549: ANALYSIS OF NEUROPROTECTIVE COLD SHOCK PROTEINS IN A MULTICENTER STUDY OF PEDIATRIC CARDIAC ARREST

Abstract

Introduction: The efficacy of hypothermic neuroprotection varies by age. Cold exposure stimulates production of cold stress hormones (CSHs) which trigger thermogenesis and may be neuroprotective. FGF21 is a neuroprotective CSH that requires the Beta-klotho (KLB) co-receptor to signal. KLB is abundant in the newborn brain, decreases with age, and is virtually absent in adults. Thus, infants and young children may uniquely benefit from FGF21/KLB mediated neuroprotection. In vitro studies revealed that FGF21 upregulates the powerful neuroprotectant RNA-Binding Motif-3 (RBM3) in developmentally immature neurons (but not mature neurons). We sought to characterize FGF21 and RBM3 serum levels in children after cardiac arrest (CA) and evaluate their interdependence. Methods: Secondary analysis of serum samples collected in a multi-institutional prospective observational study evaluating biomarkers after pediatric CA. We measured FGF21 (Luminex) and RBM3 (ELISA) levels. All patients with serum from at least two timepoints (0-24h, 24-48h, 48-72h) were included. We also included serum from healthy controls. FGF21 and RBM3 levels at each timepoint were compared to controls (Wilcoxon-Ranksum); the relationship between FGF21/RBM3 at each timepoint was also evaluated (Spearman). Results: A total of 296 samples from 111 post-arrest patients were analyzed, and 20 samples from controls. Median age of the post-arrest cohort was 31.3 months (IQR: 6.9-129.9); 37.3 months (IQR: 18.6-63.6) for controls. Median FGF21 levels in the controls was 282pg/mL (IQR: 64-736), and did not differ significantly at 0-24h, 24-48h, and 48-72h (383 [IQR: 72-867], 723 [IQR: 167-1,688] and 552 [IQR: 210-1,225], respectively, P>0.05). Median control RBM3 was 2,944pg/mL (IQR: 969-8,241), and did not differ significantly at 0-24h, 24-48h, and 48-72h (1,538 [IQR: 757-4,146], 1,454 [625-3,543] and 1,526 [IQR: 613-3,591], respectively, P>0.05). FGF21 and RBM3 were correlated at 0-24h and 48-72h (Spearman’s coefficient of 0.384 and 0.223, respectively; P< 0.05 for both). Conclusions: After pediatric CA, serum FGF21 levels trend upward and RBM3 levels downward and correlate at early and late timepoints. Ongoing studies are examining their relationship to age, demographics, CA endophenotype, use of hypothermia, other serum biomarkers, and outcomes.