What is the management and treatment for a pregnant woman with cholestasis of pregnancy (intrahepatic cholestasis of pregnancy, ICP)?

Management of Cholestasis in Pregnancy (Intrahepatic Cholestasis of Pregnancy)

Pregnant women with intrahepatic cholestasis of pregnancy (ICP) should be treated with ursodeoxycholic acid (UDCA) 15-20 mg/kg/day, monitored with weekly bile acid levels from 32 weeks, and delivered at 36 weeks if bile acids are ≥100 μmol/L or between 36-39 weeks if bile acids are <100 μmol/L. 1

Diagnostic Approach

Measure serum bile acids AND liver transaminases in all patients with suspected ICP - pruritus alone is insufficient for diagnosis. 1, 2

• Non-fasting bile acid levels are the diagnostic gold standard for ICP 1
• Normal initial labs do not exclude ICP - pruritus can precede biochemical abnormalities by several weeks 2
• If pruritus persists with normal initial testing, repeat bile acids and transaminases every 1-2 weeks until symptoms resolve or diagnosis is confirmed 2
• Screen for other causes: viral hepatitis, autoimmune hepatitis (AMA, ANA, SMA), and biliary obstruction with ultrasound 1
• Consider pre-eclampsia, HELLP syndrome, and acute fatty liver of pregnancy in the differential 1

Critical pitfall: Never start UDCA before obtaining initial laboratory confirmation, as treatment may prevent detection of elevated bile acids and make definitive diagnosis impossible 2

Risk Stratification Based on Bile Acid Levels

Once ICP is confirmed, bile acid concentration determines fetal risk and management:

• Bile acids <40 μmol/L: Lower risk, but still requires monitoring 1
• Bile acids 40-99 μmol/L: Increased risk of spontaneous preterm birth and adverse outcomes 1
• Bile acids ≥100 μmol/L: Substantially increased stillbirth risk, particularly after 35 weeks gestation 1

Monitor bile acids at least weekly from 32 weeks gestation to identify rising concentrations, as levels may increase with advancing gestation 1

Pharmacological Treatment

Ursodeoxycholic Acid (UDCA) - First-Line Therapy

UDCA is the first-line agent for ICP with dual benefits for maternal symptoms and fetal outcomes. 1

Dosing: 15-20 mg/kg/day (start at 10 mg/kg/day and increase gradually to 20 mg/kg/day if needed) 1

Maternal benefits:

• Modest improvement in pruritus (though effect is relatively small) 1
• Improves liver biochemistry 1

Fetal benefits:

• Reduces spontaneous preterm birth risk in women with bile acids >40 μmol/L 1
• May protect against stillbirth 1
• Protects against bile acid-induced fetal cardiac arrhythmias 1

Monitoring after UDCA initiation: Continue weekly bile acid measurements, but be aware that UDCA itself is measured by enzymatic bile acid assays, which may affect interpretation 1

Duration: Stop UDCA at delivery; gradually reduce over 2-4 weeks postpartum if symptoms persist 1

Alternative Therapies for Refractory Pruritus

If UDCA provides inadequate symptom relief, consider additional agents (though evidence is limited): 1

• Cholestyramine or colestipol: Separate administration from UDCA by at least 4 hours 1
• Rifampicin: Can be used from second trimester onward; monitor for hepatotoxicity (occurs in 5%); neonates require vitamin K supplementation 1
• Guar gum or activated charcoal: Limited evidence 1

Important: Anion exchange resins (cholestyramine/colestipol) may exacerbate vitamin K deficiency - monitor INR and provide vitamin K replacement if deficient 1

Fetal Surveillance

Begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing, or at time of diagnosis if made later in gestation. 1

Do NOT initiate fetal surveillance in patients with pruritus but persistently normal bile acids - evidence does not support increased fetal risk without biochemical confirmation. 2

Delivery Timing - Critical Decision Algorithm

Bile Acids ≥100 μmol/L:

Deliver at 36 0/7 weeks gestation - the risk of stillbirth increases substantially after 35 weeks in this group. 1

Bile Acids 40-99 μmol/L:

Deliver between 36 0/7 and 39 0/7 weeks gestation - balance fetal risk against prematurity complications. 1

Bile Acids <40 μmol/L:

Deliver between 36 0/7 and 39 0/7 weeks gestation - individualize based on clinical factors. 1

No Laboratory Confirmation:

Strongly recommend AGAINST preterm delivery at <37 weeks in patients with clinical suspicion but no laboratory confirmation of elevated bile acids - the risks of iatrogenic prematurity outweigh uncertain benefits. 1, 2

Administer antenatal corticosteroids for fetal lung maturity if delivering before 37 0/7 weeks and not previously given. 1

Multidisciplinary Management

Women with ICP should be managed by a multidisciplinary team including at minimum a physician, obstetrician, and midwife with expertise in liver disease in pregnancy. 1

Refer to specialized centers if local expertise is unavailable. 1

Postpartum Follow-Up

• Ensure bile acids, ALT/AST, and bilirubin return to normal within 3 months of delivery 1
• If abnormalities persist, investigate for underlying chronic liver disease 1, 2
• Consider genetic screening if there is family history of hepatobiliary disease, early onset, or severe disease 1
• Offer pre-pregnancy counseling for future pregnancies, as ICP has high recurrence risk 1

Key Clinical Pitfalls to Avoid

• Never diagnose ICP based solely on pruritus - this leads to unnecessary preterm deliveries with associated neonatal morbidity 2
• Never assume normal initial labs permanently rule out ICP - biochemical abnormalities may develop weeks after symptom onset 2
• Never deliver preterm without laboratory confirmation - resist pressure for early delivery when diagnosis remains uncertain 2
• Never start UDCA before obtaining baseline bile acid levels - this prevents accurate diagnosis 2
• Never forget vitamin K supplementation in women on cholestyramine or rifampicin, and ensure neonates of rifampicin-treated mothers receive vitamin K 1