PEDIATRICS Vol. 117 No. 5 May 2006, pp. e855-e862 (doi:10.1542/peds.2005-1338)
The Effect of Instituting a Prehospital-Discharge Newborn Bilirubin Screening Program in an 18-Hospital Health System
a NICU Development Team, Intermountain Health Care, Salt Lake City, Utah
b Department of Pediatrics, Division of Neonatology, University of Utah, Salt Lake City, Utah
| ABSTRACT |
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OBJECTIVE. Kernicterus is a rare but devastating condition. The prevention of bilirubin-induced brain injury is based on the detection of infants at risk for developing severe hyperbilirubinemia. In an 18-hospital health system, Intermountain Health Care (IHC), we initiated a program of predischarge bilirubin screening of all neonates and coupled this with a results assessment using a percentile-based nomogram. Data during 2 periods of time, before versus after initiating the program, were compared to assess the effect of the program on significant hyperbilirubinemia and rehospitalization.
METHODS. We conducted a historic cohort study involving all neonates delivered at
35 weeks' gestation, within IHC's 18-hospital system, during 2 periods of time: March 1, 2001, to December 31, 2002, versus January 1, 2003, to December 31, 2004. A bilirubin screening program, instituted in December 2002, called for a total serum bilirubin (TSB) or transcutaneous bilirubin measurement to be performed on every neonate either at the recognition of clinical jaundice or before discharge regardless of whether jaundice was observed. For nonjaundiced neonates, the nursery staff was encouraged to obtain the screening TSB at the same time they obtained the state-mandated newborn screen for inborn errors of metabolism. Bilirubin values were plotted on an hour-specific nomogram and the corresponding percentile was used to guide evaluation, therapy, and follow-up. This study compared TSB data and readmission data for a 2-year period before versus a 2-year period after implementing the program.
RESULTS. The study involved 101272 neonates: 48789 in period 1 and 52483 in period 2. Before the program, 1 in every 77 neonates born at an IHC hospital had 1 or more serum bilirubin levels >20 mg/dL. After initiating the program, the incidence fell to 1 in 142 and the number of neonates with a level >25 mg/dL fell from 1 in 1522 before to 1 in 4037 after. The rate of hospital readmission with a primary diagnosis of jaundice fell from 0.55% in period 1 to 0.43% in period 2.
CONCLUSIONS. Initiating a program of bilirubin screening in a multihospital health system, coupled with evaluating the results using a percentile-based nomogram, reduced the proportion of neonates with significant hyperbilirubinemia and reduced the rate of hospital readmissions with jaundice.
Key Words: hyperbilirubinemia neonatal jaundice kernicterus universal bilirubin screening hour-specific bilirubin nomogram
Abbreviations: TSBtotal serum bilirubin IHCIntermountain Health Care ABEacute bilirubin encephalopathy
Kernicterus is a rare but devastating bilirubin-induced brain injury.1,2 Although Rh hemolytic disease, ABO incompatibility, and other neonatal hemolytic disease processes have long been known to be risk factors for kernicterus,35 an alarming number of cases have been reported recently among apparently healthy term and near-term neonates.617 Since 1990, the Pilot Kernicterus Registry has identified kernicterus in >120 term and near-term infants in North America, who had been discharged as healthy from their birth hospital.1517
In 2001, the Joint Commission on Accreditation of Healthcare Organizations issued a sentinel event alert notifying hospitals and health care providers that kernicterus threatens otherwise healthy newborns.18 A warning on the danger of kernicterus was also issued by the Centers for Disease Control and Prevention,19 and the National Quality Forum (Agency for Healthcare Regulation of Quality) declared kernicterus and total serum bilirubin (TSB) concentrations of
30.0 mg/dL as "never events."20 The American Academy of Pediatrics recently modified the practice parameters for management of hyperbilirubinemia in healthy term and near-term newborns.21
To aid in identifying neonates at risk for kernicterus, several predischarge screening strategies have been advocated.2225 By identifying at-risk infants, these strategies provide an opportunity for preventive interventions to be initiated in a timely manner. They, therefore, have the potential to reduce the number of infants who develop damaging levels of bilirubin. Bhutani et al22 developed and used an hour-specific bilirubin nomogram to stratify infants into low (<40th percentile), intermediate (40th95th percentiles), and high (>95th percentile) risk categories for subsequent clinically significant hyperbilirubinemia. Coupled with systematic assessment of all infants before discharge, these investigators demonstrated the predictive usefulness of a bilirubin nomogram to guide intervention and follow-up.
Although the threshold concentration of bilirubin and/or the duration of hyperbilirubinemia responsible for inducing neurologic injury in "healthy" term and near-term newborn infants have not been clearly delineated, the early detection of hyperbilirubinemia and the timely initiation of therapy offers some margin of safety for the prevention of bilirubin-induced brain injury.26 As a risk-reduction strategy, we implemented a systemwide predischarge bilirubin screening program in December 2002. The primary objective of the present study was to determine if this program was associated with a reduction in the proportion of neonates with significant hyperbilirubinemia and in the proportion readmitted to the hospital with the diagnosis of hyperbilirubinemia.
| METHODS |
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We conducted a historic cohort study involving all neonates delivered at
35 weeks' gestation, within Intermountain Health Care's (IHC's) 18-hospital system, during 2 periods of time: March 1, 2001, to December 31, 2002, and January 1, 2003, to December 31, 2004. The study was approved by the IHC Institutional Review Board. A bilirubin screening program, instituted in December 2002, called for a TSB or transcutaneous bilirubin measurement to be performed on every neonate, either at the recognition of clinical jaundice or before discharge, regardless of whether jaundice was observed. For nonjaundiced neonates, the nursery staff was encouraged to obtain the screening TSB at the same time they obtained the state-mandated newborn screen for inborn errors of metabolism. TSB levels were measured in each hospital's clinical laboratory as "bilirubin, neonatal" with Vitros 950 and 250 clinical chemistry analyzers, (Ortho-Clinical Diagnostics, Rochester, NY). Two hospitals used a screening jaundice meter for transcutaneous estimation of bilirubin levels (BiliChek; SpectRx Inc, Norcross, GA). Bilirubin values were plotted on an hour-specific bilirubin nomogram.22 If a bilirubin value plotted above the 40th percentile curve, the care provider was notified and intervention, evaluation, and follow-up was arranged as deemed necessary.
Bilirubin test results and time of collection of the test were obtained from the IHC electronic data archives. The consolidated hospital case-mix database was used to identify infants born in an IHC hospital and to identify the population of patients
35 weeks' gestation. Readmissions were identified by taking the birth cohort of patients
35 weeks seen in the well nursery and then querying case mix for any admission with a matching Master Patient Index number and a diagnosis of jaundice. A
2 test was used to evaluate the differences in proportions of neonates with elevated bilirubin levels before and after the guidelines were implemented and to calculate probability values for the relationship between dichotomous variables such as whether readmission occurred with primary a diagnosis of jaundice.
| RESULTS |
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Compliance With the Program
Before the bilirubin screening program was introduced, <20% of neonates cared for in the 18-hospital system had a TSB level measured before hospital discharge. In contrast, after the program was introduced, the number increased rapidly such that by February 2003, >99% of neonates had at least 1 predischarge bilirubin level measured if they were cared for in 1 of the 16 hospitals that screened for significant hyperbilirubinemia by quantifying serum bilirubin levels (Fig 1). This high rate of compliance with the screening program was observed through the entirety of period 2 (December 31, 2004). The 2647 newborns cared for in the 2 hospitals that used a screening jaundice meter for estimation of bilirubin levels during period 2 are not included in this figure. The results obtained from the transcutaneous bilirubin measurements were recorded in the infant's chart but were not entered in IHC's electronic database.
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Modification of the Bilirubin Nomogram
During the first months of the program, it seemed that an inordinately high number of neonates had bilirubin values in the intermediate- and high-risk zones of the Bhutani et al nomogram,22 particularly when evaluated between 24 and 48 hours of age. Therefore, the 40th, 75th, and 95th percentiles of the hour-specific TSB values of the initial 4518 neonates screened between December 2002 and March 2003 were calculated and this population-specific data were used to modify the percentile tracks of the bilirubin nomogram. These modified percentile tracks were incorporated into the predictive nomogram of IHC's bilirubin risk chart (Fig 2).
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Incidence of Hyperbilirubinemia and Readmission
The number of neonates with serum bilirubin concentrations
20 mg/dL fell between periods 1 and 2 (Fig 3). In period 1, 1 neonate of every 77 born in an IHC facility had a documented bilirubin >20 mg/dL, whereas in period 2, this fell to 1 in every 142 neonates (Table 1). In period 1, 1 in 1522 neonates had a documented bilirubin level
25 mg/dL, whereas in period 2, this fell to 1 in 4037. A trend toward reducing the proportion of neonates with a serum bilirubin
30 mg/dL was seen, but this did not achieve statistical significance, likely because of the small number of infants involved (Table 1).
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In the first period, 268 of 48789 neonates (0.55%) were readmitted to the hospital for treatment of hyperbilirubinemia. As shown in Table 2, during the second period, the proportion of neonates readmitted fell to 226 of 52483 (0.43%; P < .005).
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Characteristics of Infants Who Developed Severe Hyperbilirubinemia
In the second period, 13 neonates had a TSB
25 mg/dL after being discharged from the nursery (Table 3). Three had isoimmunization; patients 4 and 9 had maternal Rh sensitization, and patient 11 had maternal anti-c sensitization. Patient 3 had galactosemia and concomitant Escherichia coli sepsis. A specific cause of the hyperbilirubinemia was not identified in the 8 others, but 7 had a predischarge bilirubin value that plotted above the 75th percentile of the nomogram. Patient 1 had no predischarge bilirubin value recorded. In addition to having high predischarge bilirubin values, risk factors were identified in 12 of the 13 patients. Patients 1, 4, 5, 6, 7, 9, and 13 were born before 38 weeks' gestation; patient 8 had a cephalohematoma and significant bruising secondary to a difficult delivery. The older sibling and father of patient 10 had a history of significant neonatal hyperbilirubinemia and the mother of patient 12 had insulin-dependent gestational diabetes. Patients 2, 4, 5, 6, and 13 were exclusively breastfed.
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A brainstem auditory evoked response test was documented in 1 of the 13 patients. Patient 11's brainstem auditory evoked response was recorded as normal. Clinical signs of acute bilirubin encephalopathy (ABE) were not observed in any of the 13 patients.
| DISCUSSION |
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In the 1990s, the United States and other developed countries noted a reemergence of kernicterus among term and near-term infants.617 Increased breastfeeding and shorter hospital stays were suggested as contributing to the reemergence27,28 as was the advocacy of a less aggressive approach to jaundiced neonates without hemolysis.6,2933
In December 2002, we implemented a systemwide prehospital-discharge bilirubin screening program aimed at reducing severe hyperbilirubinemia. Associated with the implementation of this program, we have documented a reduction in the proportion on neonates with significant hyperbilirubinemia and in the proportion readmitted to the hospital with the primary diagnosis of jaundice. Our program guidelines called for a TSB or transcutaneous bilirubin measurement on all term and near-term newborn infants before discharge. The guidelines specified that each bilirubin value be plotted on an hour-specific bilirubin nomogram to assess the hyperbilirubinemia in the context of postnatal age. Bhutani et al22 showed the importance of interpreting neonatal bilirubin values in the context of postnatal age in hours. They developed and subsequently used an hour-specific bilirubin nomogram to stratify infants postnatally into low (<40th percentile), intermediate (40th to 95th percentile), and high (>95th percentile) risk categories for subsequent clinically significant hyperbilirubinemia. Based on a predischarge bilirubin level, they used this predictive nomogram to guide evaluation, therapy, and/or follow-up.22
Other potentially predictive tools have been developed to aid in the identification of infants at risk for developing significant hyperbilirubinemia. In a retrospective study, Newman and colleagues identified 8 clinical predictors of hyperbilirubinemia using a multivariate logistic-regression model.23 The predictors included early onset of jaundice, a sibling who had jaundice, exclusive breastfeeding, bruising, East Asian parents, cephalohematoma, maternal age, and earlier gestation. These features were used to create a bilirubin risk index for predicting TSB
25 mg/dL. Newman's clinical risk factors were listed on our bilirubin risk chart, but the bilirubin nomogram was used as our primary predictive instrument.
After the implementation of our guidelines, we observed what seemed to us to be an inordinately high number of our neonates with predischarge bilirubin values within the intermediate- and high-risk zones of the nomogram. Analysis of our data demonstrated that the percentile curves of our population were indeed higher than those reported by Bhutani et al.22 We maintained that adjusting the percentile curves for our own population would allow for a more appropriate level at which to intervene. Unique characteristics of our population, including race and ethnicity, might explain the disparity in percentiles between our data and that published by Bhutani et al,22 but other possibilities must be considered. Maisel and Newman34 speculated that because postdischarge TSBs were not measured on a large number of infants screened by Bhutani et al, the sample could be deficient in participants with low predischarge bilirubin levels, leading to false high-sensitivity estimates and false low-specificity estimates.
It has been estimated that approximately 1 in 70 term and near-term newborn infants develop severe hyperbilirubinemia (
20 mg/dL), 1 in 700 develop extreme hyperbilirubinemia (
25 mL/dL), and 1 in 10000 develop hazardous hyperbilirubinemia (
30 mg/dL).17,35 In the period before we initiated the bilirubin screening program, 1 in 77 newborns in our population had a documented TSB
20 mg/dL, but after initiating the program, the occurrence was reduced by almost 50%, dropping to 1 in 142. Extreme hyperbilirubinemia (
25 mg/dL) in our population before initiating the program was 1 in 1522, which is less than the rate reported by Bhutani et al17 and Newman et al.35 After the program was initiated, the occurrence of extreme hyperbilirubinemia dropped nearly 3-fold, to 1 in 4037. Before the program, the occurrence of hazardous hyperbilirubinemia (
30 mg/dL) was approximately 1 in 9742, similar to the occurrence reported by others.17,35 Subsequently, only 3 neonates in our population had documented bilirubin levels
30 mg/dL, giving an incidence of 1 in 17494. All 3 of these cases occurred in the first months after adopting the program and none have been observed since.
The results of several studies indicate that hyperbilirubinemia is the most common cause of readmission to the hospital in the first 2 weeks of life.27,3638 Published rates of readmission range from 1.7 to 30.2 per 1000 live births.17 Before our program, our readmission rate for jaundice was 5.5 per 1000, but after implementing the guidelines, our readmission rate dropped to 4.3 per 1000.
One of the 13 neonates who developed TSB levels
25 mg/dL did not have a predischarge bilirubin value recorded. The remaining 12 did, and all were above the 75th percentile. Oversight or failure to ensure postdischarge follow-up of these patients, and the apparent lack of parental education regarding neonatal jaundice, may have contributed to the hyperbilirubinemia in these patients. Three of the 13 patients had isoimmunization; arrangements for home phototherapy were made for all 3. Unfortunately, it was not administered as prescribed. The presumed etiology of severe hyperbilirubinemia in one was galactosemia and E coli bacteremia, but a pathologic disorder responsible for producing critical levels of bilirubin could not be identified in the other 9 patients. However, all 9 had at least 1 risk factor for significant hyperbilirubinemia. The results of several studies have clearly documented that neonates 35 to 37 weeks' gestation are more likely to develop significant hyperbilirubinemia than are those 38 to 42 weeks' gestation.35,38,39 Six of those in our study population who developed bilirubin values
25 mg/dL were born at <38 weeks' gestation. One infant of partial Asian ethnicity had a cephalohematoma and bruising secondary to a difficult delivery, the older sibling and father of 1 had a history of significant neonatal hyperbilirubinemia, and 1 mother had insulin-dependent gestational diabetes.
As described by Volpe,5 the early phase of ABE involves lethargy and hypotonia. The principal signs of the next or intermediate phase of ABE are moderate stupor, irritability, and hypertonia. Increased tone is most prominent in extensor muscles manifested by backward arching of the neck (retrocollis) and the trunk (opisthotonos). The advanced phase of ABE is characterized by pronounced retrocollis and opisthotonos, shrill cry, no feeding, apnea, fever, deep stupor to coma, sometimes seizures, and death. The majority of infants that reach the advance phase of ABE go on to develop chronic postkernicteric bilirubin encephalopathy. Review of the readmission records of 12 of the 13 neonates who developed TSB levels
25 mg/dL did not identify any clinical evidence of ABE. Although the readmission record for patient 7 was not available, his follow-up neurodevelopmental examination was normal.
The results of our study demonstrate that prehospital discharge bilirubin screening, across a large hospital corporation, coupled with the evaluation of serum bilirubin concentrations using a percentile-based nomogram, can identify neonates who are at risk for severe hyperbilirubinemia. Using this screening strategy can allow decisions to be made based on predischarge risk assessment. Consequently, health care providers have the opportunity to target surveillance and provide a more selective approach to the follow-up of at-risk neonates.
| ACKNOWLEDGMENTS |
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We thank Ronald Stoddard, MD, for general encouragement and suggestions on the manuscript and Erick Henry for statistical assistance.
| FOOTNOTES |
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Accepted Nov 15, 2005.
Address correspondence to Larry D. Eggert, MD, Dixie Regional Medical Center, 544 S 400 E Campus, St George, UT 84770. E-mail: larry.eggert{at}ihc.com.
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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25 mg/dL. The lower blue line designates the number of neonates with bilirubin levels 



