Noninvasive Detection of Hemolysis with ETCOc Measurement in Neonates at Risk for Significant Hyperbilirubinemia

Abstract

<b><i>Background:</i></b> Hemolytic hyperbilirubinemia due to blood group incompatibility or glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common cause of significant hyperbilirubinemia. Hemolysis in a hyperbilirubinemic infant increases the risk of bilirubin neurotoxicity. A new portable device (CoSense) can rapidly detect breath end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc). ETCOc levels are surrogate markers of hemoglobin breakdown and bilirubin production. <b><i>Objective:</i></b> The aim was to evaluate the association between ETCOc values and hemolysis and its relevance in neonates at risk for significant hyperbilirubinemia. <b><i>Methods:</i></b> A prospective study was conducted among newborn infants born at more than 35 weeks and with a birth weight greater than 2,000 g with a G6PD deficiency, blood group incompatibility, or clinical jaundice needing phototherapy during the first 7 days of life. The recruited infants had their breath ETCOc measured twice, first on the day of recruitment and then again on the following day. <b><i>Results:</i></b> Fifty infants completed this study. Their mean ETCOc was 1.61 (±0.56) ppm. There was a linear correlation (<i>r</i> = 0.89) between increasing ETCOc values and reticulocyte counts (RC). Sixteen newborns with ABO incompatibility had a significantly higher mean ETCOc of 1.98 ppm (±0.71) as compared to 1.43 (±0.38) ppm in the nonhemolytic hyperbilirubinemia (NHH) group (<i>n</i> = 25) (<i>p</i> = 0.002). This was suggestive of hemolysis as shown by the significantly higher RC of 6.90% (±3.38) compared to 4.68 (±1.26) in the NHH group (<i>p</i> &#x3c;0.005). Neonates with an ETCOc level ≥1.8 ppm had a higher RC, a lower hemoglobin level, higher serum bilirubin levels, and a rapid rise in serum bilirubin and needed a longer duration of phototherapy. ETCOc values ≥1.8 ppm were suggestive of hemolysis (RC ≥6%), with a sensitivity of 90% and a specificity of 83%. <b><i>Conclusion:</i></b> Higher ETCOc values ≥1.8 ppm are suggestive of hemolysis and they are associated with significant hyperbilirubinemia.