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Updated: Dec 22, 2025
Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Unbound bilirubin measurements in term and late-preterm infants
Thomas Hegyi1, Dalya Chefitz1, Alan Weller1
1Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers, The State University of NJ, New Brunswick, NJ, USA.
Insights
Unbound bilirubin (Bf) levels, not total serum bilirubin (TSB), predict neurotoxicity risk in newborns. Bf levels in healthy infants are complex and unpredictable, even with phototherapy, suggesting Bf monitoring is crucial for jaundice management.
Area of Science:
- Neonatal Medicine
- Pediatric Neurology
- Clinical Chemistry
Background:
- Hyperbilirubinemia affects over 80% of newborns, posing a risk of severe neurological dysfunction and mortality.
- Unbound bilirubin (Bf) is a better predictor of neurodevelopmental handicap risk than total serum bilirubin (TSB), which is currently used for clinical management.
Purpose of the Study:
- To measure Bf levels in healthy infants.
- To determine the relationship between Bf and TSB.
- To assess the response of Bf to phototherapy.
Main Methods:
- Simultaneous measurement of TSB and Bf in 132 healthy infants.
- Collection of clinical data including gestational age, birth weight, feeding type, and phototherapy use.
- Analysis of the correlation between Bf and TSB, and Bf levels before and after phototherapy.
Main Results:
- A significant correlation was found between Bf and TSB, but this relationship weakened when TSB exceeded 12 mg/dl.
- Elevated Bf levels (>11 nM) were observed in 22.7% of infants, and >17 nM in 3.8%.
- Post-phototherapy TSB and Bf levels showed no significant change from pre-treatment levels.
Conclusions:
- The relationship between TSB and Bf in healthy infants is complex, with TSB being an unreliable predictor of Bf at elevated levels.
- Bilirubin-related neurotoxicity necessitates Bf measurements for effective jaundice management in healthy infants.
- Current management of jaundice using TSB may lead to unnecessary phototherapy exposure due to unpredictable Bf elevations.
Background:
Hyperbilirubinemia occurs in over 80% of newborns, and severe bilirubin toxicity can lead to neurological dysfunction and death. Unbound bilirubin (Bf) levels predict the risk of neurodevelopmental handicap, although total serum bilirubin (TSB) is used to manage care.
Objective:
To measure Bf levels in healthy infants, its relationship to TSB, and its response to phototherapy. We hypothesize unexpectedly high Bf levels, poor correlation with TSB and unpredictable response to phototherapy.
Design/Methods:
Healthy infants were studied with simultaneous TSB and Bf measurements. The clinical data recorded included ethnicity, gender, birth weight, gestational age, and mode of delivery, Apgar scores, breast/formula feeds, and phototherapy.
Results:
One hundred thirty-two infants (3248.9 ± 509.2g, GA 38.7 ± 1.4 weeks), at mean age of the initial sample of 28.5 ± 15.6 h, had a TSB of 7.9 ± 2.7 mg/dl, and a Bf of 5.2 ± 3.2 nM. The correlation between Bf and TSB was significant but not between Bf and TSB for TSB >12 mg/dl. Bf >11nm were in 22.7% and >17 nM in 3.8% of infants. Post-phototherapy TSB and Bf levels were similar to those before treatment.
Conclusions:
The relationship between TSB and Bf in healthy infants is complex, with the inability of one to predict the other's level in infants with elevated TSB. The mechanism of bilirubin-related neurotoxicity suggests that the management of jaundice in healthy infants requires Bf measurements. Management of jaundice with TSB may result in more infants exposed to phototherapy. However, unexpected elevations of Bf occur in an apparently healthy population.
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