What is the diagnosis and management of Intrahepatic Cholestasis of Pregnancy (ICP)?

From the Guidelines

Intrahepatic cholestasis of pregnancy (ICP) should be treated with ursodeoxycholic acid (UDCA) at a dose of 10-15 mg/kg/day, divided into 2-3 doses daily, to reduce maternal symptoms and potentially improve fetal outcomes, as recommended by the most recent and highest quality study 1.

Diagnosis and Treatment

The diagnosis of ICP is based on a serum bile acid level >10 mmol/L in the setting of pruritus, typically during the second or third trimester 1.

• The treatment should be offered with oral UDCA in a total daily dose of 10–15 mg/kg.
• Laboratory monitoring should include liver function tests and bile acid levels every 1-2 weeks.
• For severe itching that persists despite UDCA, antihistamines like diphenhydramine (25-50 mg every 4-6 hours) or hydroxyzine (25 mg 3-4 times daily) may provide symptomatic relief.

Fetal Monitoring and Delivery

Due to increased risks of preterm birth, fetal distress, and stillbirth, increased fetal monitoring is essential, including twice-weekly non-stress tests starting at 32 weeks and consideration of delivery by 37-38 weeks gestation 1.

• Patients with total bile acid levels of 100 mmol/L should be offered delivery at 36 0/7 weeks of gestation, given that the risk of stillbirth increases substantially around this gestational age.
• Patients with total bile acid levels of <100 mmol/L should be considered for delivery between 36 0/7 and 39 0/7 weeks of gestation.

Postpartum Care

After delivery, symptoms typically resolve within days to weeks, but women should be monitored with follow-up liver function tests 6-8 weeks postpartum to ensure resolution, and they should be counseled about a 60-90% recurrence risk in future pregnancies 1.

From the Research

Definition and Diagnosis of Intrahepatic Cholestasis of Pregnancy

• Intrahepatic cholestasis of pregnancy (ICP) is a reversible pregnancy-specific cholestatic condition characterized by pruritus, elevated liver enzymes, and increased serum bile acids 2.
• The diagnosis of ICP is based on symptoms of pruritus that typically include the palms and soles, as well as elevated bile acid levels 3.
• 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 3.

Incidence and Etiology of Intrahepatic Cholestasis of Pregnancy

• The incidence of ICP is higher in South American and Scandinavian countries (9.2%-15.6% and 1.5%, respectively) than in Europe (0.1%-0.2%) 2.
• The etiology of ICP is multifactorial, where genetic, endocrine, and environmental factors interact 2.

Maternal and Fetal Outcomes in Intrahepatic Cholestasis of Pregnancy

• Maternal outcome is usually benign, whereas fetal complications such as preterm labor, meconium staining, fetal distress, and sudden intrauterine fetal demise not infrequently lead to considerable perinatal morbidity and mortality 2.
• Fetal risks of ICP include increased risk of preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome, or stillbirth 3.
• There is evidence that as bile acid levels increase, so does the risk of adverse neonatal outcomes 3.

Treatment and Management of Intrahepatic Cholestasis of Pregnancy

• Ursodeoxycholic acid (UDCA) is the most efficient therapeutic agent with proven safety and efficacy in treating ICP 4, 5, 2, 3.
• UDCA treatment has been shown to improve maternal pruritus symptoms, as well as biochemical tests, but no treatment has been shown to definitively improve fetal outcomes 3.
• Management of ICP consists of careful monitoring of maternal hepatic function tests and serum bile acid levels in addition to the assessment of fetal well-being and timely delivery after completion of fetal pulmonary maturity 2.
• Delivery may be considered at 37 weeks' gestation given the increased risk of stillbirth in the setting of ICP 3.