What is the recommended management approach for intrahepatic cholestasis of pregnancy (ICP)?

Management of Intrahepatic Cholestasis of Pregnancy (ICP): Practice Pearls from SOGC 452

The cornerstone of ICP management includes ursodeoxycholic acid (UDCA) treatment for maternal symptom relief, risk stratification based on bile acid levels, and timing delivery according to disease severity.

Diagnosis and Classification

• Diagnosis requires:

  • Pruritus (typically on palms and soles)
  • Elevated serum bile acids >10 μmol/L
  • Mild to moderate elevations in liver enzymes
  • Total bilirubin <6 mg/dL 1

• Risk stratification based on bile acid levels:

  Risk Category	Bile Acid Level	Recommended Delivery Timing
  High Risk	≥100 μmol/L	35-36 weeks or at diagnosis if after 36 weeks
  Moderate Risk	40-99 μmol/L	36-39 weeks gestation
  Lower Risk	<40 μmol/L	37-39 weeks gestation 2, 1

Treatment Recommendations

• First-line treatment: Ursodeoxycholic acid (UDCA)

  • Starting dose: 10-15 mg/kg/day divided into 2-3 doses
  • Typical regimens: 300 mg 2-3 times daily or 500 mg twice daily
  • Maximum dose: 21 mg/kg/day if symptoms persist 2
  • Benefits:
    • Reduces maternal pruritus (improvement usually seen within 1-2 weeks)
    • Decreases serum bile acids and liver enzymes (improvement usually within 3-4 weeks)
    • Reduces risk of spontaneous preterm birth in singleton pregnancies
    • May be protective against stillbirth 2

• Second-line options for refractory cases:

  • Rifampicin (can be combined with UDCA)
  • Cholestyramine (less effective than UDCA with significant GI side effects)
  • S-adenosyl-methionine
  • Antihistamines (limited benefit for pruritus) 2

Monitoring and Surveillance

• Laboratory monitoring:

  • Total serum bile acids and liver function tests every 2 weeks until 32 weeks
  • Weekly monitoring thereafter until delivery 1
  • Non-fasting bile acid levels are acceptable 2

• Fetal surveillance:

  • Antenatal testing (though efficacy is uncertain as stillbirth may be a sudden event)
  • Note: Normal fetal testing does not preclude stillbirth risk, as stillbirths have been reported within days of normal testing 2

Delivery Timing

• Delivery timing should be based on bile acid levels:
  • TSBA ≥100 μmol/L: Deliver at 35-36 weeks due to markedly increased stillbirth risk
  • TSBA 40-99 μmol/L: Consider delivery at 36-39 weeks
  • TSBA <40 μmol/L: Consider delivery at 37-39 weeks 2, 1

Postpartum Management

• Stop UDCA at delivery or gradually reduce over 2-4 weeks if symptoms persist 2
• Ensure bile acids, ALT/AST, and bilirubin normalize within 3 months postpartum
• If liver tests remain abnormal beyond 3 months, investigate for underlying liver disease 2, 1
• Consider genetic screening if:
  • Family history of hepatobiliary disease
  • Early onset or severe disease
  • Persistent liver abnormalities 2, 1

Patient Education

• High recurrence risk (up to 90%) in future pregnancies
• Avoid estrogen-containing contraceptives
• Increased risk for other hepatobiliary diseases including:
  • Hepatitis C (HR 4.16)
  • Chronic hepatitis (HR 5.96)
  • Liver fibrosis/cirrhosis (HR 5.11)
  • Cholangitis (HR 4.2) 1

Common Pitfalls to Avoid

1. Failing to recognize that pruritus can precede elevated bile acids by several weeks (repeat testing if symptoms persist) 2

2. Overlooking the association between ICP and other pregnancy complications:

   • Preeclampsia (2.6-fold increased risk)
   • Gestational diabetes
   • Preterm birth 2, 1

3. Relying solely on UDCA to prevent adverse perinatal outcomes - recent evidence questions its efficacy for this purpose, though it remains valuable for maternal symptom relief 3

4. Delaying delivery in high-risk cases (TSBA ≥100 μmol/L) beyond 35-36 weeks, as stillbirth risk increases markedly after this point 2