What is the recommended management of intra‑hepatic cholestasis of pregnancy (ICP) regarding therapy, monitoring, and timing of delivery?

Management of Intrahepatic Cholestasis of Pregnancy

Start ursodeoxycholic acid (UDCA) 10–15 mg/kg/day in divided doses immediately upon diagnosis, measure serum bile acids weekly from 32 weeks onward, and plan delivery timing strictly according to peak bile acid levels: at 36 weeks for levels ≥100 μmol/L, between 36–39 weeks for 40–99 μmol/L, and between 37–39 weeks for <40 μmol/L. 1, 2

Diagnostic Confirmation

• Measure serum total bile acids (non-fasting) and liver transaminases (ALT/AST) immediately when a pregnant woman presents with pruritus, particularly if it affects palms and soles, worsens at night, and occurs in the second or third trimester without a primary rash. 1, 2

• Diagnosis requires bile acids >10 μmol/L plus pruritus; liver enzyme elevation is common but not mandatory for diagnosis. 1, 2

• If initial testing is normal but pruritus persists, repeat bile acids and transaminases in 1–2 weeks, as pruritus can precede biochemical abnormalities by several weeks. 2, 3

• Never initiate UDCA before obtaining baseline laboratory values, as treatment may mask diagnostic elevations and prevent definitive diagnosis. 3

Pharmacologic Treatment

• Initiate UDCA 10–15 mg/kg/day in divided doses immediately after confirming elevated bile acids, as this first-line therapy reduces maternal pruritus, lowers bile acid concentrations, and decreases risks of spontaneous preterm birth and possibly stillbirth. 1, 2

• Titrate UDCA up to 21–25 mg/kg/day if pruritus remains uncontrolled at standard dosing. 2

• Consider rifampicin, cholestyramine, guar gum, or activated charcoal as adjunctive therapies if UDCA alone fails to control symptoms, though evidence supporting these agents is limited. 1

• Discontinue UDCA at delivery or taper gradually over 2–4 weeks postpartum if pruritus persists after birth. 1, 4

Maternal Monitoring

• Measure serum bile acids at least weekly from 32 weeks' gestation until delivery, as concentrations can rise rapidly with advancing gestation and directly determine delivery timing. 1, 2

• Screen for preeclampsia throughout pregnancy, as ICP increases preeclampsia risk 2.6-fold; proteinuria typically precedes blood pressure elevation. 2

• Monitor for spontaneous preterm labor, as elevated bile acids activate myometrial oxytocin receptors and increase spontaneous preterm birth risk (relative risk 2.23). 2

Fetal Surveillance

• Begin antenatal fetal testing at the gestational age when delivery would be performed in response to abnormal results, or immediately if ICP is diagnosed later in pregnancy. 1, 2

• Increase testing frequency as bile acid levels rise; for bile acids ≥100 μmol/L, perform twice-weekly or more frequent monitoring due to 30-fold higher stillbirth risk. 2

• Apply continuous fetal monitoring during labor for all women with ICP, as fetal demise can occur suddenly through a non-placental mechanism even with recent reassuring testing. 1, 2

• Do not initiate routine antenatal surveillance in patients with pruritus but persistently normal bile acids, as evidence does not support increased fetal risk in this subgroup. 2, 3

Delivery Timing Algorithm (Risk-Stratified by Peak Bile Acid Level)

Severe ICP: Bile Acids ≥100 μmol/L

• Plan delivery at 36 0/7 weeks' gestation, as stillbirth risk increases markedly (approximately 30-fold) after 35 weeks at this threshold. 1, 2

• Administer antenatal corticosteroids for fetal lung maturity if not already given. 2

Moderate ICP: Bile Acids 40–99 μmol/L

• Schedule delivery between 36 0/7 and 39 0/7 weeks, favoring the earlier end of this window, as this range is associated with increased risks of preterm birth (relative risk 2.23), respiratory distress syndrome (relative risk 1.67), and meconium-stained amniotic fluid (relative risk 2.27). 1, 2

Mild ICP: Bile Acids <40 μmol/L

• Aim for delivery between 37 0/7 and 39 0/7 weeks; targeting 39 weeks is reasonable given minimal stillbirth risk in this group. 1, 2

Critical Pitfall to Avoid

• Never deliver before 37 weeks based solely on clinical suspicion without documented elevated bile acids, as premature delivery without laboratory confirmation exposes the neonate to unnecessary prematurity-related morbidity. 1, 2, 3

Postpartum Follow-Up

• Repeat serum bile acids and liver enzymes at 4–6 weeks postpartum to confirm resolution; pruritus typically resolves within days to weeks, and biochemical abnormalities should normalize within 4–6 weeks. 1, 4

• Refer to hepatology if symptoms or laboratory abnormalities persist beyond 6 weeks postpartum, as this suggests an underlying chronic hepatobiliary condition rather than isolated ICP. 1, 2, 4

• Consider genetic testing for ABCB11, ABCB4, or ATP8B1 mutations in cases with early onset, severe disease (bile acids ≥100 μmol/L), marked hyperbilirubinemia, or family history of hepatobiliary disease. 1, 2, 4

Long-Term Maternal Risks and Counseling

• Counsel patients about 40–90% recurrence risk in subsequent pregnancies, reflecting strong genetic and hormonal components. 2, 5, 6

• Inform patients of markedly elevated long-term risks: chronic hepatitis (hazard ratio 5.96), liver fibrosis/cirrhosis (hazard ratio 5.11), hepatitis C (hazard ratio 4.16), and cholangitis (hazard ratio 4.20). 2

• Offer pre-pregnancy counseling from a multidisciplinary team with expertise in managing liver diseases in pregnancy for all women with a history of ICP. 1