What is the management of cholestasis in pregnancy?

Management of Cholestasis in Pregnancy

Ursodeoxycholic acid (UDCA) at doses of 10-15 mg/kg/day should be offered as first-line treatment for intrahepatic cholestasis of pregnancy (ICP), particularly for women with serum bile acid concentrations >40 μmol/L, to reduce the risk of spontaneous preterm birth and potentially protect against stillbirth. 1, 2

Diagnosis and Risk Assessment

• Diagnosis is based on:

  • Pruritus (primary symptom)
  • Elevated serum bile acids >10 μmol/L
  • Mild to moderate elevations in liver enzymes
  • Total bilirubin <6 mg/dL 2

• Risk stratification based on bile acid levels:

  • High risk: ≥100 μmol/L (increased risk of stillbirth)
  • Moderate risk: 40-99 μmol/L
  • Lower risk: <40 μmol/L 2

• Initial workup should include:

  • Total serum bile acids (TSBA)
  • Liver function tests (ALT, AST, bilirubin)
  • Rule out other causes of liver disease (viral hepatitis, autoimmune hepatitis, extrahepatic biliary obstruction) 1

Treatment Algorithm

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

   • Dosage: 10-15 mg/kg/day in divided doses 2
   • Start with low dose of 10 mg/kg/day and slowly increase to 15-20 mg/kg/day if needed 1
   • Benefits:
     • Reduces maternal pruritus (though effect may be modest)
     • Decreases serum bile acids and liver enzymes
     • Reduces risk of spontaneous preterm birth
     • May protect against stillbirth 1, 2

2. For refractory pruritus, add second-line options:

   • Rifampicin (300-600 mg daily) 2
   • Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day)
     • Must be given at least 4 hours after UDCA
     • Monitor for vitamin K deficiency 1, 2
   • S-adenosyl-methionine can be combined with UDCA for severe cases 2

3. Non-pharmacological management of pruritus:

   • Emollients to prevent skin dryness
   • Avoid hot baths/showers
   • Use cooling gels (e.g., menthol gels)
   • Keep nails shortened 1

Monitoring and Delivery Planning

• Monitor TSBA and liver function tests:

  • Every 2 weeks until 32 weeks' gestation
  • Weekly thereafter until delivery 1

• Delivery timing based on bile acid levels:

  • TSBA ≥100 μmol/L: Recommend delivery at 35 weeks' gestation due to markedly increased stillbirth risk after this point 1
  • TSBA 40-99 μmol/L: Recommend delivery between 36-39 weeks' gestation 2
  • TSBA <40 μmol/L: Consider delivery between 37-39 weeks' gestation 2

Postpartum Management

• Stop UDCA treatment at time of delivery 1
• If symptoms persist, reduce UDCA gradually 2-4 weeks post-delivery 1
• Ensure TSBA, ALT/AST, and bilirubin return to normal within 3 months of delivery
• If liver tests remain abnormal beyond 3 months, investigate for underlying liver disease 1, 2
• Consider genetic screening if there is:
  • Family history of hepatobiliary disease
  • Early onset or severe disease 1

Important Considerations and Caveats

• UDCA is not FDA-approved for use during pregnancy according to labeling, but clinical guidelines strongly support its use for ICP 2, 3
• UDCA is considered safe during pregnancy and breastfeeding 1, 2
• Drug interactions to monitor:
  • Bile acid sequestering agents (cholestyramine, colestipol) may reduce UDCA absorption
  • Aluminum-based antacids may interfere with UDCA
  • Estrogens, oral contraceptives, and lipid-lowering drugs may counteract UDCA effectiveness 3
• Multidisciplinary team management is recommended, including a physician, obstetrician, and midwife with expertise in managing ICP 1

The management approach outlined above focuses on reducing maternal symptoms while minimizing the risk of adverse fetal outcomes, particularly stillbirth, which is the most serious complication of ICP 4, 5.