Treatment for Intrahepatic Cholestasis of Pregnancy
Treatment Methods to Treat Intrahepatic Cholestasis of Pregnancy


The treatment of Intrahepatic Cholestasis of Pregnancy involves 3 main parts: monitoring, medication treatment, and early delivery.

  • Monitoring involves following bile acid levels and fetal monitoring including non-stress testing (NSTs)
  • Medication treatment involves a first-line, albeit off-label, treatment with a medication called ursodeoxycholic acid (Ursodiol or Actigall)
  • Early delivery is recommended most often around 36 0/7-39 0/7 weeks with earlier deliveries considered on a case by case basis depending on bile acid levels.1

Below you will find more details on each of these management plans.

Diagnosis & Recommended Treatment Flowchart

Intraphepatic Cholestasis Diagnosis Treatment Flowchart


Bile acid levels: Higher bile acid levels are associated with a greater risk of stillbirth. It is recommended that bile acid levels be followed throughout pregnancy. A specific interval has not been determined but bile acids need to be monitored more closely near the end of pregnancy to plan delivery timing.2

Fetal Monitoring: Fetal monitoring is recommended in a pregnancy complicated by Intrahepatic Cholestasis of Pregnancy. A specific timing interval or recommendation has not been established but fetal monitoring usually includes both non-stress testing (NST) and ultrasound evaluations such as a biophysical profile (BPP).

A Non-stress test (NST) is a recording of the fetal heart rate that looks for specific findings including accelerations of the fetal heart rate. A biophysical profile is an ultrasound evaluation where the physician looks for fetal movement/muscle tone, breathing, and amniotic fluid levels.

A specific timeframe to begin monitoring has not been established but often begins around 32 weeks. Your provider will decide on a plan for fetal monitoring.

Fetal monitoring might be able to detect some concerns and lead to a safe delivery. It does need to be noted that stillbirth in a cholestasis pregnancy is thought to be a sudden event and that fetal monitoring will not be able to prevent all stillbirths. It is still thought to be beneficial for a pregnancy complicated by cholestasis.2

Medication Treatment

Ursodeoxycholic Acid: Ursodeoxycholic acid is a naturally occuring bile acid. This bile acid is able to compete with the other more toxic bile acids and allows for their elimination. Ursodeoxycholic Acid remains the first line of treatment for Intrahepatic Cholestasis of Pregnancy (ICP) according to the Society for Maternal-Fetal Medicine (SMFM).2,6 This medication has been shown to be safe for both patient and baby in pregnancy. It is prescribed under many different names including Actigall and Ursodiol.

The recommended daily dosing is 10-21 mg/kg per day and can be adjusted up to 2000 mg/day to help control bile acid levels. Side effects of this medication are generally mild and the most common side effects are diarrhea and headache. A recent trial of the medication showed no increase in GI symptoms between a placebo group and a treatment group and the GI side effects may be more from the Intrahepatic Cholestasis of Pregnancy rather than the treatment.6
Ursodeoxycholic acid has been shown in prior studies to have beneficial effects for the fetus and the pregnancy including reducing risk of meconium staining, protecting the baby’s heart against changes induced by bile acids, restoring the placenta’s ability to transport bile acids away from the baby, and protecting cells from damage due to bile acids.

In 2019, the PITCHES, compared a placebo medication to treatment with ursodeoxycholic acid. This study looked at a composite outcome of perinatal death, preterm delivery (<37 weeks’ gestation), or neonatal unit admission for at least 4 h. The study was unable to find an improvement in the perinatal death outcome with ursodeoxycholic acid treatment. Importantly, despite being three times larger than all previous trials combined, the study may not have had adequate power to fully assess stillbirth risk. In order to see an improvement in stillbirth risks, many more women would have needed to be included in the study and no meaningful conclusions can be made solely about stillbirth risk. 

A more recent study published in 2021 looked at the data from that trial in conjunction with other studies in the literature and was able to show that the use of ursodeoxycholic acid reduced spontaneous preterm birth. This study was not able to detect a reduction in stillbirth but, again, may not have been adequately powered to do so and more patients may need to be studied. The overall conclusion is that Ursodiol has some benefit for pregnancies complicated by cholestasis but that more research is needed. We can unfortunately not conclude that the use of Ursodiol will remove all stillbirth risk.8

The governing boards for OB care in the US still recommend that Ursodeoxycholic acid should continue to be used as a first line treatment based on the lack of harm to mother or fetus, potential benefit in maternal symptoms, and reduction in preterm labor. There is some improvement in maternal itching with medication treatment. The benefits for the fetus have become less clear but it is still thought that this medication may have benefit.2

Other Medication Options: There are several other medications that are sometimes used to treat cases of cholestasis of pregnancy. These medications are not the first choice for treatment but can be used in conjunction with Ursodiol or in the event of intolerable side effects or contraindication to Ursodiol such as hypersensitivity or biliary obstruction.

These medications include Cholestyramine, S-Adenosyl-L-methionine (SAMe), Rifampin and Vitamin K. Your provider will discuss these options further with you if they feel they are needed as they are used in only a minority of Intrahepatic Cholestasis of Pregnancy cases.

Vitamin K is a unique medication on this list as it is not used to lower bile acids. Patients with Intrahepatic Cholestasis of Pregnancy (ICP) may have an increased risk of bleeding due to the inability to absorb fat soluble vitamins in a pregnancy with ICP. It is currently not a standard of care in the United States to treat pregnancies with ICP with Vitamin K prior to delivery in the absence of other concerns regarding increased bleeding risks. However, if a patient has symptoms of a possible malabsorption syndrome such as fatty stools (will float as less dense), then they should be tested for possible bleeding risks with bloodwork and vitamin K could be considered.

For additional information, please see article: New Evidence for the Benefits of Ursodiol for Intrahepatic Cholestasis of Pregnancy

Early Delivery

Stillbirth in a pregnancy complicated by cholestasis is thought to be a sudden event that cannot be predicted. Most stillbirths occur towards the end of pregnancy and after 37 weeks which is why early delivery is recommended for preventing stillbirth.7

A recent study in 2019 on over 5000 cholestasis pregnancies determined stillbirth risk based upon bile acid levels. Stillbirth risk was: 0.13% if bile acids were 0-39; 0.28% if bile acids were 40-99 and 3.44% if bile acids were over 100. This study showed that the majority of stillbirths occurred in pregnancies where bile acids were over 100 and that these pregnancies need to be the most aggressively managed.5

The two main governing boards in the United States (SMFM – Society of Maternal Fetal Medicine and ACOG – American College of Obstetricians and Gynecologists) are in agreement regarding recommendations for delivery timing:1,2

  • Bile acids under 40: delivery is recommended at 36 0/7-39 0/7 weeks gestation.
  • Bile acids 40-99: delivery is recommended at 36 0/7-39 0/7 weeks gestation with a recommendation for delivery in the earlier portion of this window.
  • Bile acids over 100: delivery needs to occur right at 36 0/7 weeks gestation as these are the highest risk pregnancies. There is recommendation for delivery between 34-36 weeks gestation in these pregnancies with unrelieved itching, a prior stillbirth or worsening liver disease.

For a detailed discussion and explanation about where these current recommendations are derived from, please see the delivery timing in our provider section. This link will discuss the evidence behind the original recommendations for delivery between 36-37 weeks and why the recent recommendations have changed for some cases of mild ICP.3,4 Of note, these recommendations still include a 36 week delivery for all cases of ICP and management should be individualized based on circumstances. In order to consider later delivery, bile acids should be able to be followed closely and as per the SMFM recommendations, delivery in the later portion of the window should be reserved for mild cases of Intrahepatic Cholestasis of Pregnancy.

Steroid management: Betamethasone is a steroid medication that can be given in a pregnancy to help prevent complications of prematurity in the fetus and aid with lung maturity. It is currently recommended that if delivery is going to occur prior to 37 weeks of gestation that this medication should be given. It is given as an injection and is given as two doses that are 24 hours apart.

  1. Medically Indicated Late-Preterm and Early-Term Deliveries: ACOG Committee Opinion, Number 818. Obstet Gynecol. 2021 Feb 1;137(2):e29-e33. doi: 10.1097/AOG.0000000000004245. PMID: 33481529.
  2. Society for Maternal-Fetal Medicine (SMFM). Electronic address:, 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. 2020 Nov 13:S0002-9378(20)31284-9. doi: 10.1016/j.ajog.2020.11.002. Epub ahead of print. PMID: 33197417.
  3. Lo JO, Shaffer BL, Allen AJ, Little SE, Cheng YW, Caughey AB. Intrahepatic cholestasis of pregnancy and timing of delivery. J Matern Fetal Neonatal Med. 2015;28(18):2254-8. doi: 10.3109/14767058.2014.984605. Epub 2014 Nov 28. PMID: 25371372.
  4. Puljic A, Kim E, Page J, Esakoff T, Shaffer B, LaCoursiere DY, Caughey AB. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol. 2015 May;212(5):667.e1-5. doi: 10.1016/j.ajog.2015.02.012. Epub 2015 Feb 14. PMID: 25687562.
  5. Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio 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 HU, Oudijk MA, Raz Y, Rimon E, Shan D, Shao Y, Tribe R, Tripodi V, Yayla Abide C, 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. Lancet. 2019 Mar 2;393(10174):899-909. doi: 10.1016/S0140-6736(18)31877-4. Epub 2019 Feb 14. Erratum in: Lancet. 2019 Mar 16;393(10176):1100. PMID: 30773280; PMCID: PMC6396441.
  6. Chappell LC, Bell JL, Smith A, Linsell L, Juszczak E, Dixon PH, Chambers J, Hunter R, Dorling J, Williamson C, Thornton JG; PITCHES study group. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019 Sep 7;394(10201):849-860. doi: 10.1016/S0140-6736(19)31270-X. Epub 2019 Aug 1. PMID: 31378395; PMCID: PMC6739598.
  7. Williamson C, Hems LM, Goulis DG, Walker I, Chambers J, Donaldson O, Swiet M, Johnston DG. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG. 2004 Jul;111(7):676-81. doi: 10.1111/j.1471-0528.2004.00167.x. PMID: 15198757.
  8. Ovadia C, Sajous J, Seed PT, Patel K, Williamson NJ, Attilakos G, Azzaroli F, Bacq Y, Batsry L, Broom K, Brun-Furrer R, Bull L, Chambers J, Cui Y, Ding M, Dixon PH, Estiú MC, Gardiner FW, Geenes V, Grymowicz M, Günaydin B, Hague WM, Haslinger C, Hu Y, Indraccolo U, Juusela A, Kane SC, Kebapcilar A, Kebapcilar L, Kohari K, Kondrackienė J, Koster MPH, Lee RH, Liu X, Locatelli A, Macias RIR, Madazli R, Majewska A, Maksym K, Marathe JA, Morton A, Oudijk MA, Öztekin D, Peek MJ, Shennan AH, Tribe RM, Tripodi V, Türk Özterlemez N, Vasavan T, Wong LFA, Yinon Y, Zhang Q, Zloto K, Marschall HU, Thornton J, Chappell LC, Williamson C. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2021 Apr 26:S2468-1253(21)00074-1. doi: 10.1016/S2468-1253(21)00074-1. Epub ahead of print. PMID: 33915090.