REGULAR ARTICLE Identification of neonatal haemolysis: an approach to predischarge management of neonatal hyperbilirubinemia Vinod K. Bhutani (bhutani@stanford.edu) 1 , Shanmukha Srinivas 1 , Martin E. Castillo Cuadrado 1 , Janelle L. Aby 2 , Ronald J. Wong 1 , David K. Stevenson 1 1.Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA 2.Division of General Pediatrics, Stanford University School of Medicine, Stanford, CA, USA Keywords Bilirubin, Bilirubin elimination, Bilirubin production, End-tidal carbon monoxide, Newborn jaundice Correspondence Vinod K. Bhutani, MD, FAAP, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, 750 Welch Rd, Suite #315, Palo Alto, CA 94306, USA. Tel: +(650) 723-6621 | Fax: +(650) 725-7724 | Email: bhutani@stanford.edu Received 27 November 2015; revised 21 December 2015; accepted 19 January 2016. DOI:10.1111/apa.13341 ABSTRACT Aim: Relative contributions of increased production [by end-tidal carbon monoxide concentrations (ETCOc)] and decreased elimination of bilirubin to predischarge hour- specific total bilirubin (TB) levels were assessed in healthy late-preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia. Methods: TB and ETCOc (≤3 timepoints) determinations of newborns aged between six hours and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc. Results: Stratifications of ETCOc (in ppm, mean, median and interquartile ranges) by postnatal age epochs (0–24, 24–48 and 48–72) were as follows: 2.0, 1.9, 1.8–2.2 (n = 11); 1.6, 1.5, 1.1–2.0 (n = 58); and 2.0, 1.8, 1.6–2.3 (n = 9), respectively. Infants with ETCOc ≥ 2.5 were at high risk, between 1.5 and 2.5 at moderate risk and ≤1.5 were at low risk. Risk due to haemolysis alone was not independent (p < 0.01). For infants with TB >75th percentile (n = 31), 23% had ETCO ≤1.5, and 77% had ETCOc > 1.5 (p < 0.00003). Conclusion: Near-simultaneous ETCOc and TB measurements in infants with TB >75th percentile accurately identify haemolytic hyperbilirubinemia. INTRODUCTION In healthy term and late-preterm newborns, peak serum/ plasma total bilirubin (TB) levels often occur beyond 72 hours of age and, more commonly, after discharge from the birthing hospital (1). In these apparently well infants, predischarge TB measurements can predict the likelihood of developing severe hyperbilirubinemia (TB ≥95th percentile as defined on an hour-specific bilirubin nomogram (2)). This nomogram describes the rate of rise (ROR) of TB. As postnatal age increases, infants tend to remain in their predischarge-defined risk zones upon reaching a peak TB, which then declines gradually over time during the first week. Some high-risk infants, including those at risk for haemolysis, deviate from this normal pattern, with their TB levels rising and leaving their initial TB percentile risk zone in an upward trajectory. Traditionally, increased production and/or decreased elimination of bilirubin have been considered the basis for neonatal jaundice and the subsequent development of severe neonatal hyperbilirubinemia. The relative contribu- tions of these two processes to a healthy late-preterm or term newborn’s predischarge hour-specific bilirubin per- centile risk zone have been characterised in a recent study (3). Increased bilirubin production has been previously identified as a clinical risk factor for early-onset jaundice that is due to haemolysis secondary to Rh disease, ABO blood group incompatibility, cephalohematoma or bruising (4,5) as well as in infants of diabetic mothers (6). Abbreviations AAP, American Academy of Pediatrics; BW, Birthweight; CO, Carbon monoxide; COHbc, Carboxyhaemoglobin, corrected for ambient CO; ETCOc, End-tidal carbon monoxide (CO), corrected for ambient CO; G6PD, Glucose-6-phosphate dehydrogenase; GA, Gestational age; IQR, Interquartile range; POC, Point-of-care; ROR, Rate of rise; TB, Total serum/plasma bilirubin. Key Notes  This study tests the capacity of a novel, bedside end- tidal carbon monoxide (ETCO) monitor to accurately assess the risk for developing hyperbilirubinemia in neonates.  Total serum/plasma bilirubin levels adjusted to deter- minations of ETCOc (ETCO corrected for ambient CO) within six-hour tests for haemolytic hyperbilirubinemia.  Assessment of risk (or lack) of haemolytic hyperbiliru- binemia can inform practicing clinicians to appro- priately select structured strategies for optimal intervention. ©2016 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2016 105, pp. e189–e194 e189 Acta Pædiatrica ISSN 0803-5253