Stringent fire prevention regulations have caused a rapid expansion in the use of flame retardants. The focus of this proposal is on health effects of polybrominated diphenyl ethers (PBDEs), a group of flame retardants that are used as additives in virtually all plastic containing products and may disrupt thyroid function. PBDEs are used as additives in polymers, including polystyrene, at up to 30% by weight, especially TVs, computers and furniture. The North American population is highly exposed to PBDEs as a result of both their high concentrations in home dust and time spent indoors, as well as because of their incorporation into the biota and food chain. We will leverage a unique opportunity within the GESTE birth cohort study, in which PBDEs were detected in all mothers during pregnancy at levels similar to those commonly found across the US and 5-10-fold higher than in Europe. GESTE is the first and still the only human study to correlate PBDE concentrations in pregnant women with neonatal thyroid disruption. Our previous animal experiments with pregnant ewes and rats exposed to doses of PBDEs similar to those found in North American populations showed offspring thyroid alterations in both animal models that resulted in behavioral disruption in the rat offspring (not determined in the sheep). These doses were 1000-fold lower than those found to be toxic in previous animal studies. However, PBDE effects on behavior of human offspring have not yet been characterized. We hypothesize that exposure to PBDEs is responsible for the specific and irreversible impairment of motor and cognitive skills in preschool children due to thyroid disruption. In GESTE, we will determine the relationship between prenatal exposure to PBDEs and visual skills, attention, and fine motor skills at 6.5 years of age (Aim 1). An association between PBDEs and more basic visual processes (e.g. contrast sensitivity), which exhibit dependence on thyroid hormones earlier in development than higher order processing (e.g. attention), will be indicative of an early impact of PBDEs through altered thyroid function. We will also determine the relationship between exposure to PBDEs, measured at 6.5 years of age, and thyroid hormone levels, as well as language and long term memory skills at 6.5 years of age (Aim 2). Our study will be the first in humans to provide clear evidence concerning the potential toxicity of prenatal exposure to this widely used group of thyroid-disrupting chemicals. This information is crucial to assess risks and develop preventive strategies aimed at reducing these exposures during appropriate developmental periods. For example, if prenatal exposure is found to be harmful, prevention should be oriented towards protection during pregnancy, a limited time window of exposure when plasticity is highest and opportunities for prevention are abundant. GESTE is based in Sherbrooke, Quebec, an area just 30 minutes from the US border. The proximity of the study location will facilitate interaction with the team at Harvard. Most importantly, GESTE allows investigating a population with high similarity to the US population.