Abstract
BACKGROUND: Neonatal hyperbilirubinemia risk factors determination is challenging due to the lack of quantifiable indicators for bilirubin production, resulting in phototherapy decisions made without real-time information. End-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) may be helpful for identifying hemolysis, but evidence on the application of ETCOc as a risk factor for the development of neonatal hyperbilirubinemia is scarce. This study aimed to evaluate whether the use of ETCOc to adjust neonatal hyperbilirubinemia risk categories and thus phototherapy thresholds can reduce the rate of phototherapy within the first seven days of life. METHODS: This is a randomized clinical trial including near-term and term infants with a transcutaneous bilirubin > 40th percentile within 72 hours after birth in a single center in Guangdong, China. Newborns were randomized to receive ETCOc-adjusted risk assessment or empirical assessment per local practice to establish phototherapy thresholds. The primary outcome was the rate of phototherapy within seven days of life. Secondary outcomes were postnatal hours at phototherapy, total serum bilirubin and ETCOc before phototherapy, severe hyperbilirubinemia and phototherapy duration. RESULTS: A total of 2500 infants were enrolled and randomized. Phototherapy within seven days of life occurred in 237 infants (18.9%) in the intervention group and 281 infants (22.5%) in the control group [adjusted relative risk: 0.85; 95% confidence interval (CI): 0.73, 0.98]. The ETCOc before phototherapy was 0.28 parts per million higher (95% CI: 0.10, 0.46) in the intervention group. The rate of subsequent severe hyperbilirubinemia was not significantly different, and other secondary outcomes were comparable between the two groups. CONCLUSIONS: For near-term and term infants at risk of neonatal hyperbilirubinemia, the use of ETCOc to adjust neonatal hyperbilirubinemia risk categories can decrease the rate of phototherapy at seven days of life. Integrating the ETCOc to adjust the phototherapy threshold is helpful in the management of severe hyperbilirubinemia.