Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.
OBJECTIVE
To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy.


METHODS
Prospective longitudinal cohort study.


METHODS
A level IV neonatal ICU in a freestanding children's hospital.


METHODS
Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period.


METHODS
Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia.


RESULTS
Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase.


CONCLUSIONS
Serum S100B and neuron-specific enolase levels in babies with neonatal encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.
1Department of Neonatology, Children's National Medical Center, Washington, DC. 2Department of Pediatrics, The George Washington University School of Medicine, Washington, DC. 3Department of Neurology, Children's National Medical Center, Washington, DC. 4Department of Neurology, The George Washington University School of Medicine, Washington, DC. 5Department of Biostatistics and Informatics, Children's National Medical Center, Washington, DC. 6Department of Epidemiology and Biostatistics, The George Washington University School of Medicine, Washington, DC. 7Department of Psychiatry and Behavioral Sciences, Children's National Medical Center, Washington, DC.
An N
AN
Massaro
Taeun
T
Chang
Stephen
S
Baumgart
Robert
R
McCarter
Karin B
KB
Nelson
Penny
P
Glass
D015415:Biomarkers / Q000097:blood; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D002657:Child Development / Q000502:physiology; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007223:Infant; D007231:Infant, Newborn; D015931:Intensive Care, Neonatal; D008297:Male; D009048:Motor Skills / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011237:Predictive Value of Tests; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D016896:Treatment Outcome
D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase