What is the management and treatment for a pregnant woman diagnosed with Intrahepatic Cholestasis of Pregnancy (ICP)?

Management of Intrahepatic Cholestasis of Pregnancy

Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses immediately upon diagnosis, and deliver at 36 weeks for bile acids ≥100 μmol/L or between 36-39 weeks for bile acids <100 μmol/L. 1

Diagnostic Confirmation

Measure serum total bile acids (non-fasting) and liver transaminases (ALT/AST) immediately in any pregnant woman with pruritus, particularly in the second or third trimester. 1

• Bile acids >10 μmol/L are diagnostic of ICP 1
• Pruritus typically affects palms and soles, worsens at night, and occurs without a primary rash (only excoriations from scratching) 1
• Liver transaminases are usually elevated (2-30 fold) but not required for diagnosis, typically <500 U/L 1
• Critical pitfall: If initial bile acids are normal but pruritus persists, repeat testing in 1-2 weeks, as pruritus can precede laboratory abnormalities by several weeks 1

Exclude life-threatening conditions first: HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and acute fatty liver of pregnancy carry significant maternal mortality risk and require immediate delivery 2

Risk Stratification by Bile Acid Levels

The fetal risk directly correlates with maternal bile acid levels 1:

• Bile acids <40 μmol/L: Minimal fetal risk, similar outcomes to women without ICP 1
• Bile acids 40-99 μmol/L: Moderate risk, IUFD prevalence 0.3% 1
• Bile acids ≥100 μmol/L: High risk, IUFD prevalence 3.4% 1

Pharmacologic Treatment

Start UDCA 10-15 mg/kg/day in divided doses as first-line therapy for all confirmed ICP cases. 1

• UDCA improves maternal pruritus, reduces bile acid levels, and decreases adverse outcomes including preterm birth and stillbirth 1
• All medications appear safe in pregnancy 1

For refractory pruritus despite UDCA: Add antihistamines, rifampicin, or SAMe, though evidence for benefit beyond symptom relief is limited 1

• Avoid high-dose cholestyramine: Can exacerbate vitamin K deficiency and increase risk of fetal intracranial hemorrhage 1
• Monitor PT and treat with vitamin K if elevated, due to increased postpartum hemorrhage risk 1

Fetal Surveillance

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

• Increase frequency of testing with higher bile acid levels, especially ≥100 μmol/L 1
• No method of fetal monitoring has been shown to predict adverse outcomes or reduce IUFD risk, so follow best obstetrical practice 1
• Place all ICP patients on continuous fetal monitoring during labor due to increased stillbirth risk 1

Delivery Timing (Based Strictly on Peak Bile Acid Levels)

Bile acids ≥100 μmol/L: Deliver at 36 0/7 weeks of gestation 1, 2

Bile acids 40-99 μmol/L: Deliver between 36 0/7 and 39 0/7 weeks 1, 2

Bile acids <40 μmol/L: Consider delivery at term (39 weeks) 2

If diagnosed after 37 weeks: Deliver at diagnosis 1

Critical pitfall: Never deliver before 37 weeks based on clinical suspicion alone without laboratory confirmation of elevated bile acids—this causes iatrogenic prematurity-related morbidity 2, 3

Genetic Testing Considerations

Consider genetic testing in women with:

• Severe ICP (total bile acids >100 μmol/L) 1
• Recurrent ICP 1
• Early-onset ICP (first or early second trimester) 1, 4

Identification of ABCB11, ABCB4, or ATP8B1 variants is relevant because these women may have risk for progressive liver disease, gallstones, cholangitis, and possibly liver cancer 1, 4

Postpartum Follow-Up

Confirm resolution of liver test abnormalities 4-6 weeks postpartum. 1

• ICP typically resolves within days to weeks after delivery 1
• If pruritus or abnormal liver tests persist beyond 6 weeks postpartum, refer to hepatology for evaluation of underlying hepatobiliary disease 1, 2
• Women with ICP history have significantly elevated risk for later developing chronic hepatitis (HR 5.96), liver fibrosis/cirrhosis (HR 5.11), and cholangitis (HR 4.2) 2
• Counsel regarding up to 90% recurrence risk in subsequent pregnancies 2

Maternal Risks and Symptom Management

Maternal complications are minimal, with no influence of aminotransferase elevations on maternal symptoms or fetal outcomes 1

• Symptomatic pruritus reduces quality of life but resolves postpartum 1
• Lifestyle measures combined with UDCA provide first-line symptom management 1
• Jaundice occurs in only 10-15% of cases with bilirubin typically <5 mg/dL; significant jaundice should prompt evaluation for HELLP syndrome or acute fatty liver of pregnancy 2

Fetal Risks

The main risks are to the fetus: preterm birth, meconium-stained amniotic fluid, neonatal respiratory depression and asphyxia, and intrauterine fetal demise 1, 5

• Proposed mechanisms include bile acid toxicity on cardiomyocytes, vasoconstrictive effects on placental chorionic veins, reduced lung surfactant, and increased fetal gut motility 1
• Maternal and fetal bile acid levels are correlated, supporting a causal relationship between bile acid levels and fetal complications 1