Macroperiodic Oscillations: A Potential Novel Biomarker of Outcome in Neonatal Encephalopathy

Purpose:Neonatal encephalopathy (NE) is a common cause of neurodevelopmental morbidity. Tools to accurately predict outcomes after therapeutic hypothermia remain limited. We evaluated a novel EEG biomarker, macroperiodic oscillations (MOs), to predict neurodevelopmental outcomes.Methods:We conducted a secondary analysis of a randomized controlled trial of neonates with moderate-to-severe NE who underwent standardized clinical examination, magnetic resonance (MR) scoring, video EEG, and neurodevelopmental assessment with Bayley III evaluation at 18 to 24 months. A non-NE cohort of neonates was also assessed for the presence of MOs. The relationship between clinical examination, MR score, MOs, and neurodevelopmental assessment was analyzed.Results:The study included 37 neonates with 24 of whom survived and underwent neurodevelopmental assessment (70%). The strength of MOs correlated with severity of clinical encephalopathy. MO strength and spread significantly correlated with Bayley III cognitive percentile (P = 0.017 and 0.046). MO strength outperformed MR score in predicting a combined adverse outcome of death or disability (P = 0.019, sensitivity 100%, specificity 77% vs. P = 0.079, sensitivity 100%, specificity 59%).Conclusions:MOs are an EEG-derived, quantitative biomarker of neurodevelopmental outcome that outperformed a comprehensive validated MRI injury score and a detailed systematic discharge examination in this small cohort. Future work is needed to validate MOs in a larger cohort and elucidate the underlying pathophysiology of MOs.