Objectives Whole blood bilirubin measured on blood gas analyzers is accepted by physicians in neonatal hyperbilirubinemia management since it requires a small sample volume. The accuracy of bilirubin measurement on blood gas analyzers is instrument dependent and remains controversial. Design and Methods Bilirubin in adult and umbilical cord whole blood samples, spiked with an unconjugated bilirubin standard, and non-spiked adult plasma samples was measured on a blood gas analyzer (GEM 4000) and a Core Laboratory Chemistry analyzer (Architect c16000) respectively. We also investigated the linear regression for neonatal and adult hemoglobin measured on the blood gas analyzer and the Core Laboratory hematology analyzer (Alinity h-Series). Results Plasma bilirubin measured on the blood gas analyzer and the chemistry analyzer was statistically identical. Adult whole blood bilirubin showed slightly increased proportional bias. When umbilical cord whole blood samples were used, the Deming regression showed GEM bilirubin =1.233(Architect) (95% CI 1.199 ~ 1.266)-44.43 ​μmol/L (95% CI -53.6 ​~ ​−35.2). The regression was significantly different from that in plasma (p ​< ​0.001) or adult whole blood (p ​< ​0.001) samples. 36.1% neonatal samples with bilirubin levels >50 ​μmol/L showed that the bias% was above laboratory standards. In addition, the regression of neonatal hemoglobin measurement between the GEM and the Alinity was significantly different from adult hemoglobin (p ​< ​0.01). Conclusions Neonatal whole blood bilirubin measurement on blood gas analyzers may be affected by neonatal hemoglobin. The method should be validated using neonatal whole blood samples or samples with a similar matrix before the analyzers are implemented into neonatal hyperbilirubinemia management.

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