Metal and Organochlorines Exposure: Impact on Adolescent Behavior and Cognition

描述(由调查人员提供)：儿童通过广泛污染食物、空气、土壤，在某些环境中还接触到水，暴露在包括金属在内的潜在神经毒物的混合物中。在发育早期暴露于神经毒物可能特别有害。此外，青春期的实质性发育和生理变化已被证明对早期生活暴露和经历很敏感。因此，青春期是早期生命暴露效应表现的关键时期，但对这一年龄段的环境流行病学研究很少。这项研究的主要目的是评估早期接触神经毒性金属混合物及其相互作用与青少年早期行为和认知的关系。被研究的金属是产前的锰、甲基汞、砷、铅和出生后的铅暴露。我们将单独和联合评估生命早期接触这些金属的关系，包括(1) 13岁儿童的行为和认知，特别是冲动或多动行为、注意力、语言技能、执行功能、记忆和学习技能；以及(2)8至13岁之间行为和认知的预期变化。(3)此外，我们将评估产前暴露于主要有机氯物质--多氯联苯(PCbs)、二氯二苯二氯乙烯(DDE)和六氯苯(HCB)--作为金属行为/认知联系的影响修饰物的作用。拟议的研究人群是一个由788名出生于1993-1998年间的儿童组成的具有良好特征的队列，他们居住在一个受到PCB金属污染的地点附近，并有低水平至中度的金属暴露。在出生时获取产前铅和有机氯暴露措施以及存档的脐带血、母亲头发和脚趾甲样本，并对儿童从出生到8岁进行发育评估。在这项研究中，将对存档的出生样本进行锰、甲基汞和砷的分析，并将在其中500名儿童13岁时进行详细的认知/行为评估。金属暴露与神经认知技能的关系将单独评估，并使用每个结果的交互术语进行评估。然后，将在单一的多结果模型中评估单个和多个暴露措施与潜在相关结果的关系。这项研究的行为和认知评估将衡量与 儿童学习和行为障碍的风险。这些日益常见的儿童期疾病是日益严重的儿童期疾病，在许多情况下，还会导致晚年发病率和公共卫生问题。这项拟议的研究提供了一个独特的机会(考虑到广泛的前瞻性暴露/发育信息和已有的标本档案)，以深入了解儿童常见行为和学习障碍的潜在可补救风险因素，此时正值青春期，早期生活中神经毒物暴露的功能和行为表现可能越来越明显。

DESCRIPTION (provided by investigator): 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.