Intrahepatic Cholestasis of Pregnancy (ICP)

Intrahepatic Cholestasis of Pregnancy (ICP) is a liver disorder which occurs during pregnancy.

This condition affects the normal flow of bile. Bile acids are chemicals in the bile of the liver that help with digestion. With ICP the bile flow begins to slow down and the bile acids build up in the blood. This results in the woman itching that can vary in severity and type. The itching can be bothersome to severe itching and is often worse at night. There is rarely jaundice when experiencing this condition. Although it has been reported as early as 5 weeks pregnant, it is more common for it to begin in the third trimester, when hormone concentrations are at their highest levels. The figure for the percentage of women for whom Intrahepatic Cholestasis of Pregnancy will recur in future pregnancies is 60% or as high as 90% for severe ICP.

Facts at-a-Glance

  1. Intrahepatic Cholestasis of Pregnancy is a condition in which the normal flow of bile is affected by the increased amounts of pregnancy hormones.
  2. Cholestasis is more common in the last trimester of pregnancy when hormones are at their peak.
  3. Cholestasis occurs in about 1 out of 1,000 pregnancies but is more common in Swedish and Chilean ethnic groups.

Information for the Newly Diagnosed

Who is at risk for ICP?

Overall, 1 to 2 pregnancies in 1,000 is affected by ICP in the USA with Latina populations at 5.6%. Risk is increased in women carrying multiples, women who have had IVF treatment and those who have had previous liver damage or issues. The incidence of ICP also shows a striking geographical pattern, with a higher prevalence in Scandinavia and South America specifically Chile where the reported prevalence is as high as 15.6%. Mothers and sisters of patients are also at higher risk of developing the condition, proving that there is a definite genetic predisposition.

What are the risks?

ICP poses several risks that are of great concern. It is associated with an increased risk of stillbirth (intrauterine fetal demise), premature labor, respiratory distress in the neonate, meconium staining, preeclampsia and gestational diabetes.

Respiratory Distress in Neonate

Cholestasis increases the risk for Respiratory Distress Syndrome after birth (RDS). The elevated bile acids are thought to interfere with the formation of a chemical called surfactant which allows the lungs to expand after birth. There is an increased risk of an infant needing respiratory support after birth.

Meconium Passage

Meconium is normally stored in the infant’s intestines until after birth; it is the baby’s first feces which is sticky, thick, and dark green. Sometimes (often in response to fetal distress) it is expelled into the amniotic fluid prior to birth, or during labor. If the baby then inhales the contaminated fluid, respiratory problems may occur. In pregnancies affected by cholestasis, meconium is often passed prior to birth.

Preterm Labor

ICP has been associated with a substantial rate of preterm birth. There is an increased risk of spontaneous preterm labor, which has been seen in as many as 60% of deliveries in some studies, however with active management most studies report rates of 30%-40%. Earlier presentations of Intrahepatic Cholestasis of Pregnancy (ICP) seem to carry an even greater risk of preterm labor, as well as twin or triplet pregnancies.

Stillbirth

Stillbirth tends to occur in the last few weeks of pregnancy. The reason this occurs is not completely understood although it is thought to be due to a cardiac arrhythmia caused by the elevated bile acids.

A recent meta-analysis was able to further clarify the risk of stillbirth in a pregnancy complicated by cholestasis and showed that this risk increases as bile acids become more elevated. With bile acids remaining under 100 µmol/L, the risk is less than 0.28% and similar to a normal pregnancy. When bile acid levels are over 100, the risk of stillbirth increases to over 3%.

What are the symptoms?

Symptoms can vary in severity and type, but the most common ones include:

  • Itching all over, but often more severe on palms and soles of the feet. The itching can be recurrent or constant. Many women find that it is worse at night and it disturbs their sleep.
  • Dark Urine and/or Pale Stools (grayish in color)
  • Preterm Labor
  • Jaundice (rare)

Other symptoms may include:

  • Right Upper Quadrant Pain
  • Nausea
  • Fatigue or Exhaustion
  • Loss of Appetite
  • Mild Depression

What causes ICP?

There is still much to be learned about the exact causes of ICP and its manifestation, but researchers are currently investigating genetic, hormonal and environmental factors. The causes are likely to be due to a number of different factors, including:

Genetic predisposition – Research thus far has identified several gene mutations involved.

ICP has been shown to extend in families. Mothers and sisters are at higher risk of developing the condition, proving that there is a definite genetic predisposition although additional research is needed to explain all cases of the condition in reference to genes.

Hormones

Pregnancy hormones estrogen and progesterone have an effect on the liver’s ability to transport certain chemicals, including bile acids. The flow of bile acids is significantly reduced and leads to the bile acids building up in the blood that causes the symptoms. Note: Women carrying multiples, women who have had IVF treatment and women who have prior liver conditions also appear to have a higher risk of cholestasis.

Environment

There are more women diagnosed with Intrahepatic Cholestasis of Pregnancy (ICP) during the winter months. Although the reason for this is not clear, it suggests that there is an environmental trigger for the condition, such as a reduced exposure to sunlight or a change in diet.

What is the treatment for ICP?

Despite the possible outcomes of ICP, proper treatment provides a great degree of reduction in both fetal risk and maternal symptoms.
The two main treatments are with a medication called ursodeoxycholic acid and proper delivery timing.

Ursodeoxycholic Acid (UDCA), also known as Actigall or Ursodiol or Urso is currently the front-line medication for the treatment of ICP. UDCA is a naturally occurring bile acid that improves liver function and may help reduce total bile acid concentration in the bloodstream. A recent trial was unable to show an improvement in a composite clinical outcome with the use of this medication but it may still have some benefit in some cases and is still recommended.

The other part of management is with proper timing of delivery. Delivery recommendations are based on bile acid levels as risks increase as bile acids become more elevated.

For bile acids greater than 100 µmol/L, delivery is at 36 0/7 weeks. There is consideration for earlier delivery in these cases with other factors. For levels under 100 µmol/L, delivery is recommended at 36 0/7-39 0/7 weeks with delivery earlier in the window if levels reach 40 µmol/L.

Patient Stories

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Visit ICP Care for additional information and resources.

Last updated on March 16th, 2023 at 03:33 pm

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