End-tidal carbon monoxide levels as a point-of-care biomarker for the early detection of hemolytic disease in Chinese neonates.

Objective: Hemolytic disease of newborn (HDN) is a leading risk factor for severe neonatal hyperbilirubinemia. While end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) reflects the endogenous rate of bilirubin production, there remain translational gaps in understanding the link between ETCOc and HDN. We aimed to evaluate ETCOc levels as an indicator of increased bilirubin production in HDN.

Methods: This secondary analysis of the HEME (Hyperbilirubinemia risk Evaluation and Management by ETCOc) trial included near-term/term neonates (≥35 weeks' gestation, birth weight ≥ 2000 g) with transcutaneous bilirubin (TcB) levels > 40th percentile within 72 h of birth. Infants diagnosed with HDN, defined as the presence of ABO HDN and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency, were compared with those without HDN. ETCOc was measured within the first 7 days of life (DOL).

Results: Of 2500 infants studied, 171 (6.8%) were diagnosed with HDN. ETCOc levels within 72 h of birth were significantly higher in HDN cases compared with controls. ETCOc percentiles within 7 DOL showed trends with fluctuations. Each 1 ppm incremental increase in ETCOc was each significantly associated with odds ratios of 3.90 (95 %CI 2.89-5.29), 2.72 (95 %CI 1.89-3.92), and 2.47 (95 %CI 1.21-5.02) of developing HDN early after life (≤ 72 h).

Conclusion: Early postnatal ETCOc was strongly associated with increased risk of HDN in newborns of Southern China. Our findings highlight the potential of ETCOc as a noninvasive point of care biomarker for early hemolysis identification. Integration of ETCOc measurements into existing screening protocols could refine risk stratification and guide timely interventions, particularly in regions with a high prevalence of HDN.