What is the recommended management for pregnant women with intrahepatic cholestasis of pregnancy (ICP) to reduce the risk of stillbirth?

Management of Intrahepatic Cholestasis of Pregnancy (ICP) to Reduce Stillbirth Risk

Women with ICP and total bile acid levels ≥100 μmol/L should be delivered at 36 0/7 weeks of gestation, while those with levels <100 μmol/L should be delivered between 36 0/7 and 39 0/7 weeks of gestation, with timing based on bile acid levels. 1, 2

Diagnosis and Risk Stratification

Diagnosis of ICP requires:

• Measurement of serum bile acids and liver transaminase levels in patients with suspected ICP (GRADE 1B) 1
• Diagnosis confirmed with bile acids >10 μmol/L, total bilirubin <6 mg/dL, and clinical symptoms (typically pruritus) 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 Recommendations

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

   • UDCA reduces pruritus, lowers serum bile acids and liver enzymes 2
   • While UDCA improves maternal symptoms, evidence for prevention of stillbirth is less definitive 3, 4

2. Second-line options for refractory cases:

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

3. Vitamin K supplementation if deficiency is detected due to cholestasis 2

Fetal Surveillance

• Begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing, or at diagnosis if made later in gestation (GRADE 2C) 1
• Continuous fetal monitoring during labor due to higher risk of stillbirth 2

Timing of Delivery

The timing of delivery is critical to prevent stillbirth:

1. High-risk patients (bile acids ≥100 μmol/L):

   • Deliver at 36 0/7 weeks or at diagnosis if after 36 weeks 1, 2

2. Moderate-risk patients (bile acids 40-99 μmol/L):

   • Deliver between 36 0/7 and 39 0/7 weeks 1, 2

3. Lower-risk patients (bile acids <40 μmol/L):

   • Deliver between 37-39 weeks gestation 2

4. Important caveat: Avoid preterm delivery at <37 weeks in patients with clinical diagnosis of ICP without laboratory confirmation of elevated bile acid levels (GRADE 1B) 1

5. Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 0/7 weeks (GRADE 1A) 1

Clinical Pitfalls to Avoid

1. Do not delay delivery based on normal fetal testing alone: Even with normal cardiotocograph results, sudden fetal death can occur in ICP 5

2. Do not rely solely on normalization of bile acids with treatment: Cases of fetal death have been reported despite good biochemical response to UDCA 5

3. Avoid expectant management beyond recommended gestational age: When lung maturity is achieved, delivery should be considered due to increasing risk of stillbirth as pregnancy progresses 6, 5

4. Do not discontinue monitoring after UDCA initiation: Continue monitoring bile acid levels and fetal well-being even after treatment begins 2

5. Recognize that risk increases with gestational age: The risk of adverse fetal outcomes increases as pregnancy progresses, regardless of bile acid levels 6

Postpartum Considerations

• UDCA should be stopped at delivery or gradually reduced over 2-4 weeks if symptoms persist 2
• Ensure bile acids, ALT/AST, and bilirubin normalize within 3 months postpartum 2
• Counsel patients on high recurrence risk (up to 90%) in future pregnancies 2

By following these evidence-based recommendations, the risk of stillbirth in women with ICP can be significantly reduced through appropriate monitoring, treatment, and timely delivery.