Newborn Hyperbilirubinemia Rate of Rise

Calculate rate of serum bilirubin rise to determine risk of severe hyperbilirubinemia


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.

This tool calculates the rate of rise between two TSB values
(Bilirubin #2 - Bilirubin #1)/Time

Rate of TSB rise >3.4 µmol/L/hour (0.2 mg/dL/hour) is a risk factor for severe hyperbilirubinemia.

Other risk factors identified by the AAP for development of severe hyperbilirubinemia (in approximate order of importance):

- TSB/TcB in high-risk zone
- Jaundice in first 24h
- ABO incompatibility with DAT+, known hemolytic disease (ex. G6PD deficiency), elevated ETCO
- Gestational age 35-36 weeks
- Sibling had phototherapy
- Cephalohematoma or bruising
- Exclusive breastfeeding, esp. with poor nursing/weight loss
- East Asian race

- TSB/TcB in high intermediate risk zone
- Gestational age 37-38 weeks
- Jaundice before discharge
- Previous sibling with jaundice
- Macrosomic infant of a diabetic mother
- Maternal age ≥25 years
- Male gender

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


AAP Subcommittee on Hyperbilirubinemia. Clinical Practice Guideline:

Pediatrics, vol. 114, no. 1, 2004, pp. 297-316.

Barrington, Kj, and K Sankaran.

Paediatrics & Child Health, vol. 12, no. suppl_B, 2007.

Sor, Callen.

Neonatal Jaundice
University of British Columbia Faculty of Medicine. 30, Jul. 2020, Vancouver. Zoom Lecture.

The Newborn Hyperbilirubinemia Rate of Rise calculator is created by QxMD.

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1. Bilirubin #1 Value?

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