What are the diagnostic criteria and treatment options for Intrahepatic Cholestasis of Pregnancy (ICP)?

Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy (ICP)

The diagnosis of Intrahepatic Cholestasis of Pregnancy (ICP) requires measurement of serum bile acid and liver transaminase levels in patients with suspected ICP, with total bile acid levels ≥10 μmol/L confirming the diagnosis in the presence of pruritus. 1

Diagnostic Criteria

Clinical Presentation

• Pruritus (itching without rash) is the hallmark symptom
  • Typically occurs in the second and third trimesters
  • Often worse at night
  • Commonly affects palms and soles but can be generalized
  • Not associated with a visible rash

Laboratory Diagnosis

• Required tests:

  • Serum bile acid levels (total bile acids)
  • Liver transaminases (ALT, AST)

• Diagnostic thresholds:

  • Total serum bile acid levels ≥10 μmol/L 1, 2
  • May have elevated liver transaminases, but can be normal
  • Bilirubin may be elevated in severe cases

Risk Stratification

• Mild ICP: Total bile acids 10-39 μmol/L
• Severe ICP: Total bile acids ≥40 μmol/L 2
• Very severe ICP: Total bile acids ≥100 μmol/L (significantly increased stillbirth risk) 1

Timing of Testing

• Random bile acid levels are generally acceptable
• Postprandial measurements may provide increased sensitivity 2

Treatment Options

Pharmacological Management

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

   • Recommended dosage: 10-15 mg/kg/day 1
   • Benefits:
     • Reduces maternal pruritus
     • Improves liver function tests
     • Reduces bile acid levels in maternal serum 3
     • Decreases bile acid transfer to the fetus 3
   • Most effective in severe ICP (bile acids ≥40 μmol/L) 4

2. Second-line options (if UDCA is ineffective):

   • Rifampin (for refractory cases) 5
   • Antihistamines (e.g., hydroxyzine) for symptomatic relief of pruritus 5

Fetal Surveillance

• Begin antenatal fetal surveillance when delivery would be performed in response to abnormal testing 1
• Weekly monitoring of bile acid levels from 32 weeks gestation 2
• Regular fetal monitoring due to increased risk of:
  • Preterm delivery
  • Meconium-stained amniotic fluid
  • Respiratory distress syndrome
  • Sudden intrauterine fetal death 6

Timing of Delivery

• For bile acids ≥100 μmol/L: Offer delivery at 36 0/7 weeks of gestation 1
• For bile acids <100 μmol/L: Recommend delivery between 36 0/7 and 39 0/7 weeks of gestation 1
• For suspected ICP without laboratory confirmation: Avoid preterm delivery before 37 0/7 weeks 1
• For delivery <37 weeks: Administer antenatal corticosteroids for fetal lung maturity 1

Special Considerations

Genetic Factors

• Consider genetic testing in cases of:
  • Early-onset ICP (before third trimester)
  • Recurrent ICP in multiple pregnancies
  • Treatment-refractory cases
  • Mutations in hepatobiliary transport proteins (MDR3, BSEP) may be present 7, 5

Postpartum Follow-up

• Symptoms typically resolve within days after delivery
• Follow-up liver function tests 6-8 weeks postpartum
• Counsel about recurrence risk in future pregnancies (up to 50-70%)

Common Pitfalls to Avoid

1. Misdiagnosis: Don't confuse ICP with other causes of pruritus in pregnancy (atopic eruption, polymorphic eruption, pemphigoid gestationis)
2. Inadequate monitoring: Weekly bile acid monitoring is essential in severe cases
3. Delayed delivery: Don't extend pregnancy beyond recommended gestational age based on bile acid levels
4. Incomplete evaluation: Always measure bile acids, not just liver enzymes, as bile acids can be elevated when liver enzymes are normal
5. Inappropriate delivery timing: Avoid preterm delivery without laboratory confirmation of elevated bile acids 1

By following these diagnostic criteria and management protocols, clinicians can effectively diagnose and treat ICP while minimizing the risk of adverse maternal and fetal outcomes.