The outcome of 45 neonates with EEG-confirmed seizures (ESZ) was analyzed at the University Hospital of the Canary Islands, La Laguna, Spain. Of 32 neonates treated with phenobarbital/phenytoin, ESZ persisted in 17; of these, 13 had a poor outcome and 4 died. Of 13 nonresponders to phenobarbital/phenytoin who were treated with midazolam early, within 1 hr, ESZ were rapidly controlled in 13, only 4 had a poor outcome and 2 died. Neonates treated with midazolam had significantly better neurodevelopment than those receiving phenobarbital (53.9% vs 11.8%). 
COMMENT. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome . In the above retrospective, nonrandomized study of neonates with refractory EEG-confirmed seizures, midazolam, a GABA agonist, is proven effective as a third-line treatment in patients who have failed to respond to phenobarbital and phenytoin. Patients who respond to midazolam and those whose electrographic seizures are controlled by conventional first line treatments show improved neurodevelopmental outcome when compared to a group with refractory neonatal seizures. Midazolam is currently employed in the treatment of status epilepticus in children; it is investigative and nonapproved for use in neonates. Prospective studies may be justified.
In an Editorial, Sankar R and Painter MJ  applaud the study of midazolam and the promising results. However, they raise concerns about potential neurotoxicity of GABA agonists in the immature brain. AMPA antagonists, such as topiramate, might be a safer class of drug to promote in IV form for trial in neonates.