Children are exposed to a mix of potential neurotoxicants, including metals, via widespread contamination of food, air, soil and, in some settings, water. Exposure to neurotoxicants during early development can be particularly deleterious. Furthermore, the substantial developmental and physiologic changes of adolescence have been shown to be sensitive to early life exposures and experience. Therefore adolescence represents a critical time for manifestations of early life exposure effects but there are few environmental epidemiologic studies of this age group. The primary aims of this study are to assess the relation of early life exposure to neurotoxic metal mixtures, and their interactions, with early adolescent behavior and cognition. The metals to be studied are prenatal manganese (Mn), methylmercury (MeHg), arsenic (As), lead (Pb) and postnatal Pb exposure. We will assess the relation of early life exposure to these metals, individually and jointly, with (1) behavior and cognition, particularly impulsive or hyperactive behaviors, attention, language skill, executive function, memory and learning skills among 13-year-olds;and (2) prospective changes in behavior and cognition between ages 8 and 13 years. (3) In addition, we will assess the role of prenatal exposure to prevalent organochlorines - polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (DDE), and hexachlorobenzene (HCB) -- as effect modifiers of metal-behavior/cognitive associations. The proposed study population is a well characterized cohort of 788 children born between 1993-1998, residing adjacent to a PCBand metal-contaminated site and with low-level to moderate metal exposures. Prenatal Pb and organochlorine exposure measures, and archived cord blood, maternal hair and toenail specimens were obtained at birth and the children had developmental assessments from birth through age 8 years. In this study, archived birth specimens will be analyzed for Mn, MeHg, and As and detailed cognitive/behavioral assessments will be performed at age13 years on 500 of the children. The relation of metal exposures with neurocognitive skills will be assessed individually and with interaction terms for each outcome. Then, the relation of individual and multiple exposure measures with potentially correlated outcomes will be evaluated in a single multiple outcomes model. The study's behavioral and cognitive assessments will measures skills directly related to the risk of childhood learning and behavioral disorders. These increasing common childhood disorders represent a growing source of childhood and, in many cases, later life morbidity and public health concern. The proposed study provides a unique opportunity (given extensive prospective exposure/developmental information and specimen archives already available) to gain insight into potentially remediable risk factors for common behavioral and learning disorders of childhood at a time, adolescence, when there may be increasingly evident functional and behavioral manifestations of early life neurotoxicant exposures.
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