What is the workup for cholestasis of pregnancy?

Workup for Cholestasis of Pregnancy

Measure serum bile acids and liver transaminases (ALT/AST) in any pregnant woman with pruritus, particularly if it occurs in the second or third trimester without a rash. 1

Initial Laboratory Testing

The diagnostic workup centers on two key tests:

• Serum total bile acids: The most sensitive and specific marker for intrahepatic cholestasis of pregnancy (ICP), with levels >10 μmol/L considered diagnostic (though some labs use >11 μmol/L as the threshold) 1
• Liver transaminases (ALT and AST): Elevated in most cases, though not required for diagnosis; typically <500 U/L in ICP 1, 2

Use enzymatic bile acid assays when rapid results are needed (4 hours to 4 days turnaround), rather than mass spectrometry methods that take 4-14 days. 1 Random (non-fasting) bile acid levels are acceptable and more convenient than fasting samples, as the difference between fasting and postprandial values is clinically insignificant. 1

Differential Diagnosis Testing

Before confirming ICP, exclude life-threatening conditions that can mimic it:

High-Priority Exclusions

• Pre-eclampsia/HELLP syndrome: Check complete blood count (platelets), LDH, blood pressure, and proteinuria 2
• Acute fatty liver of pregnancy (AFLP): Assess coagulation studies (PT/INR), glucose, and bilirubin 2
• Viral hepatitis: Consider hepatitis panel, particularly hepatitis C (which increases ICP risk 3.5-fold) 1, 2

Additional Workup for Atypical Presentations

• Hepatobiliary ultrasound: To exclude gallstones and biliary obstruction 2
• Thyroid function tests: If symptoms suggest thyroid disorder 2
• Renal function tests: To exclude renal causes of pruritus 2
• Gamma-GT: If elevated, consider ABCB4 deficiency or primary biliary/sclerosing cholangitis 2

Clinical Assessment Details

History Elements to Document

• Timing of pruritus onset: ICP typically begins in late second or third trimester 1
• Location and pattern: Pruritus often affects palms and soles, worsens at night 1
• Prior pregnancy history: Up to 90% recurrence risk in subsequent pregnancies 1
• Family history: Familial clustering suggests genetic susceptibility 1
• Pre-existing liver disease: Hepatitis C, cirrhosis, gallstones increase risk 1

Physical Examination Findings

• Absence of primary rash: Only excoriations from scratching should be present; any primary dermatologic lesions suggest alternative diagnoses (atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis) 1, 2
• Jaundice: Uncommon in ICP (only 10-15% of cases); if present with bilirubin >5 mg/dL, consider alternative diagnoses 2
• Dark urine: Not typical of ICP; suggests other hepatic pathology 1

Critical Pitfalls to Avoid

Never deliver before 37 weeks based on clinical suspicion alone without laboratory confirmation of elevated bile acids. 1 The pruritus can precede bile acid elevation by several weeks, so if initial testing is normal but symptoms persist, repeat bile acids and transaminases. 1

Do not assume ICP without excluding HELLP syndrome and AFLP, as these conditions carry significant maternal mortality risk and require immediate delivery regardless of gestational age. 2 The combination of elevated LDH, low platelets, and hemolysis points to HELLP rather than ICP. 2

Follow-Up Testing

• Repeat bile acids if symptoms persist with initially normal results: Bile acid levels can increase rapidly, particularly near term 1
• Serial weekly testing is not routinely recommended, but repeat testing at 4-6 weeks may guide delivery timing in severe cases 1
• Postpartum follow-up: If symptoms or abnormal labs persist 4-6 weeks after delivery, refer to hepatology for evaluation of underlying hepatobiliary disease 1