AMERICAN ACADEMY OF PEDIATRICS TECHNICAL REPORT Stanley Ip, MD; Mei Chung, MPH; John Kulig, MD, MPH; Rebecca O’Brien, MD; Robert Sege, MD, PhD; Stephan Glicken, MD; M. Jeffrey Maisels, MB, BCh; and Joseph Lau, MD, and the Subcommittee on Hyperbilirubinemia An Evidence-Based Review of Important Issues Concerning Neonatal Hyperbilirubinemia ABSTRACT. 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 oc- curred in infants with a bilirubin level higher than 20 mg/dL. Given the diversity of conclusions on the rela- tionship 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 con- flicting results. Evidence for efficacy of treatments for neonatal hyperbilirubinemia was limited. Overall, the 4 qualifying studies showed that phototherapy had an ab- solute 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 determina- tions. 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 ex- changed infants who were term and without serious he- molytic diseases. Regardless of the definitions and rates of BET-associated morbidity and the various pre-ex- change clinical states of the exchanged infants, in many cases the morbidity was minor (eg, postexchange ane- mia). Based on the results from the most recent study to report BET morbidity, the overall risk of permanent se- quelae in 25 sick infants who survived BET was from 5% to 10%. Pediatrics 2004;114:e130 –e153. URL: http://www. pediatrics.org/cgi/content/full/114/1/e130; evidence-based review, hyperbilirubinemia, bilirubin, exchange transfu- sion, kernicterus, brainstem auditory evoked potential, brainstem auditory evoked response. ABBREVIATIONS. AAP, American Academy of Pediatrics; AHRQ, Agency for Healthcare Research and Quality; TcB, trans- cutaneous bilirubin; GA, gestational age; EGA, estimated gesta- tional age; BET, blood exchange transfusion; Rh, rhesus; TSB, total serum bilirubin; NNT, number needed to treat; NICHD, National Institute of Child Health and Human Development; ROC, receiver operating characteristics; AUC, area under the curve; BAER, brainstem auditory evoked response; CPP, Collaborative Perinatal Project; BAEP, brainstem auditory evoked potential; CI, confi- dence interval; HPLC, high-performance liquid chromatography. T he American Academy of Pediatrics (AAP) re- quested an evidence report from the Agency for Healthcare Research and Quality (AHRQ) that would critically examine the available evidence regarding the effect of high levels of bilirubin on behavioral and neurodevelopmental outcomes, role of various comorbid effect modifiers (eg, sepsis and hemolysis) on neurodevelopment, efficacy of photo- therapy, reliability of various strategies in predicting significant hyperbilirubinemia, and accuracy of transcutaneous bilirubin (TcB) measurements. The report was used by the AAP to update the 1994 AAP guidelines for the management of neonatal hyperbi- lirubinemia. This review focuses on otherwise healthy term or near-term (at least 34 weeks’ esti- mated gestational age [EGA] or at least 2500 g birth weight) infants with hyperbilirubinemia. This article is adapted from that published report 1 with an added section on the risk of blood exchange transfu- sion (BET). Neither hyperbilirubinemia nor kernicterus are re- portable diseases, and there are no reliable sources of information providing national annual estimates. Since the advent of effective prevention of rhesus (Rh) incompatibility and treatment of elevated bili- rubin levels with phototherapy, kernicterus has be- come uncommon. When laboratory records of a 1995–1996 birth cohort of more than 50 000 California infants were examined, Newman et al 2 reported that 2% had total serum bilirubin (TSB) levels higher than 20 mg/dL, 0.15% had levels higher than 25 mg/dL, and only 0.01% had levels higher than 30 mg/dL. (These data were from infants with clinically identi- fied hyperbilirubinemia and, as such, represent a minimum estimate of the true incidence of extreme hyperbilirubinemia.) This is undoubtedly the result of successful prevention of hemolytic anemia and the The guidance in this report does not indicate an exclusive course of treat- ment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. This article is based on an evidence report produced by the Tufts-New England Medical Center’s Evidence-Based Practice Center under contract to the Agency for Healthcare Research and Quality (contract 290-97-0019). PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- emy of Pediatrics. e130 PEDIATRICS Vol. 114 No. 1 July 2004 http://www.pediatrics.org/cgi/content/full/114/1/e130 by guest on August 7, 2015 pediatrics.aappublications.org Downloaded from