This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this competing renewal, we hypothesize that the adverse fetal events common in the diabetic pregnancy (i.e. iron deficiency, hypoxemia, and hypoglycemia) will have a deleterious and specific effect on the hippocampus. This should result in selective impairments in explicit memory due to the established vulnerability of this structure to these metabolic disturbances. Our results thus far have established a consistent pattern of deficits in recognition memory, from birth through two years of age, as inferred from electrophysiological data (event-related potentials) and behavioral data (Elicited Imitation). The goal of the current proposal is to continue to study our cohort of children as they enter the elementary school years. We are focusing our efforts specifically on three areas. First, we intend to document more specifically the nature of the functional and structural deficits observed to date: thus, what types of memory are impaired, and how extensive is the damage to the hippocampus? Second, we seek to determine whether deficits in other cognitive functions emerge as our study populations makes the transition to school age; specifically, do we observe deficits in striatal or prefrontal functions? And, is there an association between such deficits and school performance? Finally, we wish to characterize further what neural circuits have been compromised by the adverse fetal environment that is common among IDMs; specifically, confirm our prediction of hippocampal damage (as inferred from reduced hippocampal volume and/or metabolism) and/or whether we observe damage to striatum, and/or whether we observe reductions in white matter due to prenatal iron deficiency. We will address these questions by conducting detailed electrophysiological (ERPs), metabolic (fMRI), anatomic (MRI), and behavioral (neuropsychologic) studies on our current samples of IDMs and comparison children. Given that approximately 10% of all pregnancies are complicated by maternal diabetes, the current project has important implications for public health.
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