Neonatal hyperbilirubinemia is a common occurrence in newborns with a small percentage of those experiencing extremely high, pathological levels of bilirubin. Left untreated severe hyperbilirubinemia leads to brain damage known as kernicterus spectrum disorder (KSD). Numerous articles and reviews have argued that the classic measure of bilirubin in the body, total serum bilirubin (TSB), is only an indirect measure of the more reliable correlation to toxicity, unbound bilirubin (Bf).1 While the use of the “Peroxidase Method”, first described in the 1970s, can successfully measure Bf in the blood,2,3 due to technical hurdles, automation of this method for clinical use has never been implemented outside of Japan. Therefore, we are pleased to see that the production of a reliable point-of-care Bf reader continues to progress. This novel Bf reader requires only 5 µl of whole blood to produce a concentration in around 60 s. Interestingly, it was reported that phototherapy (PT) is effective in decreasing TSB (as expected by decades of experience), but this decrease does not coincide with an equivalent decrease in Bf. Based on observations of Bf concentrations, infants are overtreated with PT. These data suggest possibly reducing UV exposure and promoting extended hospitalization. It was shocking to hear that among 40 drugs typically used in newborns, nearly a quarter (22%) of these drugs showed a displacing effect, increasing Bf anywhere from 80 to 1600%. A similar effect was also documented for intra-lipids, frequently administrated especially to preterm infants.

For some time now, Bf has been the demonstrated indicator for neurological damage, and the inability for the traditional TSB measurement to account for the effects of bilirubin displacing drugs makes it even more unreliable than previously thought. The development and implementation of a true point-of-care Bf measurement device would not only be expected to reduce the number of cases of kernicterus but also allow for a safe reduction in the number of unnecessary and possibly dangerous PT. However, to make the measurement of Bf a routine test, a massive global effort is now required for the approval and implementation of these devices. This effort will begin with clinical studies of efficacy in each region before new guidelines for intervention can be written and implemented.

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