Yvonne W Wu1, Michael W Kuzniewicz2, Andrea C Wickremasinghe3, Eileen M Walsh4, Soora Wi4, Charles E McCulloch3, Thomas B Newman5. 1. Department of Neurology, University of California, San Francisco2Department of Pediatrics, University of California, San Francisco. 2. Department of Pediatrics, University of California, San Francisco3Division of Research, Kaiser Permanente Northern California, Oakland. 3. Department of Epidemiology and Biostatistics, University of California, San Francisco. 4. Division of Research, Kaiser Permanente Northern California, Oakland. 5. Department of Pediatrics, University of California, San Francisco3Division of Research, Kaiser Permanente Northern California, Oakland4Department of Epidemiology and Biostatistics, University of California, San Francisco.
Abstract
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.
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.
Authors: Andrea C Wickremasinghe; Michael W Kuzniewicz; Charles E McCulloch; Thomas B Newman Journal: JAMA Pediatr Date: 2018-04-01 Impact factor: 16.193
Authors: Thomas Hegyi; Dalya Chefitz; Alan Weller; Andrew Huber; Mary Carayannopoulos; Alan Kleinfeld Journal: J Matern Fetal Neonatal Med Date: 2020-05-04