This career development award is designed to support my transition into an independent clinician-scientist dedicated to the study of genetic susceptibility to adverse neurodevelopmental outcomes. I completed a Maternal Fetal Medicine Fellowship at the University of Utah Health Sciences Center in June 2009. From July 2007 to present, I have been the recipient of the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network's Mentored Specialized Clinical Investigator Development Award (MSCIDA), which has provided support for initial training and research. This 2-year award qualifies as K-funding and will end in August 2009. I am fulfilling all of my funded training and research goals for the MSCIDA award. This research was presented at the 2009 Society of Maternal Fetal Medicine meeting (oral) and the 2009 Society for Gynecologic Investigation meeting (oral). This proposal outlines an extended training and research program that will provide me with a total of 5 years of protected, mentored time and will result in achievement of my goal of becoming an independent, extramurally funded and self-sustaining clinician-scientist. My specific career development aims are to 1) expand existing skills in study design, analysis, and interpretation of results, 2) develop additional skills in the acquisition, management, and analysis of genetic data, 3) develop additional skills in the design and implementation of clinical trials, 4) develop skills for leadership of a multi-disciplinary research team, and 5) understand the ethical and legal implications of research in clinical genetics and neurodevelopmental disability. My specific research aims are to 1) identify genetic polymorphisms that are associated with CP in preterm infants using a custom, multiplex SNP assay designed to assess ~1300 SNPs in inflammation, coagulation, vascular regulation and other genes, 2) identify genetic polymorphisms that are associated with neurodevelopmental delay in preterm infants using the same custom multiplex SNP assay, and 3) perform analyses to identify unique gene-gene and gene-environment interactions that contribute to susceptibility to adverse neurodevelopmental outcomes. This proposal represents a unique opportunity for correlation of genetic polymorphisms with well- characterized neurodevelopmental outcomes in a large cohort. It is also a unique opportunity to gain multi- disciplinary training and research experience to support my career goal of becoming a nationally-recognized expert in fetal genetic factors that contribute to adverse neurodevelopmental outcomes. PUBLIC HEALTH RELEVANCE: Although various perinatal complications increase the risk of an individual developing cerebral palsy or other forms of neurodevelopmental delay, the mechanisms by which at-risk individuals develop these complications are incompletely understood. This work will contribute to an increased understanding of the genetic risk factors predisposing a premature fetus to brain injury, and will therefore identify possible prevention strategies and may provide a basis for future prevention/ intervention trials. It will also enhance the career development of a promising young clinician-scientist within an environment with proven career-development capabilities. Dr. Clark has the enthusiastic support of her Division, Department and Institution (including at least 75% protected time and appropriate institutional funding).