ABSTRACT This proposal builds on the candidate’s dissertation research that examined the associations between prenatal exposure to perfluorinated chemicals (PFCs) and three specific neurodevelopmental outcomes, including autism, attention-deficit/hyperactivity disorder, and cerebral palsy in the Danish National Birth Cohort (DNBC) that consists of ~100,000 mothers and children. PFCs are widespread persistent organic pollutants, and pregnant women and fetuses are often involuntarily and nearly ubiquitously exposed to these synthetic compounds since the 1950s. Animal studies suggest that PFCs are developmental toxicants but evidence from human studies is sparse. Decade long collaborations between UCLA and Aarhus University enabled the candidate to gain access to the unique, large-scale, nationwide Danish cohorts and registries for research. The proposed study will greatly expand the use of DNBC and various Danish registers and allow for the very first time examination of the link between prenatal PFC exposures and an array of neurodevelopmental outcomes never investigated before, including (1) extensive neuropsychological assessments of intelligence, cognition, attention, memory and motor skills in children at age 5; (2) hospital diagnosis of epilepsy; (3) the child’s social competence and mental health at age 11; and (4) intellectual capacity and school performance up to age 16. The proposed studies will capitalize upon the valuable resource of stored maternal pregnancy blood samples from DNBC, allowing a reliable and valid assessment of PFC exposure levels during fetal development. The proposal will be pursued within the context of a strong ongoing collaboration between the UCLA Department of Epidemiology and Aarhus University, adding new partners from the UCLA Medical Psychology Assessment Center (MPAC) and Department of Human Genetics. This application builds on Dr. Liew’s expertise in environmental sciences and advanced epidemiologic methods. It will allow him to newly gain the necessary training in clinical psychology, environmental statistics, and neurobehavioral epi/genetics and to build a skillset compatible with conducting future cutting-edge epi-gene/environment interactions research that optimally uses existing large bio-sample repositories in the Nordic countries. Drs. Beate Ritz and JØrn Olsen have agreed to mentor the candidate through the K99 process. Dr. Robert Asarnow will provide training in administrating/scoring complex neuropsychological instruments and clinical knowledge of neuropsychiatric disorders. Dr. Michael Jerrett will provide training opportunities in environmental statistics and exposure assessment referred to as the ‘external exposome’. Dr. Steve Horvath will provide training in advanced gene-environment and epigenetic network analysis. The contents of this application provide a strategy to position the candidate to successfully launch into a tenured professor track position and equip him with the necessary skills to move towards independence and pursue R01 proposals.

Project Narrative Perfluorinated chemicals (PFCs) are widespread man-made persistent organic pollutants with endocrine disruptive and neurotoxic activities observed in animals. Almost all pregnant women and children in Denmark and the US were found to be involuntarily and nearly ubiquitously exposed to these synthetic compounds, but human studies that evaluate neurodevelopmental effects of PFCs are sparse. We propose to utilize data from the Danish National Birth Cohort (DNBC) to study the impact of prenatal exposure to PFCs on a broad range of critical neurodevelopmental endpoints spanning from age 5 to 16, and our study findings will advance scientific insights into biologic mechanisms of developmental brain disorders and may influence regulation of these chemical contaminants globally.