Some degree of jaundice or hyperbilirubinemia occurs in most newborns. Severe neonatal hyperbilirubinemia is associated with kernicterus, a rare condition characterized by athetoid spasticity, gaze and visual abnormalities, and sensori-neural hearing loss in survivors. It may also be associated with mental retardation. A 2003 review concluded that kernicterus has a mortality of at least 10% and a morbidity of at least 70%. The true incidence of kernicterus is unknown because it is not a mandatory reportable disease. However, a 2001 Joint Commission Sentinel Event Alert stated that cases of kernicterus have continued to be reported in recent years. Efforts have been made by clinicians and investigators to eliminate this rare disease by instituting system-level measures to screen for hyperbilirubinemia and prevent the occurrence of kernicterus. Most notable among these is a set of clinical practice guideline concerning the management of hyperbilirubinemia in infants of at least 35 weeks gestation published by the American Academy of Pediatrics (AAP) in 2004. The 2004 guideline emphasizes the attention to risk factors associated with hyperbilirubinemia, close followup of at-risk infants, and the use of phototherapy and exchange transfusion to decrease the level of hyperbilirubinemia as appropriate. Tufts-New England Medical Center Evidence-based Practice Center (Tufts-NEMC EPC) completed a review in 2003 examining the effects of bilirubin on neurodevelopmental outcomes in infants of at least 34 weeks gestation. The report also examined the efficacy of phototherapy, the accuracy of transcutaneous bilirubin (TcB), and the various strategies for predicting hyperbilirubinemia. The Center on Primary Care, Prevention and Clinical Partnerships at the Agency for Healthcare Quality and Research (AHRQ), on behalf of the US Preventive Services Task Force (USPSTF), requested an update evidence report on the effectiveness of various screening strategies to prevent the development of kernicterus. In the literature, the term "kernicterus" has been used interchangeably with both the acute and chronic findings of bilirubin encephalopathy. To avoid confusion as has been advocated by the AAP Subcommittee on Hyperbilirubinemia, we use the terms acute and chronic bilirubin encephalopathy in this report. The term "kernicterus" is reserved for the chronic form of bilirubin encephalopathy. This review examines the effectiveness of screening for hyperbilirubinemia to reduce the incidence of acute or chronic bilirubin encephalopathy. It also examines the benefits and harms of phototherapy. Populations of interests are healthy term infants, pre-term infants of at least 35 weeks gestation, and their mothers. Examples of screenings are system approach measures based on risk factors assessment, universal screening for bilirubin level (either serum or transcutaneous), or combinations of both. Outcomes of interest are the rates of acute or chronic bilirubin encephalopathy (if data are available), or surrogate measures; and any health outcomes or adverse events related to phototherapy. Key Question 1. Does screening using risk factor assessment and/or bilirubin testing reduce the incidence of acute or chronic bilirubin encephalopathy? Key Question 2. Does risk factor assessment accurately identify infants who may benefit from bilirubin testing? Key Question 3. Does bilirubin testing accurately identify infants who may benefit from phototherapy? Key Question 4. What are the harms of screening? Key Question 5. Does treatment reduce the risk of bilirubin encephalopathy in infants identified by screening? Key Question 6. What are the harms of treatment with phototherapy?