What is the management plan for cholestasis of pregnancy (intrahepatic cholestasis of pregnancy, ICP)?

Management of Intrahepatic Cholestasis of Pregnancy (ICP)

The management of intrahepatic cholestasis of pregnancy requires ursodeoxycholic acid treatment for maternal symptoms and risk stratification based on bile acid levels for timing of delivery, with early delivery at 36 weeks for those with bile acid levels ≥100 μmol/L to prevent stillbirth. 1

Diagnosis

• Diagnosis is based on:

  • Pruritus (especially on hands and soles) in the second or third trimester
  • Elevated serum bile acid levels >10 μmol/L
  • Elevated liver enzymes (ALT/AST may be up to 10-20 times normal)
  • Total bilirubin usually <6 mg/dL
  • Exclusion of other causes of liver dysfunction 2

• Initial laboratory assessment:

  • Serum bile acid levels (most accurate diagnostic marker)
  • Liver function tests (ALT, AST, bilirubin)
  • Consider testing for viral hepatitis, autoimmune hepatitis if diagnosis unclear 1

Treatment

Pharmacological Management

• First-line treatment: Ursodeoxycholic acid (UDCA)

  • Dosage: 10-15 mg/kg/day 2
  • Benefits:
    • Improves maternal pruritus
    • Reduces serum bile acid levels and liver enzymes
    • Reduces risk of spontaneous preterm birth
    • May be protective against stillbirth in women with bile acid levels >40 μmol/L 1

• Second-line options for refractory pruritus:

  • Rifampicin: Start with 150 mg twice daily, monitor for hepatotoxicity 2
  • Cholestyramine: Administer at least 4 hours apart from UDCA, monitor vitamin K status and coagulation 2

Symptomatic Relief for Pruritus

• Avoid hot baths/showers
• Use emollients to prevent skin dryness
• Apply cooling gels (e.g., menthol) to affected areas
• Keep nails short to minimize skin damage 2

Monitoring

• Measure serum bile acids at least weekly from 32 weeks' gestation 1
• Monitor liver function tests regularly
• If using cholestyramine, monitor coagulation parameters 2

Fetal Surveillance and Delivery Timing

Risk Stratification Based on Bile Acid Levels

1. Bile acid levels ≥100 μmol/L (high risk):

   • Offer delivery at 36 0/7 weeks' gestation
   • Risk of stillbirth increases substantially after 35 weeks 1

2. Bile acid levels 40-99 μmol/L (moderate risk):

   • Recommend delivery between 36 0/7 and 39 0/7 weeks' gestation
   • Consider earlier delivery within this window 1

3. Bile acid levels <40 μmol/L (lower risk):

   • Recommend delivery between 37 0/7 and 39 0/7 weeks' gestation 1

Fetal Surveillance

• Begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 1
• More frequent monitoring may be appropriate for those with bile acid levels ≥100 μmol/L 1
• Use continuous fetal monitoring during labor due to higher risk of stillbirth 1

Special Considerations

• For delivery before 37 weeks, administer antenatal corticosteroids for fetal lung maturity 1
• Consider earlier delivery (34-36 weeks) in women with:
  • Bile acid levels ≥100 μmol/L AND
  • Unremitting maternal pruritus despite treatment OR
  • History of ICP-related stillbirth before 36 weeks OR
  • Evidence of worsening hepatic function 1

Postpartum Care

• Pruritus typically resolves within days after delivery
• Liver function tests and bile acids should normalize within 2-4 weeks
• If abnormalities persist beyond 3 months, investigate for underlying liver disease 1
• Consider genetic screening if there is a family history of hepatobiliary disease, early onset, or severe disease 1

Common Pitfalls to Avoid

1. Delayed diagnosis: Pruritus can precede elevated bile acids by several weeks; repeat testing if symptoms persist 1

2. Inadequate monitoring: Bile acid levels can increase with advancing gestation; weekly monitoring after 32 weeks is essential 1

3. Relying solely on antepartum testing: Stillbirth in ICP can occur suddenly, even after normal fetal testing 1

4. Premature delivery without confirmed diagnosis: Avoid delivery before 37 weeks without laboratory confirmation of elevated bile acids 1

5. Overlooking UDCA measurement effect: Be aware that UDCA is measured by enzymatic total serum bile acid assays, which may affect interpretation of results 1

By following this management approach, healthcare providers can minimize maternal discomfort and reduce the risk of adverse fetal outcomes, particularly stillbirth, which is the most serious complication of intrahepatic cholestasis of pregnancy.