What is the best next step in managing a pregnant woman at 30 weeks gestation with severe pruritus and abnormal liver function tests, including hypercholanemia?

From the Guidelines

The best next step in management for this patient is to start ursodeoxycholic acid (UDCA) at a dose of 10-15 mg/kg/day, typically 300 mg twice daily or three times daily. This patient has intrahepatic cholestasis of pregnancy (ICP), as evidenced by her pruritus, elevated liver enzymes, and elevated total bile acids. UDCA is the first-line treatment for ICP as it helps reduce bile acid levels and alleviates pruritus by promoting bile flow and protecting hepatocytes from the toxic effects of bile acids 1.

Key Considerations

• The patient should have increased fetal surveillance with weekly non-stress tests and regular ultrasounds for fetal growth.
• Delivery planning should also be considered, typically between 36-37 weeks gestation, as ICP is associated with increased risks of fetal distress, stillbirth, and preterm birth.
• The patient should be counseled that while UDCA may take 1-2 weeks to provide symptom relief, it significantly improves maternal symptoms and may reduce fetal complications.
• Antihistamines like diphenhydramine can be continued for symptomatic relief of pruritus, but they don't address the underlying condition.

Treatment Details

• The typical starting dose for UDCA treatment is 10-15 mg/kg per day, which can be divided into 2 or 3 daily doses.
• Typical regimens are 300 mg twice or 3 times daily or 500 mg twice daily.
• The drug is usually well tolerated, although mild cases of nausea and dizziness have been reported in up to 25% of patients.
• A decrease in pruritus is usually seen within 1 to 2 weeks.
• If the pruritus is not relieved, the dose can be titrated to a maximum of 21 mg/kg per day.

Monitoring and Follow-up

• Biochemical improvement is usually seen within 3 to 4 weeks.
• The patient should be monitored regularly for signs of improvement or worsening of symptoms.
• Fetal surveillance should be continued until delivery, and the patient should be counseled on the risks and benefits of ongoing pregnancy versus delivery.

From the FDA Drug Label

Pregnancy Reproduction studies have been performed in rats and rabbits with ursodiol doses up to 200-fold the therapeutic dose and have revealed no evidence of impaired fertility or harm to the fetus at doses of 20- to 100-fold the human dose in rats and at 5-fold the human dose (highest dose tested) in rabbits There have been no adequate and well-controlled studies of the use of ursodiol in pregnant women, but inadvertent exposure of 4 women to therapeutic doses of the drug in the first trimester of pregnancy during the Ursodiol trials led to no evidence of effects on the fetus or newborn baby Although it seems unlikely, the possibility that ursodiol can cause fetal harm cannot be ruled out; hence, the drug is not recommended for use during pregnancy.

The best next step in managing a pregnant woman at 30 weeks gestation with severe pruritus and abnormal liver function tests, including hypercholanemia, is not to use ursodeoxycholic acid due to the lack of adequate and well-controlled studies in pregnant women and the potential risk of fetal harm 2.

• The patient's symptoms suggest intrahepatic cholestasis of pregnancy, a condition that requires careful management to prevent adverse outcomes for both the mother and the fetus.
• Given the potential risks associated with ursodeoxycholic acid, alternative treatments should be considered under the guidance of a healthcare provider.

From the Research

Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy (ICP)

The patient's symptoms of severe pruritus and abnormal liver function tests, including hypercholanemia, at 30 weeks gestation are consistent with a diagnosis of Intrahepatic Cholestasis of Pregnancy (ICP) 3, 4.

Key Considerations

• ICP is a condition that complicates approximately 0.2% to 2% of pregnancies and can lead to increased fetal risks, including preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome, or stillbirth 3.
• The diagnosis of ICP is based on symptoms of pruritus, typically including the palms and soles, as well as elevated bile acid levels 3, 4.
• Other liver function tests, such as alanine aminotransferase and aspartate aminotransferase, are also frequently elevated, and other causes of liver dysfunction should be ruled out 3.

Treatment Options

• Ursodeoxycholic acid (UDCA) treatment has been shown to improve maternal pruritus symptoms, as well as biochemical tests 3, 4, 5.
• The optimum dose of UDCA is not universally agreed upon, but a dose of 13.5 mg/kg/day has been suggested as effective in normalizing liver function tests 6.
• UDCA treatment can reduce serum bile acid concentrations and improve symptoms, but it is essential to monitor the patient's response to treatment and adjust the dose as needed 7, 5.

Next Steps

• The patient should be treated with UDCA to improve maternal symptoms and reduce the risk of fetal complications 3, 4, 5.
• Close obstetric surveillance is warranted, and delivery may be considered at 37 weeks' gestation due to the increased risk of stillbirth in the setting of ICP 3.
• The patient's liver function tests and bile acid levels should be monitored regularly to assess the response to treatment and adjust the dose of UDCA as needed 4, 7, 5.