The current practice for treating neonates for
jaundice centers on the recommendation that
bilirubin levels should be kept below 20 mg/dL. Preventing
bilirubin levels from exceeding 20 mg/dL, however, does not guarantee the avoidance of
kernicterus, lower IQs or neurologic abnormalities. Studies in the 1960s and 1970s reported cases of infants with clinical and pathological
kernicterus whose neonatal
bilirubin levels were well below 20 mg/dL. It is now well accepted that protein binding,
acidosis,
hypoxia,
intracranial hemorrhage and hemolytic disease play a role in facilitating
bilirubin toxicity. This paper reviews previously published studies that were instrumental in identifying the role of
hypoxia,
acidosis, hemolytic disease,
intracranial hemorrhage and protein binding in
bilirubin encephalopathy and identifies two key variables which contribute to
bilirubin flux-free
bilirubin concentration and time. The paper proposes a new approach for evaluating
bilirubin levels termed '
bilirubin index'. Future research should initially focus on healthy term infants without concomitant illness and should record free
bilirubin levels as a function of time. The area under the
bilirubin versus time curve represents the integration of
bilirubin level with respect to time, or simply termed the '
bilirubin index'. The
bilirubin index could then be correlated with parameters for measuring neurological outcome. Assuming a correlation would exist, the
bilirubin index may then become the number for guidance with respect to intervention
therapy. Attempting to address this issue by starting with a healthy population of neonates and correlating
bilirubin index with neurological outcome offers a better chance for uncovering that 'threshold of toxicity'.