Laboratory Evaluation for Suspected Cholestasis of Pregnancy
Order serum total bile acids (non-fasting) and liver transaminases (ALT/AST) immediately in any pregnant woman presenting with pruritus in the second or third trimester. 1
Essential Initial Laboratory Tests
Primary Diagnostic Tests
- Total serum bile acids (non-fasting): This is the most sensitive and specific marker for intrahepatic cholestasis of pregnancy (ICP), with levels >10 μmol/L considered diagnostic 1
- Liver transaminases (ALT and AST): Typically elevated in ICP (usually <500 U/L), though not required for diagnosis 1
- Total bilirubin: Usually <5-6 mg/dL in ICP; higher levels suggest alternative diagnoses 1
Additional Baseline Tests
- Alkaline phosphatase (ALP): Mild elevations are common in normal pregnancy during second and third trimester, but marked elevations may support ICP diagnosis 1
- Gamma-glutamyl transferase (GGT): Can help identify underlying genetic transporter defects (ABCB4 deficiency) if elevated 1, 2
- Albumin: Should be physiologically decreased in pregnancy; elevated albumin is unusual and warrants further investigation 1, 2
Critical Tests to Exclude Life-Threatening Conditions
Before confirming ICP, you must exclude HELLP syndrome and acute fatty liver of pregnancy (AFLP), which carry significant maternal mortality risk. 2
Tests for HELLP Syndrome/AFLP
- Complete blood count with platelets: Low platelets suggest HELLP syndrome 2
- Lactate dehydrogenase (LDH): Elevated in HELLP syndrome but normal in ICP 2
- Peripheral blood smear: Assess for hemolysis in HELLP syndrome 2
- Coagulation studies (PT/INR, fibrinogen): Assess for disseminated intravascular coagulation in AFLP 1, 2
- Glucose: Hypoglycemia may occur in AFLP 1
Tests to Exclude Other Causes of Cholestasis
Hepatobiliary Evaluation
- Hepatobiliary ultrasound: Exclude gallstones and biliary obstruction 1, 2
- Viral hepatitis serologies (HAV, HBV, HCV): If risk factors present or elevated transaminases disproportionate to bile acids 1
Non-Hepatic Causes of Pruritus
- Thyroid function tests (TSH): Exclude thyroid disorders causing pruritus 1, 2
- Renal function tests (creatinine, BUN): Exclude renal disease 1, 2
Practical Laboratory Considerations
Bile Acid Testing Specifics
- Random (non-fasting) samples are acceptable and preferred for patient convenience, 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) when rapid results are needed 1
- Pregnancy-specific reference ranges: non-fasting bile acids 0-19 μmol/L in second trimester, 0-10 μmol/L in third trimester 1
Timing and Repeat Testing
- If initial bile acids are normal but pruritus persists, repeat testing in 1-2 weeks, as pruritus can precede bile acid elevation by several weeks 2
- Once ICP is confirmed, measure bile acids at least weekly from 32 weeks' gestation to identify concentrations >40 μmol/L, which indicate increased risk of adverse outcomes 1
Common Pitfalls to Avoid
- Never assume ICP without excluding HELLP/AFLP first: Dark urine and jaundice are NOT typical of ICP and suggest more serious hepatic disease requiring urgent evaluation 1, 2
- Do not delay testing for fasting samples: Non-fasting bile acids are diagnostically equivalent and more practical 1
- Do not deliver based on clinical suspicion alone without laboratory confirmation: Elevated bile acids must be documented before making delivery decisions to avoid unnecessary preterm birth 2
- Recognize that normal fetal testing does not eliminate stillbirth risk in ICP: ICP-related stillbirth occurs suddenly through a non-placental mechanism 2
Postpartum Follow-Up
If pruritus or abnormal liver tests persist beyond 6 weeks postpartum, order repeat bile acids and liver function tests and refer to hepatology for evaluation of underlying chronic liver disease such as primary biliary cholangitis, primary sclerosing cholangitis, or ABCB4 deficiency 1, 2