Hyperbilirubinemia in the Newborn Infant ≥35 Weeks’ Gestation: An Update With Clarifications

Abstract

In July 2004, the Subcommittee on Hyperbilirubinemia of the American Academy of Pediatrics (AAP) published its clinical practice guideline on the management of hyperbilirubinemia in the newborn infant ≥35 weeks of gestation,1 and a similar guideline was published in 2007 by the Canadian Paediatric Society.2 Experience with implementation of the AAP guideline suggests that some areas require clarification. The 2004 AAP guideline also expressed hope that its implementation would “reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy… .” We do not know how many practitioners are following the guideline, nor do we know the current incidence of bilirubin encephalopathy in the United States. We do know, however, that kernicterus is still occurring in the United States, Canada, and Western Europe.3–7 In 2002, the National Quality Forum suggested that kernicterus should be classified as a “serious reportable event,”8 sometimes termed a “never event,”9 implying that with appropriate monitoring, surveillance, and intervention, this devastating condition can, or should, be eliminated. Although this is certainly a desirable objective, it is highly unlikely that it can be achieved given our current state of knowledge and practice.10 In certain circumstances (notably, glucose-6-phosphate dehydrogenase [G6PD] deficiency, sepsis, genetic predisposition, or other unknown stressors), acute, severe hyperbilirubinemia can occur and can produce brain damage despite appropriate monitoring and intervention.In addition to clarifying certain items in the 2004 AAP guideline, we recommend universal predischarge bilirubin screening using total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) measurements, which help to assess the risk of subsequent severe hyperbilirubinemia. We also recommend a more structured approach to management and follow-up according to the predischarge TSB/TcB, gestational age, and other risk factors for hyperbilirubinemia. These recommendations represent a consensus of expert opinion based on the available evidence, and they are supported by several independent reviewers. Nevertheless, their efficacy in preventing kernicterus and their cost-effectiveness are unknown.We reviewed the report on screening for neonatal hyperbilirubinemia published by the Agency for Healthcare Research and Quality and prepared by the Tufts-New England Medical Center Evidence-Based Practice Center,11 the current report by the US Preventive Services Task Force,12 and other relevant literature.1,3–10,13–26The 2004 AAP guideline includes 2 categories of risk factors, but the distinction between these 2 categories has not been clear to all users of the guideline.These “risk factors for hyperbilirubinemia” are listed in Table 1. Understanding the predisposition to subsequent hyperbilirubinemia provides guidance for timely follow-up as well as the need for additional clinical and laboratory evaluation.These risk factors for bilirubin neurotoxicity are listed in the figures of the 2004 AAP guideline that provide recommendations for the use of phototherapy and exchange transfusion. These “neurotoxicity risk factors” encompass those that might increase the risk of brain damage in an infant who has severe hyperbilirubinemia1 (see Fig 1 and Table 2). The neurotoxicity risk factors are used in making the decision to initiate phototherapy or perform an exchange transfusion. These interventions are recommended at a lower bilirubin level when any of the neurotoxicity risk factors is present. Some conditions are found in both risk-factor categories. For example, lower gestational age and isoimmune hemolytic disease increase the likelihood of subsequent severe hyperbilirubinemia as well as the risk of brain damage by bilirubin.The 2004 AAP guideline recommends a predischarge bilirubin measurement and/or assessment of clinical risk factors to evaluate the risk of subsequent severe hyperbilirubinemia.1 New evidence suggests that combining a predischarge measurement of TSB or TcB with clinical risk factors might improve the prediction of the risk of subsequent hyperbilirubinemia.13,14,23 In addition, when interpreted by using the hour-specific nomogram (Fig 2), measurement of TSB or TcB also provides a quantitative assessment of the degree of hyperbilirubinemia. This provides guidance regarding the need (or lack of need) for additional testing to identify a cause of the hyperbilirubinemia and for additional TSB measurements.1The TSB can be measured from the same sample that is drawn for the metabolic screen. The risk zone (Fig 2) and the other clinical risk factors (Table 3) are then combined to assess the risk of subsequent hyperbilirubinemia and to formulate a plan for management and follow-up (Fig 3). When combined with the risk zone, the factors that are most predictive of hyperbilirubinemia risk are lower gestational age and exclusive breastfeeding.13,14,23 The lower the gestational age, the greater the risk of devel