Courtney Wusthoff, MD MS, is an Assistant Professor of Neurology at Stanford whose career goal is to determine if and how the diagnosis and treatment of neonatal seizures can improve neurodevelopmental outcomes. She has unique expertise in neonatal neurology and EEG. She is a newly independent investigator with demonstrated capacity to conduct independent research and outstanding potential for future success. The proposed career development activities provide training in advanced study design and analysis so she may apply alternative study design and advanced statistical techniques to the study of neonatal seizures. The proposed research will provide experience leading a multicenter study and in analyzing a large data set. The proposed research will be the first multicenter study to prospectively collect continuous EEG (cEEG) to define seizure and EEG features in preterm neonates with encephalopathy. Converging evidence suggests neonatal seizures lead to poor neurodevelopmental outcomes in preterm neonates, but it is unknown how much seizure treatment improves outcomes. To design an adequate study for that question first requires clear understanding of the incidence, timing, and burden of seizures in preterm neonates. This project will provide that essential data by leveraging the NICHD Neonatal Research Network (NRN) trial of hypothermia for neuroprotection in preterm neonates with encephalopathy. This proposed secondary study to the NRN trial will use cEEG recorded from preterms with encephalopathy during the first 4 days after birth. Central neurophysiologists will analyze cEEG for seizure incidence and timing in both the treatment (hypothermia) and control (normothermia) groups. cEEG data will also be processed post hoc to simulate serial, ?spot? EEGs and amplitude-integrated EEGs (aEEG). The accuracy of these commonly used techniques for seizure detection will be compared to the gold standard of cEEG. In the short-term, the results will help clinicians understand seizure risk for preterms with encephalopathy and in selecting techniques for seizure diagnosis. This research will also provide needed preliminary data for an R01 proposal to study how the anti-seizure properties of a neuroprotective agent might mediate neurodevelopmental outcomes. The training plan incorporates coursework and experience in advanced study design and analysis, grant writing, and leadership. Dr. Wusthoff will have access to the opportunities provided by Stanford?s participation in the NRN, their Neurology Neonatal Intensive Care Unit, and Stanford?s Center for Clinical and Translational Education and Research (SPECTRUM). This project tackles questions urgently in need of sound evidence. The career development plan targets specific gaps with focused training so the candidate may become competitive for R01 funding. There is a clear path from the proposed work to future studies of seizures in preterm neonates. Upon conclusion of the award, Dr. Wusthoff will be optimally positioned to conduct transformative research in neonatal seizures.
Neonatal seizures are a risk factor for later neurodevelopmental problems including cerebral palsy, intellectual disability and epilepsy. The proposed study will provide a better understanding of which preterm babies with encephalopathy are at risk for seizures, when seizure risk is greatest within the first days after birth, and what technology is most accurate for diagnosing neonatal seizures in preemies. The results will provide a foundation for future work studying treatments of neonatal seizures, in hopes of improving neurodevelopmental outcomes.
