Prediction of Hyperbilirubinemia in Near-Term and Term Infants

Stevenson DK, Fanaroff AA, Maisels MJ, Young BW, Wong RJ, Vreman HJ, MacMahon JR, Yeung CY, Seidman DS, Gale R, Oh W, Bhutani VK, Johnson LH, Kaplan M, Hammerman C, Nakamura H. Prediction of hyperbilirubinemia in near-term and term infants. Pediatrics. 2001 Jul;108(1):31-9. PubMed PMID: 11433051.

Objective. The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life.

Methods
From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 ± 6 hours of life; STB also was measured at 96 ± 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study.

Results
A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 ± 4.37 mg/dL at 96 hours versus 7.63 ± 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 ± 6 hours for the total population was 1.48 ± 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 ± 0.47 ppm and 1.81 ± 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 ± 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB ≥95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 ± 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 ± 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV.

Conclusions
This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant’s risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 ± 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

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