Neonatal hyperbilirubinemia occurs in almost all newborns, and may be benign if its progression to extreme hyperbilirubinemia is recognized, monitored, and prevented or managed in a timely manner. Neonatal jaundice carries the risk of neurotoxicity, due to the deposition of bilirubin in the central nervous system. Most of the bilirubin in plasma is bound to plasma proteins (mainly serum albumin). Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or free bilirubin and his/her ability to tolerate increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors. While various methods exist to measure BBC, none have been successfully commercialized. Of these, hematofluorometry holds the greatest promise of a device that can be used at the point of care, and give rapid and accurate BBC measurements. A SBIR Phase I grant demonstrated that such a device is possible. A Phase II grant delivered improved devices to neonatal hospitals. Published clinical studies with these devices not only collaborated prior knowledge, but suggested ways in which BBC measurements may improve existing neonatal care.
The aims of this project are to transform the modernized hematofluorometers developed in Phases I and II into a final product suitable for operation in a point-of-care environment in the newborn nursery, NICU, and neonatal outpatient clinic. In year one, Aviv's goals are to develop and evaluate a single position hematofluorometer in terms of increased accuracy over prior designs; develop and evaluate kit designs that increase the ease of use; improve the use of the internal reference; develop primary standards for calibration; develop validation checks. Beginning in year 1 and continuing into year 2, Aviv will: perform shelf-life tests; determine environmental limits of operation; integrate a bar code reader and laboratory information management software support; internal quality checks into the device and software; investigate potential interferences to measurements; and incorporate guidance for use into documentation and software. During year 2 Aviv will: have a commercializable embodiment; develop methods and documentation; identify partners for manufacturing, marketing, sales, and distribution. Concurrent with these activities, Stanford University's Lucile Packard Children's Hospital will conduct clinical studies to evaluate the usefulness of BBC measurements in a clinical setting. Experienced consultants in the fields of neonatal care management, clinical lab directors, and those with hands-on experience neonatal intensive care units and clinical labs will be consulted on the suitability of the device and reagent kit. The goal is to obtain expert recommendations for the use of the BBC assay to inform additional clinically useful modifications of the hematofluorometer system.
Management of newborns with elevated unconjugated bilirubin levels in order to prevent bilirubin induced neurological dysfunction (BIND) and kernicterus remains problematical, especially for premature infants. The bilirubin binding capacity of albumin (BBC) is a determinative measure of a neonate's ability to cope with an excessive bilirubin burden. This proposal aims to complete the development of a bilirubin hematofluorometer that easily measures BCC at the points of care, and initiate its commercialization.
