Blood-based brain injury biomarkers show promise to prognosticate outcome for children resuscitated from cardiac arrest. The objective of this multicenter, observational study was to validate promising biomarkers to accurately prognosticate outcome at 1 year. Early brain injury biomarkers will be associated with outcome at one year for children with cardiac arrest. Fourteen centers in the US enrolled children aged < 18 years with in- or out-of-hospital cardiac arrest and pediatric intensive care unit admission if pre-cardiac arrest Pediatric Cerebral Performance Category score was 1-3. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1), neurofilament light (NfL), and Tau protein concentrations were measured in samples drawn post-arrest day 1 using Quanterix Simoa 4-Plex assay. The primary outcome was unfavorable outcome at one year (Vineland Adaptive Behavioral Scale < 70). Of 164 children enrolled, 120 children had evaluable data (n=50 with unfavorable outcome). Children were median (interquartile range) 1 (0-8.5) years of age, 41% female, and 60% had asphyxia etiology. Of children with unfavorable outcome, 93% had unwitnessed arrests and 43 died. While all 4 day 1 biomarkers were increased in children with unfavorable vs. favorable outcome at 1-year post-arrest, NfL had the best univariate area under the receiver operator curve to predict 1 year outcome at 0.731. In a multivariate logistic regression, NfL concentration trended toward significance on day 1 and was associated with unfavorable outcome at 1-year on days 2 and 3 (day 1: Odds Ratio [95% Confidence Interval] 1.004 [1.000-1.008], p=.062; day 2: 1.005 [1.002-1.008], p=.003, and day 3: 1.002 [1.001-1.004], p=.003, respectively). UCHL1 was associated with outcome on days 2: 1.005 [1.002-1.009], p=.003 and 3: 1.001 [1.000-1.002], p=.019) and Tau trended toward association with outcome on days 2: 1.003 [1.000-1.005], p=.08) and 3: 1.001 [1.000-1.002], p=.077. Brain injury biomarkers predict unfavorable outcome post-pediatric cardiac arrest. Accuracy of biomarkers alone and together with other prognostication tools should be evaluated to predict long term child centered outcomes post-cardiac arrest.
Early Detection of Widespread Progressive Brain Injury after Cardiac Arrest: A Single Case DTI and Post-Mortem Histology Study
