Objective. To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week.
Methods. Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined.
Results. The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (≥95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and .48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%).
Conclusions. An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels ≥95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.
- jaundice prediction
- universal bilirubin screen
- hour-specific bilirubin nomogram
- TSB =
- total serum bilirubin •
- GA =
- gestational age •
- BW =
- birth weight •
- G-6-PD =
- glucose-6-phosphate dehydrogenase •
- AAP =
- American Academy of Pediatrics •
- LR =
- likelihood ratio •
- ROC =
- receiver operating characteristic •
- BIND =
- bilirubin-induced neurologic dysfunction
Neonatal hyperbilirubinemia remains a public health concern as documented by recent reports of kernicterus in otherwise healthy term and near-term newborns born and cared for in the United States.1–7 Kernicterus in such newborns is preventable, provided excessive hyperbilirubinemia for age is promptly identified and appropriately treated.8–17 With the intent to facilitate such identification and treatment, universal screening for severity of bilirubinemia before hospital discharge may predict that extraordinary segment of the neonatal population that is at risk for excessive hyperbilirubinemia during the first week after birth.
This article will present data on the predictive value of a routine predischarge total serum bilirubin (TSB) measured at the time of the universal metabolic screen. This value is plotted on an hour-specific bilirubin nomogram that describes the range of TSB levels observed in a population of racially diverse, healthy, term and near-term newborns during the first postnatal week. The percentile curves for TSB values, in mg/dL, are marked on the nomogram, which shows that TSB levels of ≥8 mg/dL (137 μM/L) at about 24 hours, ≥14 mg/dL (239 μM/L) at about 48 hours and ≥17 mg/dL (290 μM/L) at about 84 hours age are above the 95th percentile for postnatal age in hours. Such levels of hyperbilirubinemia have been deemed significant and are generally considered to require close supervision, possible further evaluation, and sometimes intervention if brain damage is to be prevented without resort to exchange transfusion.18–21 The current nomogram appears to identify which newborns are at low, intermediate or high risk for reaching bilirubin levels above the 95th percentile in the first week after birth. It will thereby allow for a more targeted, safe, and cost-effective follow-up than is currently available.
The appeal of the predictive nomogram is its simplicity and immediate applicability. The development of more accurate noninvasive technologies for measuring bilirubin in the skin will facilitate its use. Concurrent estimation of bilirubin production by measuring exhaled carbon monoxide (COSTAT, Natus, Inc, Palo Alto, CA) should enhance its role as a predictive and interventional tool.22 ,23
PATIENTS AND METHODS
The population base for developing the nomogram consisted of all 17 854 live births that occurred at Pennsylvania Hospital during 1993 to 1997. Of these, 13 003 healthy term and near-term newborns were eligible for discharge by day 1 or 2 (vaginal births) or by day 3 (cesarean births). All these newborns had predischarge TSB level obtained at the same time as the routine metabolic screen. In some, earlier TSB values were obtained for clinical reasons. Newborns who had postdischarge TSB levels obtained over the next 1 to 6 days in a hospital supervised follow-up program were eligible for inclusion in the nomogram.
Term or near-term appropriate for gestational age (GA) newborns, as defined by a birth weight (BW) ≥2000 g for ≥36 weeks GA or BW ≥2500 g for ≥35 weeks GA.
Admission and treatment in the intensive care nursery for neonatal illness or, positive direct Coombs test. All newborns whose mothers had blood type O, were Rh-negative, or had a positive indirect Coombs test were evaluated for blood type and direct Coombs test. TSB values measured after the initiation of phototherapy were excluded from the nomogram but were documented and recorded. TSB values not measured at the hospital laboratory were excluded but were replaced by a repeat, hospital-based measurement close in time. In addition, after the initial analysis, newborns who required phototherapy before age 60 hours to control unexplained rapidly rising TSB levels were excluded from the predictive nomogram (rationale listed in “Discussion”). During this study period there was no predischarge screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
Initial Bilirubin Assessment
Newborns studied in 1993 and 1994 (n = 1042) included those healthy newborns who were electively discharged on day 1 in accordance with managed care recommendations. All these consecutively discharged newborns, with universal TSB measurements between age 20 to 28 hours and with no major blood type (ABO) or Rh isoimmunization (negative direct Coombs test) were prospectively followed to assess the ability of the predischarge bilirubin to predict degree of subsequent hyperbilirubinemia.24 Based on these preliminary observations, the Section on Newborn Pediatrics at Pennsylvania Hospital recommended universal bilirubin screening for all newborns at the time of the routine metabolic screen. Newborns studied during 1994 to 1997 were usually discharged on day 2 and included newborns discharged on day 3 after cesarean section delivery.
Outpatient follow-up was according to a Pennsylvania Hospital supervised early discharge protocol. Subsequent TSB levels were usually obtained within 24 to 48 hours after discharge and as needed thereafter. This follow-up was offered to all parents and private pediatricians and was generally accessible by insurance coverage that allowed home nursing care. TSB samples were obtained in the hospital outpatient department or by the home care nurse and transported to the hospital laboratory for analysis. Additional follow-up either involved a repeat TSB sample or a visual inspection at physician's discretion. Resolution of hyperbilirubinemia was confirmed at about age 10 days, usually through contact with the private pediatrician. This hospital-based monitoring was performed in cooperation with private pediatricians and sought to minimize tests, investigations, and interventions. All bilirubin samples were obtained after parental consent.
Serum bilirubin assay was performed by the 2,5-dichlorophenyldiazonium tetrafluoroborate (DPD) diazo method (Hitachi, 747) in the Pennsylvania Hospital Ayer Clinical Laboratories. Standard (bed) National Institute of Standard Technology guidelines were followed to maintain the accuracy and precision of the technique.23–25 The coefficient of variation for the hospital laboratory was targeted for <6%. During the study period, each of the actual variance values, assessed every 3 months, ranged from 2% to 3%.
Hospital-based or home-based phototherapy was initiated at the discretion of the pediatrician. Unless modified for specific clinical reasons, guidelines for phototherapy published by the American Academy of Pediatrics (AAP) were used.19 ,20 As stated earlier, postphototherapy TSB values were excluded from the nomogram. Pediatricians and nursing staff recommended breast milk feedings as instructed, supervised, and monitored by two full-time lactational consultants. Early and frequent breast feedings were encouraged. The ability to latch and the adequacy of intake were monitored and documented. Onset of jaundice or need for phototherapy did not lead to cessation of breastfeedings. In the event of presumed inadequate intake, feeding techniques were evaluated by joint consultation with the mother, lactational consultants, and the pediatric team. Supplements were used as needed and breast milk production was enhanced with mechanical pumping.
Clinical and Demographic Risk Factors for Hyperbilirubinemia
The following data were recorded: BW, GA, gender, racial background, history of family members or siblings with jaundice, maternal blood type, blood type, and direct Coombs of the infant (when tested). In addition, mode of delivery (especially use of vacuum or forceps assistance), presence of bruising or hematomas, and history of possible Gilbert's disease or suspected G-6-PD deficiency were recorded on the log sheet used for outpatient follow-up. Also recorded were the type of feeding, use of lactation consultants, assessment of breast milk intake, type and amount of formula supplements, stooling pattern (frequency, amount, and color), and timing and duration of phototherapy.
The nomogram database includes all measured hour-specific TSB values except for that relatively small number of values obtained before age 18 hours. Data were recorded in epochs of 4 hours (or, age ± 2 hours) for the first 48 hours and in epochs of 12 hours (or age ± 6 hours) until 96 hours age and at epochs of 24 hours (or age ± 12 hours) for age 5 to 7 days. For each epoch at least 300 data points and demonstration of a Gaussian distribution were required for inclusion in the nomogram. From these data, hour-specific TSB percentiles for each of the epochal periods were calculated.
The predictive ability of a predischarge TSB value, characterized by postnatal age in hours and measured between 18 to 72 hours, was assessed based on the frequency of any subsequent significant hyperbilirubinemia (a subsequent TSB value in the high-risk zone, ≥95th percentile, regardless of age). The relative effectiveness of this as a vector was defined by a binary outcome of either developing or not developing this specified level of hyperbilirubinemia (designated as disease or no disease for the purpose of explaining the statistical approach). The 5th, 25th, 40th, 50th, 75th, 90th, and 95th percentiles of TSB values were determined from the Gaussian distribution for each epoch and connected as percentile tracks.
Predictive ability of the hour-specific TSB vector was assessed for values above and below the percentile tracks that were used as risk demarcators. We calculated the probability, sensitivity, and specificity for values above and below the 40th, 50th, 75th, and 95th percentiles. Intervals above, between, and below the demarcators were defined as zones. The zone above the 95th percentile was labeled as high-risk and that below the 40th percentile as minimal-risk or low-risk. TSB values between 40th and 95th percentiles were designated as being in the intermediate-risk zone; this zone was further subdivided by the 75th percentile into upper- and lower-intermediate risk zones.
With the aid of software technology, it would have been possible to compute by logistic regression the risks associated with individual TSB (based on a regression model dependent on TSB level, age and the interaction of age, and TSB level). Previous studies have shown that individual TSB values (defined by age in days) might not predict outcome with a safe false-negative and false-positive rate.28–30 We chose a nonparametric assessment of the likelihood ratio (LR) for a positive result for each of the age-specific percentile ranges or risk zones.31 LR for a positive result was determined for multiple levels of TSB results as located by the density distribution in one of the risk zones.31–33 We then developed a receiver operating characteristic (ROC) curve that plotted the false-positive rate versus the true positive rate corresponding to the LR for each risk zone. As an ROC curve moves toward the upper left corner, its usefulness as a diagnostic tool is seen to increase as sensitivity and specificity are maximized.34
Visual Graphic Analysis Using the Zone-based Predictive Nomogram
The zone-based predictive nomogram graphic helps summarize serial TSB values in an individual infant. This allows for immediate visual recognition of true positive and false-negative predictions by plotting the successive risk zone positions of the serial TSB values of each infant. In addition, the possible contribution of an individual clinical or demographic risk factor can now be more easily related to the change in risk zone positions.
Computer-based Data Collection and Graphic Evaluation
Hour-specific bilirubin values, clinical and demographic risk factors, relevant clinical interventions and follow-up information were stored in a computer database program that displayed the data for each individual newborn. The software program showed a background graphic display of the nomogram's percentile tracks and risk zones. The postnatal age in hours corresponding to birth time and the time of TSB sampling was automatically calculated for each sample. Thus, serial TSB samples, accurately characterized by postnatal age (in hours), were available for automatic plotting and delineation of risk status. In this way, if TSB values in an individual newborn moved from one risk zone to another, the rate of increase or decrease and related change in risk status was immediately apparent. The progress of newborns whose TSB values remained consistently in their original (predischarge) percentile zone was also visually apparent. Each of these graphically displayed, computerized follow-up charts was scrutinized for its accuracy, risk designation, and outcome both manually and by computerized assessment.
During the entire study period, a total of 17 854 live births occurred at Pennsylvania Hospital, of which 14 793 were directly admitted to the well-baby nursery. Of these, 13 003 near-term and term newborns matched all inclusion criteria. From this population base, 2976 completed all requirements for the hospital-supervised follow-up and had at least one postdischarge TSB level measured in the hospital laboratory. From these, 118 were excluded because of transfer to the intensive care nursery for such diagnoses as sepsis proven or presumed but treated, intractable hypoglycemia or respiratory distress. In addition, 18 newborns who required phototherapy before age 60 hours because of rapidly rising predischarge bilirubin levels were excluded. The remaining 2840 healthy term and near-term newborns eligible for discharge at age 24 to 72 hours constituted the study population on which the predictive nomogram was developed. The mean ± SD value for birth weight was 3318 ± 457 g (median: 3230 g) and for gestational age 38.7 ± 1.3 weeks (median: 39 weeks). The racial distribution, mode of delivery, and mode of feeding are tabulated in Table 1. These parameters do not differ significantly from those of the entire study pool of 13 003 well newborns.
The mean age for predischarge TSB sampling for the 2840 newborns was 33.7 ± 14.6 SD hours. Hyperbilirubinemia severe enough to cause visible jaundice was often present at the time of the first predischarge sample: 13.4% had a TSB >10 mg/dL, 4.3% of the newborns had values >12 mg/dL, .4% (12/2840) had values >15 mg/dL and 2 newborns had values >18 mg/dL. The Gaussian distribution of all TSB data points (range: 300–673 per epoch) for each of the epochal periods from 18 to 132 hours age is shown in Fig 1. The 5th, 10th, 25th, 40th, 50th, 75th, 90th, and 95th TSB percentiles were constructed and the 40th, 75th, and 95th were used as risk zone demarcators (Fig 2).
A total of 230/2840 (8.1%) newborns were identified as having values above the 95th percentile track at some time (predischarge or postdischarge) during the first postnatal week. However, as shown inTable 2, only 126/2840 (4.4% or 1 of 23 newborns) had a postdischarge TSB value in the high-risk zone (significant hyperbilirubinemia). Based on these data, the ratio of newborns with and without subsequent significant hyperbilirubinemia is 126:2714 (or ≃1:22) for our study population. Table 2 lists the predictive ability of the 40th, 75th, and 95th percentile tracks as risk demarcators. The ROC curve, as shown in Fig 3, illustrates each risk zone's significant ability to predict subsequent significant hyperbilirubinemia.
The LR that determines the risk assessment for subsequent significant hyperbilirubinemia for each predischarge risk zone is tabulated inTable 3. For the 2 to 4 days after discharge, TSB levels of most newborns remained in the predischarge TSB percentile-based risk zone and subsequently decreased to lower risk zones either spontaneously or, with individualized nutritional counseling. Among the newborns with a TSB in the high-risk zone predischarge (172/2840 or 6.1% of the study population), 68 continued to have subsequent significant hyperbilirubinemia. On the other hand, in 104 the subsequent TSB decreased below the 95th percentile (Fig 4A) and the ratio of newborns with or without disease was 2:3 and LR = 14.08. TSB levels of a small but significant number from the intermediate-zone newborns (58/912, 6.4%) moved upwards to the high-risk zone after discharge. Of 356 newborns in the upper intermediate-risk zone, 46 jumped to the high-risk zone on follow-up and 310 did not (Fig 4B; ratio of newborns with and without disease was 1:7 and LR = 3.20). This compared with the 556 newborns in the lower intermediate-risk zone. Of these, 12 jumped tracks into the high-risk zone on follow-up and 544 did not (Fig 4C; ratio of newborns with and without disease was 1: 45 and LR = .48). Another 29 of these 556 newborns (5.2%) changed their risk status by moving upwards but only into the upper intermediate-risk zone.
Follow-up of newborns placed in the low-risk zone at discharge (1756/2840; 61.8%) showed them to be the most predictable. Nearly 93.6% remained in the 40th percentile-risk zone; while, only 6.4% moved up to the intermediate-risk zone. None (LR = 0) jumped up to the high-risk zone (Fig 4D). The only presumable exception could have been a near-term neonate (newborn D.F., BW = 3335 g, GA = 36 weeks, breastfed by a primiparous mother) who had a predictive TSB value at the 40th percentile (4.3 mg/dL at 18 hours age) and was discharged early at maternal request. On follow-up, at age 47 hours the TSB was 11.3 mg/dL (upper-intermediate risk zone) and reached a value of 19.3 mg/dL at age 125 hours (high-risk zone). Her clinical evaluation included demonstration of lymphocytosis that was suggestive of an acute viral infection; no other clinical risk factors were identified. Both phototherapy and nutritional support were provided. Hyperbilirubinemia resolved over the next several days.
Phototherapy was usually initiated when at least two consecutive TSB values were in the high-risk zone. This occurred in a total of 117/2840 newborns or 4.1% of the study population. In 15 newborns, phototherapy was commenced between 61 to 71 hours for a mean TSB value = 16.6 ± 1.6 SD mg/dL. For the remaining 102 newborns, phototherapy was started after age 72 hours for a mean TSB value = 17.8 ± 2 SD mg/dL at a mean age of 89.4 ± 25.9 SD hours. None of the newborns in the low-risk zone received phototherapy. No newborn in the study population required an exchange transfusion or developed a TSB value ≥25 mg/dL. None developed acute signs of bilirubin encephalopathy. None are known to have sequelae at about 1 year of age as determined by telephone interviews of parents, pediatric offices or feedback from area hospitals. To the best of our knowledge, none of the healthy newborns born from 1993 to 1997, who were not included in the nomogram because of follow-up elsewhere, developed kernicterus.
The frequency of exclusive breastfeeding in our study population was 49.3%. An additional 9.9% who were provided with individualized lactation counseling and support received expressed breast milk and formula supplementation. Percentile tracks for exclusively breastfed newborns appeared to be about 1 to 1.5 mg/dL higher than for the exclusively formula fed newborns at the 40th and 95th percentile tracks. The sample size is not adequate to draw any meaningful conclusions from these data.
Clinical experience and recent reports in the United States suggest an increased occurrence of kernicterus in otherwise healthy newborns during the late 1980s and 1990s.1–6 This has been attributed to decreased clinical concern about the toxic potential of bilirubin1–17 and increased administrative and economic pressures to limit length of hospitalization and laboratory investigations that has resulted in an era of lessened direct medical observation.35–38 Statistically, newborns with TSB of ≥17 mg/dL during the first week after birth represent a small segment of the population; our study shows that this value is above the 95th percentile at about 84 hours age and beyond. It is this group of newborns who are at potential risk for bilirubin-induced neurologic dysfunction (BIND) including kernicterus.9 39–46Strategies to prevent BIND need to be practical, safe, effective, and based on risk assessment. Recognizing this as a matter of public health concern, the AAP developed a detailed, consensus-based, practice parameter for the management of hyperbilirubinemia in healthy term newborns and the institution of preventive phototherapy.19Although effective when implemented as intended, clinical use of the guidelines has been limited by the absence of a prospective risk assessment and by dependence on visual assessment of jaundice.
Predischarge Jaundice as a Predictive Vector for Subsequent Hyperbilirubinemia
Early visual recognition of jaundice and accurate estimation of its severity is crucial for effective implementation of the AAP guidelines.19 Unfortunately, the presence of excessive jaundice for age is often missed clinically, which means that the trigger for measuring the first serum bilirubin level and electing subsequent AAP algorithm recommendations is not set. This is a potentially serious problem. Variability in the time of appearance of jaundice from newborn to newborn and in the ability of the professionals to see jaundice and estimate its severity, coupled with the considerable range of TSB values associated with its cephalo-caudal progression, have been the subject of articles spanning nearly 60 years.47–49 Even in the present study, with health care providers sensitized to the significance of clinical jaundice, there were several instances when its early appearance was missed (often attributable to confounding skin coloring) or a measured TSB was not considered excessive for the newborn's age in hours. Additionally, in most of the recently reported healthy term newborns who developed kernicterus, significant jaundice was almost certainly present before the first hospital discharge, judging from the height of TSB for age in hours at readmission.1–6 Either the early icterus had not been noted or its pathologic intensity for postnatal age was not appreciated. TSB values must be excessive for age in hours in otherwise healthy term and near-term newborns to be at potential risk for BIND. It is in the context of identifying such newborns before dangerous levels are reached that a universal TSB screen, before discharge, is recommended as a more specific predictive vector than clinically recognized jaundice.
The statistical steps we have used to guide clinical decision-making are based on a nonparametric assessment and make no distributional assumptions. The nomogram has been specifically devised to be intuitively appealing to the clinician in daily practice. The clinician is interested in the probability that the newborn will or will not develop significant hyperbilirubinemia. In this scenario, data on sensitivity and specificity, ROC curves, and negative or positive predictive values do not always suffice. Also, the application of sensitivity and specificity to test results that can have a continuous distribution of values is not clinically practical.31 In contrast, the LR has the ability to revise the prior probability of disease upwards or downwards based on the subsequent test result. For continuous variables, the LR (or likelihood quotient) is the ratio of two probabilities, the probability that a given predischarge TSB value predicts the risk of disease (the true positive fraction) divided by the probability of the same test result when there is no disease (the false-positive fraction). The use of LR for predicting an outcome of clinically significant hyperbilirubinemia or disease (outcome of a TSB level in the high-risk zone) encompasses the impact of clinical and demographic risk factors. These contributory factors affect the density distribution of the TSB values and therefore the LR summarizes all these factors into a single clinically relevant index.31–33 Because TSB values reflect the combined effects of bilirubin production and hepatic excretion, the reasons why successive TSB values that jump track require further evaluation.
Based on our data (Table 3), the probability of subsequent hyperbilirubinemia in our study population as a whole may be expressed as a ratio of 1:22 for disease and no disease (126 with and 2714 without disease). The overall risk is none in the low-risk zone, nearly halved (1:45) in the lower-intermediate zone, tripled in the upper-intermediate zone (1:7) and increased 14-fold in the high-risk zone (2:3) newborns. Considering the threshold used to rationalize predischarge screening for a variety of congenital inherited disorders, these statistics provide justification for institution of a policy of universal TSB screening. Our recommendation for universal TSB screening performed at the time of the universal metabolic screening would be cost-effective because of the targeted bilirubin follow-up facilitated and encouraged by the nomogram as opposed to medical decisions not based on risk assessment.51 ,52 Low-risk zone newborns who were screened between 18 to 72 hours age comprised 61.8% of our study population. They represent newborns who either were in the low-risk zone or moved into the low-risk zone postdischarge. None of these newborns moved into the high-risk zone, required phototherapy or other than minimal intervention, such as counseling on feeding techniques. Bilirubin follow-up of this large component of the population, once screened, could be safely limited to a visual assessment of jaundice by an experienced observer. In the future, significantly more accurate noninvasive technologies now under development to measure bilirubin staining of the skin and its relation to serum bilirubin level may suffice for both predischarge and postdischarge TSB measurements and may theoretically offer an additional estimate of toxic risk.30 ,52
This nomogram, developed from a diverse population, attempts to anticipate risk of an errant experience for a newborn who unexpectedly develops significant hyperbilirubinemia. We initially labeled the low-risk zone by the 50th percentile. Its predictive ability was nearly similar to that of the 40th percentile. However, in view of the unavoidable problems25–27 in measurement of TSB (at least ±0.5 mg/dL), and the fact that many near-term newborns (35/36 weeks GA) are discharged as if they were at term (as in the clinical case described in the “Results” section), the 40th percentile was considered a safer demarcator. We made painstaking efforts to maintain accuracy and precision in bilirubin measurements by using a single laboratory. A consistent liaison and communication between a local laboratory and the pediatrician would also be effective in monitoring for variation in bilirubin accuracy. The conservative definition of the 40th percentile low-risk zone demarcator minimizes the prospect of an errant experience that might occur in a near-term newborn with multiple risk factors, or when a universal screen is performed at 18 rather than at age 24 hours or more. The low-risk zone designated by our data, as below the 40th percentile track, may not be applicable worldwide. However, the LR for each of the bilirubin defined risk zones in our nomogram can be used at geographic sites with different prior probabilities of significant hyperbilirubinemia to calculate site-specific risk assessment (see Table 3 legend).
Newborns Who Are Placed in the High-risk Zone Before Discharge
As described earlier, we observed 18 newborns who for no identified reason were in the high-risk zone and needed phototherapy before age 60 hours. They were kept in the hospital for further evaluation and interventions. Because their predischarge serial TSB values had already placed them in the disease category, they did not belong in the nomogram to predict disease. Similarly, newborns with known increased risk secondary to ABO and Rh incompatibility with a positive Coombs test were excluded. However, when included in the nomogram, the predischarge and prephototherapy TSB values did not appear to alter the 95th percentile demarcator. Instead, they appeared to effect the low-risk demarcator at age 18 to 30 hours. As expected, the TSB values were located disproportionately in the high-risk or upper- or intermediate-risk zones depending on their rate of bilirubin production and capacity for hepatic excretion. Subsequent tracking of these newborns was markedly aided by the use of the nomogram. Further diagnostic evaluation of any newborn placed in the high- and intermediate-risk zone newborns would help characterize their hyperbilirubinemia as related to increased production (measurement of carbon monoxide production) versus a range of hepatic excretion defects compounded by an increased entero-hepatic circulation, or to a combination of all three.54 Furthermore, any newborn who reaches and remains in the high-risk zone would benefit from long-term follow-up for sequelae of both acute and chronic BIND.
In summary, we have demonstrated the predictive usefulness and clinical value of universal bilirubin sampling in all term and near-term newborns performed at the time of the routine metabolic screening. When related to its percentile distribution for postnatal age, this hour-specific TSB can define the risk of subsequent clinically significant hyperbilirubinemia as high-risk (≥95th percentile), intermediate-risk (40th–95th percentiles), and low-risk (<40th percentiles). We provide risk-based guidelines that can target evaluation, intervention, and follow-up according to the AAP's bilirubin practice parameter. Application of this predictive bilirubin nomogram would help in the prevention of BIND in the United States, including kernicterus.
We thank Drs Soraya Abbasi, John G. DeMaio, Jeffrey S. Gerdes, and Carla Weis of the Section on Newborn Pediatrics for their clinical and administrative support; the pediatric nurse practitioners: Theresa Cotton, Patricia Hewson, Diane Manning, and Barbara Medoff-Cooper; the lactation consultants: Tammy Arbeter and Susan Carson; the hospital-based bilirubin check team: Christine Dalin, Rosemary Dworanczyk, Mary Grous, Donna Spitz; and the home visiting nurses in Philadelphia and the South New Jersey area for their meticulous and caring attention to the jaundiced newborns. This research was supported by the Newborn Pediatrics Research Fund at Pennsylvania Hospital.
- Received April 30, 1998.
- Accepted July 13, 1998.
Reprint requests to (V.K.B.) Newborn Pediatrics, Pennsylvania Hospital, 800 Spruce St, Philadelphia, PA 19107.
- ↵Brown AK, Johnson L. Loss of concern about jaundice and the reemergence of kernicterus in full-term infants in the era of managed care. In: Fanaroff AA, Klaus MH, eds. The Year Book of Neonatal and Perinatal Medicine. Philadelphia, PA: Mosby Yearbook; 1996:17–28
- Stevenson DK
- Maisels MJ,
- Newman TB
- MacDonald MG
- Newman TB,
- Maisels MJ
- Brown AK,
- Seidman DS,
- Stevenson DK
- Cashore WJ
- Johnson L
- Wennberg RP
- Poland RL
- Gartner LM
- Valaes T
- American Academy of Pediatrics, Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia
- ↵American Academy of Pediatrics, Committee on Fetus and Newborn, and ACOG Committee on Obstetrics. Maternal and Fetal Medicine: Guidelines for Perinatal Care. 3rd ed. 1992:108–109
- Martinez JC,
- Maisels J,
- Otheguy L,
- et al.
- Smith DW,
- Inguilo D,
- Martin D,
- et al.
- Stevenson DK,
- Vreman HJ
- Schreiner RL,
- Glick MR
- Vreman HJ,
- Verter J,
- Stevenson DK,
- et al.
- Albert A
- American Academy of Pediatrics, Committee on Fetus and Newborn
- Braveman P
- Kessel W,
- Kiely M,
- Nora AH,
- Sumaya CV
- ↵Johnson LH, Boggs TR. Bilirubin-Dependent Brain Damage: Incidence and Indications for Treatment. Phototherapy in the Newborn: An Overview. Washington, DC: National Academy of Sciences; 1974:122–149
- Perlman M,
- Fainmesser P,
- Sohmer H,
- Tamari H,
- Wax Y,
- Pevsmer B
- Maisels MJ,
- Newman TB
- van der Bor M,
- Ens-Dokkum M,
- Schreuder AM,
- et al.
- Newman TB,
- Klebanoff MA
- Funato M,
- Tamai H,
- Shimada S,
- et al.
- Bhutani VK,
- Johnson L,
- Gourley G,
- Dworanczyk R,
- Grous M
- Copyright © 1999 American Academy of Pediatrics