In the delicate realm of neonatal care, monitoring bilirubin levels in preterm infants stands as a critical challenge fraught with significant implications for long-term neurological health. Bilirubin, a yellow pigment formed during the normal breakdown of red blood cells, requires vigilant observation because excessive accumulation in the blood can lead to neurotoxicity, including severe conditions such as kernicterus. Historically, the measurement of total serum bilirubin (TSB) has been the gold standard for diagnosing and managing neonatal hyperbilirubinemia. Despite its accuracy, TSB measurement demands invasive blood sampling, which can be stressful to fragile preterm infants and time-consuming for clinical staff. In recent years, transcutaneous bilirubinometry (TcB) has emerged as a promising alternative, offering a rapid, non-invasive, and cost-effective screening method. However, while TcB has been validated extensively in term infants, its clinical reliability among preterm neonates remains uncertain, particularly during phototherapy and in those with varying skin pigmentation.
The latest breakthrough study published in the Journal of Perinatology re-examines the correlation between TcB and TSB measurements in preterm infants, with particular attention to factors including gestational age, race, and the effects of phototherapy. This comprehensive investigation reveals a complicated landscape where TcB measurements, despite an overall strong correlation with TSB levels, exhibit significant variability influenced by multiple physiological and treatment-related variables. Phototherapy, a mainstay treatment for hyperbilirubinemia that uses light to break down bilirubin in the skin, notably diminishes the accuracy of TcB readings when applied to the exposed skin area. This decline in accuracy raises critical questions about the interchangeability of TcB and TSB measurements during therapy and challenges clinicians relying solely on non-invasive technologies for decision-making.
Preterm infants—those born before 37 weeks of gestation—possess unique vulnerabilities due to immature organ systems and distinctive skin composition, factors that further complicate bilirubin monitoring. The study elucidates that gestational age modulates the reliability of TcB, highlighting that more immature neonates demonstrate greater discrepancies between transcutaneous and serum bilirubin levels. These discrepancies implicate the developmental variability in skin thickness, melanin concentration, and bilirubin deposition patterns, all of which influence how bilirubin absorbs and reflects light wavelengths used in TcB devices. The study’s nuanced understanding beckons a more tailored approach, where gestational maturity must be considered when interpreting TcB readings in clinical practice.
Skin pigmentation also emerges as a pivotal variable affecting TcB readings. Infants with darker skin present additional challenges for non-invasive bilirubin measurement techniques, as melanin can interfere with the optical properties necessary for accurate bilirubin estimation. Prior studies have underscored this limitation in term infants; however, this new research extends the concern to preterm populations, emphasizing that skin color-related inaccuracies compound when combined with other factors such as ongoing phototherapy. The resulting reduction in TcB precision potentially risks both over- and under-treatment, thereby necessitating confirmatory serum testing and circumspect clinical judgment.
One of the most striking aspects of the investigation is the analysis of TcB performance during and after phototherapy exposure. Phototherapy is known to alter skin bilirubin concentrations and the composition of bilirubin photoisomers—molecular variants that differ from native bilirubin and impact optical measurement devices. The study documents a marked decrease in TcB accuracy on skin areas subjected to phototherapy, thereby complicating real-time bilirubin assessment during treatment. Bland–Altman analysis, a statistical method used to compare measurement techniques, convincingly demonstrates that TcB and TSB cannot be used interchangeably in preterm infants under phototherapy, as deviations exceeded clinically acceptable limits.
Another dimension of the research highlights discrepancies between TcB measurements and established clinical decision thresholds for escalation of care, such as initiating phototherapy or exchanging transfusions. The poor concordance observed signals potential risk if clinicians were to rely solely on TcB to govern treatment decisions. This gap emphasizes that while TcB provides a valuable screening tool, it cannot yet supplant blood-based measurements without jeopardizing patient safety. Consequently, the study advocates maintaining serum bilirubin checks as the cornerstone of care in preterm infants, particularly when phototherapy is involved or when infants fall within sensitive gestational age brackets.
Importantly, this research advances the neonatal clinical field by prompting a reconsideration of how non-invasive bilirubin monitoring tools are integrated into standard practice. It recommends a stratified protocol—one that acknowledges the inherent limitations of TcB devices and prioritizes serum testing when TcB readings are obtained under challenging conditions, such as phototherapy or in infants with dark skin pigmentation. By underscoring these caveats, the findings promote a more precise and individualized management strategy to prevent bilirubin-induced encephalopathy in an especially vulnerable population.
The implications extend beyond bedside clinical practice to healthcare policy, device regulation, and technological innovation. Device manufacturers may find motivation to refine TcB calibration algorithms, incorporating corrections for gestational age, skin pigmentation, and phototherapy status. Additionally, clinical guidelines might be updated to reflect these nuances, ensuring that both clinicians and caregivers understand when TcB can safely guide care and when invasive serum assays remain indispensable.
On a research front, this study opens avenues for future exploration focusing on optimizing bilirubin monitoring in preterm infants. Continual advancements in optical sensor technology, such as multi-wavelength spectroscopy, machine learning-based predictive algorithms, and integration with electronic medical records, could eventually narrow the accuracy gap between TcB and TSB. Moreover, longitudinal studies assessing long-term neurodevelopmental outcomes in infants managed with varying bilirubin monitoring strategies would provide invaluable evidence to fine-tune clinical recommendations.
The study’s robust methodology, large sample size, and comprehensive inclusion of racially and gestationally diverse preterm subjects add confidence to its conclusions while highlighting the urgent need for cautious interpretation of TcB results. By confirming that TcB’s utility in preterm infants is not uniform and is compromised under certain conditions, the research advocates an informed, context-aware approach that prioritizes patient safety and precision medicine principles.
In an era where non-invasive, rapid diagnostic tools are highly valued for their clinical efficiency and patient comfort, this study serves as a sober reminder that new technologies must be critically evaluated across diverse populations and treatment contexts. The desire to reduce needle sticks and expedite clinical decision-making is commendable, but the inherent complexity of bilirubin physiology in preterm infants demands that clinicians strike a careful balance between innovation and evidence-based caution.
In conclusion, the investigation by Cordero and colleagues fundamentally reshapes our understanding of transcutaneous bilirubinometry’s role in managing neonatal jaundice among preterm infants. It elucidates the modality’s strengths and limitations, emphasizes the persistent necessity of serum bilirubin monitoring, and charts a path forward for enhancing neonatal care through multidisciplinary collaboration. As the neonatal community grapples with safeguarding vulnerable infants from bilirubin neurotoxicity, this research stands as a crucial beacon guiding the integration of technology without compromising clinical rigor or patient welfare.
Subject of Research: Transcutaneous bilirubin measurements in preterm infants and the impact of race, gestational age, and phototherapy on measurement accuracy.
Article Title: Transcutaneous bilirubin measurements in preterm infants: the impact of race, age, and phototherapy.
Article References:
Cordero, N., Petrova, A., Halari, A. et al. Transcutaneous bilirubin measurements in preterm infants: the impact of race, age, and phototherapy. J Perinatol (2026). https://doi.org/10.1038/s41372-025-02558-w
Image Credits: AI Generated
DOI: 10.1038/s41372-025-02558-w
Keywords: neonatal hyperbilirubinemia, preterm infants, transcutaneous bilirubinometry, total serum bilirubin, phototherapy, bilirubin neurotoxicity, skin pigmentation, neonatal jaundice, non-invasive diagnostics, neonatal care
