From the Guidelines
Cholestasis of pregnancy should be managed with ursodeoxycholic acid (UDCA) at a dose of 10-15 mg/kg/day, and delivery should be considered at 36-37 weeks of gestation to prevent stillbirth risk, especially in patients with total bile acid levels >100 mmol/L. Evaluation of cholestasis of pregnancy begins with liver function tests, particularly serum bile acids, which are typically elevated above 10 μmol/L 1. Additional testing includes ALT, AST, bilirubin, and ruling out other liver disorders through hepatitis serologies and ultrasound.
Key Recommendations
- UDCA is the first-line treatment for cholestasis of pregnancy, reducing maternal itching and potentially improving fetal outcomes by decreasing bile acid levels 2, 3.
- Close fetal monitoring is essential, including weekly non-stress tests starting at 32 weeks, to prevent stillbirth risk, which increases with higher bile acid levels 4.
- Delivery should be considered at 36-37 weeks of gestation, especially in patients with total bile acid levels >100 mmol/L, to prevent stillbirth risk 2, 4.
- Antihistamines like diphenhydramine or hydroxyzine can provide symptomatic relief for pruritus, though they don't address the underlying condition 3.
Treatment and Management
- UDCA should be started at a dose of 10-15 mg/kg/day, divided into two doses, and can be titrated to a maximum of 21 mg/kg/day if necessary 3.
- Antihistamines like diphenhydramine (25-50 mg every 4-6 hours) or hydroxyzine (25 mg every 6-8 hours) can be used for symptomatic relief of pruritus 3.
- Close fetal monitoring, including weekly non-stress tests starting at 32 weeks, is essential to prevent stillbirth risk 4.
- Delivery should be considered at 36-37 weeks of gestation, especially in patients with total bile acid levels >100 mmol/L, to prevent stillbirth risk 2, 4.
Follow-up and Postpartum Care
- Liver function should be rechecked 6-8 weeks postpartum to ensure normalization 1.
- If pruritus persists after 6 weeks postpartum, further evaluation for underlying chronic liver disease should be pursued 1.
- Genetic screening should be considered if there is a family history of hepatobiliary disease, early onset, or severe disease 5.
From the Research
Evaluation of Cholestasis of Pregnancy
- Cholestasis of pregnancy is characterized by generalized pruritus and biochemical cholestasis, typically appearing during the last trimester of gestation 6.
- The most predictive and accurate markers for diagnosis and follow-up of intrahepatic cholestasis of pregnancy (ICP) are increased total bile acid levels, enhanced cholic acid percentage, and decreased glycine/taurine bile acid ratio 6.
- Elevated bile acid concentration in maternal blood is an influencing factor for adverse fetal outcomes, including increased rates of preterm birth, neonatal unit admission, and stillbirth 7.
Treatment of Cholestasis of Pregnancy
- Ursodeoxycholic acid (UDCA) treatment has been shown to reduce bile acid content in the fetal compartment, restore the ability of the placenta to carry out vectorial transfer of bile acids, and decrease bile acid levels in maternal serum 6.
- UDCA monotherapy is recommended as the first-line therapy for ICP due to its efficacy, cost-effectiveness, and convenience 8.
- UDCA therapy has been found to improve pruritus and liver function test results, although it does not demonstrably reduce adverse perinatal outcomes 7.
- S-adenosylmethionine (SAMe) is also effective in treating ICP, but UDCA is more efficacious in reducing total bile acid concentration and facilitating deliveries at term 8.
Factors Predictive of Response to Treatment
- ALT levels >175 IU/l before treatment are associated with improvement of pruritus and decreased ALT levels 9.
- ABCB4 gene mutation is not associated with response to UDCA treatment 9.
- UDCA therapy is well-tolerated, with only one patient stopping treatment before delivery in a study of 98 consecutive patients 9.