Hierarchical decision model for in vitro bilirubin content prediction from absorption spectrum of whole blood

Abstract

Significance Bilirubin forms by the breakdown of heme proteins in the liver, but a newborn’s sluggish liver can lead to elevated serum bilirubin levels that cross the blood–brain barrier and result in kernicterus. Earlier studies have used the 400 to 500 nm optical wavelength range to characterize the bilirubin content. There is not a universally established correlation among other wavelengths and the amount of bilirubin in clinical whole blood samples. Aim We demonstrated that the amount of bilirubin could be quantified with ∼82 % accuracy in a label-free, self-referenced manner using only a few wavelengths, viz. 468, 492, 500, 560, 605, 645, 660, and 675 nm, wherein band-averaged absorption measurements are used. Approach We addressed the above problem by conducting a preliminary study containing 50 neonates through an absorption spectrum measurement of whole blood in 3 to 5 μl samples from the neonates. We constructed a hierarchical decision method that first grossly divides the 30 neonates of the training set into <10 mg / dl and ≥10 mg / dl bilirubin level cohorts. A subsequent boundary condition further divides the ≥10 mg / dl group into two >15 mg / dl and ≤15 mg / dl bilirubin level cohorts. A finer measure later predicted the bilirubin content of each of these groups as low (<10 mg / dl), medium (10 to 15 mg / dl), and high (>15 mg / dl). Results Using this hierarchical decision model statistical approach, we quantified the amount of bilirubin in the 20 testing set samples with 82% accuracy. Conclusions We formulated a biostatistical model in which we automated the spectrometric determination of total bilirubin in the whole blood for patients of neonatal hyperbilirubinemia.