What are the signs and symptoms of cholestasis of pregnancy?

Signs and Symptoms of Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is characterized primarily by pruritus (itching) without a primary rash, typically occurring in the second and third trimesters, accompanied by elevated serum bile acid levels. 1, 2

Primary Clinical Presentation

• Pruritus characteristics:

  • Generalized itching, but predominantly affects the palms and soles of the feet 1, 2
  • Typically worse at night 1, 2
  • No primary rash (distinguishing feature from other pruritic conditions of pregnancy) 1
  • May develop excoriations or prurigo nodularis from intense scratching, which can be mistaken for a primary rash 1

• Timing:

  • Occurs in the second and third trimesters of pregnancy 1, 2
  • Most commonly presents in the third trimester 3

• Laboratory abnormalities:

  • Elevated serum bile acid levels (≥10 μmol/L) - the most sensitive indicator 1, 2
  • Elevated liver enzymes (ALT, AST) in most cases 1
  • Bile acid elevation may precede other liver test abnormalities 1
  • Mild jaundice with moderately elevated conjugated bilirubin occurs in only 10-15% of cases 1

Notable Absent Features

• No primary rash (key distinguishing feature from other pruritic dermatoses of pregnancy) 1, 2
• Excessive fatigue, insomnia, malaise, and abdominal pain/colic are not common with ICP 1
• Liver failure does not occur 4

Risk Factors and Epidemiology

• More common in multiple pregnancies (twins) due to higher hormonal levels 1, 2
• Incidence ranges from 0.3% to 15% in various populations, with most estimates between 0.3% and 0.5% 1
• Higher incidence in family members suggests genetic factors 1
• Early-onset ICP (before 33 weeks) may be associated with increased fetal complications 1, 2

Disease Course

• Symptoms spontaneously resolve within 4-6 weeks after delivery 1, 2
• Persistence of abnormalities after delivery should prompt investigation for other chronic liver diseases like PBC, PSC, ABCB4 deficiency, or chronic hepatitis C 1

Clinical Significance

• While ICP poses little risk to pregnant women, it confers significant risk to the fetus 1
• Associated with increased risk of:
  • Preterm delivery
  • Meconium-stained amniotic fluid
  • Fetal distress
  • Stillbirth 1, 5, 3
• Risk of adverse fetal outcomes increases with bile acid levels >40 μmol/L 2
• Significantly increased risk of stillbirth after 35 weeks gestation with bile acid levels >100 μmol/L 2

Diagnostic Approach

When evaluating a pregnant woman with pruritus, clinicians should:

1. Confirm absence of primary rash (may have secondary excoriations)
2. Measure serum bile acid levels (diagnostic if ≥10 μmol/L with pruritus)
3. Perform liver function tests (ALT, AST, bilirubin)
4. Consider other causes of pruritus without rash if laboratory findings are normal 1, 2

The diagnosis of ICP should be considered in any pregnant woman who develops new-onset pruritus without a rash in the second half of pregnancy, particularly when it affects the palms and soles and is worse at night.