Treatment of Obstetric Cholestasis (Intrahepatic Cholestasis of Pregnancy)
Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day divided into 2-3 doses is the first-line treatment for intrahepatic cholestasis of pregnancy, with typical regimens of 300 mg 2-3 times daily or 500 mg twice daily. 1
Diagnosis and Risk Stratification
Before initiating treatment, diagnosis should be confirmed based on:
- Maternal pruritus
- Elevated serum bile acids ≥11 μmol/L
- Elevated liver enzymes
- Exclusion of other causes of liver dysfunction 1
Risk stratification is essential for management and is based on total serum bile acid (TSBA) levels:
| Bile Acid Level | Risk Category | Stillbirth Risk |
|---|---|---|
| <40 μmol/L | Low | Minimal |
| 40-99 μmol/L | Moderate | 0.3% |
| ≥100 μmol/L | High | 3.4% |
Treatment Algorithm
First-Line Treatment
- UDCA (10-15 mg/kg/day) divided into 2-3 doses 1
For Persistent Symptoms Despite UDCA
- Rifampicin (300-600 mg daily) with monitoring for hepatotoxicity 1
- Anion exchange resins (cholestyramine 4-8 g/day) with monitoring for vitamin K deficiency 1
- S-adenosyl-L-methionine may have additive effects with UDCA 1
Supportive Measures for Symptom Relief
- Mild soaps and lukewarm water for bathing
- Topical emollients and cool compresses
- Loose-fitting cotton clothing 1
- Low to mid-potency topical corticosteroids for mild to moderate pruritus
- Antihistamines (diphenhydramine or hydroxyzine) for sleep improvement 1
Monitoring Protocol
- Repeat TSBA and liver function tests:
- Every 2 weeks until 32 weeks gestation
- Weekly thereafter until delivery 1
- More intensive fetal surveillance for patients with bile acids ≥40 μmol/L
- Monitor coagulation parameters, especially if using cholestyramine
- Correct vitamin K deficiency if present 1
Timing of Delivery
Delivery timing should be based on bile acid levels:
| Bile Acid Level | Recommended Delivery Time |
|---|---|
| ≥100 μmol/L | 36 weeks |
| 40-99 μmol/L | 37-38 weeks |
| <40 μmol/L | 38-39 weeks |
This approach is critical as fetal complications, including stillbirth, increase with gestational age in severe ICP 1, 3.
Postpartum Management
- UDCA can be discontinued at delivery
- If symptoms persist, taper UDCA over 2-4 weeks post-delivery
- Bile acids and liver enzymes should normalize within 3 months
- If abnormalities persist beyond 6 weeks postpartum, investigate for underlying liver disease
- Schedule follow-up after 2-3 years due to increased risk for hepatobiliary and immune-mediated diseases 1
Clinical Pearls and Pitfalls
- Important: Serum bile acid levels >40 μmol/L define severe ICP and are associated with increased risk of fetal complications 4
- UDCA treatment has been shown to reduce adverse maternal and fetal outcomes, including premature births, fetal distress, and respiratory distress syndrome 2
- Studies show UDCA treatment allows more deliveries at term (65.7% vs 12.5% in controls) and higher birth weights (approximately 500g heavier) 5
- Women with ICP have a 45-70% recurrence rate in subsequent pregnancies 1
- Consider genetic testing for variants in bile acid transport proteins in cases of severe, recurrent, or early-onset cholestasis 1
- Multidisciplinary management involving maternal-fetal medicine and hepatology is recommended for severe cases 1
By following this evidence-based approach to managing obstetric cholestasis, clinicians can significantly improve maternal symptoms and reduce the risk of adverse fetal outcomes.