Intrahepatic Cholestasis of Pregnancy (ICP) Signs and Symptoms

How is ICP Diagnosed and How is it Treated?

pregnant woman wiht jaundiced appearing skin
What is intrahepatic cholestasis of pregnancy and what does it mean for your baby?. Istockphoto.com/Stock Photo©LiudmylaSupynska

What is Intrahepatic Cholestasis of Pregnancy (ICP)?

Intrahepatic cholestasis of pregnancy (ICP) is the second most common cause of jaundice in pregnancy. It may also be called obstetric cholestasis. The condition involves a build up of bile acids in the bloodstream and skin which causes intense itching. It is thought to be caused by a combination of hormonal, genetic, and environmental factors, and usually occurs in the third trimester of pregnancy.

How Common is ICP?

The prevalence pf ICP varies significantly from country to country. In the United States, Switzerland, and France ICP occurs in roughly 1 in 100 to 1 in 1000 pregnancies. However, it is much more common among people of some ethnic backgrounds. In the Chilean population overall, the incidence is 16 percent, but it is as high as 28 percent among the Aracucanos Indians. Less common than in Chile, the condition is more common in South Asia, other parts of South America, and the Scandinavian countries than in the United Sates.

How Does ICP Appear and How Long Does it Last?

The most common symptom of intrahepatic cholestasis of pregnancy is itching which typically develops in the third trimester of pregnancy. The itching, which is usually severe and worst at night, usually begins on the palms and soles, and then spreads to the rest of the body. The rash of ICP is caused by scratching the intensely itchy skin.

Jaundice, a yellowish discoloration of the skin and the whites of the eyes occurs in 10 percent to 15 percent of women with the disease. The rash most commonly appears two to four weeks after the onset of itching. After delivery, both the itching and jaundice resolve spontaneously.

After a woman has developed ICP in one pregnancy, the chance that it will recur in subsequent pregnancies is 45 to 70 percent.

Related Signs and Symptoms of Intrahepatic Cholestasis of Pregnancy (ICP)

In addition to severe itching, the signs and symptoms of intrahepatic cholestasis of pregnancy may include:

  • Jaundice
  • Rash due to scratching (excoriations)
  • Loss of appetite (anorexia)
  • Fatigue
  • Light colored and greasy stools that float (steatorrhea)
  • Dark urine
  • Pain in the right upper quadrant and mid region of the abdomen
  • Depression
  • Nausea

What Causes ICP?

Intrahepatic cholestasis of pregnancy is thought to be a result of a combination of hormonal, environmental, and genetic causes.

Hormonally, the high estrogen levels associated with pregnancy are one important cause. Intrahepatic cholestasis of pregnancy is caused by an impairment of bile secretion in the liver. Hormones produced in pregnancy affect the gallbladder (for example, the risk of gallstones is increased by pregnancy.) The function of the gallbladder is to act as a storage house for bile that is produced in the liver. Bile, in turn, is used to break down fats in the digestive tract.

When the bile duct is blocked, bile acids back up in the liver. As the level of bile in the liver increases, it overflows into the bloodstream. It is these bile acids that enter the bloodstream and are deposited in the skin that cause the intense itching. Estrogen interferes with the clearance of bile from the liver and progesterone interferes with the clearance of estrogen from the liver. Hormone levels such as estrogen and progesterone are approximately 1000 times higher during pregnancy than when a woman is not pregnant.

Genetic causes play a role, and the disease commonly runs in families. Some gene mutations are also linked with an increased risk. Around 15 percent of women with ICP appear to have a mutation (actually several different mutations) in the adenosine triphosphate binding cassette, subfamily B,member 4 (ABCB4/abcb4) gene (also called multidrug resistant protein 3 (MDR3).

Environmental factors also appear to have some role, with the condition being more common in winter, and also associated with a deficiency of the mineral selenium.

Risk Factors for Intrahepatic Cholestasis of Pregnancy

There are several conditions which raise the risk of developing ICP. It's important to note that these are not necessarily causes, but only associated with a higher risk that the condition will occur. Some risk factors include:

  • A personal history of ICP (as noted earlier, the condition recurs in subsequent pregnancies roughly half of the time)
  • A family history of ICP (women who have a mother or sister who has had ICP are at greater risk of developing the condition
  • A family history of gallstone development while taking oral contraceptives
  • Ethnic background - As noted earlier, the condition is much more common in some parts of the worlds, such as Chile
  • Older maternal age
  • Multiparity (having more children)
  • Multiples - ICP is roughly five times more common in twin pregnancies than in single child pregnancies
  • Prior history of oral contraceptive use
  • Women who have a sensitivity to estrogen (such as those who have had problems with taking oral contraceptives in the past) appear to be at an increased risk
  • ICP is more common in the winter months

Diagnosis of Intrahepatic Cholestasis of Pregnancy (ICP)

The diagnosis of ICP is usually based on a careful history and physical, plus blood tests showing an elevated level of bile salts and certain liver enzymes (liver function tests). The presence of itching without a primary rash also helps to confirm the diagnosis. A liver biopsy or ultrasound are rarely needed to establish the diagnosis. Overall, ICP is primarily a diagnosis of exclusion (excluding other possible causes of jaundice and itching during pregnancy.)

Looking at specific lab tests, serum bile acids are often greater than 10 (and can be as high as 40.) Liver function tests are usually significantly elevated. Serum bilirubin is usually elevated, but often less than five. Labs also may show an increased level of cholic acid, chenoeoxycholic acid, and alkaline phosphatase.

Other Causes of Jaundice in Pregnancy - Differential Diagnosis

ICP is largely a diagnosis exclusion—meaning that the diagnosis is partly made by excluding other possible causes of jaundice and itching. Some conditions which can mimic some of the symptoms of ICP include:

  • Acute fatty liver of pregnancy
  • HEELP syndrome and pre-eclamptic liver disease
  • Other skin diseases of pregnancy (which can cause the rash and itching but not the abnormal liver tests or jaundice)
  • Gallstones
  • Non-pregnancy-related liver conditions including viral hepatitis, autoimmune hepatitis, and chronic liver disease.

Complications of ICP for the Mother

The complications of ICP, with the exception of itching which can be very severe, are usually much less serious for the baby than the mother. Urinary tract infections are more common in women with ICP than unaffected pregnant women. In addition, vitamin K deficiency may result after a prolonged course of ICP, which can, in turn, result in bleeding problems.

Complications for the Baby (Effect on the Baby)

ICP can be very serious for the baby, resulting in preterm delivery and intrauterine death (stillborn babies.) Thankfully, newer treatments for mothers with ICP and more careful monitoring of babies has resulted in many fewer complications for the baby than in the past.


The liver of a healthy fetus has a limited ability to remove bile acids from the blood. The fetus normally has to rely on the maternal liver to perform this function. Therefore, the elevated levels of maternal bile cause stress on the fetal liver. Management of these risks is discussed below.

Intrahepatic cholestasis of pregnancy increases the risk to the baby of meconium staining during delivery, preterm delivery, and intrauterine death. Women with ICP should be monitored closely, and serious consideration should be given to inducing labor as soon as fetal lung maturity is confirmed.

Treatment for the Mother (and Baby)

Due to potential complications for the baby, the treatment of ICP should begin immediately after the disease is diagnosed. Treatment methods include both those designed to eliminate bile acids and supportive methods to control the symptoms. In addition, close monitoring of the baby is essential.

The current best treatment and "standard of care" for intrahepatic cholestasis of pregnancy is ursodeoxycholic acid or UDCA. This medication is usually initiated immediately and continued through delivery. In contrast to previous treatments, UDCS appears to significantly improve the outcomes for both the mother and baby with ICP. It's not certain exactly how this medication works.

With the use of UDCA, the itching improves in three out of four women and may result in complete disappearance of the condition in up to 25 percent. Since mothers are often much more worried about their baby than themselves, results with the use of this treatment can be reassuring. Pregnant women treated with UDCA have fewer preterm births, the babies are less likely to experience fetal distress or respiratory distress syndrome, and are less likely to require admission to the neonatal intensive care unit. Babies whose mothers have been treated with UDCA also tend to be born later—at a more advanced gestational age than babies who have mothers who are not treated.

Other medications that have been used due to their effects on bile secretion, though less effective, include S-adenosylmethionine (SAMe) and cholestryramine. Cholestyramine, in particular, seems to lack effectiveness, and may also worsen the low vitamin K levels commonly found. High dose oral steroids such as dexamethasone may also be a possible treatment for ICP.

The itching of ICP can be treated with emollients, antihistamines, soothing baths, primrose oil, and anti-itching products such as Sarna. Here are some tips on how to put a stop to itching, but those who are not coping with the disorder should realize that the itching that results from this condition is not ordinary itching. Some people have said that they would much rather cope with pain than this type of itching, and some people have even had suicidal thoughts. If your loved one is coping with ICP, support her in any way you can.

Managing Pregnancy Complicated by ICP - Taking Care of the Baby

The most important part of managing a baby whose mother has ICP is to plan delivery as soon as maturity of the fetal lungs has been documented. Historically, this time has been considered 37 weeks, but with the availability now of UDCA, some pregnancies have been allowed to progress longer than this.

Prior to delivery it's recommended that mothers have twice weekly fetal non-stress testing. Hearing about the risk of stillbirths can be totally anxiety provoking for women coping with the condition. Thankfully, they can take some reassurance in the fact that fetal death related to ICP is rare before 36 weeks gestation.

In some studies, the incidence of meconium staining during delivery has been elevated, so delivery should take place in a setting in which the obstetrician has ready access to any supplies she may need to prevent aspiration (keep the baby from inhaling the meconium) which can cause meconium aspiration syndrome.

ICP and Hepatitis C

Scientists are not sure of the exact significance, but women who have chronic hepatitis C infections are more likely to develop ICP, and women who have experienced ICP are more likely to be found to have chronic hepatitis C infections. Those who experience ICP may wish to talk to their doctors about hepatitis C screening.

Coping with ICP - A Word from Verywell

If you've been diagnosed with ICP you're likely frightened—both for your own sake and that of your baby. Thankfully, the treatment of this condition has improved dramatically, decreasing risks to both the mother and baby. In addition, careful monitoring of babies has decreased the risk of heartbreaking complications such as stillbirth, with a 2016 study finding no stillbirths among a group of women who were treated and carefully monitored following their diagnosis.

Treatment is also making it possible to delay delivery until a baby is more likely to have matured to a point at which respiratory distress is not a concern.

Still, keep in mind that any complication of pregnancy is traumatic. Ask for and accept help. Some people find it helpful to access support groups and talk to other women who have lived with the condition. A word of caution is in order if you do this, however. Much of the recent success and advances in treatment are very recent—and those you may chat with who coped with the disease even a year or so ago may have faced very different outcomes.

Sources:

Bacq, T., le Besco, M., Lecuyer, A., Gendrot, C., Potin, J., Andres, C., and A. Aubourg. Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment. Digestive and Liver Disease. 2016 Oct 20. (Epub ahead of print).

Dixon, P., and C. Williamson. The Pathophysiology of Intrahepatic Cholestasis of Pregnancy. Clinical Research in Hepatology and Gastroenterology. 2016. 40(2):141-53.

Kong, X., Kong, Y., Zhang, F., Wang, T., and J. Yan. Evaluating the Effectiveness and Safety of Ursodeoxycholic Acid in Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-Analysis (A Prisma-Compliant Study). Medicine (Baltimore). 2016. 95(40):e4949.

Tran, T., Ahn, J., and N. Reau. ACG Clinical Guideline: Liver Disease and Pregnancy. American Journal of Gastroenterology. 2016. 111(2):176-94.

Wijarnpreecha, K., Thongprayoon, C., Sanguankeo, A., Upala, S., Ungprasert, P., and W. Cheungprasitporn. Hepatitis C Infection and Intrahepatic Cholestasis of Pregnancy: A Systematic Review and Meta-Analysis. Clinical Research in Hepatology and Gastrenterology. 201 Aug 16. (Epub ahead of print).

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