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Standardized approaches to the treatment of neonatal seizures remain undeveloped. We assessed the type and number of anticonvulsants selected, blood levels attained, and postdischarge anticonvulsant treatment of neonatal seizures among five neonatal intensive care units in the United States between 2000-2003. Almost all of the 480 neonates (94%) with seizures were treated, initially with phenobarbital (82%), lorazepam (9%), phenytoin (2%), other anticonvulsants (1%), or a combination of the first two drugs (6%). While the majority of neonates were treated with one drug (59%), the number of anticonvulsants varied (P<0.0001), as did the peak serum phenobarbital levels (P<0.0001). The majority (75%) of survivors received anticonvulsant treatment after discharge. These neonates were more likely to have had abnormal electroencephalography or brain imaging, or to have needed a second anticonvulsant, compared with neonates whose drug therapy was discontinued. Anticonvulsant therapy is used in the majority of neonates with seizures, mostly with phenobarbital, and treatment is continued beyond discharge. The observed wide therapeutic variability may reflect a lack of standardized diagnostic and treatment approaches, particularly for seizures refractory to initial phenobarbital therapy. Trials of anticonvulsants with long-term neurodevelopmental follow-up are needed to develop evidence-based treatment guidelines.

Hydrogen peroxide (H2O2) accumulates during hypoxic-ischemic brain injury and may mediate neurotoxicity in the immature brain. To determine whether H2O2 causes maturation specific neurotoxicity, primary neuronal cultures were exposed to H2O2 (25, 50, 100 microM) for 5 min or 24 h during in vitro development, and toxicity was assessed. Immature neurons incurred marked and dose dependent injury after both brief and prolonged H2O2 exposures, and marked dose dependent death following prolonged H2O2 exposures. Mature neurons incurred marked injury following prolonged but not brief H2O2 exposures, and were relatively resistant to H2O2 induced death following both brief and prolonged exposures. Thus, H2O2 is selectively toxic to immature neurons in vitro. Neuronal vulnerability to H2O2 during in vivo development is unknown and warrants investigation.