What is the treatment for cholestasis of pregnancy?

Treatment for Intrahepatic Cholestasis of Pregnancy

Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day is the first-line treatment for intrahepatic cholestasis of pregnancy and should be initiated immediately upon diagnosis. 1, 2, 3

Primary Pharmacologic Treatment

UDCA is the only medication with strong evidence for both maternal symptom relief and potential improvement in perinatal outcomes:

• Start UDCA at 10-15 mg/kg/day, typically divided into 2-3 daily doses (common regimens: 300 mg twice or three times daily, or 500 mg twice daily) 1
• Maternal pruritus typically improves within 1-2 weeks of treatment 1, 2, 3
• Biochemical improvement (liver enzymes and bile acids) usually occurs within 3-4 weeks 1, 3
• If pruritus persists despite initial dosing, titrate up to a maximum of 21-25 mg/kg/day 1, 3
• UDCA is safe for both mother and fetus, with minimal side effects (mild nausea and dizziness in up to 25% of patients) 1, 4
• Continue UDCA until delivery, then discontinue 2, 3

The evidence for UDCA's effect on perinatal outcomes is mixed but favors treatment: Multiple meta-analyses show UDCA reduces preterm birth, fetal distress, respiratory distress syndrome, and NICU admissions 1. However, a large 2019 randomized trial (n=605) found no difference in composite perinatal outcomes when combined with standard fetal monitoring and planned early delivery, though maternal pruritus still improved 1. Despite this, recent meta-analyses continue to show decreased adverse outcomes including preterm birth and stillbirth 1.

Second-Line Treatments for Refractory Pruritus

If UDCA alone fails to control symptoms at maximum dosing, add the following agents sequentially:

• Rifampicin 300-600 mg daily can be combined with UDCA for refractory cases 1, 2, 3
• Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day) given at least 4 hours after UDCA to avoid binding 1, 2
• S-adenosyl-methionine may improve pruritus but is less effective than UDCA 1, 2, 3
• Antihistamines (diphenhydramine or hydroxyzine) have limited benefit but can be tried 1, 2
• Topical antipruritics (menthol creams, calamine lotion) provide minimal relief as itching is typically widespread 1, 2

Essential Adjunctive Management

Vitamin K supplementation is critical to prevent coagulopathy:

• Cholestasis and use of anion exchange resins or rifampicin cause vitamin K deficiency 1, 2
• Administer vitamin K replacement to women with steatorrhea or confirmed deficiency 1, 2
• Monitor coagulation tests in women treated with these medications 2
• Neonates of mothers treated with rifampicin should receive vitamin K at birth 2

Delivery Timing Based on Bile Acid Levels

Delivery timing should be risk-stratified by total bile acid levels to prevent stillbirth:

• Bile acids ≥100 μmol/L: Deliver at 36 0/7 weeks or at diagnosis if after 36 weeks 1, 3
• Bile acids <100 μmol/L: Deliver between 36 0/7 and 39 0/7 weeks 1, 3
• Bile acids <40 μmol/L: Consider delivery at term (39 weeks) 1, 3
• Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 weeks 3
• The risk of stillbirth increases significantly with bile acids >100 μmol/L, particularly after 35 weeks 1

Monitoring Strategy

Serial monitoring guides treatment escalation and delivery timing:

• Repeat bile acid levels and liver function tests to assess treatment response and guide delivery timing 3
• Begin antepartum fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 3
• Higher bile acid levels (≥100 μmol/L) correlate with increased risk of intrauterine fetal demise 1, 2, 3

Post-Delivery Management

ICP should resolve after delivery, but persistent symptoms require investigation:

• Discontinue UDCA at delivery 2, 3
• If symptoms persist, consider gradual reduction of UDCA 2-4 weeks postpartum 3
• If symptoms or abnormal liver tests persist for 4-6 weeks after delivery, investigate for underlying chronic liver disease (primary biliary cholangitis, primary sclerosing cholangitis, viral hepatitis) 1, 2, 3

Critical Pitfalls to Avoid

• Do not delay UDCA initiation while waiting for bile acid results if clinical suspicion is high—pruritus with elevated transaminases warrants empiric treatment 1
• Do not give cholestyramine simultaneously with UDCA—separate by at least 4 hours to prevent binding and reduced UDCA absorption 1, 2
• Do not continue pregnancy to term in patients with bile acids ≥100 μmol/L—the stillbirth risk is unacceptably high after 36 weeks 1, 3
• Do not forget vitamin K supplementation in patients on rifampicin or cholestyramine—maternal and neonatal coagulopathy can occur 1, 2