The incidence of kernicterus is low but not negligible in developed countries, approximate 0.4 to 2.7 per live

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1 Total Serum Bilirubin Exceeding Exchange Transfusion Thresholds in the Setting of Universal Screening Valerie J. Flaherman, MD, MPH 1, Michael W. Kuzniewicz, MD, MPH 1,2, Gabriel J. Escobar, MD 2, and Thomas B. Newman, MD, MPH 1,2,3 Objective To describe the incidence and predictors of total serum bilirubin (TSB) levels that meet or exceed American Academy of Pediatrics (AAP) exchange transfusion (ET) thresholds in the setting of universal screening. Study design We conducted a retrospective cohort analysis of electronic data on newborns $35 weeks gestation born at Northern California Kaiser Permanente Medical Care Program hospitals implementing universal TSB screening in 2005 to 2007, with chart review for subjects with TSB levels reaching the AAP threshold for ET. Results The outcome developed in 22 infants (0.12%); 14 (63.6%) were <38 weeks gestation. Only one infant received an ET; none of the infants had documented sequelae. The first TSB was at least high-intermediate risk on the AAP risk-nomogram for all 22 infants and high-risk for those $38 weeks, but was less than the phototherapy level in 15 infants (68%). Of these 15 infants, 2 failed phototherapy and 13 did not have a TSB repeated in <24 hours. However, re-testing all infants at high-intermediate risk or greater would have required 2166 additional bilirubin tests. Conclusion Screening was sensitive but not specific for predicting exchange threshold. (J Pediatr 2012;160: ). The incidence of kernicterus is low but not negligible in developed countries, approximate 0.4 to 2.7 per live births. 1-7 The American Academy of Pediatrics (AAP) issued guidelines on the management of hyperbilirubinemia in 2004, which included a graph categorizing infant risk of future hyperbilirubinemia on the basis of an hour-specific serum bilirubin level and treatment graphs identifying total serum bilirubin (TSB) thresholds for phototherapy and exchange transfusion (ET). 8 The risk-defining graph may be used to interpret screening TSB results and was based on a similar graph developed by Bhutani in The guidelines suggest ET when TSB exceeds ET treatment graph thresholds for infants in whom phototherapy has failed, who have symptoms of bilirubin encephalopathy, and with TSB levels $5 mg/dl higher than the thresholds. These guidelines were supplemented in 2009 by recommendations drafted by a panel of bilirubin experts. 10 The authors recommended universal screening and more structured follow-up. Specifically, they recommend follow-up TSB within 24 hours for all infants with screening TSB in the high-risk category of the AAP risk nomogram and within 24 hours for all infants <38 weeks with screening TSB in the high-intermediate risk category or higher. Although universal newborn bilirubin screening has been recommended by these and other experts for the prevention of serious outcomes of hyperbilirubinemia, 10,11 the United States Preventive Services Task Force recently concluded that there is insufficient evidence to recommend for or against universal bilirubin screening. 12,13 One piece of evidence needed to assess the effectiveness of universal screening is why severe hyperbilirubinemia still develops in some infants despite universal screening. Kuzneiwicz et al found that the incidence of TSB $25 mg/dl levels decreased by >70% after implementation of universal bilirubin screening in the Kaiser Permanente Medical Care Program (KPMCP). 14 However, although reduced in frequency, TSB levels $25 mg/dl still occurred despite universal screening. Whether the continuing occurrence of severe hyperbilirubinemia was caused by falsely reassuring screening TSB levels or ineffective or insufficient follow-up or treatment of infants known to be at risk is unknown. Taking advantage of a universal screening program implemented at 5 Northern California KPMCP hospitals that used TSB to implement universal screening, we examined the incidence in 2005 to 2007 of the development of TSB levels that ever met or exceeded AAP-recommended thresholds for ET. We report on the sensitivity of the risk-defining graph for predicting this outcome and compare the treatment and follow-up received by these newborns with that recommended by guidelines AAP DAT ET G6PD KPMCP PT TSB 796 American Academy of Pediatrics Direct antiglobulin tests Exchange transfusion Glucose-6-phosphate dehydrogenase deficiency Kaiser Permanente Medical Care Program Phototherapy Total serum bilirubin From the 1 Department of Pediatrics, and 3 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; and 2 Kaiser Permanente, Division of Research, Oakland, CA V.F. was supported by National Center for Research Resources (grant KL2 RR024130), National Institute of Child Health and Human Development (grant 5 K12 HD ), and National Institute of Child Health and Human Development (grant 1 K23HD059818). T.N., M.K., and G.E. were supported by National Institute of Children Health and Human Development (R01 HD047557). The authors declare no conflicts of interest /$ - see front matter. Copyright ª 2012 Mosby Inc. All rights reserved /j.jpeds

2 Vol. 160, No. 5 May 2012 in existence during the cohort period and with new recommendations published subsequently. Methods A total of babies were born at $35 weeks gestation in 2005 to 2007 at 5 KPMCP hospitals (Sacramento, Santa Clara, South Sacramento, Vallejo, and Walnut Creek) during universal TSB screening, defined as occurring during months in which $95% of all infants had at least one TSB level and KPMCP policy included a guideline recommending universal screening. These 5 hospitals had adopted policies mandating TSB screening on all infants before discharge. We were unable to study the hospitals that implemented transcutaneous bilirubin screening because these test results were not captured electronically. Decisions to initiate phototherapy, readmit infants, and schedule follow-up testing were made at the discretion of the treating physicians. We excluded 124 babies (0.6%) who had no TSB documented, leaving babies. Because infants with TSB first measured at very early or very late ages may have been more likely to have their TSB drawn for clinical indications, we included only the infants (82.1%) whose TSB was drawn at 18 to 60 hours of age. This study was approved by the UCSF Committee on Human Research and the KPMCP Institutional Review Board. Predictor Variables From existing KPMCP databases, we obtained data on sex, gestational age, race/ethnicity, and birth hospital for all infants. We extracted all direct antiglobulin tests (DAT) and TSB values for the first month after birth, with methods previously described Almost all TSB measurements (99.9%) were obtained with the Vitros BuBc platform (Ortho Clinical Diagnostics, Rochester, New York). We defined the screening TSB as a first TSB drawn when the infant was at least 18 hours and <60 hours of age and before discharge from birth hospitalization. For each screening TSB value, we compared the value to the 2004 AAP risk-defining graph by parameterizing the curve using visual estimation of slope and intercept in 6- to 12-hour intervals. We labeled each screening TSB as high risk, high-intermediate risk, low-intermediate risk, or low risk according to the risk-defining graph. Outcome Variables To determine whether an infant s maximum TSB level ever reached or exceeded AAP-recommended thresholds for phototherapy or ET, we compared each TSB level to the 2004 treatment threshold level for phototherapy and ET on the basis of the treatment curve for the appropriate infant risk group. 8 We assigned risk group on the basis of gestational age and DAT result (low risk, $38 weeks and without positive DAT; medium risk, $38 weeks and positive DAT or <38 weeks and without positive DAT; high risk, <38 weeks and positive DAT). We reviewed the medical records of the infants in whom TSB levels equal to or greater than AAP thresholds for ET developed. We collected reported feeding method, use and timing of phototherapy, use and timing of ET, presence of cephalohematoma or other bruising, and report of additional medical problems and pre- or co-existing conditions. Statistical Methods We performed all analyses with Stata software version 9.2 (Stata Corp, College Station, Texas). For those infants whose TSB ever met or exceeded AAP-recommended thresholds for ET, examining the medical records augmented the electronic data and confirmed no discrepancies between electronic measures and paper medical record. We report clinical characteristics of infants whose TSB met or exceeded AAPrecommended ET levels and test characteristics of the AAP risk graph with descriptive statistics. Results Demographic characteristics and initial laboratory tests of the entire cohort and of infants eventually exceeding AAPrecommended thresholds for ET are contrasted in the Table. Approximately half the infants, 9253 (51.2%), underwent screening TSB in the high-intermediate-risk or high-risk zone of the AAP risk-defining graph, including 2584 infants (14.3%) in the high-risk zone. For the 3 treatment groups for the AAP guideline defined on the basis of the risk of bilirubin toxicity, in our cohort infants (85.8%) were in the low-risk treatment group, 2548 (14.1%) were in the medium-risk treatment group, and 14 (0.1%) were in the high-risk treatment group before screening. The maximum TSB value of 22 babies (0.12%; 95% CI, 0.08%-0.18%) reached or exceeded the ET threshold. Their mean screening TSB value was mg/dl (range, mg/dl), measured at hours (range, hours). Their mean maximum TSB level was 23.7 mg/dl 2.4 (range, mg/dl). Three of these 22 infants (13.6%) were DAT-positive; in the entire cohort, 188 infants (1.0%) were DAT-positive. Thus, DAT-positivity was a strong predictor of eventually meeting or exceeding AAP-recommended ET thresholds, with a relative risk of 13.2 (95% CI, ). Seven of these 22 infants were tested for glucose-6-phosphate dehydrogenase deficiency (G6PD); one infant had a G6PD level of 4.5, potentially consistent with mild G6PD, and the other 6 had normal levels. None of the 22 infants received a diagnosis of any other hematologic abnormality, none were documented with asphyxia, significant lethargy, temperature instability, sepsis, acidosis or hypoalbuminemia, and none had signs of bilirubin encephalopathy or sequelae documented in their medical records. All infants except one were breastfed. Three infants were noted to have cephalohematomas or extensive bruising before discharge from birth hospitalization. Other than breastfeeding, bruising, lower gestational age, potential mild G6PD deficiency, and positive DAT, no other pre-existing or coexisting conditions were identified that might have contributed to hyperbilirubinemia in the 22 infants. Of the 22 infants, 14 (63.6%) were <38 weeks gestation, giving a relative risk of 10.7 (95% CI, ) when compared with infants $38 weeks gestation. One of these

3 THE JOURNAL OF PEDIATRICS Vol. 160, No. 5 Table. Demographic and clinical characteristics of cohort and infants meeting or exceeding AAP-recommended threshold for ET Infants meeting or exceeding AAP-recommended Entire cohort (n = ) threshold for ET (n = 22) Male sex 9381 (51.9%) 12 (54.5%) White non-hispanic 7074 (39.1%) 8 (36.4%) Asian non-hispanic 4210 (23.3%) 5 (22.7%) Black non-hispanic 1209 (6.7%) 1 (4.5%) Hispanic 4121 (22.8%) 6 (27.3%) Other race 1475 (8.2%) 2 (9.1%).98 Gestational age <38 weeks 2388 (13.2%) 14 (63.6%) <.0005 Screening TSB level, mg/dl <.0005 Max TSB level, mg/dl <.0005 Positive DAT results 188 (1%) 3 (13.6%) <.0005 Screening TSB greater than high risk on AAP 2584 (14.3%) 14 (63.6%) <.0005 risk-defining graph Screening TSB greater than high-intermediate 9253 (51.2%) 22 (100%) <.0005 risk on AAP risk-defining graph Low-risk treatment group* (85.8%) 6 (27.3%) Medium-risk treatment group 2548 (14.1%) 15 (68.2%) High-risk treatment group z 14 (0.1%) 1 (4.6%) <.0005 *Infants $38 weeks without positive DAT results. Infants 35 to 37-6/7 weeks without positive DAT results and infants $38 weeks with positive DAT results. zinfants 35 to 37-6/7 weeks with positive DAT results. P value infants did not undergo screening of TSB because of discharge from birth hospitalization at 2 hours of life against medical advice. Of the 21 infants with screening TSB before discharge, 15 infants (including all of the infants $38 weeks gestation) had screening TSB levels in the high-risk zone of the AAP risk-defining graph. The other 6 had screening TSB in the high-intermediate risk zone of the AAP riskdefining graph (Figure 1). Of the 21 infants with timely screening, one had screening TSB already higher than the AAP ET threshold (Figure 2; available at This infant was 20 hours old at the age of screening and was not documented to have appeared icteric before that time; he received an ET at 52 hours after birth and had a G6PD level of 4.5 reported after discharge. Five additional infants had screening TSB already higher than the AAP phototherapy threshold, although only Figure 1. Screening TSB levels by age for infants whose TSB eventually met or exceeded AAP-recommended thresholds for ET. two of these 5 received phototherapy during their birth hospitalization. In the entire cohort, 294 of 363 infants (81.0%) with a screening TSB level at or greater than the AAP phototherapy threshold received phototherapy during their birth hospitalization. Therefore, of 69 infants who did not receive timely phototherapy after screening TSB levels greater than the AAP-recommended thresholds for phototherapy, TSB greater than AAP-recommended thresholds for ET developed in 3 (4.3%). Of 294 cohort infants with screening TSB equal to or greather than the AAP phototherapy threshold who did receive timely phototherapy, the study outcome developed in two (0.68%): one had a high rebound TSB level after discontinuing phototherapy, and one had a rise in TSB despite phototherapy. Fifteen infants were below the AAP-recommended threshold for phototherapy at screening. Of these 15 infants, two were retested within 24 hours of screening TSB and 13 were not, including 7 infants in the high-risk zone and 6 infants with gestational age <38 weeks in the high-intermediate-risk zone. We also examined follow-up bilirubin testing in the entire cohort. Of 2223 cohort babies with screening TSB levels in the high-risk zone but less than the phototherapy threshold, 1446 (65%) did not receive a second test within 24 hours. Similarly, of 932 infants <38 weeks with screening TSB levels in the highintermediate-risk zone, 720 (77%) did not have a repeat test within 24 hours. A total of 159 infants received phototherapy during the birth hospitalization despite screening TSB levels less than the AAP high-intermediate risk. Management subsequent to the development of our main outcome of TSB meeting recommended ET thresholds was as follows. Of the 22 infants in whom the outcome developed, one received an ET and 16 had documented declines in TSB after initiation of phototherapy (PT). Start times for PT were sometimes not well documented, but on the basis of rapidly declining TSB levels, it appears that these 16 infants 798 Flaherman et al

4 May 2012 ORIGINAL ARTICLES were treated in accordance with AAP guidelines. Five infants were not observed according to guidelines, because they were not documented to have received either ET or phototherapy for their first TSB level greater than the exchange level. In 3 cases, the TSB was documented to decline without phototherapy, and in two cases, phototherapy was initiated after a subsequent higher TSB level, after which it declined quickly. Discussion In the setting of universal TSB screening, we found that the incidence of ever meeting or exceeding AAP-recommended thresholds for ET was low but not negligible at a ratio of 1.2 per 1000 live births. Of the 22 infants who ever had this outcome in the setting of universal screening, we found that 4 outcomes (18%) might be attributable to incomplete adherence to existing guidelines, including one infant who was not screened before hospital discharge and 3 infants who did not receive timely phototherapy after a screening TSB exceeded the AAP s recommended thresholds for phototherapy. We also found that 13 outcomes might have been prevented by follow-up according to 2009 recommendations. 10 However, in these 22 infants, no evidence of short-term morbidity or sequelae associated with hyperbilirubinemia was found with a chart review. Only one infant received ET, and that infant was treated according to AAP guidelines. All 22 infants were described as recovering uneventfully, but longer-term outcomes are not available. Infants of <38 weeks gestational age were at much higher risk of eventual TSB level meeting or exceeding AAPrecommended thresholds for ET, with a 10-fold increase in incidence compared with term infants. Gestational age remained a strong predictor in our study, even in the subgroup of infants with screening TSB levels meeting or exceeding AAPrecommended thresholds for phototherapy. This may be largely be because the 2004 guidelines define lower ET thresholds for infants born at <38 weeks. Race/ethnicity was not a predictor of TSB level meeting AAP-recommended thresholds of PT, perhaps suggesting that clinicians correctly estimate the clinical risk for these infants and tailor follow-up and treatment plans accordingly. Our study also found that 51.2% of newborns had screening TSB levels greater than the high-intermediate risk threshold of the AAP risk-defining graph. This is concerning because a screening test that identifies more than half of all healthy infants as at-risk for a future outcome may be inefficient because of low specificity. However, an encouraging result is that the AAP risk-defining graph highintermediate risk line had 100% sensitivity rate for predicting eventual TSB meeting or exceeding thresholds for ET. For infants $38 weeks, the high-risk line also had 100% sensitivity. These findings suggest that term infants with screening TSB less than the high-risk levels and infants <38 weeks with screening TSB less than high-intermediate risk levels are at low risk of the eventually development of significant hyperbilirubinemia. Although infants with positive DAT results were at higher risk of the outcome, only 3 of 188 (1.6%) ever exceeded exchange thresholds. This is somewhat surprising, because positive DAT results lead to a lower AAP threshold for exchange. It seems likely that early identification of infants with positive DAT results led to management that successfully prevented the TSB from meeting ET thresholds. Of 2223 cohort babies with screening TSB levels in the high-risk zone but less than the phototherapy threshold, 1446 (65%) did not receive a second test within 24 hours, and of 932 infants <38 weeks with screening TSB levels in the high-intermediate-risk zone, 720 (77%) did not have a repeat test within 24 hours. Therefore, implementation of new recommendations to repeat TSB within 24 hours when screening TSB is in the high-risk zone or when the newborn is <38 weeks gestation with screening TSB in the highintermediate-risk zone would have required 2166 additional babies to receive follow-up testing within 24 hours in this cohort. These 2166 babies would need to be re-tested within 24 hours to prevent (at most) 13 from exceeding the AAP-recommended threshold for ET. Thus, if the followup testing and resulting treatment were 100% effective, approximately 167 infants would need to receive follow-up TSB testing to potentially prevent one outcome. Our analysis of patient treatment subsequent to the development of the outcome of TSB level exceeding recommended ET thresholds identified 17 infants who were treated according to AAP guidelines after the development of TSB levels exceeding the ET threshold. Five infants were not treated according to the AAP guidelines after the development of TSB exceeding the ET threshold. Further research is needed to determine risks associated with management in discordance with AAP guidelines once TSB has exceeded the recommended threshold for ET. Our study has several important limitations. First, all study infants received routine clinical care, including phototherapy. Some infants received phototherapy during the birth hospitalization despite screening TSB levels less than the AAP highintermediate risk, which may have prevented some of these lower-risk infants TSB levels from exceeding the AAP ET, raising apparent sensitivity. Testing for potential hemoloytic conditions such as G6PD occurred at the discretion of the treating physician, and therefore some infants may have had conditions that were not identified. Second, almost all TSB levels were measured with the Vitros method of analysis. A recent study by Lo et al suggested that the Vitros method may overestimate TSB levels by approximately 10% to 15%. 17 Falsely high TSB levels may be an explanation for the 100% sensitivity rate observed in our study for the AAP risk-defining graph. However, over-diagnosis of hyperbilirubinemia does not explain the low incidence of TSB meeting or exceeding ETs. Third, we may have some loss to follow-up because some infants born at KPMCP may have received care at non-kpmcp facilities after discharge from birth hospitalization. However, because all infants born to mothers who are members of KPMCP are covered members for the first month after birth, substantial error from this cause is unlikely. Fourth, the recommended AAP treatment thresholds vary not just with direct antiglobulin test status and gestational age, but also with G6PD deficiency, Total Serum Bilirubin Exceeding Exchange Transfusion Thresholds in the Setting of Universal Screening 799

5 THE JOURNAL OF PEDIATRICS Vol. 160, No. 5 asphyxia, significant lethargy, temperature instability, sepsis, acidosis, and albumin levels. Data on these factors were not available for all cohort infants, although we did conduct chart review for the 22 infants in our study with an outcome of TSB meeting ET thresholds and did not find evidence of these risk factors in any of the 22 infants. Our study demonstrates a low incidence of TSB levels meeting or exceeding AAP-recommended thresholds for ET in a setting of universal screening. In our study, adherence to AAP guidelines was incomplete, which is consistent with earlier literature on guideline adherence in this field. 14,18-21 New recommendations might further decrease the incidence of TSB levels meeting or exceeding AAP-recommended thresholds for ET, but would require greatly increased rates of TSB re-testing within 24 hours. Greater use of transcutaneous bilirubin measurement would reduce the need for many TSB tests. 22 We also demonstrate that infants of <38 weeks gestation remain at increased risk for bilirubin levels exceeding AAP-recommended exchange thresholds even in a setting of universal screening. Further studies are needed to see whether these findings apply in other settings and to weigh the benefit of preventing TSB levels greater than the AAP exchange threshold with the cost and inconvenience of large increases in repeat TSB testing. n Submitted for publication Apr 4, 2011; last revision received Aug 26, 2011; accepted Sep 29, Reprint requests: Valerie J. Flaherman, MD, MPH, Assistant Professor of Pediatrics, University of California, San Francisco, 3333 California St, Box 0503, San Francisco, CA FlahermanV@peds.ucsf.edu References 1. Manning D, Todd P, Maxwell M, Jane Platt M. Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed 2007;92:F Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006;175: Bjerre JV, Petersen JR, Ebbesen F. Surveillance of extreme hyperbilirubinaemia in Denmark. A method to identify the newborn infants. Acta Paediatr 2008;97: Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR, et al. Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr 2005;94: Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM. Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, Pediatrics 2009;123: Brooks JC, Fisher-Owens SA, Wu YW, Strauss DJ, Newman TB. Evidence suggests there was not a resurgence of kernicterus in the 1990s. Pediatrics 2011;127: Burgos AE, Flaherman VJ, Newman TB. Screening and follow-up for neonatal hyperbilirubinemia: a review. Clin Pediatr (Phila). Epub ahead of print. 8. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114: Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103: Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the newborn infant > or =35 weeks gestation: an update with clarifications. Pediatrics 2009;124: Bhutani VK, Johnson LH, Schwoebel A, Gennaro S. A systems approach for neonatal hyperbilirubinemia in term and near-term newborns. J Obstet Gynecol Neonatal Nurs 2006;35: Trikalinos TA, Chung M, Lau J, Ip S. Systematic review of screening for bilirubin encephalopathy in neonates. Pediatrics 2009;124: Adhikari M. Tuberculosis and tuberculosis/hiv co-infection in pregnancy. Semin Fetal Neonatal Med 2009;14: Kuzniewicz MW, Escobar GJ, Newman TB. Impact of universal bilirubin screening on severe hyperbilirubinemia and phototherapy use. Pediatrics 2009;124: Kuzniewicz MW, Escobar GJ, Wi S, Liljestrand P, McCulloch C, Newman TB. Risk factors for severe hyperbilirubinemia among infants with borderline bilirubin levels: a nested case-control study. J Pediatr 2008;153: Newman TB, Kuzniewicz MW, Liljestrand P, Wi S, McCulloch C, Escobar GJ. Numbers needed to treat with phototherapy according to American Academy of Pediatrics guidelines. Pediatrics 2009;123: Lo SF, Jendrzejczak B, Doumas BT. Laboratory performance in neonatal bilirubin testing using commutable specimens: a progress report on a College of American Pathologists study. Arch Pathol Lab Med 2008; 132: Newman TB, Liljestrand P, Escobar GJ. Jaundice noted in the first 24 hours after birth in a managed care organization. Arch Pediatr Adolesc Med 2002;156: Atkinson LR, Escobar GJ, Takayama JI, Newman TB. Phototherapy use in jaundiced newborns in a large managed care organization: do clinicians adhere to the guideline? Pediatrics 2003;111(5 Pt 1):e Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/=2000 grams at birth: a population-based study. Pediatrics 2000;106(2 Pt 1): Newman TB, Liljestrand P, Escobar GJ. Infants with bilirubin levels of 30 mg/dl or more in a large managed care organization. Pediatrics 2003; 111(6 Pt 1): Maisels MJ, Engle WD, Wainer S, Jackson GL, McManus S, Artinian F. Transcutaneous bilirubin levels in an outpatient and office population. J Perinatol 2011;31: Flaherman et al

6 May 2012 ORIGINAL ARTICLES 22 Infants 1 not screened 21 screened 15 with screening TSB below phototherapy threshold 6 with screening TSB meeting or exceeding phototherapy threshold 13 did not have TSB rechecked in 24 hours 2 with phototherapy had repeat TSB exceeding exchange 5 with screening TSB greater than phototherapy threshold and below exchange threshold 1 with screening TSB exceeding exchange threshold 3 had delayed phototherapy 2 had timely phototherapy TSB ET despite adherence to both guidelines and new recommendations TSB ET was potentially preventable by adherence to existing guidelines TSB ET was potentially preventable by adherence to new recommendations Figure 2. Possible impact of existing guidelines and new recommendations on eventual outcome of one or more TSB levels meeting or exceeding thresholds recommended by the AAP for treatment with ET. Total Serum Bilirubin Exceeding Exchange Transfusion Thresholds in the Setting of Universal Screening 800.e1