Bhutani Nomogram for Neonatal Hyperbilirubinemia Assessment
The Bhutani nomogram remains the gold standard tool for assessing risk of severe hyperbilirubinemia in newborns ≥35 weeks gestation, plotting hour-specific total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) values to stratify infants into risk zones that guide follow-up timing and phototherapy decisions. 1
Core Principles of the Nomogram
The nomogram divides infants into four risk zones based on predischarge bilirubin measurements plotted against postnatal age in hours 1:
- High-risk zone (≥95th percentile): Infants require close follow-up within 24 hours of discharge 1
- High-intermediate risk zone (75th-94th percentile): Follow-up recommended within 24-48 hours 1
- Low-intermediate risk zone (40th-74th percentile): Follow-up within 48-72 hours 1
- Low-risk zone (<40th percentile): Routine follow-up appropriate 1
Patient Population and Applicability
The nomogram applies to 1:
- Infants ≥36 weeks gestational age with birth weight ≥2000g, OR
- Infants ≥35 weeks gestational age with birth weight ≥2500g
The nomogram should NOT be used to represent the natural history of neonatal hyperbilirubinemia—it is strictly a risk prediction tool. 1
Measurement Requirements
When to Measure Bilirubin
Measure TSB or TcB immediately if 1:
- Jaundice appears in the first 24 hours of life (mandatory measurement)
- Jaundice appears excessive for the infant's age
- Any doubt exists about the degree of jaundice (visual estimation is unreliable, especially in darkly pigmented infants)
Critical Interpretation Rule
All bilirubin levels must be interpreted according to the infant's age in hours, not days. 1 This hour-specific approach is essential because bilirubin rises rapidly in the first 72-96 hours of life, and even small time differences significantly affect risk stratification.
Predischarge Risk Assessment Protocol
Before discharge, every newborn requires systematic assessment for hyperbilirubinemia risk, particularly those discharged before 72 hours of age. 1 The American Academy of Pediatrics recommends two clinical options 1:
- Predischarge TSB or TcB measurement plotted on the nomogram (most evidence-based approach)
- Clinical risk factor assessment (can be combined with bilirubin measurement)
Performance Characteristics
Recent validation studies demonstrate the nomogram's predictive ability 2, 3:
- Sensitivity: 87-97% depending on percentile cutoff used
- Negative predictive value: 95-98% for the 40th percentile tract
- Area under curve: 0.88-0.93 for predicting need for phototherapy
The 40th percentile curve provides the best balance, with 97.9% sensitivity and 98.5% negative predictive value for identifying infants who will need phototherapy 4.
High-Risk Populations Requiring Special Attention
G6PD Deficiency
G6PD deficiency is a critical cause of severe hyperbilirubinemia and kernicterus that requires immediate identification. 1, 5
- Occurs in 11-13% of African Americans and higher rates in Mediterranean and Asian populations 1, 5
- Accounted for 31.5% of kernicterus cases in one major series 1, 5
- Test for G6PD when: TSB approaches exchange levels, bilirubin fails to respond to phototherapy, or severe hyperbilirubinemia occurs in at-risk ethnic groups 1, 5
ABO Incompatibility with Positive Coombs Test
The nomogram performs reliably in infants with direct Coombs-positive results 3:
- Sensitivity and specificity (74.2% and 97.1% for high-risk zone) compare favorably to Coombs-negative infants
- Likelihood ratio of 25.8 for high-risk zone—twice that of the original Bhutani cohort
- All infants in high-intermediate and high-risk zones with positive Coombs require postdischarge follow-up 3
Laboratory Workup Based on Clinical Scenario
For Jaundice in First 24 Hours or Excessive Jaundice
- Measure TcB and/or TSB immediately 1
For Rapidly Rising TSB or Infant on Phototherapy
Obtain 1:
- Blood type and Coombs test (if not done with cord blood)
- Complete blood count with smear
- Direct or conjugated bilirubin
- Consider: reticulocyte count, G6PD, end-tidal CO (if available)
- Repeat TSB in 4-24 hours depending on age and level
For TSB Approaching Exchange Levels or Not Responding to Phototherapy
- Reticulocyte count
- G6PD level (critical)
- Albumin
- End-tidal CO (if available)
For Jaundice Present at or Beyond 3 Weeks
Measure 1:
- Total and direct (or conjugated) bilirubin
- If direct bilirubin elevated, evaluate for cholestasis
- Check newborn thyroid and galactosemia screening results
Recent Advances and Alternative Approaches
Newer predictive models incorporating the difference between predischarge TSB and phototherapy threshold (Δ-TSB) show superior discrimination compared to the traditional Bhutani nomogram (AUC 0.93-0.95 vs 0.88), and may be simpler to use clinically. 2 These models predict postdischarge phototherapy need ranging from 56% risk when TSB is 0-1 mg/dL below threshold to 0.008% when >7 mg/dL below threshold. 2
Population-specific nomograms developed for Thai and North Indian populations show slightly better performance in high-prevalence populations, with the 40th percentile serving as the optimal cutoff. 6, 4
Common Pitfalls to Avoid
- Never rely on visual assessment alone—it leads to errors, especially in darkly pigmented infants 1
- Never use days instead of hours when plotting values on the nomogram 1
- Never discharge infants with jaundice in the first 24 hours without measuring bilirubin 1
- Never fail to obtain G6PD testing in high-risk ethnic groups with severe hyperbilirubinemia 1, 5
- Never assume low-risk zone infants require no follow-up—2.2% still developed significant hyperbilirubinemia in validation studies 7
Follow-Up Timing Based on Risk Zone
Appropriate follow-up after discharge is essential regardless of which assessment method is used 1:
- High-risk zone: Follow-up within 24 hours
- High-intermediate risk zone: Follow-up within 24-48 hours
- Low-intermediate risk zone: Follow-up within 48-72 hours
- Low-risk zone: Routine follow-up, but parents should be educated about jaundice monitoring