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PEDIATRICS Vol. 108 No. 1 July 2001, pp. 31-39
,
,,,
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.
ABSTRACT
Top
Abstract
Methods
Results
Discussion
Conclusion
References
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.
Managed care has been associated with shortened hospital
stays for mothers and infants, thus curtailing the time for
hospital-based professional assessment of infant feeding, instruction
about breastfeeding, and the detection of jaundice.1 In
1994, the American Academy of Pediatrics (AAP) published a practice
guideline to provide pediatric practitioners with criteria for safe and
early management of hyperbilirubinemia in healthy term
neonates.2 However, compliance with the guideline often is
lacking. For example, many pediatricians do not exclude infants with
hemolysis or those <37 weeks' gestation, as suggested in the
guideline. This has led to the inappropriate early discharge of infants
with unrecognized hemolytic disease as well as near-term infants who
are having difficulty with feeding. A recent report3
reconfirmed that hyperbilirubinemia and problems related to feeding are
the main reasons for hospital readmission during the first week of life.4-7
The AAP practice guideline relies on the ability of the physician to
recognize significant jaundice as an indication for the determination
of serum total bilirubin (STB) levels. Unfortunately, there is
considerable variability in the accuracy of assessing the degree of
jaundice among observers.8,9 Furthermore, with very early
discharge, modest but unacceptable elevation of the STB might not be
recognized clinically, thus placing the infant at risk for severe
hyperbilirubinemia (STB The objective of this study was to determine whether a measurement of
ETCOc obtained at 30 ± 6 hours after birth alone or in a
combination with an STB measurement obtained at the same time could
predict the development of severe hyperbilirubinemia during the first 7 days (168 hours) of life with a high sensitivity and an acceptable
specificity for practical clinical use.
Participant Criteria
Infants were eligible for the study if their gestational age was
Study Design
This cohort study included all infants who met the eligibility
criteria and for whom informed consent was obtained and had mandatory
measurements of ETCOc and STB performed at 30 ± 6 hours of age
and STB at 96 ± 12 hours. Additional STB measurements were performed according to a flow diagram (Fig
1) and an hourly bilirubin table (Table
1) based on a racially diverse population
of 17 854 term- and near-term infants, with 15 014 neonates
contributing STB values for the period of 18 to 24 hours.10 Enrollment consisted of neonates from 9 clinical
sites, 4 domestic and 5 international. Each study site enrolled
eligible infants serially on a schedule determined by the circumstances
and restraints imposed by clinical operations and personnel limitations
at the respective institutions. Each site maintained an enrollment log
identifying all infants eligible to be studied and selected as well as
the reasons for nonenrollment of any eligible neonate. The CO-Stat
End-Tidal Breath Analyzer with single-use disposable nasal sampler was
used to analyze the breath of all infants for ETCOc.13,14
The device was calibrated locally every 30 days. The accuracy of the analyzer is ± 0.3 ppm (or µL/L) or 10% of the reading
(whichever is greater) for respiratory rates between 10 and 60 breaths/min and ± 0.3 ppm or 15% of the reading (whichever is
greater) for breathing rates >60. In a previous bedside evaluation
study of the instrument,13 the reproducibility and
coefficient of variation of ETCOc measurements when sampling neonates
and adults were determined to be better than other methods tested, such
as hand sampling and semiautomatic electrochemical detection. In
addition to ETCOc, other parameters measured by the device include
breath CO concentration (uncorrected for ambient CO), ambient CO
concentration (reflecting inhaled air), end-tidal carbon dioxide
(ETCO2), and respiratory rate. The device uses
side-stream sampling to draw nasal air continuously through the sampler
at 60 mL/min. The sampler is made of a clear polymer with an inner and
outer diameter of 0.8 and 1.5 mm, respectively. Adhesive wings (8 × 5 mm) allow a maximum insertion depth of 6.0 mm before coming into
contact with the lower edge of the nostril. Because participants are
not required to control their breathing patterns, this device can be
used with infants and others who are unable to accomplish breath
control.
TABLE 195th percentile).10 The AAP
guideline also requires that hemolysis be ruled out in infants who
exhibit significant jaundice. The measurement of carbon monoxide (CO)
in end-tidal breath corrected for ambient CO (ETCOc), an index of total
bilirubin production, can alert the physician to possible hemolysis as
well as other conditions associated with increased bilirubin production
irrespective of the timing or presence of jaundice.11-14
Moreover, the combination of hours of age-specific STB and ETCOc
measurements may provide valuable insight into the dynamics of
bilirubin production and elimination in individual infants. This
practice also may improve the early recognition of infants who are at
risk for severe hyperbilirubinemia after discharge and who may require
close follow-up and/or additional diagnostic evaluation.
METHODS
Top
Abstract
Methods
Results
Discussion
Conclusion
References
35 weeks as determined by best obstetric estimate and if enrollment
could be accomplished within the first 36 hours of life during the
period of February 20, 1998, through February 22, 1999. Exclusion
criteria were neonates having any illness that would require admission
to the neonatal intensive care unit (NICU) before 24 hours (a workup to
rule out sepsis in a neonate who appeared to be well or maternal
treatment with antibiotics were not exclusion criteria) or severe
congenital anomalies. Also excluded were infants who were in
incubators; who had pulmonary disease requiring oxygen or ventilatory
assistance via hood, tent, nasal cannula, continuous positive airway
pressure, or ventilator; who had significant nasal obstruction in
either naris; who had a birth weight of 850 g or less; or who had
respiratory rates 
10 or 100 breaths per minute (operating range for
the CO-Stat End-Tidal Breath Analyzer [Natus Medical Inc., San Carlos,
CA]).
View larger version (18K):
[in a new window]
Fig. 1.
Study protocol decision-making flow diagram.
Hours of Age-Specific Serum Total Bilirubin (STB)*
Blood was collected and the serum was analyzed for STB in each enrolled
infant (Fig 1). Each site used its own clinical laboratory and method
for all STB measurements (Hitachi 917 Spectrophotometrix Analyzer
[Roche-Diagnostics, Inc, Tokyo, Japan], Unistat Bilirubinometer [Reichert Jung, Vienna, Austria] at 2 sites, and the Hitachi 747 (Roche-Diagnostics, Inc] at all other sites).15 Infants were defined as hyperbilirubinemic if their hours of age-specific STB
at any time during the study was 95th percentile, as defined by Table
1. In addition, during the first 24 hours, the attending physician had
the option of measuring the STB for an infant who exhibited visible
jaundice. For infants whose STB was 95th percentile, an ETCOc
measurement was performed and the infant was excluded from further
study. Infants who were not excluded before 24 hours had the first
scheduled STB and ETCOc measurements performed at 30 ± 6 hours in
coordination with state-mandated newborn screening for inborn errors of
metabolism and additional required tests. Infants with STB 95th
percentile exited the study at this time. All other infants remained in
the study. From 24 to 84 hours, measurements of STB were performed at
the discretion of the physician. If the physician elected to perform an
STB between 24 and 84 hours, then the infant exited the study if the
level was 95th percentile. If the STB was not 95th percentile or if no STB was obtained between 24 and 84 hours, then the infant had a
mandatory STB performed at 96 ± 12 hours. If the STB was 95th percentile or <40th percentile, then the infant exited the study. Any
STB between the 40th and the 94th percentiles required a repeat STB in
24 to 48 hours based on the result. If the 96 ± 12 hour measurement was 75th percentile and <95th percentile, then the STB
was repeated within 24 hours. If the 96 ± 12 hour measurement was
>40th percentile and <75th percentile, then the STB was repeated within 48 hours. An infant who had an STB between the 40th and the 94th
percentiles continued to have STB measured every 24 to 48 hours until
the STB was 95th percentile or <40th percentile, the most recent STB
was less than or equal to the STB result 24 to 48 hours earlier, or the
infant attained 168 hours of life. At 168 hours, all infants exited the
study with ongoing care provided at the discretion of the physician.
Statistical Methods
Of the 1895 participants who were enrolled in the study, 1370 completed the study. Of the excluded infants, 88 were enrolled in the study but did not participate in the testing, 272 were lost to follow-up, 131 had technical problems with preproduction samplers, 32 could not be tested with the CO-Stat device for other reasons (eg, hydrogen interference, irregular breath patterns), and 175 did not adhere to the study protocol. In addition, another 131 infants were tested at a tenth site but were excluded from analysis because measurements of STB were taken with a transcutaneous bilirubinometer rather than performed with the standard blood test. Some infants were excluded for multiple reasons.
The study was conducted in 2 phases. In phase I, 577 infants were tested with a preproduction CO-Stat nasal sampler; in phase II, 793 infants were tested with the production sampler. The ETCOc results from phase I showed a higher mean ± standard deviation (SD) than those values from phase II (1.70 ± 0.54 vs 4.48 ± 0.49 ppm, respectively). This was attributable to a slight outgassing of CO from a material used in the preproduction sampler. The ETCOc data from the 2 phases of the study were combined and normalized by converting the measurements to Z scores (ie, standardized deviation of the measurement from the mean, in SD units). All analyses were conducted in Z units, and the ETCOc values reported throughout this article have been converted back to ppm with the distribution having the mean and SD of phase II.
Receiver operator characteristic (ROC) analyses16-18 for
the prediction of hyperbilirubinemia were performed for 3 different
parameters of predicting hyperbilirubinemia: ETCOc at 30 ± 6 hours, STB percentile (as defined by the table) at 30 ± 6 hours,
and a combination of STB and ETCOc test at 30 ± 6 hours. A
positive result for the combined test was defined as either an STB
between the 75th and 95th percentile or an ETCOc greater than the
population mean or both at 30 ± 6 hours. Infants who presented
with STB 95th percentile at 30 ± 6 hours were excluded from the
STB and combined ROC analyses because they had been found to be
hyperbilirubinemic at the predicting measurement. These infants were
not excluded from the ETCOc ROC analysis, because the predicting and
outcome measurements were different although they occurred in the same
time window.
Two stepwise logistic regression analysis models for the prediction of hyperbilirubinemia (as defined above) were performed on the data: 1 for noninvasive (ie, ETCOc) measurements and 1 for invasive measurements (ie, STB). The following variables were used in the noninvasive model: ETCOc at 30 ± 6 hours, presence of bruising, feeding type (breast milk, formula, or both), birth weight, race (Asian, white or Hispanic, black, other), maternal diabetes, type of labor (vaginal or cesarean section), gender, infection, cephalhematoma, pregnancy-induced hypertension/preeclampsia, gravidity, parity, maternal blood type, and maternal Rh status.
At each step in building the first model, the variable that reduced the total squared error was added first. Two stopping rules were used: 1) the addition of the next variable reduced the overall squared error by <1%, and 2) the probability of hyperbilirubinemia was not statistically different for the candidate variable to be added to the model.
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RESULTS |
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Abstract
Methods
Results
Discussion
Conclusion
References
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The distributions of STB for the total population at 30 ± 6 hours and at 96 ± 12 hours show that approximately 9% (120 of 1370) of infants had an STB 95th percentile. Four of 620 (0.65%, with a 95% confidence interval of 0.02% to 1.30%) infants had an STB
<40th percentile at 30 ± 6 hours but subsequently had an STB
>95th percentile. Infants who were breastfed had higher mean STB
levels at 96 hours (8.92 ± 4.37 mg/dL) compared with those who
were fed formula exclusively (7.63 ± 3.58 mg/dL;
P < .0001).
The distribution of ETCOc at 30 ± 6 hours is shown in Fig
2. The mean ETCOc for the total
population (N = 1370) was 1.48 ± 0.49 ppm (range:
0.2-3.5; median: 1.5) at 30 ± 6 hours of life (Table
2). The mean ETCOc for the
nonhyperbilirubinemic infants (N = 1250) was 1.45 ± 0.47 ppm (range: 0.1-3.1; median: 1.4) compared with 1.81 ± 0.59 ppm (range: 0.4-3.6; median: 1.9) for the hyperbilirubinemic
infants (N = 120; P < .0001).
Ninety-two (76%) of 120 hyperbilirubinemic participants had an ETCOc
greater than the total population mean. Center variabilities of the
mean ETCOc at 30 ± 6 hours of each site's total population and
of infants with STB 95th percentile are shown in Table
3.
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Logistic regressions show that the following variables were found to be significant for the first stopping rule (in order of addition): ETCOc, feeding type, birth weight, race, parity, maternal diabetes, maternal blood type, and bruising. The second, more conservative, stopping rule found (in order of addition) ETCOc, feeding type, and birth weight to be the most significant variables.
The second logistic regression analysis model included the above variables as inputs as well as the STB percentiles at the 30 ± 6 hour measurement as defined by Table 1. For this analysis, the following variables were found to be significant (in order of addition): STB percentile, bruising, maternal blood type, race, maternal diabetes, feeding type, gravidity, and ETCOc. The more conservative stopping rule found that only STB percentile and bruising were significant.
ROC curves are shown in Fig 3. For the 3 parameters of predicting hyperbilirubinemia at a specificity of 80%
(1 
specificity = 20%), the sensitivity at 30 ± 6 hours ranges from approximately 50% (ETCOc alone) to approximately
65% (with 30 ± 6 hour STB). For 50% specificity, the
sensitivities increase to 75% and 90%. Positive and
negative predictive values (PPV and NPV, respectively) were calculated.
ETCOc greater than the mean at 30 ± 6 hours yielded a 13.0% PPV
with a 95.8% NPV (Table 4). STB >75th
percentile at 30 ± 6 hours resulted in a 16.7% PPV with a 98.1%
NPV when infants with STB >95th percentile at <36 hours of age were
excluded. The combination of the 2 measurements if either ETCOc was
more than the mean or STB >75th percentile yielded a 6.4% PPV with a
99.0% NPV as a result of the low prevalence of hyperbilirubinemia in
the study population. With these levels of sensitivity and specificity,
the PPV and NPV of early (30 ± 6 hours) measurements of ETCOc or
ETCOc in combination with STB for reliable prediction of
hyperbilirubinemia are not achievable.
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DISCUSSION |
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Top
Abstract
Methods
Results
Discussion
Conclusion
References
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Neonatal jaundice is a syndrome with many causes but, ultimately,
is the result of an imbalance between bilirubin production and
elimination. On the basis of a nomogram for hours of age-specific STB
levels,10 120 (8.8%) of 1370 infants had an STB 95th
percentile between 24 and 36 hours and 168 hours of life. Total
bilirubin formation, as indexed by ETCOc, was 24.7% higher in the
hyperbilirubinemic infants with the majority (76%) of these infants
having an ETCOc greater than the mean of the whole population. However,
it is important to note that some infants with very low bilirubin
production still become hyperbilirubinemic. This strongly suggests that
the elimination of bilirubin is sufficiently impaired to cause
significant jaundice in approximately one quarter of the infants who
develop hyperbilirubinemia. Conversely, many infants with high
bilirubin production rates do not develop significant jaundice because
they can deal with this increased load. Thus, given the low prevalence
of severe hyperbilirubinemia, it was unlikely that either an hours of
age-specific STB or ETCOc, alone or in combination, would have a high
PPV, which is what was observed in this study. Nonetheless, the
combination of STB and ETCOc measurements provides insight into the
underlying processes that give rise to hyperbilirubinemia but does not
materially improve the predictive ability of an hours of
age-specific STB in this study population. For instance, if
both STB and ETCOc measurements fall below a set threshold, the least
worrisome circumstance could be assumed. Thus, the absence of both an
elevated hours of age-specific STB and elevated ETCOc, which has a high
NPV, would support the clinical decision to limit laboratory testing
and to shorten the hospital stay for such low-risk infants.
On the basis of a review of the ROC curves, a clinician might be tempted to rely on STB alone for the prediction of hyperbilirubinemia. Practically, this decision would not be unreasonable because increased bilirubin production, as indexed by ETCOc, is a major component of most hyperbilirubinemia as indicated by the proportion of infants (76%) with increased bilirubin production in the hyperbilirubinemic group. However, an ETCOc measurement in combination with the STB identifies precisely those infants who are most likely to have hemolysis versus those with conjugation incapacities, such as Gilbert's disease19-21 or the G71R missense mutation in the bilirubin glucuronosyltransferase gene.22 The added benefit of diagnosing hemolysis by measurement of the ETCOc ensures compliance with the AAP guideline that requires identification of infants with increased hemolysis.2 In addition, the possibility of diagnosing conjugation defects becomes more likely among infants with a high STB and a normal or low ETCOc. Moreover, improved diagnostic differentiation of jaundiced infants might direct specific therapeutic interventions as new treatment options become available, for example, metalloporphyrin therapy for high producers of the pigment23-26 or gene therapy for conjugation defects.27 In the meantime, high-risk infants could be targeted for close follow-up to avoid unexpected significant hyperbilirubinemia and readmission to the hospital.
In fact, logistic regression models can be used to predict later
significant elevation in STB. Without using STB at 30 ± 6 hours
as a predictor, the variables that are most significant are (in order
of addition) ETCOc, feeding type, birth weight, race, parity, maternal
diabetes, maternal blood type, and bruising. A simplified model,
generated by using a rule to stop adding variables when the category of
the variable was not significantly different with regard to the
probability of hyperbilirubinemia, includes 3 variables: ETCOc, feeding
type, and birth weight. Thus, increased bilirubin production, exclusive
breastfeeding, and birth weight (a likely surrogate for gestational age
in this study, which included infants with gestational ages 35
weeks) represent useful predictors for whether a particular infant
develops hyperbilirubinemia. The STB percentile at 30 ± 6 hours,
together with the presence of bruising (a surrogate for increased
bilirubin production), provides a simplified prediction model, somewhat
superior to ETCOc and the other variables available.
The common practice of using Coombs' testing as a surrogate for the
identification of hemolysis is not a reliable strategy. In this study,
only 18.5% (10 of 54) of infants with a positive direct Coombs' test
had an STB 95th percentile and mean ETCOc values of 1.89 ± 0.63 ppm (P < .00932 when compared with the population mean), suggesting that most infants with a positive direct Coombs' test either can handle the bilirubin load well or do not have hemolysis. Conversely, 54 (10.4%) of 519 infants who had STB 95th percentile and a mean ETCOc value of 1.89 ± 0.55 ppm had a
negative direct Coombs' test, consistent with the possibility that
some infants with a negative direct Coombs' test may have hemolysis. Although not all infants (only 573 of 1370, or 41.8%) had a Coombs' test performed during the course of this study, these observations suggest that an ETCOc measurement might represent a more direct way to
identify noninvasively infants who do not need Coombs' testing or
other laboratory tests before discharge and routine follow-up.
In addition, the guidelines for management of hyperbilirubinemia may
need to vary between centers, as the percentage of infants with STB
95th percentile as based on a US population varied from 5% to 39%
among centers (Table 3). The propensity for jaundice in a particular
population was variably related to increased ETCOc, suggesting that
defects in conjugation or persistent enterohepatic circulation of
bilirubin play important causative roles among infants in certain
settings. The marked increased percentage of infants with STB 95th
percentile in Kobe, Japan, is consistent with the high proportion of
infants with defective glucuronosyltransferase in this
population.22 It also is interesting to note that the
Chinese population in this study had a lower incidence of
hyperbilirubinemia than previously reported,28-30 which
suggests that there may have been changes in environmental factors.
There also was a high incidence observed in the Jewish population and
may be due to the small sample size of this group. Furthermore, it is
interesting to note that in our total population, 4 (0.65%) of 620 infants had an STB <40th percentile at 30 ± 6 hours but
nevertheless subsequently developed an STB 95th percentile. In
addition, the differences in the percentage of infants with STB 95th
percentile observed at each center also may be confounded by the known
interlaboratory variability in STB measurements.13 This
fact alone warrants the use of other measurement parameters, in concert
or alone, to provide additional information for the identification and
follow-up of infants who are at risk for hyperbilirubinemia.
Breastfeeding was associated with a slight increase in the STB, and, as indicated by the ETCOc, there was increased bilirubin production associated with breastfeeding. Although increased production was not observed previously in smaller studies,11,31 relative caloric deprivation associated with the initiation of exclusive breastfeeding perhaps could explain this phenomenon.32 More important, the possibility that increased bilirubin production compounds the effect of an increased enterohepatic circulation in exclusively breastfed infants supports further the clinical observation that breastfed-only infants have a propensity for higher STB levels after birth and suggests that the definition of physiologic jaundice should be reconsidered in this context. Furthermore, in addition to identifying infants with hemolysis or other causes of increased bilirubin production, the need to observe closely and evaluate the adequacy of breastfeeding before discharge might reduce both morbidity and the frequency of readmission to the hospital.33 We also confirmed that hemolysis and bruising, as expected, increased bilirubin production and the propensity for jaundice.
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CONCLUSION |
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Top
Abstract
Methods
Results
Discussion
Conclusion
References
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This prospective cohort study supports previous observations that the practice of measuring STB before discharge may provide some assistance in predicting infants who are at risk for the subsequent development of hyperbilirubinemia.10,34,35 However, this measurement together with an ETCOc provides insight into the processes that contribute to the condition. The combination of STB and ETCOc measurements as early as 30 ± 6 hours of life will increase the chance of identifying an infant with hemolysis or other causes of increased bilirubin production as well as infants with conjugation defects. Such combination screening could identify infants who might need early intervention with phototherapy or additional diagnostic workup and/or follow-up for jaundice after discharge. It is important to recognize that infants with increased bilirubin production, who may handle the bilirubin load well, also may have other clinical problems that require diagnosis and follow-up, such as late anemia in the presence of hemolysis. Finally, differences in the incidence of hyperbilirubinemia and its causes may vary from one center to another. Although the screening procedures might be similar across institutions, the criteria used for decision making may need to vary depending on the prevalence and unique characteristics of the particular population and practice patterns.
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ACKNOWLEDGMENTS |
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This study was supported by a grant from Natus Medical, Inc (San Carlos, CA) and the H. M. Lui Research Fund.
We thank Ann Olthof, RN, and Petra A. Swidler, MD (Lucile Salter Packard Children's Hospital), Sue Bergant, RN (Rainbow Babies' and Children's Hospital), Elizabeth Kring, RN (William Beaumont Hospital), Dr. Ka-Yin Wong (Queen Mary and Tsan Yuk Maternity Hospitals), Angelita Hensman, RN (Women and Infants Hospital), and Christine Dalin, RN (Pennsylvania Hospital). Advice on protocol decision and statistical analysis from Professor B. W. Brown is gratefully acknowledged.
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FOOTNOTES |
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Drs Stevenson, Vreman, and Fanaroff are consultants to Natus Medical, Inc.
Received for publication Jun 19, 2000; accepted Nov 13, 2000.
Reprint requests to (D.K.S.) Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208.
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ABBREVIATIONS |
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AAP, American Academy of Pediatrics; STB, serum total bilirubin; CO, carbon monoxide; ETCOc, end-tidal carbon monoxide corrected for ambient CO; NICU, neonatal intensive care unit; ETCO2, end-tidal carbon dioxide; SD, standard deviation; ROC, receiver operator characteristic; PPV, positive predictive value; NPV, negative predictive value.
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REFERENCES |
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Methods
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Discussion
Conclusion
References
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This article has been cited by other articles:
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  H. Ozkan, H. Oren, M. Tatli, H. Ates, A. Kumral, and N. Duman Erythroid Apoptosis in Idiopathic Neonatal Jaundice Pediatrics, May 1, 2008; 121(5): e1348 - e1351. [Abstract] [Full Text] [PDF]
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R. Keren, X. Luan, S. Friedman, S. Saddlemire, A. Cnaan, and V. K. Bhutani A Comparison of Alternative Risk-Assessment Strategies for Predicting Significant Neonatal Hyperbilirubinemia in Term and Near-Term Infants Pediatrics, January 1, 2008; 121(1): e170 - e179. [Abstract] [Full Text] [PDF]
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M. J. Maisels and E. Kring Transcutaneous Bilirubin Levels in the First 96 Hours in a Normal Newborn Population of >=35 Weeks' Gestation Pediatrics, April 1, 2006; 117(4): 1169 - 1173. [Abstract] [Full Text] [PDF]
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J. C. Martinez Argentinean Perspective of the 2004 AAP Hyperbilirubinemia Guidelines NeoReviews, January 1, 2006; 7(1): e4 - e6. [Full Text] [PDF]
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 R Keren, V K Bhutani, X Luan, S Nihtianova, A Cnaan, and J S Schwartz Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches Arch. Dis. Child., April 1, 2005; 90(4): 415 - 421. [Abstract] [Full Text] [PDF]
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 T. B. Newman, P. Liljestrand, and G. J. Escobar Combining Clinical Risk Factors With Serum Bilirubin Levels to Predict Hyperbilirubinemia in Newborns Arch Pediatr Adolesc Med, February 1, 2005; 159(2): 113 - 119. [Abstract] [Full Text] [PDF]
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 C M Harrison and C C Andersen Exhaled breath measures of inflammation: are they useful in neonatal chronic lung disease? Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2005; 90(1): F6 - F10. [Abstract] [Full Text] [PDF]
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M. J. Maisels Conflict of Interest and Purpose in Bilirubin Screening: In Reply Pediatrics, October 1, 2004; 114(4): 1133 - 1134. [Full Text] [PDF]
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M. Kaplan, M. Herschel, C. Hammerman, J. D. Hoyer, and D. K. Stevenson Hyperbilirubinemia Among African American, Glucose-6-Phosphate Dehydrogenase-Deficient Neonates Pediatrics, August 1, 2004; 114(2): e213 - e219. [Abstract] [Full Text] [PDF]
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Subcommittee on Hyperbilirubinemia Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation Pediatrics, July 1, 2004; 114(1): 297 - 316. [Abstract] [Full Text] [PDF]
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S. Ip, M. Chung, J. Kulig, R. O'Brien, R. Sege, S. Glicken, M. J. Maisels, J. Lau, and Subcommittee on Hyperbilirubinemia An Evidence-Based Review of Important Issues Concerning Neonatal Hyperbilirubinemia Pediatrics, July 1, 2004; 114(1): e130 - e153. [Abstract] [Full Text] [PDF]
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S. U. Sarici, M. A. Serdar, A. Korkmaz, G. Erdem, O. Oran, G. Tekinalp, M. Yurdakok, and S. Yigit Incidence, Course, and Prediction of Hyperbilirubinemia in Near-Term and Term Newborns Pediatrics, April 1, 2004; 113(4): 775 - 780. [Abstract] [Full Text] [PDF]
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 V. K. Bhutani and L. H. Johnson Urgent Clinical Need for Accurate and Precise Bilirubin Measurements in the United States to Prevent Kernicterus Clin. Chem., March 1, 2004; 50(3): 477 - 480. [Full Text] [PDF]
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S.-C. Chou, R. H. Palmer, S. Ezhuthachan, C. Newman, B. Pradell-Boyd, M. J. Maisels, and M. A. Testa Management of Hyperbilirubinemia in Newborns: Measuring Performance by Using a Benchmarking Model Pediatrics, December 1, 2003; 112(6): 1264 - 1273. [Abstract] [Full Text] [PDF]
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M. C. Javier, A. Krauss, and M. Nesin Corrected End-Tidal Carbon Monoxide Closely Correlates With the Corrected Reticulocyte Count in Coombs' Test-Positive Term Neonates Pediatrics, Decemb |
),
STB measurements alone at 30 ± 6 hours (
), and combined ETCOc
and STB measurements at 30 ± 6 hours (
) at a specificity of
80%. Dotted diagonal line = no discrimination.