What are the maternal risks and management of intrahepatic cholestasis of pregnancy (ICP)?

Maternal Risks and Management of Intrahepatic Cholestasis of Pregnancy (ICP)

Intrahepatic cholestasis of pregnancy (ICP) poses minimal direct risk to maternal health during pregnancy but carries significant long-term health implications for affected women, including increased risk for future hepatobiliary, immune-mediated, and cardiovascular diseases. 1, 2

Maternal Risks of ICP

Immediate Risks During Pregnancy

• Pruritus (primary symptom) - typically affects palms and soles
• Mild to moderate elevations in liver enzymes
• Increased risk of preeclampsia (2.6-fold higher risk) 1
• Higher rates of gestational diabetes
• Increased risk of spontaneous and iatrogenic preterm birth 1

Long-term Maternal Risks

• High recurrence rate (up to 90%) in subsequent pregnancies 2
• Increased risk for future hepatobiliary diseases
• Higher risk for immune-mediated disorders
• Elevated risk for cardiovascular diseases 3
• Women with ICP should avoid estrogen-containing contraceptives 2

Diagnosis of ICP

Diagnostic Criteria

• Pruritus without rash, typically in second or third trimester
• Elevated serum bile acids >10 μmol/L
• Total bilirubin <6 mg/dL
• Exclusion of other causes of liver dysfunction 2

Laboratory Monitoring

• Measure serum bile acids and liver transaminase levels in patients with suspected ICP (GRADE 1B) 1
• Random bile acid levels can be used for diagnosis (fasting not required) 1
• Monitor total serum bile acids and liver function tests:
  • Every 2 weeks until 32 weeks
  • Weekly thereafter until delivery 2

Risk Stratification

ICP severity is categorized based on bile acid levels:

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

Management of ICP

Pharmacological Treatment

• First-line treatment: Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day in divided doses (GRADE 1A) 1, 2

  • Typical starting dose: 500 mg twice daily
  • Benefits: reduces pruritus, lowers serum bile acids and liver enzymes, decreases adverse outcomes
  • No evidence of fetal harm

• Second-line options for refractory cases:

  • Rifampicin
  • Anion exchange resins
  • S-adenosyl-methionine 2

• Vitamin K supplementation if cholestasis is severe (to prevent vitamin K deficiency) 2

Timing of Delivery Based on Risk Category

• High Risk (≥100 μmol/L): Deliver at 36 0/7 weeks or at diagnosis if after 36 weeks (GRADE 1B) 1, 2
• Moderate Risk (40-99 μmol/L): Deliver between 36 0/7 and 39 0/7 weeks (GRADE 1C) 1, 2
• Lower Risk (<40 μmol/L): Deliver between 37 0/7 and 39 0/7 weeks 2

Antenatal Monitoring

• Begin antenatal fetal surveillance when delivery would be performed in response to abnormal testing or at diagnosis if made later in gestation (GRADE 2C) 1
• Normal fetal testing does not preclude stillbirth risk 2
• Continuous fetal monitoring during labor due to higher risk of stillbirth 2

Additional Considerations

• Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 0/7 weeks (GRADE 1A) 1, 2
• Avoid preterm delivery at <37 weeks without laboratory confirmation of elevated bile acid levels (GRADE 1B) 1

Postpartum Care

• Discontinue 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 2
• If liver tests remain abnormal beyond 3 months, investigate for underlying liver disease 2
• Consider genetic counseling if:
  • Family history of ICP
  • Severe or early-onset disease
  • Persistent liver abnormalities 2

Common Pitfalls and Caveats

• Don't miss the diagnosis: ICP can be confused with other pruritic conditions of pregnancy
• Don't rely solely on transaminases: Elevated bile acids are the diagnostic hallmark
• Don't delay treatment: UDCA should be started promptly once diagnosis is confirmed
• Don't ignore maternal symptoms: While fetal risks are emphasized, maternal pruritus can be debilitating and requires treatment
• Don't forget postpartum follow-up: Ensure liver function normalizes after delivery
• Don't overlook genetic factors: Consider genetic testing in early-onset, recurrent, or treatment-refractory cases 4