From the Guidelines
The workup of cholestasis in pregnancy should begin with serum bile acid levels, liver function tests, and ruling out other causes of liver dysfunction, with ursodeoxycholic acid (UDCA) being the first-line treatment for intrahepatic cholestasis of pregnancy (ICP) at a dose of 10-15 mg/kg/day, as recommended by the most recent guidelines 1. When a pregnant woman presents with pruritus (especially on palms and soles) and elevated bile acids (>10 μmol/L), a diagnosis of ICP should be considered. Initial laboratory testing should include:
- Total bile acids
- ALT
- AST
- Bilirubin
- Alkaline phosphatase
- GGT Additional testing to exclude other liver disorders includes:
- Hepatitis serologies
- Autoimmune markers (ANA, anti-smooth muscle antibody)
- Abdominal ultrasound to rule out biliary obstruction Once diagnosed, management includes UDCA, which helps reduce pruritus and may improve fetal outcomes, with antihistamines like diphenhydramine (25-50 mg every 4-6 hours) or hydroxyzine (25 mg every 6-8 hours) available for symptom relief, and cholestyramine (4-8 g daily) considered for refractory pruritus, though it's less effective than UDCA, as noted in recent studies 1. Fetal surveillance should include weekly non-stress tests starting at 32 weeks and consideration of delivery by 36-37 weeks due to increased risk of stillbirth, especially with bile acids >40 μmol/L, with the Society for Maternal-Fetal Medicine recommending delivery at 36 weeks for patients with total bile acid levels of 100 mmol/L or higher, and between 36 and 39 weeks for those with levels below 100 mmol/L 1. The condition typically resolves after delivery, but follow-up liver function tests 6-8 weeks postpartum are recommended to ensure resolution and rule out underlying liver disease, as ICP occurs due to increased sensitivity to estrogen and progesterone metabolites during pregnancy, which impair bile flow and cause bile acid accumulation in the maternal circulation, as discussed in the latest clinical practice update 1.
From the Research
Diagnosis of Cholestasis in Pregnancy
- The diagnosis of intrahepatic cholestasis of pregnancy (ICP) is based on symptoms of pruritus, typically including the palms and soles, as well as elevated bile acid levels 2.
- Other liver function tests, such as alanine aminotransferase and aspartate aminotransferase, are also frequently elevated, and other causes of liver dysfunction should be ruled out 2.
- The most accurate marker for diagnosis and follow-up of ICP is increased total bile acid levels (above 11.0 micro mol/L) 3, 4.
Management of Cholestasis in Pregnancy
- Ursodeoxycholic acid treatment has been shown to improve maternal pruritus symptoms, as well as biochemical tests 2, 3, 4, 5, 6.
- However, no treatment has been shown to definitively improve fetal outcomes 2, 5.
- Delivery may be considered at 37 weeks' gestation due to the increased risk of stillbirth in the setting of ICP 2, 5.
Fetal Risks Associated with Cholestasis in Pregnancy
- Fetal risks of ICP include increased risk of preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome, or stillbirth 2.
- There is evidence that as bile acid levels increase, so does the risk of adverse neonatal outcomes 2, 4, 6.
- Ursodeoxycholic acid treatment may reduce the bile acid content in the fetal compartment and improve fetal outcomes 4.