This proposal builds on eight years of the candidate's previously conducted research on adverse prenatal exposures using the Danish Civil Registration System and Danish medical registers, and outcomes in the offspring. Through existing collaborations with Danish colleagues, the candidate has gained access and extensive experience with these unique, large-scale, nationwide registries. She now proposes to apply these resources to conduct the largest and most comprehensive study to date to examine the relationship between maternal diabetes and an array of neurodevelopmental outcomes that include markers of cognition, behavior, attention and motor skills. This application proposes a series of nationwide population cohort studies that will utilize the Danish Civil Registration System and Danish medical registers. It has the unique advantage of also incorporating a very large previously established cohort that is nested in the total population of Denmark and contains extensive maternal demographic histories in addition to household, environmental, and occupational exposures; this will inform the study on co-adversities in the fetal environment. Furthermore, another unique advantage of this study is the ability to asses an array of neurodevelopmental outcomes in the same population cohort, minimizing many sources of bias, and aiding the interpretation of these findings. This Mentored Research Scientist Development Award will be pursued within the context of a strong ongoing collaborative relationship between the UCLA Department of Epidemiology, Aarhus University and the UCLA Center for Autism Research and Treatment (CART). This application will provide training in neurobehavioral genetics so that the candidate can build a skillset compatible with analyzing data from large repositories available for research in the Nordic biobanks, and obtain depth in understanding of fetal programming of neurodevelopmental outcomes. Drs. Beate Ritz and Jorn Olsen have agreed to mentor the candidate through the K99 process. Dr. Dan Geschwind will oversee the candidate's training in neurobehavioral genetics, Dr. Diana Schendel will provide scientific and technical guidance on the project and Dr. Tania Esakoff will inform the project with her clinical experience in managing diabetes in pregnancy. The contents of this application provide a strategy to position the candidate such that she can launch successfully into a tenured professor track position, and gain the necessary experience to move towards independence and pursue R01 proposals.
Diabetes affects up to 15% of pregnancies worldwide and there is accumulating evidence that abnormal levels of blood glucose during pregnancy is associated with the most severe and most common neurodevelopmental impairments in the children; autism and attention deficit hyperactivity disorder, respectively. Previous research supports this link but the number of studies is limited and more powerful investigations are needed. The proposed series of nationwide population cohort studies, which incorporate a nested cohort study with extensive maternal histories and environmental variables, will elucidate what is known about the fetal programming effects of maternal diabetes on an array of neurodevelopmental outcomes in the offspring.
