This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sixty percent of otherwise healthy newborns have clinicaljaundice associated with increased concentration of total serum bilirubin (TSB). The outcome for the majority benign, but infants with untreated extremely high TSB levels can develop kernicterus, a neurologically devastating condition due to bilirubin toxicity. TSB levels typically peak at age 3 to 5 days, usually after routine hospital discharge. Assessment before discharge of the risk for subsequent hyperbilirubinemia should facilitate appropriate follow-up and management; however the most effective strategy to assess this risk is unknown. Two options recommended by the American Academy of Pediatrics are analysis of bilirubin expressed as a risk zone on an hour-specific monogram and/or assessment of clinical risk factors. The relative accuracy of these strategies used alone or in combination is not known. This prospective multicenter cohort study tests the following hypotheses in a large racially diverse US population: 1) the pre-discharge (<72 hr of age) bilirubin risk zone plotted on an hour-specific nomogram more accurately predicts the risk of severe hyperbilirubinemia than the use of clinical risk factors alone; and 2) the combined use of pre-discharge bilirubin risk zone and clinical risk factors more accurately predicts significant hyperbilirubinemia than using either method alone. We will measure serial bilirubin levels (TSB and transcutaneous, TcB) in 2000 healthy newborns at age 24+6 hours, 36 to 48 hours (pre-discharge), 3 to 5 days, and 7 to 14 days. Prospective identification of known clinical risk factors, pre-discharge TSB/TcB levels and the increment in TcB levels prior to discharge will be used to develop prediction rules for the outcome of subsequent severe hyperbilirubinemia (>95th percentile for age in hours) and need for phototherapy. Identifying the optimal pre-discharge assessment for risk of subsequent hyperbilirubinemia will ensure a safer transition from the infant's birth hospital to home and may prevent kernicterus.