PEDIATRICS Vol. 108 No. 1 July 2001, pp. 31-39
Received Jun 19, 2000; accepted Nov 13, 2000.
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From the * Department of Pediatrics, Lucile Salter Packard
Children's Hospital, Stanford, California; 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 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.
Department of
Neonatology, Rainbow Babies' and Children's Hospital, Cleveland,
Ohio; § Department of Pediatrics, William Beaumont Hospital, Royal Oak,
Michigan;
Department of Paediatrics, Pamela Youde Nethersole Eastern
Hospital, Hong Kong, China; ¶ Department of Paediatrics, Queen Mary
Hospital/Tsan Yuk Maternity Hospital, Hong Kong, China; # Departments of
Neonatology and Obstetrics and Gynecology, Bikur Cholim Hospital,
Jerusalem, Israel; ** Department of Pediatrics, Women and Infants
Hospital, Providence, Rhode Island, 
Department of Pediatrics,
Pennsylvania Hospital, Philadelphia, Pennsylvania; §§ Department of
Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel; and
|| Department of Pediatrics, University of Kobe, Kobe, Japan.
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.
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