title: Incidence, etiology, and outcomes of hazardous hyperbilirubinemia in newborns.
abstract: OBJECTIVE
  Total serum bilirubin (TSB) levels ≥ 30 mg/dL are rare but potentially hazardous. A better understanding of their incidence, causes, and outcomes could help inform preventive efforts.
  
  
  METHODS
  We identified infants born ≥ 35 weeks' gestational age from 1995-2011 in Kaiser Permanente Northern California (n = 525409) and examined the medical records of infants with a TSB ≥ 30 mg/dL to determine etiology and the occurrence of acute bilirubin encephalopathy. We reviewed inpatient and outpatient encounters through 2013 for evidence of sensorineural hearing loss (SNHL) or cerebral palsy (CP).
  
  
  RESULTS
  We identified 47 infants with TSB ≥ 30 mg/dL (8.6 per 100000 births). In 44 infants (94%), the hyperbilirubinemia occurred after the initial birth hospitalization. The etiology was not identified in 33 (70%). Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in only 25 (53%) of whom 10 (40%) were deficient. Four children had acute bilirubin encephalopathy of whom 2 developed both CP and SNHL, and 1 developed isolated SNHL. These 3 infants all had G6PD deficiency and TSB >40 mg/dL. One additional 35-week infant with TSB 38.2 mg/dL had SNHL.
  
  
  CONCLUSIONS
  Hazardous (≥ 30 mg/dL) hyperbilirubinemia is a rare event. No etiology could be identified from the clinical record in most cases. G6PD deficiency was the leading cause of hazardous hyperbilirubinemia when an etiology was identified, but many were not tested. Chronic, bilirubin-induced neurotoxicity was uncommon and occurred only in the setting of additional risk factors and TSB values well over (>15 mg/dL) the American Academy of Pediatrics exchange transfusion thresholds.
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California; Departments of Pediatrics, michael.w.kuzniewicz@kp.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kuzniewicz
authors.affiliation: Department of Pediatrics, Kaiser Permanente Santa Clara, Santa Clara, California Epidemiology and Biostatistics, and.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Wickremasinghe
authors.affiliation: Departments of Pediatrics, Neurology, University of California, San Francisco, San Francisco, California; and.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Epidemiology and Biostatistics, and.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California;
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Walsh
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California;
authors.forename: Soora
authors.initials: S
authors.lastname: Wi
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California; Departments of Pediatrics, Epidemiology and Biostatistics, and.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Newman
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000628:therapy; D006801:Humans; D006932:Hyperbilirubinemia / Q000453:epidemiology* / Q000209:etiology* / Q000628:therapy; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D016896:Treatment Outcome
keywords: hyperbilirubinemia; kernicterus; neonate; neurotoxicity