What blood investigations are recommended for diagnosing cholestasis in pregnancy?

Blood Investigations for Cholestasis in Pregnancy

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

Essential Laboratory Tests

Primary Diagnostic Tests

Total serum bile acids is the most sensitive and specific marker for intrahepatic cholestasis of pregnancy (ICP), with levels >10 μmol/L considered diagnostic when combined with pruritus and exclusion of other causes. 1

• Random (non-fasting) samples are acceptable and more convenient than fasting samples, as the difference between fasting and postprandial values is clinically insignificant. 1
• Enzymatic assay provides results in 4 hours to 4 days and is preferred over mass spectrometry (4-14 days turnaround). 1
• Bile acid levels >10 μmol/L confirm diagnosis; levels ≥100 μmol/L indicate severe disease requiring delivery at 36 weeks. 1

Liver transaminases (ALT and AST) are typically elevated in ICP but are not required for diagnosis. 1

• Transaminase levels are usually <500 U/L in ICP. 1
• ALT is elevated in 100% of cases and AST in 99% of cases based on older diagnostic criteria. 2
• These support the diagnosis but cannot replace bile acid testing. 1

Additional Laboratory Tests to Exclude Other Conditions

The following tests should be ordered to exclude pregnancy-specific and non-pregnancy-specific causes of elevated liver enzymes: 1

• Complete blood count with platelets - to exclude HELLP syndrome (hemolysis, elevated liver enzymes, low platelets <50,000/μL). 1
• Coagulation studies (PT/INR) - to exclude acute fatty liver of pregnancy (AFLP), which presents with coagulopathy. 1
• Glucose level - hypoglycemia suggests AFLP rather than ICP. 1
• Bilirubin (total and direct) - typically <5 mg/dL (<85 μmol/L) in ICP; higher levels suggest HELLP or AFLP. 1
• LDH - normal in ICP; elevated in HELLP syndrome due to hemolysis. 1

Tests for Underlying Hepatobiliary Disease

In women with elevated bile acids before the second trimester or with persistent abnormalities postpartum, additional testing is warranted: 1

• Gamma-glutamyl transferase (GGT) - typically normal in ICP; elevated GGT suggests ABCB4 deficiency, primary biliary cholangitis (PBC), or primary sclerosing cholangitis (PSC). 1, 3
• Hepatobiliary ultrasound - to exclude gallstones and biliary obstruction. 1
• Hepatitis C antibody - women with hepatitis C have 3.5-fold increased risk of ICP. 1
• Thyroid function tests - to exclude thyroid disorders as a cause of pruritus. 1
• Renal function tests - to exclude renal disease causing pruritus. 1

Timing and Frequency of Testing

Initial Testing Strategy

Order bile acids and transaminases immediately when ICP is suspected based on pruritus. 1

• Do not wait for symptoms to worsen before testing. 1
• 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. 1
• Pruritus can precede bile acid elevation by several weeks. 1

Serial Monitoring After Diagnosis

Measure serum bile acids at least weekly from 32 weeks' gestation to identify concentrations >40 μmol/L, which indicate increased risk of adverse pregnancy outcomes. 1

• Peak bile acid levels determine delivery timing and fetal surveillance intensity. 1
• Bile acid levels can increase rapidly during pregnancy, particularly near term. 1

Critical Diagnostic Pitfalls to Avoid

Never diagnose ICP or make delivery decisions based on pruritus alone without laboratory confirmation of elevated bile acids. 1

• Delivering before 37 weeks based on clinical suspicion alone without elevated bile acids leads to unnecessary preterm deliveries with associated neonatal morbidity. 1
• Normal initial labs do not permanently rule out ICP if symptoms persist. 1

Always exclude HELLP syndrome and AFLP before assuming ICP, as these conditions carry significant maternal mortality risk and require immediate delivery. 1

• HELLP presents with hemolysis, elevated LDH, low platelets, and elevated transaminases. 1
• AFLP presents with liver failure, coagulopathy, hypoglycemia, and encephalopathy. 1

Distinguish excoriations from scratching from primary dermatologic rashes. 1

• ICP causes pruritus without a primary rash, only secondary excoriations. 1
• Presence of a primary rash suggests dermatologic conditions rather than ICP. 1

Postpartum Follow-Up Testing

Repeat bile acids and liver transaminases 4-6 weeks postpartum if symptoms or abnormal laboratory values persist. 1

• ICP typically resolves completely after delivery. 1
• Persistent abnormalities suggest underlying chronic liver disease (PBC, PSC, ABCB4 deficiency, chronic hepatitis C) that was unmasked by pregnancy. 1
• Refer to hepatology if results remain abnormal at 6 weeks postpartum. 1