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Cholestasis of Pregnancy, Intrahepatic

Cholestasis of Pregnancy, Intrahepatic is a topic covered in the 5-Minute Clinical Consult.

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  • Intrahepatic cholestasis of pregnancy (ICP) is characterized by generalized pruritus without skin lesions in pregnancy, accompanied by elevated serum bile acid levels +/− elevated serum transaminase levels (1,2).
  • It occurs classically in the 3rd trimester but may begin in the 2nd trimester.
  • It is a self-limited condition that resolves shortly after delivery.
  • ICP is associated with adverse fetal outcomes, including premature delivery, meconium-stained amniotic fluid, respiratory distress, and fetal death (1,2).


  • Varies between 0.2% and 25% worldwide (1)
  • ICP is most common in China, Latin American, and Scandinavian countries.

Reports vary according to geography and ethnicity.

Etiology and Pathophysiology

  • Genetic, endocrine, and environmental factors influence the risk of developing ICP (2).
  • Its onset coincides with rising progesterone levels (2).
  • Maternal pruritus may be related to a TGR5-mediated signaling pathway in sensory nerves, induced by bile acid (3).
  • Sulfated progesterones and lysophosphatidic acid also play a role in pruritus (2,3).
  • Some fetal complications may be due to bile salt accumulation in fetal tissues, leading to fetal arrhythmias and liver damage (4).
  • Bile acids may vasoconstrict the chorionic veins, leading to decreased perfusion to the fetus (4).
  • Bile acids may also increase oxytocin activity, leading to preterm delivery (4).

  • Heterozygous mutations in the ABCB4 gene, which encodes a hepatocanalicular transporter, have been implicated in many cases (3).
  • Heterozygous mutations of other transporter genes, such as ABCB11 play a smaller role (3).

Risk Factors

  • 2nd or 3rd trimester of pregnancy
  • Multiple gestation (1)
  • Family history of ICP
  • History of ICP in a previous pregnancy
  • Advanced maternal age (1)
  • Hepatitis C (1)
  • Winter season/low vitamin D level (1)
  • Low selenium level (1)

Commonly Associated Conditions

  • Oral contraceptive-induced pruritus (3)
  • Incidence of concomitant hepatitis C infection is higher in women with ICP (1).
  • Pregnancy complications: postpartum hemorrhage (4), preeclampsia (2), gestational diabetes (2), and 19–60% increased risk preterm delivery (5)
  • Neonatal complications: 17.9% risk of meconium passage, 29% risk of respiratory distress syndrome (5)
  • The most severe complication is fetal death.
  • Fetal mortality has been reported as high as 20% but averages 0.75–7% (5).

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Stephens, Mark B., et al., editors. "Cholestasis of Pregnancy, Intrahepatic." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816694/all/Cholestasis_of_Pregnancy__Intrahepatic.
Cholestasis of Pregnancy, Intrahepatic. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816694/all/Cholestasis_of_Pregnancy__Intrahepatic. Accessed April 26, 2019.
Cholestasis of Pregnancy, Intrahepatic. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816694/all/Cholestasis_of_Pregnancy__Intrahepatic
Cholestasis of Pregnancy, Intrahepatic [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 26]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816694/all/Cholestasis_of_Pregnancy__Intrahepatic.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Cholestasis of Pregnancy, Intrahepatic ID - 816694 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816694/all/Cholestasis_of_Pregnancy__Intrahepatic PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -