Cholestasis of Pregnancy Part 2: For the Patient

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In the last post, I discussed the important points regarding Cholestasis of Pregnancy from the research article listed. In this post, I will discuss their findings as it relates to the patient.

Diken Z, Usta IM, Nassar AH. A Clinical Approach to Intrahepatic Cholestasis of Pregnancy. American Journal of Perinatology, EFirst (2013).

Intrahepatic Cholestasis of Pregnancy (ICP) was first described in 1883. It’s prevalence ranges from 0.3 to 5.6% of pregnancies in the US. It is thought to be due to abnormal formation or secretion of bile acids.


There are many factors that increase the risk of developing ICP. These include being pregnant with twins, having preeclampsia, being over 35, having hepatitis C, or having had ICP in a previous pregnancy. It is multifactorial, caused by an interaction between environment and hormones, and to a very small degree, genetics. Environmental factors include occurring more often in winter, as well as with a deficiency in selenium (a mineral found in garlic, onions, sunflower seeds, and mushrooms). Hormonal changes are thought to play a role because ICP is most likely to occur at the end of pregnancy, when estrogen and progesterone are at their highest, as well as in pregnancies with twins. Women may also experience ICP while taking oral contraceptives, and tend to have worse nausea. Genetically, sisters of women with ICP are 12 times more likely to experience it themselves, but a genetic mutation associated with ICP is only found in a very small percentage of patients with the disease.

Signs and Symptoms
The classic presentation is itching of the palms and soles of feet that can spread to the entire body. Itching is usually worse at night. There is no rash, other than marks present from scratching. Itching usually begins in the second or third trimester, though it can start as early as 8 weeks. Occasionally, yellow skin, greasy stools, abdominal pain, or weight loss may be seen.

Itching is a common symptom in even healthy pregnancies and can be caused by many things. Itching in ICP is thought to be due to the buildup of bile acids in the skin. ICP must be confirmed by lab tests to rule out hepatitis and gallbladder disease.

Lab Abnormalities
The most frequent lab abnormality is an elevated total bile acid (TBA) concentration. Mild ICP is defined as a TBA of 10-40, while severe ICP is a TBA over 40. Liver function tests can also be abnormal, but there is no standard level used for diagnosis. Labs usually normalize 2-8 weeks after delivery.

 Associated Obstetric Complications
If you are diagnosed with ICP, your pregnancy will be considered high risk. There is a 7% fetal mortality rate, and 90% of these cases occur after 37 weeks. The highest risk of complication appears to with a TBA level over 40, and especially over 100. It is thought that your bile acids cross the placenta and accumulate in the fetus, cord blood, and amniotic fluid. Excessive bile acids have been found to cause abnormal cardiac activity in rats, which could explain the sudden cardiac death seen in the fetus. Studies have also found that bile acids deplete an enzyme in the fetal lungs, resulting in an increased risk of respiratory distress and the baby having difficulty breathing.

ICP also puts you at increased risk of postpartum hemorrhage. This is because excessive bile acids can cause malabsorption of Vitamin K, a vitamin used by the body for clotting.


The goal of treatment is to minimize your symptoms and decrease the risk to your baby. Typically, a medicine called ursodeoxycholic acid (UDCA), also known as Actigall or Ursodiol, is given. This medicine decreases itching and normalizes bile acid levels. Improvement is usually seen in 1-2 weeks. There are no reported cases of fetal toxicity with UDCA.

Fetal Well Being
There is no ideal method of fetal testing for patients with ICP. Typically, nonstress tests (NSTs) are ordered. However, fetal death is often sudden and they have been unable to predict outcome with NSTs in several studies. There is also no need for frequent growth ultrasounds in women with ICP, as growth restriction is uncommon and is not a usual complication. The cause of fetal death is not due to the placenta being affected resulting in a chronic problem, but instead because of a sudden cardiac arrest in the baby; this makes it difficult to predict.

Expectant vs. Active Management

There are two options available: expectant management and active management. Expectant management takes a “wait and see” approach, waiting for spontaneous labor, while active management tends to be more aggressive in treatment and recommends delivery at 37 weeks.

Expectant Management
Keep in mind that there is an intrauterine mortality rate of 7%, with 90% of cases occurring after 37 weeks gestation. Waiting to deliver until spontaneous labor carries higher risk of adverse pregnancy outcomes and higher incidence of fetal death even after reassuring antenatal testing. This option may be reasonable when TBA levels are less than 40 (mild ICP), as some studies find no rise in fetal complications until TBA levels exceed 40. Typical management for mild ICP includes: 1) Manage at outpatient 2) Antihistamines for itching 3) Start UDCA 4) Weekly non-stress tests 5) Weekly liver function tests, TBA, and prothrombin time (if increased, start 10mg Vitamin K daily) 6) Wait for spontaneous labor and delivery.

Active Management
Because of the increased risks of sudden death to the fetus, most providers are not comfortable with expectant management, even in cases of mild ICP. Some sources recommend amniocentesis at 36 weeks to detect meconium and fetal lung maturity. An amniocentesis uses a needle to withdraw amniotic fluid through the mother’s abdomen. If meconium is present, it means the fetus had a bowel movement, typically due to stress at this early age. The presence of meconium detected by amniocentesis is associated with 86-100% risk of fetal death in patients with ICP.

Recommendations for active management include: 1) Start UDCA 2) Twice weekly non-stress test and biophysical profile 3) Twice weekly liver function tests, TBA levels, and prothrombin time 4) Consider course of betamethasone (steroid injections that help mature the baby’s lungs) if less than 34 weeks gestation 5) Consider inpatient management 6) Consider amniocentesis at 36 weeks. If meconium fluid found during amniocentesis, deliver promptly. If no meconium, deliver at 37 weeks.


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