735 - End-Tidal Carbon Monoxide (ETCOc): A Feasible and Potent Biomarker for Hyperbilirubinemia Screening in Preterm Infants born at 32-34 Weeks

Publication Number: 1712.735

Wenxin Zhu, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Ge Yang, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Yue Du, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Zhaoxian Zhou, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Ningjing Yang, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Meiqing Zhang, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Kun Zhang, Guangzhou Women and Children's Medical Center,Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Li Deng, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, guangzhou, Guangdong, China (People's Republic); Shu xiao, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Fan Li, Guangzhou women and children medical center, Guangzhou, Guangdong, China (People's Republic); Zhiyan Chen, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China (People's Republic); Huayan Zhang, Children's Hospital of Philadelphia-University of Pennsylvania, Philadelphia, PA, United States

Background: End-tidal carbon monoxide (CO)-corrected for ambient CO (ETCOc), a non-invasive measure of heme catabolism, has been validated to screen for hyperbilirubinemia in late-preterm and term infants. Its utility in more vulnerable infants below 35 weeks-who are at higher risk due to hepatic immaturity and increased heme turnover-remains unestablished.

Objective: To evaluate early postnatal ETCOc in infants born at 32-34 6/7 weeks for: 1) its association with phototherapy (PT)-requiring hyperbilirubinemia within 5 days of life (DOLs), and 2) the safety and feasibility of ETCOc monitoring.

Design/Methods: This prospective cohort study enrolled non-intubated preterm infants born at 32-34 6/7 weeks' gestation in our center from March, 10 to September, 30, 2025. Daily paired ETCOc (Capnia CoSense™) and bilirubin (TcB/TSB) levels were measured for 5 days after birth or until PT was initiated as per clinical indication. For infants on non-invasive respiratory support, respiratory support was briefly paused to obtain valid breath samples. The primary outcome was hyperbilirubinemia requiring PT within the first 5 DOLs. Vital signs were recorded before and after each measurement (0, 5, and 10 minutes). Logistic and linear regression were used to analyze associations. Feasibility and safety were assessed by success rates and vital sign changes, respectively.

Results: Of the 108 neonates included, 81 (75.0%) developed hyperbilirubinemia requiring PT. Pre-phototherapy ETCOc levels were significantly higher in the hyperbilirubinemia group (2.2 ± 0.6 vs. 1.6 ± 0.4 ppm, P < 0.01) (Table 1). Each 1 ppm increase in ETCOc was associated with a >20-fold increased odds of requiring PT (aOR = 22.15, 95% CI: 4.08-120.15, P < 0.01) (Table 2). Higher ETCOc was also associated with earlier PT initiation and longer total PT duration (Table 2). Overall measurement success was 84.1%, though varied by respiratory support (highest on CPAP, lowest on NIPPV/BiPAP) (Table 3). Mean measurement time to obtain valid breath sample was 20 seconds (range: 1-120). No significant vital sign changes or adverse events occurred.

Conclusion(s): Early ETCOc is significantly associated with hyperbilirubinemia requiring PT in preterm infants at 32-34 6/7 weeks. Measurements are feasible and safe in most neonates, though challenging during NIPPV/BiPAP. Implementing ETCOc-based risk stratification may facilitate a paradigm shift from reactive monitoring to proactive management. Elevated ETCOc level justifies intensified bilirubin monitoring and earlier intervention, while lower levels may safely reduce unnecessary blood sampling and resource use.

Table 1. Basic characteristics of study population (N = 108)
Definition of abbreviation: IQR, interquartile range; SD, standard deviation; G6PD, glucose-6-phosphate dehydrogenase; DOLs, days of life; HHHFNC, heated, humidified, high-flow nasal cannula; CPAP, continuous positive airway pressure; NIPPV, non-invasive positive pressure ventilation; BIPAP, bi-level positive airway pressure; ETCOc, end-tidal carbon monoxide (CO)-corrected for ambient CO. **P <0.01, *P <0.05.

Table 2. Association of ETCOc and the risk of phototherapy and phototherapy characteristics (N = 108)
Significant numbers were in bold. Definition of abbreviation: DOLs, days of life; ETCOc, end-tidal carbon monoxide (CO)-corrected for ambient CO; G6PD, glucose-6-phosphate dehydrogenase;
1 Parameter estimates (odds ratios or beta coefficients) from multivariable logistic or linear regressions.
2 Maternal comorbidities were defined as the occurrence of one of the comorbidities including hypertensive disorders in pregnancy, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, chorioamnionitis, hypothyroidism and preterm rupture of the membranes.

Table 3. Comparison of successful rate of ETCOc measurement attempts in preterm infants, stratified by gestational age and respiratory support status
Definition of abbreviation: ETCOc, end-tidal carbon monoxide (CO)-corrected for ambient CO; GA, gestational age; HHHFNC, heated, humidified, high-flow nasal cannula; CPAP, continuous positive airway pressure; NIPPV, non-invasive positive pressure ventilation; BIPAP, bi-level positive airway pressure
1 Respiratory support status refers to the type of respiratory support provided at the moment each ETCOc measurement was attempted.