Related Experiment Video
Updated: Feb 13, 2026

Transcutaneous Microcirculatory Imaging in Preterm Neonates
Published on: December 31, 2015
Unbound bilirubin measurements by a novel probe in preterm infants
Thomas Hegyi1, Alan Kleinfeld2, Andrew Huber2
1a Rutgers Robert Wood Johnson Medical School New Brunswick , New Brunswick , NJ , USA.
Insights
Free bilirubin levels in preterm infants are highly variable and frequently exceed dangerous thresholds. Measuring free bilirubin, not just total bilirubin, is crucial for assessing neurotoxicity risk in newborns.
Area of Science:
- Neonatal Medicine
- Pediatric Neurology
- Biochemistry
Background:
- Hyperbilirubinemia affects over 80% of newborns, posing a risk of neurological damage, particularly in preterm infants.
- Current assessment relies on total serum bilirubin (TSB), but free bilirubin (Bf) levels are more accurate predictors of neurotoxicity.
- Understanding Bf dynamics is critical for timely and effective intervention in neonatal jaundice.
Purpose of the Study:
- To investigate free bilirubin (Bf) levels in preterm infants during the first week of life.
- To determine the frequency of Bf levels exceeding established neurotoxic thresholds.
- To evaluate the relationship between Bf, total serum bilirubin (TSB), and gestational age.
Main Methods:
- Studied 130 preterm infants (500-2000g birth weight; 23-34 weeks gestation).
- Measured Bf using the BL22P1B11-Rh fluorescent sensor and TSB via standard methods.
- Calculated bilirubin-albumin dissociation constants (Kd) and analyzed hearing screening outcomes based on gestational age.
Main Results:
- Mean Bf was 13.6 ± 9.0 nM, with significant variability observed.
- A substantial proportion of Bf measurements surpassed reported neurotoxic thresholds.
- The correlation between Bf and TSB was weak (r²=0.17) and diminished at high Bf levels. Infants <28 weeks gestation had higher rates of hearing screening failure.
Conclusions:
- Free bilirubin levels in preterm infants are highly variable in the first week of life.
- A significant percentage of preterm infants exhibited Bf levels above neurotoxic thresholds.
- These findings underscore the importance of monitoring Bf for accurate risk assessment of bilirubin neurotoxicity in vulnerable newborns.
Background:
Hyperbilirubinemia occurs in over 80% of newborns and severe bilirubin toxicity can lead to neurological dysfunction and death, especially in preterm infants. Currently, the risk of bilirubin toxicity is assessed by measuring the levels of total serum bilirubin (TSB), which are used to direct treatments including immunoglobulin administration, phototherapy, and exchange transfusion. However, free, unbound bilirubin levels (Bf) predict the risk of bilirubin neurotoxicity more accurately than TSB.
Objective:
To examine Bf levels in preterm infants and determine the frequency with which they exceed reported neurotoxic thresholds.
Methods:
One hundred thirty preterm infants (BW 500-2000 g; GA 23-34 weeks) were enrolled and Bf levels measured during the first week of life by the fluorescent Bf sensor BL22P1B11-Rh. TSB and plasma albumin were measured by standard techniques. Bilirubin-albumin dissociation constants (Kd) were calculated based on Bf and plasma albumin.
Results:
Five hundred eighty samples were measured during the first week of life, with an overall mean Bf of 13.6 ± 9.0 nM. A substantial number of measurements exceeded potential toxic thresholds levels as reported in the literature. The correlation between Bf and TSB was statistically significant (r2 0.17), but this weak relationship was lost at high Bf levels. Infants <28-week gestations had more hearing screening failures than infants ≥28-week gestation.
Conclusions:
Unbound (free) bilirubin values are extremely variable during the first week of life in preterm infants. A significant proportion of these values exceeded reported neurotoxic thresholds.
Related Concept Videos
Drug Dosing: Infants and Children
Labeling DNA Probes
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
Measures of Central Tendency
Measurement: Standard Units
Measuring Reaction Rates
Uncertainty in Measurement: Significant Figures

