Laboratory Tests for Neonatal Hyperbilirubinemia
For neonatal hyperbilirubinemia, total serum bilirubin (TSB) and/or transcutaneous bilirubin (TcB) measurements should be ordered as the primary diagnostic tests. 1, 2
Primary Diagnostic Tests
Initial Assessment
- Total Serum Bilirubin (TSB): The gold standard laboratory test for diagnosing and managing neonatal hyperbilirubinemia 3
- Transcutaneous Bilirubin (TcB): Non-invasive alternative that provides valid estimates of TSB levels when TSB is <15 mg/dL 1
When to Order These Tests
- Jaundice appearing in the first 24 hours of life (mandatory testing) 1
- When jaundice appears excessive for infant's age 1
- When there is any doubt about the degree of jaundice (visual estimation can lead to errors, especially in darkly pigmented infants) 1, 2
Additional Laboratory Tests
When TSB levels are rising rapidly, crossing percentiles on the hour-specific nomogram, or when the infant is receiving phototherapy, additional tests should be ordered 1:
- Blood type and Coombs' test (if not obtained with cord blood)
- Complete blood count and smear (to evaluate for hemolysis)
- Direct or conjugated bilirubin measurement
- Optional tests: Reticulocyte count, G6PD testing
Special Circumstances
For TSB approaching exchange levels or not responding to phototherapy:
- Reticulocyte count
- G6PD testing
- Albumin level
For elevated direct/conjugated bilirubin:
- Urinalysis and urine culture
- Evaluation for sepsis if indicated by history and physical examination
For jaundice present at or beyond 3 weeks, or in sick infants:
- Total and direct (conjugated) bilirubin levels
- Evaluation for causes of cholestasis if direct bilirubin is elevated
- Check results of newborn thyroid and galactosemia screening 1
Interpretation of Results
- All bilirubin levels should be interpreted according to the infant's age in hours 1
- TSB results should be plotted on the hour-specific Bhutani nomogram to assess risk 1, 2
- If TSB is ≤5 mg/dL (85 μmol/L), a direct bilirubin >1.0 mg/dL is considered abnormal 1
Important Considerations
Timing matters: Infants who require phototherapy within the first 48 hours of life are significantly more likely to have an underlying pathologic cause (45.5% vs 6.8%) 4
Capillary vs. venous samples: Most published data on TSB levels and outcomes are based on capillary blood samples. Obtaining a venous sample to "confirm" an elevated capillary TSB is not recommended as it delays treatment 1
Direct vs. conjugated bilirubin: These terms are often used interchangeably in clinical practice, though they represent different measurements. Direct-reacting bilirubin reacts directly with diazotized sulfanilic acid, while conjugated bilirubin is bilirubin bound with glucuronic acid 1
Routine direct bilirubin testing: Has low yield and poor specificity in term newborns with uncomplicated jaundice 5
Future Developments
While TSB remains the current standard, research suggests that measurement of unbound bilirubin (the fraction not bound to albumin) may be a better predictor of neurotoxicity and could improve management of neonatal hyperbilirubinemia in the future 6.
Point-of-care bilirubin measurement methods like BiliSpec and Bilistick are being developed, which would particularly benefit newborns in low and middle-income countries with limited access to laboratory facilities 3.