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. Hypothesis: 1. The pre-discharge (age <72 hrs) bilirubin risk zone will more accurately predict significant hyperbilirubinemia than the use of clinical risk factors alone in a racially-diverse US population of term and near-term newborn infants. 2. The combined use of pre-discharge bilirubin risk zone and clinical risk factors will more accurately predict significant hyperbilirubinemia than using either method alone. Goals: Sixty percent of otherwise healthy newborns have clinical jaundice associated with increased concentration of total serum bilirubin (TSB). The outcome for the majority is 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. The two options recommended by the American Academy of Pediatrics (AAP) are: 1) an analysis of TSB measurement expressed as a risk zone on an hour-specific nomogram and/or 2) an assessment of clinical risk factors. The relative accuracy of these strategies used alone or in combination is not known, and 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. The only currently available clinical test that can be used to predict the risk of subsequent severe hyperbilirubinemia is measurement of TSB plotted on an hour-specific nomogram. The nomogram was constructed and evaluated in a study of 2840 healthy infants with hour-specific TSB measurements prospectively measured before and after discharge. Among infants with TSB values in the high-risk zone (>95th percentile) before discharge, 39.5 percent remained in that zone after discharge. For infants with pre-discharge TSB levels in the low-risk zone (<40th percentile), none developed TSB values in the high-risk zone. In addition, by expressing TSB values in terms of risk zones, rather than using an actual TSB value, the imprecision of TSB measurement is reduced. Epidemiologic risk factors for hyperbilirubinemia and kernicterus include male gender, East Asian race and Mediterranean, Arabic and Chinese ancestry associated with G6PD deficiency. As the pattern of US demographics changes, increasing multi-racial ancestry may increase the occurrence of severe hyperbilirubinemia. The maximum TSB value of 12.9 mg/dL, equivalent to the 90th percentile at day 3, remains the current threshold that designates neonatal hyperbilirubinemia, and was determined by data collected on 132 White, predominantly urban and formula-fed New York City infants of lower-income families for the first 10 days after birth. More recent guidelines are based on hour-specific TSB in healthy term and near-term neonates for the first week after birth for a heterogeneous mid-Atlantic US population, but still are not an accurate reflection of US demographics. Data on racial ancestry and ethnicity provided in the proposed study will improve our understanding of their impact on the risk of hyperbilirubinemia and lead to improved strategies to prevent bilirubin-induced neurologic injury. Several studies have identified additional risk factors (maternal race, method of feeding, gestational age, birth weight, and others) associated with hyperbilirubinemia and some have developed multivariable logistic regression models that can be used to predict its development. Most have been based on retrospective analysis of the population to derive the prediction rules. When compared, the pre-discharge TSB (expressed as a risk zone on the bilirubin nomogram) had better discrimination than the clinical risk factor score and generated a wider range of likelihood ratios. However, it is not known whether the combination of TSB measurement and clinical risk factor assessment would result in a safer and more accurate prediction rule. We propose to prospectively test two methods to assess the risk of severe neonatal hyperbilirubinemia in a large racially-diverse US population: 1) the use of a single prediction rule based on either a pre-discharge TSB measurement expressed as a risk zone on an hour-specific nomogram or a prediction rule based on clinical risk factors alone; and 2) the use of a combined prediction rule of clinical risk factors and hour-specific TSB values.
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