Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

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 first-line 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.

Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring.

PURPOSE: Continuous video electroencephalography (cEEG) monitoring is the recommended gold standard of care for at-risk neonates but is not available in many Neonatal Intensive Care Units (NICUs). To conduct a randomized treatment trial of levetiracetam for the first-line treatment of neonatal seizures (the NEOLEV2 trial), we developed a monitoring infrastructure at five NICUs, implementing recent technological advancements to provide continuous video EEG monitoring and real-time response to seizure detection. Here, we report on the feasibility of providing this level of care. METHODS: Twenty-five key informant interviews were conducted with study neurologists, neonatologists, coordinators, and EEG technicians from the commercial EEG monitoring company Corticare. A general inductive approach was used to analyze these qualitative data. RESULTS: A robust infrastructure for continuous video EEG monitoring, remote review, and real-time seizure detection was established at all sites. At the time of this survey, 260 babies had been recruited and monitored for 2 to 6 days. The EEG technician review by the commercial EEG monitoring company was reassuring to families and neonatologists and led to earlier detection of seizures but did not reduce work load for neurologists. Neurologists found the automated neonatal seizure detector algorithm provided by the EEG software company Persyst useful, but the accuracy of the algorithm was not such that it could be used without review by human expert. Placement of EEG electrodes to initiate monitoring, especially after hours, remains problematic. CONCLUSIONS: Technological advancements have made it possible to provide at-risk neonates with continuous video EEG monitoring, real-time detection of and response to seizures. However, this standard of care remains unfeasible in usual clinical practice. Chief obstacles remain starting a recording and resourcing the real-time specialist review of suspect seizures.

Human milk oligosaccharide composition differs between donor milk and mother's own milk in the NICU.

BACKGROUND: Human milk oligosaccharides (HMO) represent the third most abundant component of human breast milk. More than a hundred structurally distinct HMO have been identified, and the HMO composition varies between mothers as well as over the course of lactation. Some newborn infants receive donor milk (DM) when their mother's own milk (MOM) volume is inadequate or unavailable. OBJECTIVE: This study aimed to compare HMO content between DM and MOM. METHODS: We used high performance liquid chromatography analysis of fluorescently labeled HMO to analyze the variation in HMO amount and composition of 31 different batches of DM (each pooled from 3 individual donors) provided by the Mothers' Milk Bank in San Jose, California, and compared it to 26 different MOM samples donated by mothers with infants in our neonatal intensive care unit (NICU). RESULTS: Total HMO amount as well as concentrations of lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose 1, and disialyllacto-N-tetraose were significantly lower in DM than in MOM, whereas the concentrations of 3'-sialyllactose and 3-fucosyllactose were significantly higher in DM. CONCLUSION: Our data show that infants in our NICU who receive DM are likely to ingest HMO at different total amounts and relative composition from what they would receive with their MOM. Recent in vitro and animal studies have started to link individual HMO to infant health and disease. Future studies are needed to assess the importance of a mother-infant match with regard to HMO composition.