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Evaluation of Early Transcutaneous Bilirubinometry to Predict Subsequent Hyperbilirubinemia in Neonates Admitted to a Well-Baby Nursery
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Gregory L. Jackson, MD, MBA Meghan Saumur, BA Vinita Chandwani, BA William D. Engle, MD
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Gregory L. Jackson, MD, MBA, Department of Pediatrics, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063
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Original Article
1
Evaluation of Early Transcutaneous Bilirubinometry to Predict Subsequent Hyperbilirubinemia in Neonates Admitted to a Well-Baby Nursery Gregory L. Jackson, MD, MBA1
Meghan Saumur, BA2,
1 Department of Pediatrics, The University of Texas Southwestern
Q1
Medical Center, Dallas, Texas 2 TheQ1 University of Texas Southwestern Medical Center, Dallas, Texas,
Supported in part by the UT Southwestern Summer Medical Student Research Program.
Vinita Chandwani, BA2,
William D. Engle, MD1
Address for correspondence Gregory L. Jackson, MD, MBA, Department of Pediatrics, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063 (e-mail:
[email protected]). Q2
Am J Perinatol 2015;00:1–8.
Abstract Q3
Keywords
► jaundice ► neonate ► transcutaneous bilirubinometry ► hyperbilirubinemia
Q4
Objective The aim of this study is to determine whether a transcutaneous bilirubinometry (TcB) Q3value obtained within 6 hours of birth (early transcutaneous bilirubinometry [ETcB]) either alone, or used to calculate an early rate of rise (E-ROR) in TcB, will identify those neonates who are at a higher risk for subsequent jaundice. Study Design ETcB values were obtained from a convenience sample of neonates admitted to the newborn nursery. E-ROR was calculated as the average hourly increase between ETcB and subsequent TcB obtained at 18 to 36 hours of age. TcB percentile values at various ages were obtained from a previously published and cross-validated nomogram. The predictive values relating ETcB, E-ROR, and TcB at 18 to 36 hours of age to TcB at 42 to 66 hours of age were determined, and receiver-operator characteristic curves were compared. Results A total of 516 late preterm and term neonates were studied. ETcB was higher (p ¼ 0.003) in those neonates who subsequently received phototherapy (n ¼ 15), and negative predictive value was always 0.96; positive predictive value (PPV) ranged from 0.04 to 0.06. Compared with ETcB, TcB at 18 to 36 hours was more likely to predict significant jaundice at 42 to 66 hours of age. Conclusion Given the observed low PPV, ETcB is not useful in identifying infants who develop subsequent hyperbilirubinemia. However, it may be helpful in identifying those neonates at a low risk of subsequent hyperbilirubinemia.
ClinicalQ4 Perspective • Transcutaneous bilirubinometry is utilized frequently in newborn nurseries and birthing centers since it is easy to use, noninvasive, and results are available immediately. • An early ( 6 hours of age) transcutaneous bilirubinometry (ETcB) may be helpful in identifying those late preterm and
received March 25, 2014 accepted after revision December 12, 2014
term neonates who are at a low risk of subsequent hyperbilirubinemia. Neonatal bilirubin levels typically peak after hospital discharge,1 and there is great interest in the development of strategies to predict which neonates are at a risk of subsequent elevated values.2 Transcutaneous bilirubin (TcB)
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0035-1544190. ISSN 0735-1631.
Q2
2
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Jackson et al.
determinations are performed using a handheld device that sends light to and receives light from the skin3 and, using proprietary algorithms, the device provides an estimate of serum bilirubin (TSB). TcB is well established for monitoring neonatal bilirubin levels noninvasively,4 and TcB values have been shown to predict subsequent hyperbilirubinemia,2,5,6 particularly when combined with other risk factors.7 It is unclear when the initial screening TcB should be performed, and it is not known whether a determination obtained soon after birth has predictive value. Calculation of rate of rise (ROR) in TSB was initiated primarily to assist in the management of neonates with hemolytic disease of the newborn (typically due to Rhisoimmunization). Subsequently, ROR has been used in neonates without apparent hemolysis as a method to assess a worrisome increase in TSB levels.8 In theory, utilizing TcB values to calculate a ROR might be helpful, but data describing the clinical use of ROR in this setting are limited. De Luca et al9 performed a formal systematic review of data used to develop four TcB nomograms10–13; they found that the value for ROR needed to cross nomogram percentile lines (“exaggerated ROR”) varied among the studies, and also that ROR decreased with increasing postnatal age. The earliest time period analyzed in this study was 12 to 24 hours. We recently modified our TcB screening protocol to include a value within the first 6 hours of life (“early TcB,” ETcB). The purpose of this study is to determine whether the ETcB value, and/or early ROR (E-ROR; calculated using ETcB and a subsequent TcB value), will assist in distinguishing between those neonates who are at a higher risk for subsequent hyperbilirubinemia with or without treatment with phototherapy (PHT) and those neonates who are not at an increased risk for these outcomes.
Materials and Methods Neonates were eligible for this study if they were admitted to the Newborn Nursery (NBN) at Parkland Memorial Hospital. Criteria for admission to the NBN are (1) birth weight 2,100 g, (2) gestational age 35 weeks, and (3) stable cardiorespiratory status and no major abnormalities noted in the delivery room. This study utilized a convenience sample of neonates cared for in NBN during the period June 2011 through May 2012. At the Parkland Memorial Hospital NBN, daily TcB screening has been performed on all newborns utilizing the Dräger JM-103 (Dräger Medical Systems, Inc., Telford, PA) since April 2009; the patient care protocol dictated that the initial TcB determination would be made within the first 24 hours after birth. Beginning in April 2011, an additional TcB determination was obtained within 6 hours after birth on all newborns. During the study period, TSB and direct antiglobulin test determinations were not routinely performed in the NBN, but were typically ordered when TcB values were of concern and/or a neonate appeared to have significant jaundice, especially those who underwent PHT. All ETcB and subsequent daily TcB determinations were made utilizing the JM-103, and quality assurance testing was American Journal of Perinatology
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performed daily on each device. A single reading was made over the infant’s mid-sternum by a nurse or pediatric nurse practitioner, and the date and time of determination and result were recorded in the electronic medical record (EMR). Study data subsequently collected from the EMR included demographic information, ETcB value, subsequent TcB values, TSB values (if obtained for clinical reasons), and whether or not treatment with PHT, utilizing American Academy of Pediatrics (AAP) guidelines, was begun during the birth hospitalization or during hospital readmission.14 The NBN has a follow-up clinic for selected neonates whose providers have concerns about jaundice at the time of discharge. These neonates are typically seen the day after discharge, and they can be readmitted (usually to the adjacent Children’s Medical Center at Dallas) if PHT is required. Neonates not seen in our clinic may have chosen other facilities for follow-up, and are not included in this analysis. A previously published and subsequently validated agespecific nomogram11,15 that was developed in our predominately Hispanic nursery population was used to identify hyperbilirubinemia, defined as having TcB values > 95th percentiles. E-ROR (expressed as mg/dL per hour) was calculated as a subsequent TcB performed between 18 and 36 hours minus ETcB, divided by the number of hours elapsed between the values. Infants later treated with PHT could be included in this analysis if the appropriate TcB values were available. The relationship between demographic variables and ETcB was determined, and correlations between ETcB and TcB at 24 (range, 20–28 hours), 36 (32–40 hours), and 48 (44–52 hours) hours of age were calculated. ETcB, TcB at 18 to 36 hours, and E-ROR were compared in neonates who did or did not receive subsequent treatment with PHT.14 Predictive indices and receiver-operator characteristic (ROC) curves relating ETcB to subsequent TcB between 18 and 36 hours of age, and ETcB, E-ROR, and TcB at 18 to 36 hours of age to subsequent TcB values between 42 and 66 hours postnatally were determined using various cut-off values in all neonates in whom the appropriate data were available. In addition, predictive indices and ROC curve were determined for ETcB with the outcome of PHT. VassarStats (www.vassarstats.net) was used to calculate and compare ROC values. Chi square, Fisher exact test, Mann–Whitney, and t-tests were used as appropriate, and a p value of < 0.05 was considered significant. The University of Texas Southwestern Medical Center Institutional Review Board approved this study, and informed consent was not required.
Results Characteristics of the study population are shown in ►Table 1. For all study neonates, ETcB (mean standard deviation [SD]) was 1.1 1.0 mg/dL (median 0.9 mg/dL, range 0–5.7 mg/dL), and median postnatal age at the time of ETcB determination was 3.8 hours (range 1.1–6.0 hours, 10–90th percentiles 2.9–5.4 hours; the correlation between ETcB and postnatal age was r ¼ 0.06 [p ¼ 0.15]). Correlations between ETcB and subsequent TcB values at 24 (n ¼ 161), 36 (n ¼ 173), and 48 hours (n ¼ 141) were r ¼ 0.31, 0.40, and
Early Transcutaneous Bilirubinometry
Jackson et al.
Table 1 Study population Number Birth weight (g) (range)
a
516 a
3,401 468 (2,275–4,940)
Gestational age (wks) (range)
39.0 1.4b (35–42)
Gender (% male)
53
Hispanic (%)
83
Oxytocin in labor, %
46
Route of delivery, % vaginal
71
Apgar, 1 min (median, range)
8 (1, 9)
Apgar, 5 min (median, range)
9 (7, 10)
Feedings, predominantly breastfed, %
78
Mean standard deviation. Fourteen studied neonates were late preterm (35.8 0.4 wks).
b
0.32, respectively (all p values < 0.001); correlation between ETcB and umbilical cord blood pH was r ¼ 0.06 (p ¼ 0.17). No relationship was observed between ETcB and gestational age (r ¼ 0.05, p ¼ 0.22). There was no relationship between ETcB and route of delivery (p ¼ 0.13) or gender (p ¼ 0.07), and ETcB did not differ in those neonates predominantly breastfed versus those not predominantly breastfed (p ¼ 0.30). For those 15 neonates (3% of the total sample) who received PHT, data for blood type were available on 12 mother–baby pairs: of those, 7 had maternal blood type of O and an infant whose blood type was either A or B; the direct antiglobulin test was positive in 3 of these neonates. The median age of initiation of PHT was 41 hours (mean: 54.6 46.0 hours, range: 4.5–164.5 hours). Six of the 15 neonates were < 36 hours of age when PHT was initiated and, of those 6, 2 were < 12 hours of age. When comparing those neonates who received PHT versus those who did not, no differences were observed in route of delivery (p ¼ 0.38), gender (p ¼ 0.13), or type of feeding (p ¼ 1.0). There was an inverse relationship between ETcB and age of initiation of PHT (r ¼ 0.59, p ¼ 0.02). As shown in ►Table 2, ETcB was significantly lower in those neonates who subsequently did not receive PHT (mean SD 1.0 0.9 mg/dL) versus those who were later treated with PHT (2.2 1.7 mg/dL; p ¼ 0.003). Also, shown in ►Table 2 are TcB results for non-PHT versus PHT neonates at 18 to 36 hours and E-ROR results for the 373 neonates in whom it could be calculated. In each instance, TcB was higher in those infants who subsequently received PHT. Predictive indices for ETcB for the outcome of PHT are shown in ►Table 3. Negative predictive value (NPV) was at least 0.96 at each ETcB cut-off value. Of note, in the 127 infants with ETcB < 0.3 mg/dL (24.4% of the study population), none received PHT. The ROC curve relating ETcB to subsequent PHT is shown in ►Fig. 1. There was no significant relationship between E-ROR and gender (p ¼ 0.37) or gestational age (r ¼ 0.01, p ¼ 0.84).
Conversely, E-ROR was significantly higher in those neonates who were predominantly breastfed versus those who were not predominantly breastfed (mean SD 0.19 0.01 vs. 0.16 0.02, respectively; p ¼ 0.0007). ►Table 4 demonstrates predictive indices for ETcB with the outcomes of TcB > 95th percentile (using the previously referenced nomogram) at 18 to 36 hours of age and at 42 to 66 hours of age. Also, shown in ►Table 4 are predictive indices for E-ROR and TcB at 18 to 36 hours of age with the outcome of TcB at 42 to 66 hours of age. Values for sensitivity, specificity, and positive predictive values (PPV) in general were lower than those for NPV; ►Fig. 2 displays the ROC curve for ETcB and TcB at 42 to 66 hours of age. ►Fig. 3 provides the ROC curve relating TcB at 18 to 36 hours to subsequent TcB > 95th percentile at 42 to 66 hours of age, and ►Fig. 4 shows the ROC curve relating E-ROR to subsequent TcB > 95th percentile at 42 to 66 hours of age. Area under the curve values and comparisons among them are summarized in ►Table 5. Significant differences existed in those neonates whose TcB at 42 to 66 hours was > 95th percentile (compared with those with a value 95th percentile) in the following characteristics: breastfeeding predominance (p ¼ 0.02), lower gestational age (p ¼ 0.048), and lower birth weight (p ¼ 0.004). There were no significant differences for gender (p ¼ 0.41) or mode of delivery (0.84). TcB was > 95th percentile at 42 to 66 hours of age in 31% of those with E-ROR 0.25 mg/dL per hour (vs. 5.5% with E-ROR < 0.25 mg/dL per hour; p < 0.00003). There was a significant correlation between E-ROR and subsequent TcB at 42 to 66 hours of age (r ¼ 0.54, p < 0.0001). Of those neonates who subsequently were treated with PHT, when E-ROR could be calculated (n ¼ 8), the E-ROR was 0.30 mg/dL per hour in five (63%).
Discussion Primarily because of relatively short postbirth hospitalization periods, there is great interest in developing ways to predict, American Journal of Perinatology
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Jackson et al.
Table 2 Summary data for ETcB and subsequent TcB values used to determine E-ROR and predictive indices in those neonates who did not or did receive treatment with phototherapy p
No phototherapy
Phototherapy
n
501
15
ETcB (mg/dL)
1.0 0.9 0.9 (0–4.8)
2.2 1.7 1.6 (0.3–5.7)
0.003
Age (h)
3.9 0.8 3.9 (1.1–6.0)
3.7 0.5 3.5 (3.1–4.7)
0.34
n
365
8a
TcB (mg/dL)
5.1 1.9 5.2 (0–13.6)
7.8 2.8 7.7 (3.0–12.3)
0.0001
Age (h)
26.8 5.4 27.0 (18.0–36.0)
27.4 4.5 27.1 (21.5–34.8)
0.76
n
365
8a
E-ROR (mg/dL per hour)
0.18 0.07 0.18 (0.03–0.42)
0.27 0.13 0.30 (0.07–0.44)
ETcB
TcB at 18–36 h
Rate of rise (mg/dL per hour) 0.0005
AbbreviationsQ7: E-ROR, early rate of rise; ETcB, early transcutaneous bilirubinometry; SD, standard deviation; TcB, transcutaneous bilirubinometry. Note: Data are expressed as mean SD and median (range). a Numbers are smaller than the initial n ¼ 15, since the TcB device was not utilized after phototherapy was initiated.
before discharge, which neonates are at the highest risk for subsequent hyperbilirubinemia.7 This effort was greatly advanced by the development of a TSB-based nomogram16 that emphasized the critical relationship between bilirubin and age in hours (not days). Following the use of TcB to monitor bilirubin levels, several nomograms in various populations10–13,17–23 have been published, and the use of TcB to screen for hyperbilirubinemia is well established. It appears that the combination of hyperbilirubinemia risk factors and predischarge TcB has greater value in predicting subsequent hyperbilirubinemia than either variable alone.7,24 The purpose of this study was to determine if an “early” TcB assessment (within the first 6 hours postnatally) had any predictive value related to subsequent hyperbilirubinemia
with or without the use of PHT. The AUC for the ability of ETcB to predict to subsequent TcB > 95th percentile at 42 to 66 hours of age (0.62) was significantly lower than the AUC for EROR (0.79) or TcB at 18 to 36 hours of age (0.86). This is not surprising since both of the latter calculations incorporate TcB values obtained closer to the end point (TcB at 42–66 hours of age) than use of ETcB alone. It appears that the primary use of an ETcB might be to help identify neonates at a relatively low risk of subsequent hyperbilirubinemia. In addition, determination of ETcB allows calculation of a ROR beginning soon after birth. Fouzas et al19 studied late preterm neonates and assessed ROR and subsequent need for PHT. Similar to the current study of primarily term (97.3%) neonates, these investigators
Table 3 Predictive indices for ETcB, using the outcome of phototherapy (n ¼ 15) versus no phototherapy (n ¼ 501) ETcB (mg/dL)
Sens
Spec
PPV
NPV
Positive LR
Negative LR
pa
0.3
1.0
0.25
0.04
0.96
0.04 (0.02–0.07)
0
0.03
0.80
0.87
0.45
0.04
0.99
0.05 (0.03–0.08)
0.01 (0–0.04)
0.02
0.90
0.73
0.50
0.04
0.98
0.04 (0.02–0.08)
0.02 (0.01–0.04)
0.11
1.00
0.73
0.53
0.04
0.99
0.05 (0.03–0.08)
0.01 (0.01–0.04)
0.06
1.10
0.73
0.57
0.05
0.99
0.05 (0.03–0.09)
0.01 (0.01–0.04)
0.03
1.20
0.60
0.59
0.04
0.98
0.04 (0.02–0.08)
0.02 (0.01–0.04)
0.18
2.00
0.40
0.82
0.06
0.98
0.07 (0.03–0.15)
0.02 (0.01–0.04)
0.04
Abbreviations: ETcB, early transcutaneous bilirubinometry; LR, likelihood ratio (95% confidence interval) weighted for prevalence; NPV, negative predictive value; PPV, positive predictive value; sens, sensitivity; spec, specificity. a Fisher exact test. American Journal of Perinatology
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Q7
Early Transcutaneous Bilirubinometry
Q6
Fig. 1 Receiver-operator characteristic curve relating early transcutaneous bilirubin (cut-off values 0.3–2.0 mg/dL) to subsequent phototherapy (area under the curve ¼ 0.66).Q6
found significant overlap in ROR values in those who did and did not require PHT. Unlike in the current study in which a TcB value obtained before 6 hours of age was used, these investigators used TcB values that were obtained after 24 hours of age to calculate ROR. Significant correlations were observed between ETcB and subsequent TcB values, and NPV was 0.92 for both ETcB and E-ROR when subsequent TcB greater than the 95th percentile was the outcome. ETcB and E-ROR were higher in those
Jackson et al.
neonates who subsequently underwent PHT (as determined by usage of the American Academy of Pediatrics Q11[AAP] phototherapy nomogram, incorporating various risk factors) compared with those who did not. Although the number of neonates in this study requiring PHT was small, the mean ETcB was increased more than twofold, and mean E-ROR was increased approximately 1.5-fold in infants who were treated with PHT versus infants who were not treated with PHT. ETcB was < 0.3 mg/dL in just under 25% of the study population, and none of these infants subsequently received PHT. Many factors influence the passage of bilirubin from the circulation to the skin.25–27 The leakage of bilirubin–albumin complexes into the extravascular space and the precipitation of bilirubin in its acidic form in biological membranes appear to be of most significance. Examination of these mechanisms was beyond the scope of this study; we did observe that there was no significant relationship between umbilical cord pH and ETcB. Many study infants had very low ETcB values, and this might be anticipated during the first 6 hours postnatally as, due to placental clearance, almost all neonates are born with low TSB. Even infants with brisk hemolysis in utero have relatively low bilirubin levels at birth, although their TSB values may be significantly higher than values in the general population of neonates, and they often increase significantly very early in the postnatal period.8 Maisels et al28 studied the contribution of hemolysis to early jaundice (defined as TSB > 75th percentile for age in hours16 using corrected end-tidal carbon monoxide [ETCOc] to estimate bilirubin production [a surrogate for hemolysis]). ETCOc values were higher in the jaundiced group as early as the 1st postnatal day. In Maisels’ study, information regarding ABO incompatibility or other potentially pathologic causes of hemolysis, such as glucose-6-phosphate dehydrogenase (G6PD) deficiency, generally was not available. We also did not have
Table 4 Predictive indices for ETcB with the outcome of TcB > 95th percentilea at 18 to 36 hours of age,b and 42 to 66 hours of agec (also shown are predictive indices for E-RORd and TcB at 18–36 hours of agee with the outcome for both being TcB > 95th percentile at 42–66 hours of age)Q10 Sens
Spec
PPV
NPV
Positive LR
Negative LR
pf
0.15
0.99
0.18 (0.13–0.25)
0.01 (0.00–0.04)
< 0.00001
0.02
0.92
0.26 (0.18–0.36)
0.08 (0.05–0.14)
0.002
0.95
0.22 (0.15–0.32)
0.05 (0.02–0.11)
0.001
0.97
0.55 (0.38–0.80)
0.04 (0.01–0.08)
< 0.00001
ETcB ( 0.90 mg/dL)b 0.94
0.53
ETcB ( 0.90 mg/dL)c 0.70
0.57
E-ROR ( 0.18 mg/dL) 0.83
0.49
e
0.18
TcB at 18 to 36 hours of age ( 6 mg/dL) 0.79
0.80
0.35
f
Abbreviations: E-ROR, early rate of rise; ETcB, early transcutaneous bilirubinometry; LR, likelihood ratio (95% confidence interval) weighted for prevalence; NPV, negative predictive value; PPV, positive predictive value; Sens, sensitivity; Spec, specificity; TcB, transcutaneous bilirubinometry. a Evaluated using local TcB nomogram.11 b n ¼ 373 neonates with ETcB and TcB at 18 to 36 hours of age; in 23 (6%) neonates, the TcB value was > 95th percentile. c n ¼ 296 neonates with ETcB and TcB at 42 to 66 hours of age; in 40 (13.5%) neonates, the TcB value was > 95th percentile. d n ¼ 239 with E-ROR calculated as defined in the methods and a subsequent TcB at 42 to 66 hours of age; in 29 (12.1%) neonates, the TcB was > 95th percentile. e n ¼ 239 with TcB at 18 to 36 hours of age and TcB at 42 to 66 hours of age; in 29 (12.1%) neonates, the TcB value was > 95th percentile. f Chi square test. American Journal of Perinatology
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Fig. 2 Receiver-operator characteristic curve relating early transcutaneous bilirubin (cut-off values 0.3–2.0 mg/dL) to subsequent transcutaneous bilirubinometry > 95th percentile at 42 to 66 hours (area under the curve ¼ 0.62).
complete data on maternal–infant blood group incompatibility, but for those neonates, in the current study, who required PHT, 7 of 12 in whom data were available had the potential for ABO isoimmunization; however, only three of these had a positive direct antiglobulin test. Nevertheless, it is likely that unproven hemolysis29 may have played a role in some instances of elevated ETcB and/or elevated E-ROR. Data regarding other causes of increased bilirubin production, such as elevated hematocrit, were not generally available in this group of neonates.
Fig. 3 Receiver-operator characteristic curve relating transcutaneous bilirubin (TcB) at 18 to 36 hours (cut-off values 3.0–9.0 mg/dL) to subsequent TcB > 95th percentile at 42 to 66 hours (area under the curve ¼ 0.86). American Journal of Perinatology
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Fig. 4 Receiver-operator characteristic curve relating early rate of rise (cut-off values 0.05–0.30 mg/dL per hour) to subsequent transcutaneous bilirubin > 95th percentile at 42 to 66 hours (area under the curve ¼ 0.79).
Other investigators have studied the value of either cord TSB or TSB values obtained relatively soon after birth with varying results; while some have found these early TSB values to be useful,30–32 others have not.33 Risemberg et al34 measured cord blood TSB in neonates with ABO incompatibility and observed that all neonates with a value > 4 mg/dL developed severe hyperbilirubinemia and required exchange transfusion. More recently, Sarici et al35 measured TSB at 6 hours of age in neonates with ABO incompatibility. They observed that values of 4 Q12and 6 mg/dL predicted nearly all neonates who developed significant hyperbilirubinemia and severe hemolytic disease of the newborn, respectively. Predictive bilirubin values in this study were somewhat lower than in the study by Sarici et al,35 since the age of determination in our study was earlierQ13, and we did not focus on neonates with blood group incompatibility. All of these previous studies measured only TSB, and to the best of our knowledge, ours is the first study to assess the value of TcB determination performed soon after birth. There are some limitations to this study. This was a convenience sample involving a predominantly Hispanic population which may limit its generalizability to other groups. We did not have complete data regarding clinical risk factors, and the number of late-preterm neonates included was not sufficient to provide specific information regarding this group. The time period chosen to calculate E-ROR (from the ETcB to a range of 18–36 hours of age) was fairly broad; this was done to include a larger number of infants. We did not follow Q14as outpatients those babies who had mild degrees of jaundice, only those whose provider had concerns at the time of discharge. The infants identified as needing PHT
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Early Transcutaneous Bilirubinometry Table 5
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Screening mode
Outcome
Area under the ROC curve
1. ETcB
TcB at 42–66 h of age
0.62a
2. E-ROR
0.79b
3. TcB at 18–36 h of age
0.86
Abbreviations: AUC, area under the curve; E-ROR, early rate of rise; ETcB, early transcutaneous bilirubin; ROC, receiver operator characteristic; TcB, transcutaneous bilirubin. Note:Q9 The AUC for the ROC curve relating ETcB to TcB at 18 to 36 hours of age was 0.83. a Versus AUC for E-ROR (#2), p ¼ 0.02; versus AUC for TcB at 18 to 36 hours of age (#3), p ¼ 0.0004. b Versus AUC for TcB at 18 to 36 hours of age (#3), p ¼ 0.31.
postdischarge were those infants seen in our NBN follow-up clinic and may not include others who were seen elsewhere. In addition, it is likely that neonates analyzed at 42 to 66 hours of age were somewhat different than the entire original group, and in 40 (13.5%) the subsequent TcB value at 42 to 66 hours was > 95th percentile; many vaginally delivered infants presumably were discharged before that time. Also, we were not able to consider gestational age and low birth weight in comparing ROC curves. Currently, there is considerable interest in the development of “Early Warning Scores” that will predict subsequent deterioration in patients before its occurrence.36–38 Use of an inexpensive, rapid, noninvasive ETcB test may represent a somewhat less dramatic example of this concept, although several of the neonates who subsequently received PHT had very high ETcB values (e.g., 3.6, 4.9, and 5.7 mg/dL), suggesting that an “early warning” signal was present. However, as noted in ►Table 3, overall PPV was relatively low. Thus, it appears that the primary value of this test is its ability to predict the absence of subsequent hyperbilirubinemia (NPV). It is important to note that, while the negative predictive ability was quite good, the clinician would not want to rely solely on an ETcB value, and ongoing screening is indicated. Early followup is still indicated for all neonates discharged within 48 to 72 hours after birth, as recommended by the AAP, and particularly in light of the observation that TSB frequently has not peaked by the time of discharge.1 In conclusion, our results suggest that in a predominantly Hispanic population there may be value in obtaining the initial screening TcB during the first 6 hours postnatally. It appears that ETcB may have utility in the identification of term neonates who are at a relatively low risk of developing subsequent hyperbilirubinemia; however, its PPV is limited. Further investigation in other groups will be important to determine the generalizability of these results.
Conflict of Interest None.
Acknowledgments The authors acknowledge the assistance of the nursing staff at Parkland Memorial Hospital in obtaining TcB values, as well as the support of the University of Texas
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Southwestern Medical Center Summer Medical Student Research Program.
References 1 Maisels MJ, Kring E. Length of stay, jaundice, and hospital read-
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Evaluation and Risk Assessment for Universal Screening for Hyperbilirubinemia Study Group. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr 2013;162(3):477–482.e1 DeLuca D, Engle WD. Devices for non-invasive measurement of bilirubin. In: deLuca D, Engle WD, Jackson GL, eds. Transcutaneous Bilirubinometry. New York: Nova Science Publishers, Inc.; 2013: 19–36 Maisels MJ. Historical perspectives: Transcutaneous bilirubinometry. NeoReviews. 2006;7:e217–e225Q15 Wickremasinghe AC, Karon BS, Saenger AK, Cook WJ. Effect of universal neonatal transcutaneous bilirubin screening on blood draws for bilirubin analysis and phototherapy usage. J Perinatol 2012;32(11):851–855 Wainer S, Parmar SM, Allegro D, Rabi Y, Lyon ME. Impact of a transcutaneous bilirubinometry program on resource utilization and severe hyperbilirubinemia. Pediatrics 2012;129(1): 77–86 Maisels MJ, Deridder JM, Kring EA, Balasubramaniam M. Routine transcutaneous bilirubin measurements combined with clinical risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol 2009;29(9):612–617 Kaplan M, Wong RJ, Sibley E, Stevenson DK. Neonatal jaundice and liver disease. In: Martin RJ, Fanaroff AA, Walsh MC, eds. NeonatalPerinatal Medicine: Diseases of the Fetus and Infant. St. Louis: Elsevier Publishing Co.; 2011:1443–1496 De Luca D, Jackson GL, Tridente A, Carnielli VP, Engle WD. Transcutaneous bilirubin nomograms: a systematic review of population differences and analysis of bilirubin kinetics. Arch Pediatr Adolesc Med 2009;163(11):1054–1059 De Luca D, Romagnoli C, Tiberi E, Zuppa AA, Zecca E. Skin bilirubin nomogram for the first 96 h of life in a European normal healthy newborn population, obtained with multiwavelength transcutaneous bilirubinometry. Acta Paediatr 2008;97(2):146–150 Engle WD, Lai S, Ahmad N, Manning MD, Jackson GL. An hourspecific nomogram for transcutaneous bilirubin values in term and late preterm Hispanic neonates. Am J Perinatol 2009;26(6): 425–430 Maisels MJ, Kring E. Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of > or ¼ 35 weeks’ gestation. Pediatrics 2006;117(4):1169–1173 Sanpavat S, Nuchprayoon I, Smathakanee C, Hansuebsai R. Nomogram for prediction of the risk of neonatal hyperbilirubinemia, American Journal of Perinatology
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