What is the management of cholestasis of pregnancy?

Management of Cholestasis of Pregnancy

The management of intrahepatic cholestasis of pregnancy (ICP) should include ursodeoxycholic acid (UDCA) as first-line treatment at 10-15 mg/kg/day in divided doses, with delivery timing based on bile acid levels: at 36 weeks for bile acids ≥100 μmol/L, 36-39 weeks for 40-99 μmol/L, and 37-39 weeks for <40 μmol/L. 1

Diagnosis and Initial Workup

• Diagnosis requires:

  • Pruritus (primary symptom)
  • Elevated serum bile acids >10 μmol/L
  • Mild to moderate elevations in liver enzymes
  • Total bilirubin <6 mg/dL 1

• Initial laboratory testing:

  • Total serum bile acids (most sensitive marker)
  • Liver function tests (ALT, AST)
  • Rule out other causes of liver disease 1

• Monitoring schedule:

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

Treatment Algorithm

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

   • Dosage: 10-15 mg/kg/day in divided doses
   • Typical starting dose: 500 mg twice daily
   • Adjust based on symptom response 1
   • Benefits:
     • Improves maternal pruritus
     • Reduces serum bile acids and liver enzymes
     • May decrease adverse fetal outcomes 1

2. Second-line options for refractory cases:

   • Rifampicin
   • Anion exchange resins
   • S-adenosyl-methionine 1
   • Note: Monitor for drug interactions with these agents

3. Avoid medications that may worsen cholestasis:

   • Estrogens and oral contraceptives
   • Cholesterol-lowering drugs like clofibrate
   • Aluminum-based antacids 2

Delivery Planning Based on Bile Acid Levels

Risk Category	Bile Acid Level	Recommended Delivery Timing
High Risk	≥100 μmol/L	36 weeks or at diagnosis if after 36 weeks
Moderate Risk	40-99 μmol/L	36-39 weeks gestation
Lower Risk	<40 μmol/L	37-39 weeks gestation or at term

• Fetal monitoring should be intensified as delivery approaches 1
• Early delivery is recommended due to increased risk of stillbirth, particularly with bile acids ≥100 μmol/L 1, 3

Postpartum Management

1. Medication management:

   • Stop UDCA at delivery or gradually reduce over 2-4 weeks if symptoms persist 1

2. Laboratory follow-up:

   • Check total serum bile acids, ALT/AST, and bilirubin within 3 months postpartum
   • All values should normalize by 3 months 1
   • If liver tests remain abnormal beyond 3 months, investigate for underlying liver disease 1

3. Patient education:

   • High recurrence risk (up to 90%) in future pregnancies
   • Avoid estrogen-containing contraceptives 1, 2
   • Consider hepatitis C screening due to increased risk 1

Important Caveats and Considerations

• Fetal risks associated with ICP:

  • Preterm birth
  • Fetal distress
  • Respiratory disorders
  • Increased perinatal mortality 3

• Maternal prognosis:

  • Generally good with resolution after delivery
  • Increased long-term risk of hepatobiliary diseases including chronic hepatitis, liver fibrosis/cirrhosis, and cholangitis 1

• Genetic considerations:

  • Consider genetic counseling if there is family history of ICP, severe/early-onset disease, or persistent liver abnormalities
  • Genetic variants in ABCB4, ABCB11, or ATP8B1 may indicate underlying chronic liver disease 1

• UDCA safety considerations:

  • Generally well-tolerated with no evidence of liver damage
  • Lithocholic acid (a metabolite of UDCA) is potentially liver-toxic but less efficiently formed from UDCA than from chenodiol 2
  • No evidence of teratogenicity in animal studies at therapeutic doses 2

While a 2020 Cochrane review noted that UDCA may have a small effect on pruritus reduction 4, the American College of Gastroenterology and American College of Obstetricians and Gynecologists still recommend it as first-line therapy for its multiple beneficial effects 1.