What are the management guidelines for Intrahepatic Cholestasis of Pregnancy (ICT) positive pregnancies in the third trimester?

Management of Intrahepatic Cholestasis of Pregnancy (ICP) in the Third Trimester

For ICP-positive pregnancies in the third trimester, timing of delivery should be based on bile acid levels: deliver at 36 weeks for bile acids ≥100 μmol/L and between 36-39 weeks for bile acids <100 μmol/L. 1

Diagnosis Confirmation and Risk Assessment

• Confirm diagnosis with:

  • Elevated serum bile acid levels (>10 μmol/L)
  • Elevated liver enzymes (AST, ALT may be up to 10-20 times normal)
  • Presence of pruritus (especially on hands)
  • Exclusion of other liver disorders 2

• Risk stratification based on bile acid levels:

  • High risk: ≥100 μmol/L
  • Moderate risk: 40-99 μmol/L
  • Lower risk: <40 μmol/L 2

Treatment Protocol

1. First-line medication: Ursodeoxycholic acid (UDCA)

   • Dosage: 10-15 mg/kg/day divided into 2-3 doses (typical regimens: 300 mg 2-3 times daily or 500 mg twice daily)
   • Expected response: Pruritus improvement within 1-2 weeks, biochemical improvement within 3-4 weeks
   • Maximum dose: Can be titrated up to 21 mg/kg/day if pruritus persists 1

2. Alternative treatments for refractory cases:

   • S-adenosyl-methionine (less effective than UDCA)
   • Cholestyramine (separate from UDCA by at least 4 hours)
   • Rifampin (can be combined with UDCA for severe cases) 1, 2

3. Symptomatic management of pruritus:

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

Fetal Surveillance Protocol

1. Antenatal testing:

   • Begin at a gestational age when delivery would be performed in response to abnormal results
   • More frequent monitoring for bile acids ≥100 μmol/L
   • Third trimester assessment of fetal growth 1, 2

2. During labor:

   • Continuous fetal monitoring due to higher risk of stillbirth
   • Avoid internal fetal monitors and early artificial rupture of membranes unless clinically necessary 1

Delivery Timing Algorithm

1. Bile acids ≥100 μmol/L:

   • Offer delivery at 36 0/7 weeks gestation
   • Administer antenatal corticosteroids if delivering before 37 weeks 1, 2

2. Bile acids 40-99 μmol/L:

   • Recommend delivery between 36 0/7 and 39 0/7 weeks gestation 1, 2

3. Bile acids <40 μmol/L:

   • Recommend delivery between 37 0/7 and 39 0/7 weeks gestation 1, 2

4. Additional considerations for earlier delivery (34-36 weeks):

   • Unremitting maternal pruritus despite treatment
   • History of ICP-related stillbirth
   • Evidence of worsening hepatic function 2

Monitoring Protocol

• Measure bile acid levels at least weekly from 32 weeks' gestation
• Monitor liver function tests regularly
• If bile acids decrease after UDCA treatment, continue to monitor as levels may rise again 2

Important Caveats and Pitfalls

1. Do not delay diagnosis if pruritus precedes elevated bile acids; repeat testing if symptoms persist

2. Do not rely solely on antepartum testing, as sudden stillbirth can occur even after normal fetal testing

3. Do not deliver preterm (<37 weeks) without laboratory confirmation of elevated bile acid levels 1

4. Do not miss screening for viral hepatitis in patients with ICP diagnosed at an early gestational age or with high bile acid levels 1

5. Do not forget postpartum follow-up:

   • Liver function tests and bile acids should normalize within 2-4 weeks
   • If abnormalities persist beyond 6 weeks, evaluate for underlying chronic liver disease 2

ICP management requires vigilant monitoring and timely intervention to prevent adverse fetal outcomes, particularly stillbirth, which is the most serious complication associated with this condition 3, 4.