Forest Plot of Relative Risks (RRs) From Least Absolute Shrinkage and Selection Operator–Selected Multivariable Models
tumor necrosis, hypoxic ischemic encephalopathy
ADHESION, TUMOR NECROSIS, HYPOXIC ISCHEMIC ENCEPHALOPATHY
A, All biomarkers selected at least 50% of the bootstrapped least absolute shrinkage and selection operator models. B, The 5 most selected biomarkers by bootstrapped least absolute shrinkage and selection operator samples. A set of 9 biomarkers at baseline, day 2, and day 4 remained significant in multivariable analyses after adjustment for hypoxic ischemic encephalopathy severity, treatment assignment, and site. BDNF indicates brain-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; ICAM-1, intercellular adhesion molecule 1; IL, interleukin; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; NGB, neuroregulin-1-b-1; NSE, neuron-specific enolase; s100b, S100 calcium-binding protein B; TNF-α, tumor necrosis factor–α; UCHL1, ubiquitin carboxy-terminal hydrolase-L1; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.To leverage biomarker data across time points, we selected a curated set of biomarkers from the LASSO-based multivariable models that included the pro-inflammatory proteins C5a and IL-6 at baseline, the anti-inflammatory protein IL-8 at day 4, and brain-specific proteins NSE (baseline), tau (day 4), and UCHL1 (day 4). We developed a cumulative model that included our biomarker data sets (baseline, day 2, day 4, and curated set) as well as pertinent clinical data known at study enrollment.