Diagnostic methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments

Abstract

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices.

Preparation of bilirubin standard solutions for assay calibration

“…Analysis of bilirubin in clinical laboratories is performed by automated methods 4 . For highly sensitive analysis of bilirubin in complex biological matrices, a number of other analytical methods have been introduced, based on HPLC and coupled with advanced detectors, various sensors, molecularly imprinted surfaces, or the uorescent bilirubin-binding protein UnaG 5-7 .…”

Accuracy and Reliability of Whole Blood Bilirubin Measurements Using a Roche Blood Gas Analyzer for Neonatal Hyperbilirubinemia Screening and Risk Stratification

“…Although most forms of jaundice are physiological and self-limiting, severe cases will result in overwhelming bilirubin deposition in the brain without timely treatment, leading to irreversible neurological damage, namely, kernicterus ( 1 , 2 ). Bilirubin measurements are fundamental for diagnosis, risk stratification, and treatment decision-making in cases of neonatal hyperbilirubinemia ( 3 ). The initiation of phototherapy for neonates with severe hyperbilirubinemia or at high risk of subsequent severe hyperbilirubinemia is commonly assessed using a combination of risk factors evaluation and the Bhutani’s hour-specific bilirubin nomogram, which was established on the basis of total serum bilirubin (TSB) measurements obtained by the diazo method ( 1 , 2 , 4 ).…”

“…In recent decades, the technology underlying bilirubin assays has evolved significantly. New methods such as trace sample-based blood gas bilirubin measurements performed by Co-oximetry now provide more choices and convenience for clinicians ( 3 ). Blood gas analyzers such as the Roche Cobas models support multi-test panels and deliver test results quickly; consequently, they are commonly used in neonatal intensive care units (NICUs).…”

“…Blood gas analyzers such as the Roche Cobas models support multi-test panels and deliver test results quickly; consequently, they are commonly used in neonatal intensive care units (NICUs). However, an important prerequisite for these blood gas analyzers is that their whole blood bilirubin measurements must be comparable to measurements obtained with TSB, which remains the gold standard ( 3 ). In the current study, we compared whole blood bilirubin measurements on a Roche blood gas analyzer (Roche TBiL; Roche Diagnostics GmbH, Germany) with TSB measurements obtained by the Ortho VITROS 4600 chemistry system (Ortho TSB; Ortho Clinical Diagnostics, United States) from 309 hospitalized neonates to evaluate the accuracy and clinical reliability of Roche TBiL measurements.…”

A System-on-Chip Assay for Bilirubin Levels Measurement in Whole Blood

“…Several studies on BR levels estimation have been reported [7,8], but these techniques suffer from the instrument complexity and cost. This mini-paper investigated the dualwavelength (DWL) technique for BR estimation using a system-on-chip (SoC).…”