent studies noting a markedly increased risk of stillbirth with serum levels above 100 µmol/L as compared to levels below this threshold. Liver enzymes may be elevated, but this is not necessary for the diagnosis. 

Ursodeoxycholic acid (UDCA) is the preferred treatment for symptomatic ICP.  Liver indices, bile acids, and pruritis may improve with treatment. When considering only randomized controlled trials, UDCA was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of UDCA as a first-line agent.

Measurement of serum bile acid and liver transaminase levels in patients with suspected

ICP is recommended. Antenatal fetal surveillance is recommended at a gestational age when delivery would be performed in response to abnormal fetal testing results or at the time of diagnosis if the diagnosis is made later in gestation, although fetal benefit has yet to be demonstrated. .  Both ACOG and SMFM recommend that patients with total bile acid levels of 100 mmol/L be offered delivery at 36 0/7 weeks of gestation, and between 36 0/7 and 39 0/7 weeks of gestation for patients with ICP and total bile acid levels of <100 mmol/L. Preterm delivery at <37 weeks of gestation in patients with a clinical diagnosis of ICP without laboratory confirmation of elevated bile acid levels is not recommended.

 

Further Reading: 

1. Ovadia C, Sajous J, Seed PT, Patel K, et. al; Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2021 Jul;6(7):547-558. doi: 10.1016/S2468-1253(21)00074-1. Epub 2021 Apr 27. PMID: 33915090; PMCID: PMC8192305.
2. Horgan R, Bitas C, Abuhamad A. Intrahepatic cholestasis of pregnancy: a comparison of Society for Maternal-Fetal Medicine and the Royal College of Obstetricians and Gynaecologists' guidelines. Am J Obstet Gynecol MFM. 2023 Mar;5(3):100838. doi: 10.1016/j.ajogmf.2022.100838. Epub 2022 Dec 9. PMID: 36503152.
3. 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 Feb;224(2):B2-B9. doi: 10.1016/j.ajog.2020.11.002. Epub 2020 Nov 13. PMID: 33197417.
4. Smith DD, Rood KM. Intrahepatic Cholestasis of Pregnancy. Clin Obstet Gynecol. 2020 Mar;63(1):134-151. doi: 10.1097/GRF.0000000000000495. PMID: 31764000.

Initial Approval: November 2018; Reaffirmed July 2020; Reaffirmed January 2022; Rev ised September 2023

 

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This document is designed to aid practitioners in providing appropriate obstetric and gynecologic care. Recommendations are derived from major society guidelines and high-quality evidence when available, supplemented by the opinion of the author and editorial board when necessary. It should not be construed as dictating an exclusive course of treatment or procedure to be followed.

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