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Objective We aimed to test the hypothesis that computational features of the first several minutes of EEG recording can be used to estimate the risk for development of acute seizures in comatose critically-ill children. Methods In a prospective cohort of 118 comatose children, we computed features of the first five minutes of artifact-free EEG recording (spectral power, inter-regional synchronization and cross-frequency coupling) and tested if these features could help identify the 25 children who went on to develop acute symptomatic seizures during the subsequent 48 hours of cEEG monitoring. Results Children who developed acute seizures demonstrated higher average spectral power, particularly in the theta frequency range, and distinct patterns of inter-regional connectivity, characterized by greater connectivity at delta and theta frequencies, but weaker connectivity at beta and low gamma frequencies. Subgroup analyses among the 97 children with the same baseline EEG background pattern (generalized slowing) yielded qualitatively and quantitatively similar results. Conclusions These computational features could be applied to baseline EEG recordings to identify critically-ill children at high risk for acute symptomatic seizures. Significance If confirmed in independent prospective cohorts, these features would merit incorporation into a decision support system in order to optimize diagnostic and therapeutic management of seizures among comatose children.