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What is ICP?

The following is an overall summary of ICP. More detailed information about the causes, diagnosis, treatment and management of the condition can be found by following the links at About ICP.

  • Intrahepatic cholestasis of pregnancy (ICP) is also known as obstetric cholestasis (OC). It affects around 5,500 women and birthing people a year in the UK, but is more common in other parts of the world. It is associated with premature labour, fetal distress and, in the worst cases, stillbirth.
  • ICP occurs when the flow of bile, which is produced in the liver and stored in the gallbladder, becomes sluggish. The bile acids in bile help us to digest food, but they are toxic in large amounts. As the flow of bile slows down, these bile acids build up and flow into the blood stream. They are not life-threatening for the mother-to-be, but they do cross the placenta and reach the baby. Some researchers believe that at very high levels they may cause the baby’s heart to stop working.
  • ICP usually starts from 28 weeks onward in pregnancy, but it can occur as early as 7 weeks. The first sign is usually itching. The itch can be anywhere on the body, but it is usually most noticeable on the hands and feet. Most women agree that it is worse at night. Other symptoms include dark urine and pale poo. Some women also feel a dull ache or pain on their right-hand side, just underneath the rib cage.
  • The causes of ICP are thought to be a combination of genetics (it runs in families), environment (it’s worse during winter) and hormones (the levels of these are much higher in pregnancy).

    Causes of ICP

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  • ICP is diagnosed by ruling out other causes of itching and by a range of blood tests to check the liver and measure non-fasting bile acid levels in the blood.

New classification of ICP

The revised RCOG Guideline (published August 2022) introduced a new classification for ICP, agreed in conjunction with ICP Support following a survey carried out by the charity in 2020/21. This classification also introduces a new threshold for diagnosing ICP, as defined by Mitchell et al. (2021).

Table 1: Terminology for pregnant women with itching of normal skin
Diagnosis Clinical features
Gestational pruritus Itching and peak bile acid concentrations <19 μmol/La
Mild ICP Itching and raised peak bile acid concentrations 19–39 μmol/L
Moderate ICP Itching and raised peak bile acid concentrations 40–99 μmol/L
Severe ICP Itching and raised peak bile acid concentrations ≥100 μmol/L

Note: Peak bile acid concentrations refer to the highest bile acid concentration recorded during a woman's pregnancy. Thus a woman's diagnosis may progress in severity during pregnancy.

a The upper limit of normal bile acid concentrations in pregnancy is 18 μmol/L.

  • Treatment often involves drugs such as ursodeoxycholic acid (UDCA) and rifampicin. The most recent trial of UDCA (called PITCHES; Chappell et al 2019) has shown that this drug is of no benefit to women who have ICP. However, some researchers still feel that it may be useful for the small group of women who have very severe ICP, but further research is needed on this. Rifampicin may be of benefit to some women, and a new trial, called TURRIFIC, is currently under way in Australia to evaluate its efficacy. ICP Support is a collaborator on this study.
  • Other treatments include using aqueous cream with menthol to soothe the skin. Sometimes an antihistamine is prescribed, but although this does not help the itch, it causes drowsiness and may help the woman to sleep.
  • Because of the risk of stillbirth, most women with ICP have been giving birth to their babies early. Induction has typically been recommended at around 37–38 weeks of pregnancy, but research published in 2019 suggests that around 90 per cent of women will be able to delay induction until 39 weeks of pregnancy. However, some women with severe ICP (greater than 100 micromol/L) may need to meet their babies from 34–35 weeks of pregnancy onward.
  • After the baby is born, more blood tests will be needed to make sure that everything has gone back to normal. Researchers recommend that this happens around 6–12 weeks after the birth.
  • ICP has also been shown to overlap with conditions such as gestational diabetes (GDM) and pre-eclampsia. Quite why it does is not fully understood by researchers, so more research is needed, but it will mean that your pregnancy needs to be managed even more carefully.

Should I fast?

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References

Girling J, Knight CL, Chappell L; on behalf of the Royal College of Obstetricians and Gynaecologists. Intrahepatic cholestasis of pregnancy. BJOG 2022; 1–20. https://doi.org/10.1111/1471-0528.17206.

Chappell LC, Bell JL, Smith A, Linsell L, Juszczak E, Dixon PH, Chambers J, Hunter R, Dorling J, Williamson C, Thornton JG. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. The Lancet 2019; 394(10201): 849–860. https://doi.org/10.1016/S0140-6736(19)31270-X

Mitchell A, Ovadia C, Syngelaki A, Souretis K, Martineau M, Girling J, Vasavan, T, Fan HM, Seed PT, Chambers J, Walters JRF, Nicolaides K, Williamson C. Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy: case-control and cohort study. Br J Obstet Gynaecol 2021; https://doi.org/10.1111/1471-0528.16669

Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Illio C, Chambers J, Kohari K, Bacq Y, Bozkurt N, Brun-Furrer R, Bull L, Estiú MC, Grymowicz M, Gunaydin B, Hague WM, Haslinger C, Hu Y, Kawakita T, Kebapcilar AG, Kebapcilar L, Kondrackienė J, Koster MPH, Kowalska-Kańka A, Kupčinskas L, Lee RH, Locatelli A, Macias RIR, Marschall H-U, Oudijk MA, Raz Y, Rimon E, Shan D, Shao Y, Tribe R, Tripodi V, Abide CY, Yenidede I, Thornton JG, Chappell LC, Williamson C. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. The Lancet 2019; 393(10174): 899–909. https://doi.org/10.1016/S0140-6736(18)31877-4.

Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Illio C, Chambers J et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. The Lancet 2019; 393(10174): 899–909. https://doi.org/10.1016/S0140-6736(18)31877-4.

Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World Journal of Gastroenterology 2009; 15(17): 2049–2066. http://dx.doi.org/10.3748/wjg.15.2049.

Ovadia C, Williamson C. Intrahepatic cholestasis of pregnancy: recent advances. Clin Dermatol 2016; 34: 327–34. https://doi.org/10.1016/j.clindermatol.2016.02.004.

Reyes H, Gonzalez MC, Ribalta J, Aburto H, Matus C, Schramm G, Katz R, Medina E. Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med 1978; 88: 487–493. https://doi.org/10.7326/0003-4819-88-4-487.

Raz Y, Lavie A, Vered Y, Goldiner I, Skornick-Rapaport A, Landsberg Asher Y, Maslovitz S, Levin I, Lessing JB, Kuperminc MJ, Rimon E. Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. Am J Obstet Gynecol 2015; 213: 395–8. https://doi.org/10.1016/j.ajog.2015.05.011

Marathe JA, Lim WH, Metz MP, Scheil W, Dekker GA, Hague WM. A retrospective cohort review of intrahepatic cholestasis of pregnancy in a South Australian population. Eur J Obstet Gynecol Reprod Biol 2017; 218: 33–8. https://doi.org/10.1016/j.ejogrb.2017.09.012.

Majewska A, Godek B, Bomba-Opon D, Wielgos M. Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis. Ginekol Pol 2019; 90(8): 458–63. https://doi.org/10.5603/GP.2019.0079.