Intrahepatic Cholestasis of Pregnancy

pregnant woman wiht jaundiced appearing skin

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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.


The prevalence of ICP varies significantly from country to country. It is much more common among people of some ethnic backgrounds. In the Chilean population overall, the incidence is 16%. Among the Aracucanos Indian population, it's as high as 28%.

The condition is also more common in South Asia, other parts of South America, and the Scandinavian countries than it is in the United States.

In the United States, Switzerland, and France, ICP occurs in roughly 1 in 100 to 1 in 1000 pregnancies.


The most common symptom of intrahepatic cholestasis of pregnancy is itching, which typically develops in the third trimester. The itching is typically severe and worst at night. It usually begins on the palms and soles of the feet, then spreads to the rest of the body.

The rash of ICP is caused by scratching the intensely itchy skin. It most commonly appears two to four weeks after the onset of itching. Jaundice, a yellowish discoloration of the skin and the whites of the eyes occurs in 10% to 15% of women with the disease. After delivery, both the itching and jaundice resolve spontaneously.

Related Signs and Symptoms

In addition to severe itching, other signs and symptoms of intrahepatic cholestasis of pregnancy 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


Intrahepatic cholestasis of pregnancy is thought to be caused by 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.


Genetics also play a role, and the disease commonly runs in families. Some gene mutations are also linked with an increased risk.

Around 15% 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

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

  • Personal history of ICP: The condition recurs in subsequent pregnancies roughly half of the time
  • Family history of ICP: Women who have a mother or sister who has had ICP are at greater risk of developing the condition
  • Family history of gallstone development while taking oral contraceptives
  • Ethnic background: The condition is much more common in some parts of the world, 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
  • History of oral contraceptive use
  • Sensitivity to estrogen: Women who have had problems with taking oral contraceptives in the past appear to be at an increased risk
  • Season: ICP is more common in the winter months


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.

Looking at specific lab tests, serum bile acids are often greater than 10 (and can be as high as 40). A liver biopsy or ultrasound are rarely needed to establish the diagnosis. 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

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

  • Acute fatty liver of pregnancy
  • HELLP 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 for the Mother

With the exception of itching. which can be very severe, the complications of ICP are usually much less serious for the mother than for the baby.​ 

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. This can, in turn, result in bleeding problems.

Complications for the Baby

The liver of a healthy fetus only has a limited ability to remove bile acids from the blood. Normally, the fetus has to rely on the maternal liver to perform this function. Therefore, the elevated levels of maternal bile cause stress in the fetal liver.

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

ICP increases the risk 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.


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, UDCA 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. In up to 25% of affected women, it may completely resolve the condition.

Since mothers are often much more worried about their baby than themselves, results from 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 cholestyramine.

Cholestyramine seems to lack effectiveness, and may also worsen low vitamin K levels. 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. Those who are not coping with the disorder should realize that the itching that results from this condition is not ordinary itching.

If your loved one is coping with ICP, support her in any way you can. Women with ICP have said that they would much rather cope with pain than this type of itching. Some people have even had suicidal thoughts.

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

Managing Pregnancy 

Managing a baby whose mother has ICP typically involves planning to deliver as soon as the fetal lungs are mature. Historically, this has been considered 37 weeks, but with the availability of UDCA, some pregnancies have been allowed to progress longer.

Prior to delivery, mothers may have twice weekly fetal non-stress testing. Hearing about the risk of stillbirths can cause anxiety 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 the delivery should take place in a setting in which the obstetrician has ready access to any supplies they 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.

If you have ICP, you may want to ask your doctor about hepatitis C screening.

Living With ICP

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.

Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Heather L. Brannon, MD
Heather L. Brannon, MD, is a family practice physician in Mauldin, South Carolina. She has been in practice for over 20 years.