P50 Pilot Project 8J

(PI: Jessie R. Maxwell, MD, Assistant Professor, Division of Neonatology, Department of Pediatrics, Co-I: Lauren L. Jantzie, PhD, Assistant Professor, Department of Pediatrics & Neurosciences, July 2017-June 2019). Although it is known that PAE and placental insufficiency result in brain injury, the impact on the neurological outcomes from the combined injury is poorly understood. This study fills a gap in knowledge about the connection between placental insufficiency and PAE and the cumulative effects in the developing brain, as there is currently no clinical methods to diagnostically or prognostically stratify infants with PAE and placental insufficiency. The hypothesis is that the combination of PAE+PI significantly worsens brain injury and function compared to either in utero insult alone. Utilizing 7T magnetic resonance imaging, the investigators predict a reduction of major white matter tracts, frontal cortex and hippocampal volumes that will correlate with significantly decreased fractional anisotropy and increased radial diffusivity, axial diffusivity and mean diffusivity in PAE + placental insufficiency offspring compared to controls and either prenatal insult alone. Further, it is predicted that the combination of PAE + placental insufficiency will result in impaired reversal learning and spatial navigation, behaviors sensitive to damage in the frontal cortex and hippocampal formation, respectively. These studies will examine both the microstructural and functional abnormalities during a critical period of neurodevelopment, and could provide vital translational clues to the specific functional brain damage of PAE and placental insufficiency I. Completion of this investigation could facilitate the development of diagnostic clinical biomarkers and novel therapeutic strategies in this underserved pediatric patient population. Dr. Maxwell is currently preparing a K08 grant in which she proposes to continue this line of research. Drs. Jantzie and Savage will serve as mentors on the K08 application.