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)
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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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
Orbach, Sharon A; Bonifacio, Sonia L; Kuzniewicz, Michael W et al. (2014) Lower incidence of seizure among neonates treated with therapeutic hypothermia. J Child Neurol 29:1502-7
Glass, Hannah C (2014) Neonatal seizures: advances in mechanisms and management. Clin Perinatol 41:177-90
Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore et al. (2014) Maternal or neonatal infection: association with neonatal encephalopathy outcomes. Pediatr Res 76:93-9
Glass, Hannah C; Wusthoff, Courtney J; Shellhaas, Renée A et al. (2014) Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology 82:1239-44
Fox, Christine K; Glass, Hannah C; Sidney, Stephen et al. (2013) Acute seizures predict epilepsy after childhood stroke. Ann Neurol 74:249-56
Glass, Hannah C; Wusthoff, Courtney J; Shellhaas, Renee A (2013) Amplitude-integrated electro-encephalography: the child neurologist's perspective. J Child Neurol 28:1342-50
Tymofiyeva, Olga; Hess, Christopher P; Ziv, Etay et al. (2013) A DTI-based template-free cortical connectome study of brain maturation. PLoS One 8:e63310
Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L et al. (2012) Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy. J Pediatr 161:88-93
Glass, Hannah C; Kan, Jessica; Bonifacio, Sonia L et al. (2012) Neonatal seizures: treatment practices among term and preterm infants. Pediatr Neurol 46:111-5

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