Newborn Hyperbilirubinemia Assessment

Predict risk of newborn (GA >35 weeks) developing hyperbilirubinemia and determine follow-up recommendations


60% of term infants and 80% of preterm newborns develop jaundice, a condition characterized by yellowing of the skin or whites of the eyes, arising from elevated serum bilirubin levels. Bilirubin is a product of heme breakdown and exists in conjugated and unconjugated forms.

Bilirubin is a product of heme breakdown and exists in conjugated and unconjugated forms

Extreme hyperbilirubinemia is neurotoxic. Unconjugated bilirubin can cross the blood-brain barrier as it is lipid-soluble and then deposit in brain tissue, mainly the basal ganglia and brainstem nuclei.
Acute Bilirubin Encephalopathy (ABE) is a clinical syndrome of lethargy, hypotonia and poor suck, which may progress to hypertonia (with opisthotonos/retrocollis), high pitched cry, fever, seizures, and coma.
Chronic bilirubin encephalopathy (CBE) or Kernicterus, is associated with permanent neurologic sequelae, such as choreoathetoid cerebral palsy, upward gaze abnormalities, enamel dysplasia of deciduous teeth, and sensorineural impairment.

An approach to neonatal hyperbilirubinemia can be determined using this calculator. The bilirubin ranges are based on a study conducted in 1999 by Dr. Bhutani. TSB levels were obtained from healthy term and near-term newborns between 18 to 72 hours of life at the same time as routine metabolic screening (pre-discharge) and subsequently in a hospital supervised follow-up program (post-discharge). Newborns with sepsis (proven or presumed but treated), a positive direct Coombs test, requiring phototherapy before age 60 hours, intractable hypoglycemia or respiratory distress were excluded.

A percentile-based bilirubin nomogram was constructed from hour-specific TSB values (n = 2840; median BW = 3230 g and median gestational age = 39 weeks). The study demonstrated that timed measurement of TSB concentration at discharge (between 18 and 72 hours of age) could predict a later TSB measurement greater than the 95th percentile within stated confidence limits.

The pre-discharge TSB (at 18 - 72 hours) in 6.1% of the study population (172/2840) was in the high-risk zone (>95th percentile); of these, 39.5% (68/172) remained in that zone.
(likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%).

The pre-discharge TSB in 32.1% of the population (912/2840) was in the high intermediate-risk zone (76 - 94 percentile) and low intermediate risk zone (40 - 75 percentile).
In a clinically significant minority of these newborns (58/912 or 6.4%), the post-discharge TSB moved into the high-risk zone.
(LR = 3.2 from the high-intermediate zone; probability = 12.9%)
(LR = .48 from the low-intermediate risk zone; probability = 2.2%)

The pre-discharge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia
(LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%).


Phototherapy can be used to prevent severe hyperbilirubinemia in infants with a moderately elevated TSB concentration and as initial therapy in those with severe hyperbilirubinemia. Blue light of 460-490 nm induces conformational change in the bilirubin molecule, converting it to water-soluble isomers (Z-lumirubin) which is then excreted into bile and urine.

A modified Bhutani curve can be used to determine the threshold for phototherapy taking into account an infant's gestational age (only published for infants 35 or more weeks' gestation) and neurotoxicity risk factors. These guidelines are based on the consensus of the American Academy of Pediatrics' Subcommittee on Hyperbilirubinemia. Despite the limited direct evidence available for these guidelines, they are the most appropriate currently available standard.

Etiology of Neonatal Jaundice

  1. Excessive bilirubin production
    • 2-3x higher than in adults due to higher Hct (0.50-0.60) and shorter life span of fetal RBC (85 days vs 120 days)
    • Hemolysis due to ABO/Rh incompatibility
    • Hemolysis due to inherited RBC membrane defects
      • Glucose-6-phosphate dehydrogenase (G6PD) deficiency → increased cellular oxidative damage → early cellular death
      • Pyruvate kinase deficiency → decrease ATP production → early cellular death
      • Congenital erythropoietic porphyria
    • Hemolysis due to sepsis
    • Polycythemia - increased load of bilirubin precursors
    • Cephalohematoma: sequestration of blood within a closed space
  2. Decreased bilirubin clearance due to UGT1A1 deficiency
    • Crigler-Najjar syndrome
      • Type 1: Absent UGT1A1 activity (most severe)
      • Type 2: Low UGT1A1 activity
    • Gilbert syndrome
      • Mutation in promoter region of UGT1A1 leading to reduced enzyme activity and therefore increased unconjugated bilirubin
  3. Increased enterohepatic circulation of bilirubin
    • Breast milk jaundice
      • Persistence of physiologic jaundice beyond the 1st week of age due to an unidentified breast milk substance inhibiting bilirubin clearance (β-glucuronidase is implicated)
    • Breastfeeding failure jaundice
      • Inadequate feeding leads to decreased stooling and urination, thereby increasing enterohepatic circulation of bilirubin
    • Impaired intestinal motility by functional or anatomical obstruction


Stevenson DK, Fanaroff AA, Maisels MJ, et al.

Pediatrics. 2001;108(1):31-9.

AAP Subcommittee on Hyperbilirubinemia. Clinical Practice Guideline

Pediatrics, vol. 114, no. 1, 2004, pp. 297-316., doi:10.1542/peds.114.1.297.

Barrington, Kj, and K Sankaran.

Paediatrics & Child Health, vol. 12, no. suppl_B, 2007, doi:10.1093/pch/12.suppl_b.1b.

Longhurst, Christopher, et al.

The Joint Commission Journal on Quality and Patient Safety, vol. 35, no. 5, 2009, pp. 256-262., doi:10.1016/s1553-7250(09)35035-7.

The Newborn Hyperbilirubinemia Assessment calculator is created by QxMD.

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