Intrahepatic Cholestasis of Pregnancy (ICP)

Summary

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder of late pregnancy characterized by pruritus and elevated serum bile acids. Maternal prognosis is good, but fetal risks include preterm birth, meconium-stained amniotic fluid, and stillbirth. Diagnosis is confirmed by bile acids >10 μmol/L, and management involves ursodeoxycholic acid, fetal monitoring, and planned delivery at 36–39 weeks, with resolution postpartum but frequent recurrence

Definition

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-associated liver disorder, typically presenting in the second or third trimester. It is characterized by maternal pruritus, particularly nocturnal and most pronounced on the palms and soles, and elevated maternal serum bile acid levels. The condition is of major clinical concern due to its association with adverse perinatal outcomes, while maternal prognosis remains favorable.

Epidemiology

ICP occurs in approximately 0.4–10% of pregnancies, with prevalence varying by geographic and ethnic background. It has a high recurrence rate in subsequent pregnancies (60–90%).

Etiology and Risk Factors

The condition results from a combination of genetic predisposition, hormonal influences (elevated estrogen and progesterone), and occasionally drug-induced hepatotoxicity. Risk factors include advanced maternal age (>35 years), multiple gestations, and a history of ICP.

Clinical Features

• Pruritus (hallmark symptom, especially on palms and soles, often worse at night)

• Jaundice (in 10–20% of cases)

• Dark urine, pale stools, nausea, fatigue, and anorexia (less common)

• Steatorrhea and malabsorption (rare)

Diagnosis

Diagnosis is confirmed by serum bile acids >10 μmol/L in a pregnant woman with pruritus after excluding other causes.

• Elevated ALT, AST; bilirubin is usually normal or mildly increased.

• GGT and ALP may also be elevated but are less specific.

• Transaminase elevation is not required for diagnosis.

Management

• Pharmacological therapy:

• Ursodeoxycholic acid (UDCA) is first-line, improving pruritus and lowering bile acid levels.

• Oral antihistamines may provide symptomatic relief but have limited efficacy.

• Fetal surveillance: Antepartum monitoring is recommended, although its predictive value for fetal demise is limited.

• Peripartum management: Delivery is generally recommended between 36–39 weeks, depending on bile acid concentration and symptom severity. Corticosteroids are administered if preterm birth is anticipated.

• Postpartum: Symptoms and laboratory abnormalities typically resolve after delivery.

Complications

While ICP does not significantly affect maternal health, it is associated with important fetal risks:

• Intrauterine fetal demise (≈1.2% after 37 weeks)

• Fetal growth restriction

• Preterm labor and increased risk of preterm birth

• Meconium-stained amniotic fluid

• Neonatal respiratory depression