What is the management of cholestasis (intrahepatic cholestasis of pregnancy) in pregnancy?

Management of Intrahepatic Cholestasis of Pregnancy

Ursodeoxycholic acid (UDCA) at a dose of 10-15 mg/kg/day divided into 2-3 daily doses is the first-line treatment for intrahepatic cholestasis of pregnancy (ICP) to reduce maternal symptoms and potentially improve perinatal outcomes. 1, 2

Diagnosis

• Diagnosis based on:

  • Pruritus (typically worse at night, often starting on palms and soles)
  • Elevated serum bile acids (≥11 μmol/L)
  • Elevated liver enzymes (ALT/AST) in most cases
  • No other explanation for symptoms

• Stratify risk based on bile acid levels:

  • Low risk: <40 μmol/L
  • Moderate risk: 40-99 μmol/L (0.3% stillbirth risk)
  • High risk: ≥100 μmol/L (3.4% stillbirth risk) 1, 2

Pharmacological Management

First-line Treatment

• UDCA 10-15 mg/kg/day divided into 2-3 daily doses (typical regimens: 300 mg 2-3 times daily or 500 mg twice daily) 1, 2
• Improvement in pruritus usually occurs within 1-2 weeks
• If symptoms persist, increase dose up to 21-25 mg/kg/day 1
• UDCA is safe during pregnancy and breastfeeding 1, 3

Second-line Options for Refractory Pruritus

• Rifampicin (300-600 mg daily) can be added to UDCA 1, 2

  • Monitor for hepatotoxicity (occurs in ~5% of patients)
  • Neonates of women treated with rifampicin should receive vitamin K

• Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day) 1

  • Must be administered at least 4 hours apart from UDCA
  • May exacerbate vitamin K deficiency
  • Monitor coagulation (INR)

• S-adenosyl-L-methionine may have additive effects with UDCA 1

Non-pharmacological Measures

• Emollients to prevent skin dryness
• Avoid hot baths/showers
• Use cooling gels (e.g., menthol)
• Keep nails short
• Wear loose-fitting cotton clothing 2

Monitoring

• Weekly total serum bile acids and liver function tests 1
• Monitor coagulation parameters, especially if using cholestyramine 1, 2
• Correct vitamin K deficiency if present, particularly important in patients with steatorrhea or those using anion exchange resins 1

Fetal Surveillance and Delivery Timing

Fetal Surveillance

• Begin antenatal fetal surveillance at diagnosis 1, 2
• More intensive monitoring for patients with bile acids ≥40 μmol/L

Delivery Timing Based on Bile Acid Levels

• Bile acids <40 μmol/L: Consider delivery at 38-39 weeks
• Bile acids 40-99 μmol/L: Consider delivery at 37-38 weeks
• Bile acids ≥100 μmol/L: Consider delivery at 36 weeks 1, 2

Post-Delivery Management

• UDCA can be stopped at delivery
• If symptoms persist, taper UDCA over 2-4 weeks post-delivery 1
• Ensure bile acids and liver enzymes return to normal within 3 months
• If abnormalities persist beyond 6 weeks postpartum, investigate for underlying liver disease 1, 2

Common Pitfalls to Avoid

• Inadequate UDCA dosing (start with appropriate dose and titrate if needed)
• Not separating UDCA and cholestyramine administration by at least 4 hours
• Overlooking vitamin K deficiency, especially when using cholestyramine
• Delaying treatment, which prolongs maternal discomfort
• Insufficient monitoring of bile acid levels, which may rise rapidly near term
• Failure to recognize that ICP can recur in subsequent pregnancies (45-70% recurrence rate) 1, 2

Multiple studies have demonstrated UDCA's efficacy in improving maternal symptoms and biochemical parameters 4, 5, 6. While earlier studies showed promising results for reducing adverse perinatal outcomes, the most recent meta-analysis found UDCA had no significant effect on stillbirth alone but did reduce the composite outcome of stillbirth and preterm birth when considering only randomized controlled trials 7.