We read with interest the report of the Newborn Electrographic Seizure Trial (NEST) comparing treatment of clinically evident seizures (clinical seizure group (CSG)) vs. electrographic seizures detected by amplitude-integrated electroencephalography (aEEG) (electrographic seizure group (ESG)), which aimed to answer the question: “should all electrographic seizures, even without a clinical correlate, be treated to reduce the risk of subsequent impairment, or do the treatments themselves contribute to neurological disruption and injury?”1 The results of the trial showed that children who were treated based on aEEG results did not have lower rates of death or disability (primary outcome) but the authors “report an association of improved cognitive outcomes at 2 years in the CSG.”

As for the two similar but smaller trials published earlier,2,3 enrollment, data collection, and analysis in the NEST study was challenging and resulted from the efforts of many investigators at their 13 sites. Ultimately, the trial of Hunt et al. was terminated early after publication of the trial conducted in St. Louis that suggested benefit from treatment of electrographic seizures, leading to loss of equipoise among the investigators. The effect of this publication was that it precluded enrollment of the planned 300 subjects per group (instead of the reported 106 per group) that would have yielded more statistical power. Although we agree that it is important for the authors to publish the results of their trial, we offer commentary regarding the trial design and data presented to express caution about the study’s conclusions.

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