Accumulating evidence suggests that seizures harm the developing brain, however little is known about their impact in preterm infants. Dr. Hannah Glass'proposed research will use the infrastructure of her mentor's ongoing longitudinal cohort study to examine magnetic resonance measures of brain injury, brain development, and outcome in preterm infants with seizures. This parent study enrolls infants born <32 weeks gestation, examines them with MRI at two neonatal time points and follows them through school age. There are currently no routine seizure measurements in this study, and seizures in this age group are difficult to detect clinically and without prolonged monitoring. Improving seizure detection for the parent study will allow Dr. Glass to use the high-quality MRI and follow-up data from that study to investigate whether seizures act to alter brain development and lead to impaired neurodevelopmental outcome in the preterm population.
The specific aims for this proposal are to compare seizure characteristics (presence, ictal lobar onset, evolution, etc) in preterm newborns with: (1) qualitatitve patterns of injury on conventional MRI;(2) quantitative measures of the hippocampus (size, metabolism and microstructure);and (3) developmental outcome. To improve seizure detection, we will add gold standard video-EEG monitoring to the parent study. MRI data from the parent study will be used to examine novel measures of the hippocampus (volume, microstructure using diffusion tensor imaging, and metabolites using 3D MR spectroscopic imaging). This project is part of an application for a K23 award for Dr. Glass, an Assistant Professor in Neurology &Pediatrics at the University of California, San Francisco, who is establishing herself as a young investigator in patient-oriented clinical and translational research in neonatal neurology. This K23 award will enable her to accomplish the following career goals: (1) to become expert in patient-oriented research in neonatal neurology and to develop an independent clinical research career;(2) to conduct clinical investigations of seizures in preterm infants using advanced MRI methods and EEG;and (3) to implement advanced biostatistical methods in clinical studies. To achieve these goals, Dr. Glass has assembled a mentoring team comprised of Dr. Donna Ferriero, who conducts basic science and clinical investigations in neonatal neurology), and Dr. A. James Barkovich (a radiologist who focuses on neuroimaging in newborns), and two scientific advisors: Dr. David Glidden (an expert in study design and biostatistical analysis) and Dr. Joseph Sullivan (epileptologist with expertise in neonatal neurophysiology).

Public Health Relevance

Preterm birth accounts for 12.5% of deliveries in the United States. Advances in care are resulting in rising numbers of intensive care nursery survivors, many of whom are at risk for disabilities. Understanding the impact of seizures in preterm infants will lay the foundation for future multi-center studies testing new strategies for preventing and treating seizures in this population. We expect that reducing seizure burden will lead to improved neurodevelopmental outcomes following preterm birth.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Neurological Sciences Training Initial Review Group (NST)
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Hirtz, Deborah G
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Lemmon, Monica E; Boss, Renee D; Bonifacio, Sonia L et al. (2017) Characterization of Death in Neonatal Encephalopathy in the Hypothermia Era. J Child Neurol 32:360-365
Glass, Hannah C; Rowitch, David H (2016) The Role of the Neurointensive Care Nursery for Neonatal Encephalopathy. Clin Perinatol 43:547-57
Glass, Hannah C; Shellhaas, Renée A; Wusthoff, Courtney J et al. (2016) Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr 174:98-103.e1
Wietstock, S O; Bonifacio, S L; Sullivan, J E et al. (2016) Continuous Video Electroencephalographic (EEG) Monitoring for Electrographic Seizure Diagnosis in Neonates: A Single-Center Study. J Child Neurol 31:328-32
Gano, Dawn; Andersen, Sarah K; Partridge, J Colin et al. (2015) Diminished white matter injury over time in a cohort of premature newborns. J Pediatr 166:39-43
Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y et al. (2015) Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia. J Neurosci 35:11946-59
Glass, Hannah C (2015) Bumetanide for treatment of seizures in neonates. Lancet Neurol 14:456-7
Glass, Hannah C; Costarino, Andrew T; Stayer, Stephen A et al. (2015) Outcomes for extremely premature infants. Anesth Analg 120:1337-51
Mrelashvili, Anna; Bonifacio, Sonia L; Rogers, Elizabeth E et al. (2015) Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis. J Child Neurol 30:1453-8
Wietstock, Sharon O; Bonifacio, Sonia L; McCulloch, Charles E et al. (2015) Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication. J Child Neurol 30:1135-41

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