What are the diagnostic criteria for intrahepatic cholestasis of pregnancy?

Diagnostic Criteria for Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is diagnosed based on the presence of pruritus in the second or third trimester of pregnancy with serum bile acid levels >10 μmol/L. 1, 2

Clinical Presentation

• Pruritus (itching) without a rash, typically occurring in the second or third trimester of pregnancy 1
• Itching is often generalized but predominantly affects the palms and soles of feet 1
• Symptoms are typically worse at night 1
• Rarely, ICP can present in the first trimester, which requires close monitoring 3

Laboratory Criteria

• Essential diagnostic criterion: Total serum bile acid levels >10 μmol/L 1, 2
• Liver transaminases (ALT/AST) are often elevated but not required for diagnosis 1
  • Typically <500 U/L in ICP 2
• Bilirubin levels are usually <5 mg/dL, with mild jaundice occurring in only 10-15% of cases 2
• Normal LDH levels are expected in ICP 2

Diagnostic Algorithm

1. Evaluate pregnant women with pruritus without rash in second or third trimester 1
2. Order serum bile acid levels and liver transaminases 1
3. If available, use pregnancy-specific reference ranges for serum bile acid levels 1
4. In absence of pregnancy-specific ranges, total bile acid level >10 μmol/L is diagnostic 1
5. Random (non-fasting) bile acid levels can be used for diagnosis 1
6. Exclude other causes of pruritus and elevated bile acids (see differential diagnosis) 1

Risk Stratification Based on Bile Acid Levels

• Total bile acid levels ≥100 μmol/L: High risk for adverse fetal outcomes 1, 2
• Total bile acid levels <100 μmol/L: Lower risk for adverse fetal outcomes 1, 2

Differential Diagnosis

Consider other causes of pruritus without rash and elevated bile acids 1:

• Pre-existing hepatobiliary disease 1
• Viral hepatitis 1
• Biliary obstruction 1
• Chronic liver disease 1
• Other conditions associated with pruritus without rash:
  • Chronic renal failure, thyroid disorders, malabsorption, parasitosis 1

Special Considerations

• ICP is more common in women with:
  • History of ICP in previous pregnancies 1
  • Multiple gestations 1
  • Advanced maternal age 1
  • Pre-existing hepatobiliary disease, especially hepatitis C 1
  • Family history of ICP (suggesting genetic component) 1

Management Implications of Diagnosis

• First-line treatment with ursodeoxycholic acid (10-15 mg/kg/day) 1, 2
• Timing of delivery based on bile acid levels:
  • ≥100 μmol/L: Delivery at 36 weeks gestation 1, 2
  • <100 μmol/L: Delivery between 36-39 weeks gestation 1, 2
• Antenatal fetal surveillance should begin at a gestational age when delivery would be performed in response to abnormal testing 1

Important Pitfalls to Avoid

• Do not diagnose ICP based on clinical symptoms alone without laboratory confirmation 1
• Do not recommend preterm delivery (<37 weeks) without laboratory confirmation of elevated bile acid levels 1
• Do not assume normal transaminases exclude ICP; bile acid elevation is the key diagnostic criterion 1, 2
• Do not fail to exclude other causes of liver dysfunction in pregnancy, particularly when presentation is atypical 1