What is the management of intrahepatic cholestasis of pregnancy (ICP)?

Management of Intrahepatic Cholestasis of Pregnancy

Start ursodeoxycholic acid (UDCA) 10-15 mg/kg/day immediately upon diagnosis to reduce maternal pruritus and potentially prevent stillbirth, then stratify delivery timing based on bile acid levels: deliver at 36 weeks for bile acids ≥100 μmol/L, between 36-39 weeks for bile acids <100 μmol/L, and at term for bile acids <40 μmol/L. 1, 2

Diagnostic Confirmation

• Diagnose ICP based on pruritus (typically involving palms and soles) with total serum bile acids >10 μmol/L 1, 2
• Measure serum bile acids, ALT, AST, and bilirubin to confirm diagnosis 2
• If initial bile acids are normal but pruritus persists, repeat testing as bile acid elevation may lag behind symptoms 2
• Liver biopsy is not warranted for diagnosis 1, 2
• Rule out other pregnancy-specific liver diseases including preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy 1

Pharmacological Treatment Algorithm

First-Line Therapy

• Initiate UDCA at 10-15 mg/kg/day (typically 300 mg twice or three times daily, or 500 mg twice daily) as first-line treatment 1, 2
• Expect pruritus improvement within 1-2 weeks and biochemical improvement within 3-4 weeks 1, 2
• UDCA reduces spontaneous preterm birth risk and may protect against stillbirth in women with bile acids >40 μmol/L 1

Dose Escalation for Inadequate Response

• If pruritus persists after 1-2 weeks, titrate UDCA up to maximum 21-25 mg/kg/day 1, 2
• Monitor for mild side effects including nausea and dizziness, which occur in up to 25% of patients 1

Alternative and Adjunctive Therapies

• Consider S-adenosyl-methionine combined with UDCA for additive effect if UDCA alone is insufficient 1, 2
• Rifampicin can be combined with UDCA for refractory pruritus 1, 2
• Cholestyramine, guar gum, and activated charcoal may improve pruritus but have limited evidence and significant gastrointestinal side effects 1
• Antihistamines (diphenhydramine, hydroxyzine) and topical antipruritics have limited benefit given widespread nature of itching 1

Important caveat: The largest placebo-controlled trial (n=605) showed UDCA improved maternal pruritus but did not demonstrate improvement in the composite perinatal outcome when standard fetal monitoring and planned early delivery were implemented 1. However, UDCA remains strongly recommended for symptom relief and potential fetal protection, particularly at higher bile acid levels 1.

Monitoring Protocol

Bile Acid Surveillance

• Measure serum bile acids at least weekly from 32 weeks' gestation onward to identify concentrations >40 μmol/L, which indicate increased risk of adverse outcomes 1
• Bile acids can increase rapidly near term, requiring serial monitoring 1
• Be aware that UDCA itself is measured by enzymatic bile acid assays, which may affect interpretation 1

Fetal Surveillance

• Initiate antepartum fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 2
• For bile acids ≥100 μmol/L, begin immediate fetal monitoring at diagnosis given 30-fold increased stillbirth risk 3
• Consider twice-weekly or more frequent testing for severe cases 3

Maternal Monitoring

• Monitor for preeclampsia development, which occurs in ICP patients at 2.6-fold increased risk, typically 2-4 weeks after ICP diagnosis 3

Risk-Stratified Delivery Timing

Critical Threshold: Bile Acids ≥100 μmol/L

• Deliver at 36 0/7 weeks of gestation or at diagnosis if already beyond 36 weeks 1, 2, 3
• The stillbirth risk increases markedly from 35 weeks' gestation at this threshold (hazard ratio 30.50) 1, 3
• Consider earlier delivery (34-36 weeks) if: excruciating unremitting pruritus despite maximum therapy, prior stillbirth before 36 weeks due to ICP with recurrence, or worsening hepatic function 3

Moderate Risk: Bile Acids 40-99 μmol/L

• Deliver between 36 0/7 and 39 0/7 weeks of gestation 2
• UDCA should be offered to reduce spontaneous preterm birth risk 1

Lower Risk: Bile Acids <40 μmol/L

• Consider delivery at term 2
• Continue UDCA for symptom management 1

Antenatal Corticosteroids

• Administer for fetal lung maturity if delivery planned before 37 weeks 2

Postpartum Management

• Discontinue UDCA at delivery 2, 3
• If symptoms persist, consider gradual UDCA reduction 2-4 weeks postpartum 2
• Repeat biochemical testing if symptoms or abnormal liver tests persist 4-6 weeks after delivery 2, 3
• Persistent abnormalities warrant investigation for underlying chronic liver diseases including primary biliary cholangitis, primary sclerosing cholangitis, ABCB4 deficiency, or chronic hepatitis C 1, 2
• Consider genetic screening if family history of hepatobiliary disease, early onset, or severe disease 1

Multidisciplinary Care

• Manage women with ICP through a multidisciplinary team including a physician, obstetrician, and midwife with expertise in the condition 1
• Refer to specialized centers if local expertise is unavailable 1
• Offer pre-pregnancy counseling for future pregnancies, as recurrence risk approaches 90% 1, 3