Bilirubin Encephalopathy.

PURPOSE OF REVIEW: Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries. RECENT FINDINGS: The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study.

BACKGROUND: Hyperbilirubinemia is one of the most common diagnosis in newborn nurseries in United States. Universal pre-discharge bilirubin screening decreased the incidence of extreme hyperbilirubinemia and risk of kernicterus. OBJECTIVES: We sought to assess temporal population trends of hyperbilirubinemia, kernicterus and usage of phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. DESIGN/METHODS: Data from Healthcare Cost and Utilization Project (HCUP)-the Kids' Inpatient Database (KID) obtained for years 1997-2012. All neonatal discharges with ICD-9 codes for neonatal jaundice (774.2, 774.6), kernicterus (773.4, 774.7) and procedure codes for phototherapy (99.83), IVIG infusion (99.14), exchange transfusion (99.01) were extracted. We compared the trends of diagnosis of hyperbilirubinemia, kernicterus, use of phototherapy, IVIG, and exchange transfusion. RESULTS: During the study period, the proportion of infants diagnosed with hyperbilirubinemia increased by 65% (9.4% vs. 15.5%; p<.001) in term infants and 34.5% (33.5% vs. 45%; p<.001) in preterm infants, respectively. Rate of kernicterus discharges significantly reduced from 7 to 1.9 per 100,000 newborns. Overall, the number of exchange transfusions has decreased by 67% during study period while phototherapy and IVIG use increased by 83% and 170%, respectively. CONCLUSIONS: In last two decades, there was a significant decrease in neonatal discharges with a history of exchange transfusion or with a diagnosis of kernicterus. However, there was a significant increase in number of neonates discharged home with a history of phototherapy during birth hospitalization and decreased number of exchange transfusions were observed during the study period. Incremental implementation of universal predischarge bilirubin screening and treatments based on 2004 AAP recommended risk-based strategies might have contributed to timely interventions in infants with significant hyperbilirubinemia.

Neonatal Jaundice in Preterm Infants with Bilirubin Encephalopathy.

INTRODUCTION: The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). METHODS: We asked the responders to an earlier nationwide Japanese survey on pBE to provide additional information. pBE was diagnosed based on the criteria used in the nationwide survey. We collected data on serum total bilirubin (TB), direct bilirubin (DB), albumin, and unbound bilirubin (UB) levels during the first 8 weeks of life, and on phototherapy and exchange transfusion treatments. RESULTS: We obtained clinical data from 75 patients with pBE from 58 hospitals (response rate of 59%), who were born between 2002 and 2016. The average peak TB level was 12.6 mg/dL (215 µmol/L), and the average age at peak attainment was 19.7 days after birth. Albumin level was <2.5 g/dL in 44 patients, and the peak DB level was ≥2 mg/dL (34.2 µmol/L) in 20 patients. The average peak bilirubin/albumin (B/A) (mg/g) ratio was 3.8 (molar ratio of 0.475), and the average age at peak attainment was 18.6 days. The average peak UB level was 0.67 µg/dL (11.5 nmol/L). The median duration of phototherapy was 6 days, and the median day of the last session was 12. The peak TB level occurred after the last day of phototherapy in 30 of the 61 patients available for comparison. CONCLUSIONS: Most patients with pBE lacked marked elevations in serum TB levels and the B/A ratio, the peaks of which were sometimes delayed to >4 weeks after birth.

[An update on unconjugated neonatal hyperbilirubinaemia in Denmark].

Approximately 60% of term newborn infants are jaundiced during the first week of life, which is caused by unconjugated bilirubin. Bilirubin encephalopathy is seen with severe hyperbilirubinaemia, when unbound bilirubin crosses the blood-brain barrier. The chronic form is called kernicterus spectrum disorder. To avoid this devastating condition, the treatment of choice for neonatal hyperbilirubinaemia is phototherapy, which is most efficient with LED light of 478-nm wavelength. In this review, we argue, that a systematic approach to hyperbilirubinaemic infants as well as surveillance of extreme neonatal hyperbilirubinaemia is highly important.

Extreme neonatal hyperbilirubinemia and kernicterus spectrum disorder in Denmark during the years 2000-2015.

OBJECTIVE: To determine the incidence and etiology of extreme neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥450 µmol/L, and kernicterus spectrum disorder (KSD) in Denmark between 2000 and 2015. STUDY DESIGN: We identified all infants born between 01.01.2000 and 31.12.2015 with TSB ≥450 µmol/L, ratio of conjugated to TSB <0.30, gestational age ≥35 weeks, and postnatal age ≤4 weeks, using Danish hospitals' laboratory databases. RESULT: We included 408 infants. The incidence of extreme neonatal hyperbilirubinemia among infants with gestational age ≥35 weeks was 42/100,000 during the study period with a seemingly decreasing incidence between 2005 and 2015. Twelve of the 408 infants developed KSD, (incidence 1.2/100,000) Blood type ABO isohemolytic disease was the most common explanatory etiology. CONCLUSIONS: Our study stresses the importance of a systematic approach to neonatal jaundice and ongoing surveillance of extreme neonatal hyperbilirubinemia and KSD.

Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden.

Importance: Neonatal hyperbilirubinemia can cause lifelong neurodevelopmental impairment (kernicterus) even in high-resource settings. A better understanding of the incidence and processes leading to kernicterus may help in the design of preventive measures. Objectives: To determine incidence rates of hazardous hyperbilirubinemia and kernicterus among near-term to term newborns and to evaluate health care professional adherence to best practices. Design, Setting, and Participants: This population-based nationwide cohort study used prospectively collected data on the highest serum bilirubin level for all infants born alive at 35 weeks' gestation or longer and admitted to neonatal care at all 46 delivery and 37 neonatal units in Sweden from 2008 to 2016. Medical records for newborns with hazardous hyperbilirubinemia were evaluated for best neonatal practices and for a diagnosis of kernicterus up to 2 years of age. Data analyses were performed between September 2017 and February 2018. Exposures: Extreme (serum bilirubin levels, 25.0-29.9 mg/dL [425-509 µmol/L]) and hazardous (serum bilirubin levels, ≥30.0 mg/dL [≥510 µmol/L]) neonatal hyperbilirubinemia. Main Outcomes and Measures: The primary outcome was kernicterus, defined as hazardous neonatal hyperbilirubinemia followed by cerebral palsy, sensorineural hearing loss, gaze paralysis, or neurodevelopmental retardation. Secondary outcomes were health care professional adherence to national guidelines using a predefined protocol with 10 key performance indicators for diagnosis and treatment as well as assessment of whether bilirubin-associated brain damage might have been avoidable. Results: Among 992 378 live-born infants (958 051 term births and 34 327 near-term births), 494 (320 boys; mean [SD] birth weight, 3505 [527] g) developed extreme hyperbilirubinemia (50 per 100 000 infants), 6.8 per 100 000 infants developed hazardous hyperbilirubinemia, and 1.3 per 100 000 infants developed kernicterus. Among 13 children developing kernicterus, brain injury was assessed as potentially avoidable for 11 children based on the presence of 1 or several of the following possible causes: untimely or lack of predischarge bilirubin screening (n = 6), misinterpretation of bilirubin values (n = 2), untimely or delayed initiation of treatment with intensive phototherapy (n = 1), untimely or no treatment with exchange transfusion (n = 6), or lack of repeated exchange transfusions despite indication (n = 1). Conclusions and Relevance: Hazardous hyperbilirubinemia in near-term or term newborns still occurs in Sweden and was associated with disabling brain damage in 13 per million births. For most of these cases, health care professional noncompliance with best practices was identified, suggesting that a substantial proportion of these cases might have been avoided.

The Turkish Neonatal Jaundice Online Registry: A national root cause analysis.

BACKGROUND: Neonatal jaundice (NNJ) is common, but few root cause analyses based on national quality registries have been performed. An online registry was established to estimate the incidence of NNJ in Turkey and to facilitate a root cause analysis of NNJ and its complications. METHODS: A multicenter prospective study was conducted on otherwise healthy newborns born at ≥35 weeks of gestation and hospitalized for only NNJ in 50 collaborator neonatal intensive care units across Turkey over a 1-year period. Patients were analyzed for their demographic and clinical characteristics, treatment options, and complications. RESULTS: Of the 5,620 patients enrolled, 361 (6.4%) had a bilirubin level ≥25 mg/dL on admission and 13 (0.23%) developed acute bilirubin encephalopathy. The leading cause of hospital admission was hemolytic jaundice, followed by dehydration related to a lack of proper feeding. Although all infants received phototherapy, 302 infants (5.4%) received intravenous immunoglobulin in addition to phototherapy and 132 (2.3%) required exchange transfusion. The infants who received exchange transfusion were more likely to experience hemolytic causes (60.6% vs. 28.1%) and a longer duration of phototherapy (58.5 ± 31.7 vs. 29.4 ± 18.8 h) compared to infants who were not transfused (p < 0.001). The incidence of short-term complications among discharged patients during follow-up was 8.5%; rehospitalization was the most frequent (58%), followed by jaundice for more than 2 weeks (39%), neurological abnormality (0.35%), and hearing loss (0.2%). CONCLUSIONS: Severe NNJ and bilirubin encephalopathy are still problems in Turkey. Means of identifying at-risk newborns before discharge during routine postnatal care, such as bilirubin monitoring, blood group analysis, and lactation consultations, would reduce the frequency of short- and long-term complications of severe NNJ.

Effectiveness of universal hyperbilirubinemia screening on newborn health: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to assess the effectiveness of the universal hyperbilirubinemia screening program on common newborn health outcomes.Specifically, the review will assess: the incidence of severe hyperbilirubinemia/kernicterus/exchange transfusion, rate of readmission due to jaundice, length of hospital stay on birth admission, rate and utilization of phototherapy during birth hospitalization, and jaundice related emergency visits.

The enigma of low bilirubin kernicterus in premature infants: why does it still occur, and is it preventable?

Low bilirubin kernicterus in preterm neonates, though rare, remains an unpredictable and refractory form of brain injury. Hypoalbuminemia, co-morbid CNS insult(s), infection, and inflammation are contributing causes that, in many cases, appear to interact in potentiating bilirubin neurotoxicity. Despite compulsive attention to serum bilirubin levels, and clinical and laboratory indices of neurotoxicity risk, low bilirubin kernicterus continues to be seen in contemporary NICUs. While efforts to refine and improve current treatment guidelines are certainly needed, such revision(s) will also have to take into account the risks and benefits of any intervention, including phototherapy.

Prevention of neurodevelopmental sequelae of jaundice in the newborn.

Although its cause, jaundice in the newborn, is extremely common, the disabling neurological disorder kernicterus is very rare. Kernicterus may be prevented by selecting those infants who are at risk of extreme jaundice or who may be particularly vulnerable to bilirubin neurotoxicity. Because the tools for achieving that goal are inadequate, a secondary strategy is needed. This involves a plan for emergency treatment of severely jaundiced infants, in particular those who present with neurological symptoms. In this paper I review the strategies for preventing extreme jaundice, and for reversing neurotoxicity in those infants for whom the principal strategies fail. Briefly, the tools for prevention include measurement of bilirubin while the infant is staying in the maternity unit, plotting the value on an hour-specific chart, assessing other risk factors for jaundice, and educating the parents. Emergency treatment should include immediate, high-irradiance phototherapy, consideration of intravenous immune globulin, and preparation for an exchange transfusion.

Current Italian practices regarding the management of hyperbilirubinaemia in preterm infants.

AIM: To assess the current practices existing in Italy for the management of jaundice in preterm infants as preliminary achievement to a call for national guidelines and establishment of a kernicterus registry. METHODS: A questionnaire (in Supporting Information online) was sent to the 109 level III neonatal units in Italy to ascertain existing guidelines for total bilirubin monitoring and treatment of hyperbilirubinaemia in preterm infants and occurrence of kernicterus. RESULTS: There was a 61% (67/109) response rate. Eighty-five per cent of responding units had either written guidelines coming from different literature sources or locally developed. The monitoring of bilirubin varied greatly in timing before, during and after jaundice development. Phototherapy and exchange transfusion were given to 56.0 ± 21.0% and 0.2 ± 0.4% of admitted preterm infants in participating centres. Five cases of kernicterus in preterm infants and eleven cases in term infants were documented over the last 10 years. CONCLUSION: The management of hyperbilirubinaemia in preterm infants is not uniform in Italy and would benefit from shared national guidance together with establishment of a kernicterus registry to guide therapy.

Neonatal hyperbilirubinemia and kernicterus - not gone but sometimes forgotten.

The introduction of exchange transfusion made it possible to prevent severe hyperbilirubinemia and kernicterus, but kernicterus has never completely disappeared and it is still occurring in North America and, more frequently in Western Europe and the developing world. I discuss the epidemiology and major causes of severe hyperbilirubinemia and the potential root causes and system failures associated with the development of extreme hyperbilirubinemia and, subsequently, kernicterus. In the Western world, kernicterus remains a rare cause of cerebral palsy but, in contrast to the other causes of cerebral palsy, kernicterus should almost always be preventable. The key elements in preventing kernicterus are risk assessment and appropriate follow-up for the newborn infant and these are presented in a recently developed algorithm. Implementation of this approach might contribute to the prevention of severe hyperbilirubinemia and bilirubin encephalopathy.

Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, 1988-2005.

CONTEXT AND OBJECTIVE: Recent reports have raised global concerns about a reemergence of kernicterus. Accurate information on the incidence of kernicterus is unavailable because of the rarity of the condition and the lack of a systematic surveillance strategy. We used nationally representative hospital discharge data to evaluate trends in the diagnosis and management of neonatal jaundice and the incidence of kernicterus in relation to the American Academy of Pediatrics hyperbilirubinemia clinical practice guideline. PATIENTS AND METHODS: The data came from the Healthcare Cost and Utilization Project family of databases. The Nationwide Inpatient Sample and the Kids' Inpatient Database were combined to generate trend data for the years 1988-2005. All neonatal discharges with primary or secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes for jaundice or kernicterus occurring within the first 30 days of life were selected with population incidence rates calculated from estimates of term and preterm newborn hospitalizations derived from the Healthcare Cost and Utilization Project data. To increase the reliability of identified kernicterus hospitalizations, newborns with a diagnosis of kernicterus and a procedure code for phototherapy or exchange transfusion were included as cases. RESULTS: Hospital diagnosis codes for kernicterus likely included a substantial number of rule-out cases, because approximately 70% did not include a procedure code for phototherapy or exchange transfusion. Including only cases with a procedure code for phototherapy or exchange transfusion resulted in 2.7 per 100000 diagnosed with kernicterus over the entire study period. A diagnosis code for jaundice was recorded for 15.6% of newborns. The diagnosis of jaundice and kernicterus differed according to race and gender. Rates also were elevated in preterm relative to term infants for both jaundice and kernicterus. Trends in diagnosis for newborn jaundice were u-shaped, with rates falling in the years before the initial American Academy of Pediatrics guideline (1988-1993) and increasing in the years after publication of the guideline (1997-2005). In contrast, the number of newborn hospitalizations with a diagnosis of kernicterus generally declined throughout the study period. Most of the decline in hospitalizations for term infants with a diagnosis of kernicterus occurred before and immediately after publication of the 1994 guideline, going from 5.1 per 100000 in 1988 to 1.5 per 100000 in the years from 1994 to 1996 and has since remained constant. CONCLUSIONS: Nationally representative hospital data indicate a declining incidence of hospitalizations with a diagnosis of kernicterus in newborn infants over the period 1988-2005. The decline occurred before and immediately after publication of the 1994 American Academy of Pediatrics guideline on hyperbilirubinemia. Epidemiologic findings were mostly consistent with other studies. Healthcare Cost and Utilization Project data provide an important system for monitoring hospitalizations of uncommon newborn conditions such as kernicterus.

Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria.

BACKGROUND: Since exchange blood transfusion (EBT) is associated with serious complications, phototherapy has been made more powerful to reduce the need for EBT in the developed world. This study was undertaken to determine the indications for EBT in neonatal jaundice (NNJ) at our unit and what proportion of EBTs was possibly avoidable. METHODS: All the babies who had EBT for hyperbilirubinemia over a three-year period were included. Age, sex, weight, place of delivery, blood group of baby and mother, other investigations, management, and the outcome of the babies were recorded. RESULTS: Of the 1686 babies admitted to the neonatal unit, 90 (5.3%) had EBT. Fourteen (15.6%) were inborn while 76 (84.4%) were out-born babies. Fifty-six (62.2%) babies were admitted primarily for NNJ while 34 (37.8%) developed NNJ during admission. Thirty-six (40.0%) of the babies had phototherapy for more than 24 hours prior to EBT either because they were of very low birthweight or NNJ was detected very early and therapy was so commenced. Sixty-eight (75.6%) babies had single EBT while the remaining 22 (24.4%) had two sessions of EBT. Factors associated with severe NNJ in babies requiring EBT included low birthweight (<2500 g, 44.4%), ABO incompatibility (30.0%), glucose-6-phosphate dehydrogenase deficiency (34.4%) and septicemia (26.1%). Twenty-seven (30.0%) of the neonates developed features of kernicterus: 26 before admission while 1 during admission; all except one were delivered outside the hospital. CONCLUSIONS: The EBT rate in our center was high. With more effective phototherapy, EBT could be avoided in most of the babies who initially had phototherapy for more than 24 hours before EBT and repeated EBT sessions. Health education of the population at risk, especially pregnant women, and early referral at the primary health care level will reduce the burden of severe NNJ.

Clinical report from the pilot USA Kernicterus Registry (1992 to 2004).

To identify antecedent clinical and health services events in infants (>/=35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age 0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age 35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.

Neonatal hyperbilirubinemia.

Evidence of bilirubin-related brain damage has been reported in infants with kernicterus discharged as healthy from well-baby nurseries. Lapses in care have been attributed as root causes for kernicterus in an era when there should be no barriers to safe and effective bilirubin reduction strategies. Between 1984 and 2002, at least 125 cases of kernicterus occurred in the United States. This may be an underestimate because kernicterus is not a reportable condition in this country. In almost all cases, kernicterus is a preventable condition. The updated 2004 American Academy of Pediatrics guidelines recommend a systems approach, which, if implemented by all birthing institutions, should prevent virtually all cases of kernicterus in term and near-term infants.

Management of neonatal hyperbilirubinemia: pediatricians' practices and educational needs.

BACKGROUND: Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994. METHODS: A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia. RESULTS: The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37-38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility. CONCLUSION: The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern.

An evidence-based review of important issues concerning neonatal hyperbilirubinemia.

This article is adapted from a published evidence report concerning neonatal hyperbilirubinemia with an added section on the risk of blood exchange transfusion (BET). Based on a summary of multiple case reports that spanned more than 30 years, we conclude that kernicterus, although infrequent, has at least 10% mortality and at least 70% long-term morbidity. It is evident that the preponderance of kernicterus cases occurred in infants with a bilirubin level higher than 20 mg/dL. Given the diversity of conclusions on the relationship between peak bilirubin levels and behavioral and neurodevelopmental outcomes, it is apparent that the use of a single total serum bilirubin level to predict long-term outcomes is inadequate and will lead to conflicting results. Evidence for efficacy of treatments for neonatal hyperbilirubinemia was limited. Overall, the 4 qualifying studies showed that phototherapy had an absolute risk-reduction rate of 10% to 17% for prevention of serum bilirubin levels higher than 20 mg/dL in healthy infants with jaundice. There is no evidence to suggest that phototherapy for neonatal hyperbilirubinemia has any long-term adverse neurodevelopmental effects. Transcutaneous measurements of bilirubin have a linear correlation to total serum bilirubin and may be useful as screening devices to detect clinically significant jaundice and decrease the need for serum bilirubin determinations. Based on our review of the risks associated with BETs from 15 studies consisting mainly of infants born before 1970, we conclude that the mortality within 6 hours of BET ranged from 3 per 1000 to 4 per 1000 exchanged infants who were term and without serious hemolytic diseases. Regardless of the definitions and rates of BET-associated morbidity and the various pre-exchange clinical states of the exchanged infants, in many cases the morbidity was minor (eg, postexchange anemia). Based on the results from the most recent study to report BET morbidity, the overall risk of permanent sequelae in 25 sick infants who survived BET was from 5% to 10%.