Risk for Cerebral Palsy in Infants With Total Serum Bilirubin Levels at or Above the Exchange Transfusion Threshold: A Population-Based Study | Neurology | JAMA Pediatrics | JAMA Network
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Original Investigation
Journal Club
March 2015

Risk for Cerebral Palsy in Infants With Total Serum Bilirubin Levels at or Above the Exchange Transfusion Threshold: A Population-Based Study

Journal Club PowerPoint Slide Download
Author Affiliations
  • 1Department of Neurology, University of California, San Francisco
  • 2Department of Pediatrics, University of California, San Francisco
  • 3Division of Research, Kaiser Permanente Northern California, Oakland
  • 4Department of Epidemiology and Biostatistics, University of California, San Francisco
JAMA Pediatr. 2015;169(3):239-246. doi:10.1001/jamapediatrics.2014.3036

Importance  Exchange transfusion is recommended for newborns with total serum bilirubin (TSB) levels thought to place them at risk for cerebral palsy (CP). However, the excess risk for CP among these infants is unknown.

Objective  To quantify the risks for CP and CP consistent with kernicterus that are associated with high TSB levels based on the 2004 American Academy of Pediatrics exchange transfusion threshold (ETT) guidelines.

Design, Setting, and Participants  We enrolled 2 cohorts from a population of 525 409 infants in the Late Impact of Getting Hyperbilirubinemia or Phototherapy (LIGHT) birth cohort. Eligible infants were born at a gestational age of at least 35 weeks at 15 hospitals within the Kaiser Permanente Northern California integrated medical care delivery system from January 1, 1995, through December 31, 2011.

Exposures  The exposed cohort included all 1833 infants with at least 1 TSB measurement at or above the ETT based on age at testing, gestational age, and results of direct antiglobulin testing. The unexposed cohort was a 20% random sample of 104 716 infants with TSB levels below the ETT.

Main Outcomes and Measures  A pediatric neurologist blinded to the TSB levels reviewed medical records to determine the presence of CP, defined as a nonprogressive congenital motor dysfunction with hypertonia or dyskinesia. Cerebral palsy was judged to be consistent with kernicterus if magnetic resonance imaging of the brain revealed bilateral globus pallidus injury in the setting of dyskinetic CP.

Results  We identified CP in 7 of 1833 exposed (0.4%) vs 86 of 104 716 unexposed (0.1%) infants (relative risk, 4.7 [95% CI, 2.2-10.0]). Absolute risk differences were 0.2% (95% CI, 0%-0.5%) for a TSB level 0 to 4.9 mg/dL above the ETT (n = 1705), 0.9% (95% CI, 0.1%-5.3%) for a TSB level 5.0 to 9.9 mg/dL above the ETT (n = 102), and 7.6% (95% CI, 2.1%-24.1%) for a TSB level 10 mg/dL or more above the ETT (n = 26). Cerebral palsy consistent with kernicterus occurred in 3 infants (incidence, 0.57 per 100 000 births); all 3 had TSB levels of more than 5.0 mg/dL above the ETT and at least 2 risk factors for neurotoxicity, such as prematurity, glucose-6-phosphate dehydrogenase deficiency, or hypoxia-ischemia.

Conclusions and Relevance  Cerebral palsy consistent with kernicterus occurred only in infants with 2 or more risk factors for neurotoxicity and TSB levels of more than 5 mg/dL above the ETT. Among infants with lower degrees of TSB level elevation, the excess risk for CP is minimal.