Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy
Diagnose ICP by measuring non-fasting serum total bile acids and liver transaminases immediately in any pregnant woman with pruritus—particularly affecting palms and soles—and confirm with bile acids >10 μmol/L; then initiate ursodeoxycholic acid 10-15 mg/kg/day in divided doses and plan delivery timing strictly according to peak bile acid levels. 1
Diagnostic Approach
Initial Laboratory Testing
Order serum total bile acids (non-fasting) and liver transaminases (ALT/AST) immediately when a pregnant woman presents with pruritus in the second or third trimester, especially if it involves palms and soles and worsens at night. 1, 2
Bile acids >10 μmol/L combined with pruritus confirm the diagnosis; fasting samples are unnecessary as the difference between fasting and postprandial values is clinically insignificant. 1, 2
Liver transaminases are typically elevated (<500 U/L) but are not required for diagnosis. 1
Exclude Life-Threatening Conditions First
Before confirming ICP, you must rule out conditions with significant maternal mortality:
Order complete blood count with platelets to exclude HELLP syndrome (platelets <50,000/μL, hemolysis, elevated liver enzymes). 2
Check coagulation studies (PT/INR) and glucose to exclude acute fatty liver of pregnancy, which presents with coagulopathy and hypoglycemia. 2
Measure total and direct bilirubin; levels are typically <5 mg/dL in ICP, whereas higher levels suggest HELLP or AFLP. 1, 2
HELLP and AFLP carry maternal mortality risks of 1-25% and 7-18%, respectively, and require immediate delivery. 1
Clinical Features That Support ICP
Pruritus is generalized, predominates on palms and soles, worsens at night, and occurs without a primary rash—only excoriations from scratching are present. 1
Approximately 80% of cases present after 30 weeks gestation, though earlier onset (second trimester) may indicate more severe disease. 1
Jaundice is uncommon (10-15% of cases) and mild when present. 1
Repeat Testing Strategy
If initial bile acids are normal but pruritus persists without alternative explanation, repeat testing every 1-2 weeks until symptoms resolve or diagnosis is confirmed, as pruritus can precede bile acid elevation by several weeks. 1, 2
Measure bile acids at least weekly from 32 weeks' gestation until delivery, as concentrations can rise rapidly and directly guide delivery timing. 1, 2
Pharmacologic Treatment
Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in 2-3 divided doses immediately after confirming bile acids >10 μmol/L (GRADE 1A evidence). 1
UDCA reduces maternal pruritus, lowers bile acid levels, decreases spontaneous preterm birth, and may lower stillbirth risk. 1
If pruritus remains uncontrolled, titrate UDCA up to 21-25 mg/kg/day. 1
Discontinue UDCA at delivery or taper gradually over 2-4 weeks postpartum if pruritus persists. 1, 3
Fetal Surveillance
Begin antenatal fetal testing immediately after diagnosis at the gestational age when delivery would be performed for abnormal results. 1
Increase testing frequency as bile acid levels rise; for bile acids ≥100 μmol/L, perform at least twice-weekly monitoring because stillbirth hazard rises approximately 30-fold. 1
Apply continuous fetal monitoring during labor for all women with ICP, as fetal demise can occur suddenly through a non-placental mechanism even after recent reassuring testing. 1
Delivery Timing Algorithm (Risk-Stratified by Peak Bile Acid Level)
This is the most critical management decision and must be based on laboratory values, not clinical suspicion alone:
Severe ICP: Bile Acids ≥100 μmol/L
Deliver at 36 0/7 weeks gestation (GRADE 1B). 1
Stillbirth risk rises approximately 30-fold at this threshold, with intrauterine fetal demise prevalence of 3.4%. 1
Moderate ICP: Bile Acids 40-99 μmol/L
Deliver between 36 0/7 and 39 0/7 weeks, favoring the earlier end of this window (GRADE 1C). 1
This range is associated with increased risks: preterm birth (RR 2.23), respiratory distress syndrome (RR 1.67), and meconium-stained fluid (RR 2.27). 1
Mild ICP: Bile Acids <40 μmol/L
- Deliver between 37 0/7 and 39 0/7 weeks; targeting 39 weeks is reasonable given minimal stillbirth risk (approximately 0.1%). 1
Critical Pitfall to Avoid
Never deliver before 37 weeks based solely on clinical suspicion without documented elevated bile acids (GRADE 1B). 1
Premature delivery without laboratory confirmation exposes the neonate to unnecessary prematurity-related morbidity. 1
Maternal Monitoring
Screen for preeclampsia, as ICP is associated with a 2.6-fold increased risk; proteinuria typically precedes the rise in blood pressure. 1
Monitor for spontaneous preterm labor, as elevated bile acids activate myometrial oxytocin receptors (pooled RR 2.23). 1
Postpartum Follow-Up
Repeat serum bile acids and liver transaminases at 4-6 weeks postpartum to confirm resolution; ICP typically resolves within days to weeks after delivery. 1, 2, 3
Refer to hepatology if symptoms or laboratory abnormalities persist beyond 6 weeks postpartum, as this indicates an underlying chronic hepatobiliary disorder (primary biliary cholangitis, primary sclerosing cholangitis, ABCB4 deficiency, chronic hepatitis C) that was unmasked by pregnancy. 1, 2, 3
Genetic Considerations and Long-Term Risks
Consider genetic testing for ABCB11, ABCB4, or ATP8B1 mutations in cases with early onset (second trimester), severe disease (bile acids ≥100 μmol/L), marked hyperbilirubinemia, or family history of hepatobiliary disease. 1
Counsel patients about 40-90% recurrence risk in subsequent pregnancies, reflecting a strong genetic component. 1
Women with ICP history have markedly higher risks of chronic liver conditions: chronic hepatitis (HR 5.96), liver fibrosis/cirrhosis (HR 5.11), hepatitis C (HR 4.16), and cholangitis (HR 4.2). 1
Offer pre-pregnancy counseling by a multidisciplinary team experienced in liver disease during pregnancy to all individuals with prior ICP. 1