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BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS:The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a firstline treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists.RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P , .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS:In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.WHAT'S KNOWN ON THIS SUBJECT: In 1999, a randomized controlled trial comparing phenobarbital and phenytoin in neonates revealed that each drug had 45% efficacy. These treatments remain the standard of care for neonatal seizures. Levetiracetam has a better safety profile; however, its efficacy is unproven in neonates.WHAT THIS STUDY ADDS: In this study conducted in the hypothermia era and with near real-time response to continuous video EEG monitoring, phenobarbital was more effective than levetiracetam in achieving seizure cessation. Dose-finding studies and phase III trials with long-term outcomes are needed.

Tracheobronchomalacia is common in neonates with bronchopulmonary dysplasia who undergo bronchoscopy and is associated with longer and more complicated hospitalizations.

Previous fetal studies indicated that endocrine factors control surfactant maturation, whereas mechanical forces affect lung growth, but not surfactant. We altered mechanical forces in fetal sheep lungs at 100-108 days gestation by tracheal ligation (TL, n = 15, 7 successful studies) to accelerate lung growth, transection of cervical spinal cord (TCSC, n = 17, 6 successful studies) to produce lung hypoplasia, or sham operation (n = 11, 6 successful studies). The reasons for the high mortality rates are not known. At delivery (130-142 days), groups were similar in gestational age, weight, and cortisol. Effects on lung growth were similar to, but effects on surfactant differed from, previous reports. TL increased lung growth but decreased saturated phosphatidylcholine (SatPC) and surfactant protein (SP)A and apparently decreased SP-B and relative numbers of alveolar type II cells (based on immunohistochemical studies of 1 animal in each group); TCSC had opposite effects. In contrast to a previous study (J. A. Kitterman, G. C. Liggins, G. A. Campos, J. A. Clements, C. S. Forster, C. H. Lee, and R. K. Creasy, J. Appl. Physiol, 51: 384-390, 1981), SatPC did not correlate with cortisol. We conclude that altering mechanical forces in fetal lung affects not only lung growth but also surfactant maturation and possibly alveolar epithelial differentiation and disturbs the normal correlation between cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF-I; increased by TL, P = 0.003) suggest a possible role for IGF-I in these effects.