Other presentations
ICP can present from the first trimester, although typical onset is in the third trimester.[3]Stulic M, Culafic D, Boricic I, et al. Intrahepatic cholestasis of pregnancy: a case study of the rare onset in the first trimester. Medicina (Kaunas). 2019 Aug 9;55(8):454.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723234
http://www.ncbi.nlm.nih.gov/pubmed/31404990?tool=bestpractice.com
[4]Lin J, Gu W, Hou Y. Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study. J Matern Fetal Neonatal Med. 2019 Mar;32(6):997-1003.
http://www.ncbi.nlm.nih.gov/pubmed/29065754?tool=bestpractice.com
The presenting symptom is maternal itch in the absence of a rash, although excoriative lesions are commonly seen.[5]Ovadia C, Williamson C. Intrahepatic cholestasis of pregnancy: recent advances. Clin Dermatol. 2016 May-Jun;34(3):327-34.
http://www.ncbi.nlm.nih.gov/pubmed/27265070?tool=bestpractice.com
Although the classic distribution of itch is in the palms and soles, it can occur at any site of the body and typically worsens overnight.[6]Kenyon AP, Tribe RM, Nelson-Piercy C, et al. Pruritus in pregnancy: a study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis. Obstet Med. 2010 Mar;3(1):25-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989767
http://www.ncbi.nlm.nih.gov/pubmed/27582836?tool=bestpractice.com
[7]ICP Support. Myth busting. 2022 [internet publication].
https://www.icpsupport.org/myths.shtml
[8]Steele G. Reflection on a pregnancy complicated by obstetric cholestasis. Pract Midwife. 2012 Oct;15(9):30-2.
http://www.ncbi.nlm.nih.gov/pubmed/23252070?tool=bestpractice.com
Itch alone is not enough for a presumptive diagnosis, but it often precedes biochemical derangement.[6]Kenyon AP, Tribe RM, Nelson-Piercy C, et al. Pruritus in pregnancy: a study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis. Obstet Med. 2010 Mar;3(1):25-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989767
http://www.ncbi.nlm.nih.gov/pubmed/27582836?tool=bestpractice.com
[9]Kenyon AP, Piercy CN, Girling J, et al. Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis. BJOG. 2001 Nov;108(11):1190-2.
http://www.ncbi.nlm.nih.gov/pubmed/11762661?tool=bestpractice.com
In addition to raised serum bile acid concentrations, around 80% of women with ICP have evidence of liver dysfunction, and dark-coloured urine frequently occurs.[10]Conti-Ramsden F, McEwan M, Hill R, et al. Detection of additional abnormalities or co-morbidities in women with suspected intrahepatic cholestasis of pregnancy. Obstet Med. 2020 Dec;13(4):185-91.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726172
http://www.ncbi.nlm.nih.gov/pubmed/33343695?tool=bestpractice.com
[11]Tuson A, Chambers J. Top 10 things to know about intrahepatic cholestasis of pregnancy (ICP). Essentially MIDIRS. 2013 Nov;4(10):27-30.
https://www.icpsupport.org/pdf/MIDIRS_2013.pdf
A minority experience symptoms of steatorrhoea, hyperbilirubinaemia, or yellowing of conjunctivae.[5]Ovadia C, Williamson C. Intrahepatic cholestasis of pregnancy: recent advances. Clin Dermatol. 2016 May-Jun;34(3):327-34.
http://www.ncbi.nlm.nih.gov/pubmed/27265070?tool=bestpractice.com
[10]Conti-Ramsden F, McEwan M, Hill R, et al. Detection of additional abnormalities or co-morbidities in women with suspected intrahepatic cholestasis of pregnancy. Obstet Med. 2020 Dec;13(4):185-91.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726172
http://www.ncbi.nlm.nih.gov/pubmed/33343695?tool=bestpractice.com
[12]Reyes H, Radrigan ME, Gonzalez MC, et al. Steatorrhea in patients with intrahepatic cholestasis of pregnancy. Gastroenterology. 1987 Sep;93(3):584-90.
https://www.gastrojournal.org/article/0016-5085(87)90922-X/pdf
http://www.ncbi.nlm.nih.gov/pubmed/3609667?tool=bestpractice.com
Women with steatorrhoea may have malabsorption of fat-soluble vitamins, including vitamin K, and are at risk of postnatal or fetal haemorrhage.[13]Sadler LC, Lane M, North R. Severe fetal intracranial haemorrhage during treatment with cholestyramine for intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol. 1995 Feb;102(2):169-70.
http://www.ncbi.nlm.nih.gov/pubmed/7756215?tool=bestpractice.com
[14]Girling J, Knight CL, Chappell L, et al. Intrahepatic cholestasis of pregnancy: green-top guideline no. 43 June 2022. BJOG. 2022 Aug 9 [Epub ahead of print].
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17206
http://www.ncbi.nlm.nih.gov/pubmed/35942656?tool=bestpractice.com
[15]Bicocca MJ, Sperling JD, Chauhan SP. Intrahepatic cholestasis of pregnancy: review of six national and regional guidelines. Eur J Obstet Gynecol Reprod Biol. 2018 Dec;231:180-7.
http://www.ncbi.nlm.nih.gov/pubmed/30396107?tool=bestpractice.com
Women with ICP have high rates of cholelithiasis (around 12%) and often report symptoms of right upper quadrant pain and fatigue.[16]Kenyon AP, Piercy CN, Girling J, et al. Obstetric cholestasis, outcome with active management: a series of 70 cases. BJOG. 2002 Mar;109(3):282-8.
http://www.ncbi.nlm.nih.gov/pubmed/11950183?tool=bestpractice.com
[17]Marschall HU, Wikström Shemer E, Ludvigsson JF, et al. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology. 2013 Oct;58(4):1385-91.
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.26444
http://www.ncbi.nlm.nih.gov/pubmed/23564560?tool=bestpractice.com
They also have higher rates of gestational diabetes mellitus and pre-eclampsia, with their attendant presenting symptoms.[18]Martineau M, Raker C, Powrie R, et al. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes. Eur J Obstet Gynecol Reprod Biol. 2014 May;176:80-5.
http://www.ncbi.nlm.nih.gov/pubmed/24462052?tool=bestpractice.com
[19]Mor M, Shmueli A, Krispin E, et al. Intrahepatic cholestasis of pregnancy as a risk factor for preeclampsia. Arch Gynecol Obstet. 2020 Mar;301(3):655-64.
http://www.ncbi.nlm.nih.gov/pubmed/32034507?tool=bestpractice.com
[20]Arafa A, Dong JY. Association between intrahepatic cholestasis of pregnancy and risk of gestational diabetes and preeclampsia: a systematic review and meta-analysis. Hypertens Pregnancy. 2020 Aug;39(3):354-60.
http://www.ncbi.nlm.nih.gov/pubmed/32326772?tool=bestpractice.com
Due to the increased risk of preterm birth, women may present with spontaneous preterm labour; reduced (or altered) fetal movements may herald the diagnosis of stillbirth in women with severe disease.[2]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 Mar 2;393(10174):899-909.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396441
http://www.ncbi.nlm.nih.gov/pubmed/30773280?tool=bestpractice.com
[21]Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004 Aug;40(2):467-74.
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.20336
http://www.ncbi.nlm.nih.gov/pubmed/15368452?tool=bestpractice.com