What is Intrahepatic Cholestasis of Pregnancy (ICP)?

Intrahepatic Cholestasis of Pregnancy (ICP)

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by pruritus and elevated serum bile acid levels that typically occurs in the second and third trimesters, posing significant risk to the fetus including preterm delivery, meconium-stained amniotic fluid, and stillbirth. 1, 2

Definition and Pathophysiology

• ICP results from increased flux of bile acids from mother to fetus, with elevated bile acid levels in maternal serum, amniotic fluid, cord blood, and meconium 2
• The condition has a multifactorial pathogenesis involving:
  • Genetic factors (mutations in hepatobiliary transport proteins)
  • Hormonal influences (elevated gestational hormones)
  • Environmental factors 2
• ICP is typically reversible with spontaneous resolution within 4-6 weeks after delivery 2

Epidemiology

• Incidence ranges from 0.3% to 15% in various populations, with most estimates between 0.3% and 0.5% 1, 2
• Higher prevalence in:
  • South American and Scandinavian countries 3
  • Multiple gestations (due to higher hormonal levels) 2
  • Women with preexisting hepatobiliary disease 1
  • Women with previous history of ICP (risk of recurrence) 1

Clinical Presentation

• Pruritus (itching) is the cardinal symptom
  • May precede biochemical abnormalities by several weeks
  • Often worse at night
  • Typically affects palms and soles but can be generalized
  • No associated rash 2
• Jaundice occurs in only 10-15% of cases 2
• Other symptoms may include:
  • Steatorrhea
  • Postpartum hemorrhage (due to vitamin K deficiency) 2

Diagnosis

• Based on:

  1. Clinical presentation of pruritus
  2. Elevated serum bile acid levels ≥10 μmol/L
  3. Exclusion of other causes of pruritus and liver dysfunction 1, 2

• Laboratory findings:

  • Elevated serum bile acid levels (most sensitive indicator)
  • Elevated liver enzymes (ALT, AST) in most cases
  • Mild jaundice with elevated conjugated bilirubin in 10-15% of cases 2

• Important diagnostic considerations:

  • Random bile acid levels can be used (fasting not required) 1
  • If initial bile acid levels are normal but clinical suspicion is high, repeat testing is essential 2
  • Consider other etiologies if elevated bile acid levels occur before the second trimester 1

Maternal and Fetal Risks

Maternal Risks

• Generally benign for the mother 1
• Symptoms resolve after delivery 2

Fetal Risks

• Increased risk of adverse outcomes correlates with bile acid levels:

  • 10 μmol/L: Diagnostic threshold for ICP

  • 40 μmol/L: Increased risk of adverse pregnancy outcomes

  • 100 μmol/L: Significantly increased risk of stillbirth after 35 weeks gestation 2

• Specific fetal complications include:

  • Preterm delivery (both spontaneous and iatrogenic)
  • Meconium-stained amniotic fluid
  • Fetal distress
  • Stillbirth (estimated at approximately 1.2% after 37 weeks) 1, 2

Management

Pharmacological Treatment

• First-line treatment: Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day 1, 2
  • Reduces maternal symptoms
  • May improve fetal outcomes by reducing bile acid transfer to the fetus 2
  • Note that UDCA treatment can affect total bile acid measurements 2

Fetal Surveillance

• Begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 1, 2
• Weekly monitoring is recommended from 32 weeks gestation 2

Timing of Delivery

• For bile acids ≥100 μmol/L: Offer delivery at 36 0/7 weeks of gestation 1, 2
• For bile acids <100 μmol/L: Recommend delivery between 36 0/7 and 39 0/7 weeks of gestation 1, 2
• Administer antenatal corticosteroids for fetal lung maturity if delivering before 37 0/7 weeks 1
• Avoid preterm delivery at <37 weeks without laboratory confirmation of elevated bile acid levels 1

Postpartum Follow-up

• If symptoms persist for 4-6 weeks after delivery:
  • Repeat biochemical testing
  • If test results remain abnormal, refer to a liver specialist 2
• Prolonged post-partum symptoms should prompt investigation for other liver conditions such as primary biliary cirrhosis 2

Key Clinical Pitfalls

• Pruritus may precede biochemical abnormalities by several weeks - repeat testing is essential if clinical suspicion is high 2
• Early-onset ICP (before 33 weeks) is associated with increased fetal complications and may warrant genetic evaluation 2, 4
• Do not rely solely on liver enzymes for diagnosis - bile acid elevation is the most sensitive indicator 2
• Avoid preterm delivery without laboratory confirmation of elevated bile acid levels 1