Intrahepatic cholestasis of pregnancy

It is 33 weeks. She cannot sleep. The itch is on her palms and soles, it is worse at night, and there is no rash — only the linear excoriations her own nails have left. You order bile acids. If they are over 40 you will change the trajectory of her pregnancy; if they are over 100 you will deliver her next week. This topic is that decision tree.^[1][11]

Overview and definition

ICP is a reversible cholestatic disorder unique to pregnancy, characterised by maternal pruritus and elevated serum bile acids that resolve after delivery. The definition has two parts, and examiners test both.^[5][11]

• Clinical: pruritus, typically of the palms and soles, worse at night, in the absence of a primary skin lesion. The itch is the disease; the rash is the scratching.^[11]
• Biochemical: serum bile acids above 10 micromol/L using the standard threshold; above 19 micromol/L using the higher-threshold definition that has gained favour after the Mitchell 2021 re-evaluation (which showed many healthy pregnancies have bile acids between 10 and 19).^[5]
• Course: onset in the late second or third trimester; resolution of pruritus within 48 hours to 2 weeks postpartum; bile acids normalise within 2-6 weeks. If they do not, it was not ICP.^[11]

The single sentence that frames the topic: it is the bile acids that drive fetal risk, not the itch. The itch is treatable; the stillbirth risk is preventable by delivery.^[1]

References16ShowHide

1. [1]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 Lancet, 2019.PMID 30773280
2. [2]Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial Lancet, 2019.PMID 31378395
3. [3]Chappell LC, Gurung V, Seed PT, et al. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial BMJ, 2012.PMID 22695903
4. [4]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.PMID 33915090
5. [5]Mitchell AL, Ovadia C, Syngelaki A, et al. Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy: case-control and cohort study BJOG, 2021.PMID 33586324
6. [6]Bacq Y, le Besco M, Lecuyer AI, et al. Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment Dig Liver Dis, 2017.PMID 27825922
7. [7]Kawakita T, Parikh LI, Ramsey PS, et al. Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy Am J Obstet Gynecol, 2015.PMID 26071912
8. [8]Bacq Y, Sentilhes L, Reyes HB, et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis Gastroenterology, 2012.PMID 22892336
9. [9]Dixon PH, Sambrotta M, Chambers J, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy Sci Rep, 2017.PMID 28924228
10. [10]Di Mascio D, Quist-Nelson J, Riegel M, et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review J Matern Fetal Neonatal Med, 2021.PMID 31744346
11. [11]Westbrook RH, Dusheiko G, Williamson C Pregnancy and liver disease J Hepatol, 2016.PMID 26658682
12. [12]Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA Liver disease in pregnancy Lancet, 2010.PMID 20159293
13. [13]Yang X, Williamson NJ, Sajous J, et al. Characteristics associated with alterations in pruritus severity across gestation in intrahepatic cholestasis of pregnancy: a longitudinal cohort study Eur J Obstet Gynecol Reprod Biol, 2025.PMID 40714624
14. [14]Borges Manna L, Williamson C Nuclear Receptors in Pregnancy and Outcomes: Clinical Perspective Adv Exp Med Biol, 2022.PMID 36107310
15. [15]Fleminger J, Seed PT, Smith A, et al. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial BJOG, 2021.PMID 33063439
16. [16]Arthur C, Mahomed K Intrahepatic cholestasis of pregnancy: diagnosis and management; a survey of Royal Australian and New Zealand College of Obstetrics and Gynaecology fellows Aust N Z J Obstet Gynaecol, 2014.PMID 24506294