How should intrahepatic cholestasis of pregnancy be managed in a second- or third-trimester pregnant woman presenting with pruritus on the palms and soles, no rash, and laboratory evidence of elevated serum bile acids (≥10 µmol/L) and mildly increased transaminases?

Management of Intrahepatic Cholestasis of Pregnancy

Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses immediately upon diagnosis, and plan delivery timing strictly based on the peak total bile acid level: deliver at 36 0/7 weeks for bile acids ≥100 µmol/L, between 36-39 weeks for bile acids 40-99 µmol/L (favoring earlier delivery in this range), and between 37-39 weeks for bile acids <40 µmol/L. 1

Immediate Pharmacologic Management

• Start UDCA at 10-15 mg/kg/day in divided doses as first-line therapy for all confirmed ICP cases. 1 This improves maternal pruritus, reduces bile acid levels, and decreases adverse outcomes including preterm birth and stillbirth. 2

• UDCA is the only medication with strong evidence for both maternal symptom relief and potential reduction in adverse fetal outcomes (GRADE 1A). 2

• Antihistamines may be added for symptomatic relief of pruritus but do not address the underlying pathophysiology or reduce fetal risk. 3

Fetal Surveillance Protocol

• Begin antenatal fetal testing at the gestational age when you would deliver in response to abnormal results, or immediately if diagnosed later in gestation. 2 For example, if bile acids are ≥100 µmol/L and you plan delivery at 36 weeks, start testing at 36 weeks or upon diagnosis if already at that gestational age.

• Increase surveillance frequency with higher bile acid levels, particularly when ≥100 µmol/L. 2

• Place all ICP patients on continuous fetal monitoring during labor due to increased stillbirth risk that can occur suddenly even with recent reassuring testing. 2, 4 ICP-related fetal demise occurs through a non-placental mechanism, making traditional fetal surveillance less predictive. 4

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

This is the most critical management decision and must be based on laboratory-confirmed bile acid levels:

Bile Acids ≥100 µmol/L:

• Deliver at 36 0/7 weeks of gestation (GRADE 1B). 1 The risk of stillbirth increases substantially at this gestational age when bile acids reach this threshold. 1

• Administer antenatal corticosteroids for fetal lung maturity if not previously given. 1

• Consider delivery between 34-36 weeks only if: excruciating unremitting pruritus not relieved by pharmacotherapy, history of stillbirth before 36 weeks due to ICP with recurrence in current pregnancy, or preexisting/acute hepatic disease with worsening function. 1

Bile Acids 40-99 µmol/L:

• Deliver between 36 0/7 and 39 0/7 weeks of gestation (GRADE 1C), favoring earlier delivery within this range. 1 Women with bile acids ≥40 µmol/L should be considered for earlier delivery. 1

Bile Acids <40 µmol/L:

• Deliver between 37 0/7 and 39 0/7 weeks of gestation, with management toward 39 weeks reasonable given the low stillbirth risk. 1, 2 This population has minimal increased fetal risk. 1

Laboratory Monitoring Strategy

• Do not perform routine serial weekly bile acid testing. 2 Repeat testing is indicated only when symptoms persist with initially normal results or to guide delivery timing in severe cases, particularly after 32 weeks gestation. 2

• Peak bile acid levels determine delivery timing decisions. 5 A single measurement near term is often sufficient for delivery planning unless clinical circumstances change. 2

• Monitor liver transaminases alongside bile acids, though transaminases are typically <500 U/L in ICP and are not required for diagnosis. 2, 4

Critical Pitfalls to Avoid

• Never deliver before 37 weeks based on clinical suspicion alone without laboratory confirmation of elevated bile acids (GRADE 1B). 1, 5 This exposes the neonate to unnecessary prematurity-related morbidity. 5

• Do not assume normal fetal testing eliminates stillbirth risk—ICP-related stillbirth occurs suddenly and unpredictably. 4, 6

• Exclude life-threatening conditions that mimic ICP: HELLP syndrome (maternal mortality 1-25%) and acute fatty liver of pregnancy (maternal mortality 7-18%) must be ruled out immediately. 2, 7 Check for hemolysis, thrombocytopenia, coagulopathy, hypoglycemia, and renal dysfunction. 2

• If pruritus preceded bile acid elevation, repeat testing in 1-2 weeks if symptoms persist, as biochemical abnormalities can develop weeks after symptom onset. 5, 3

Postpartum Follow-Up

• Repeat bile acids and liver transaminases at 4-6 weeks postpartum if symptoms or abnormal laboratory values persist. 2 ICP should resolve completely after delivery. 1, 8

• Refer to hepatology if serologic abnormalities persist beyond 6 weeks postpartum, as this suggests underlying hepatobiliary disease (chronic hepatitis, cirrhosis, hepatitis C, or cholangitis). 1 Women with ICP history have significantly elevated risk for chronic hepatitis (HR 5.96), liver fibrosis/cirrhosis (HR 5.11), hepatitis C (HR 4.16), and cholangitis (HR 4.2). 1

• Counsel regarding up to 90% recurrence risk in subsequent pregnancies. 1