Methyl Mercury Effect on Adolescent Development Renewal

描述(由申请人提供)：本申请是授予5-R01ES008442“甲基汞对青少年发展的影响”的竞争性续期申请。塞舌尔儿童发育研究(SCDS)一直在检验这样一种假设，即食用高含量鱼类的饮食导致甲基汞(MeHg)暴露与不利的健康后果有关。食用鱼类而暴露于甲基汞被认为会损害心脏的认知和神经调节。自1989年以来，我们一直在跟踪调查779名受试者，这些受试者的母亲在怀孕期间平均每周吃12顿鱼。受试者现在都快21岁了。研究人员对受试者进行了认知和行为发展评估。2006年，该项目利用一项与之竞争的补充项目的资金进行了扩展，将自主心脏调节的测量包括在内。受试者自己习惯性地食用富含鱼类的饮食。鱼含有甲基汞和营养物质，包括对大脑发育和心脏功能有益的长链多不饱和脂肪酸(LCPUFA)。初步数据表明，鱼在出生前和出生后暴露于甲基汞和低氯不饱和脂肪酸的联合暴露可能与不同的结果模式有关。然而，有关出生后暴露的信息有限。我们将在大约21岁和23岁时检查SCDS队列，以评估出生后暴露于甲基汞的净累积风险以及最近的LCPUFA状态对认知结果和心血管参数的影响。统计分析将采用创新的参数和非参数模型，旨在确定出生后共同暴露于这些终点的影响，并根据产前甲基汞暴露和/或终身累积(产前和出生后)甲基汞暴露，以及最近暴露于低氯不饱和脂肪酸的情况进行调整，以确定伴随这些暴露而来的单独风险。塞舌尔的人口与美国有许多相似之处，因此可以作为鱼类消费风险和好处的哨兵。随访率低提供了一个独特的机会，可以继续研究这一特征很好的队列，并在其成员从青春期进入青年生活的过程中区分产前和产后甲基汞的影响。这项研究的结果将是重要的，因为政府机构继续评估关于高鱼类饮食的毒性影响和营养益处的科学数据。这项研究还应该阐明食用鱼类与神经认知和心脏疾病相关的风险和好处，这些疾病可能要到成年以后才能在临床上显现出来。 与公共卫生相关：人类对甲基汞的暴露几乎完全来自鱼类消费，所有鱼类都含有一些甲基汞。但鱼类也提供其他高度有益的营养物质，如对中枢神经系统(CNS)的发育和功能至关重要的长链多不饱和脂肪酸(LCPUFA)，似乎可以减轻产前汞暴露的一些影响。过去供资期间的调查结果表明，产前甲基汞的有益影响，但出生后甲基汞对不同的神经认知和行为功能的不利影响，以及对心脏的神经调节的有利影响，表明这些功能的不同净风险或收益取决于时间和器官，因此可能需要不同的公共卫生风险考虑和文件修订，如国家研究委员会报告(2002年)。这项拟议的研究创新性地利用了我们充分描述的队列，首次确定了LCPUFA是否与一生和最近出生后的甲基汞暴露相互作用，调节其对神经认知和心脏功能的影响。LCPUFA实际上对中枢神经系统有持续的影响。这一结果应该对建议公众食用鱼类的机构产生直接和重要的公共卫生影响。如果LCPUFA与出生后的甲基汞暴露没有相互作用，就像对产前的甲基汞暴露一样，我们的研究结果将表明，与这两种暴露相关的公共健康风险可能是不同的，必须区别对待。

DESCRIPTION (provided by applicant): This application is a competing renewal of Grant 5-R01ES008442 entitled "Methyl Mercury Effects on Adolescent Development." The Seychelles Child development Study (SCDS) has been testing the hypothesis that methyl mercury (MeHg) exposure from consumption of a diet high in fish is associated with adverse health outcomes. Exposure to MeHg from fish consumption is thought to impair cognition and neuro-regulation of the heart. Since 1989, we have been following a cohort of 779 subjects born to mothers who consumed an average of 12 fish-meals per week during pregnancy. The subjects are now approaching 21 years of age. The subjects have been assessed for cognitive and behavioral development. In 2006, the project was expanded with funds from a competing supplement to include measurements of autonomic heart regulation. The subjects themselves habitually consume a diet high in fish. Fish contain both MeHg and nutrients including long-chain polyunsaturated fatty acids (LCPUFA) which are beneficial to brain development and heart function. Preliminary data suggest that prenatal and postnatal exposures to combined MeHg and LCPUFA in fish may be associated with distinct patterns of results. Limited information is available on postnatal exposures however. We will examine the SCDS cohort at approximately 21 and 23 years of age to assess the net cumulative risk of exposure to postnatal MeHg and recent LCPUFA status on cognitive outcomes and cardiovascular parameters. Statistical analyses will employ innovative parametric and non-parametric modeling designed to ascertain the effects on these endpoints of co-exposures to postnatal, adjusted for prenatal MeHg exposure, and/or lifetime cumulative (prenatal and postnatal) exposure to MeHg, and recent exposure to LCPUFA to ascertain the separate risks attendant to these exposures. The Seychelles population has many similarities with that of the US and can therefore serve as a sentinel for the risks and benefits of fish consumption. The low loss to follow-up provides a unique opportunity to continue to study this very well characterized cohort and differentiate prenatal from postnatal MeHg effects as its members move from adolescence to young adult life. The findings from this study will be important as governmental agencies continue to evaluate the scientific data regarding toxic effects and nutrient benefits of a high fish diet. The study should also clarify the risks and benefits of fish consumption in relation to neurocognitive and cardiac morbidity that may not become clinically manifest until later in adulthood. PUBLIC HEALTH RELEVANCE: Human exposure to MeHg is almost exclusively from fish consumption and all fish contain some MeHg. But fish also provide other highly beneficial nutrients, such as long chain polyunsaturated fatty acids (LCPUFA) that are essential for development and function of the central nervous system (CNS) and appear to mitigate some effects of prenatal mercury exposure. Findings during the past funding period demonstrate beneficial effects of prenatal MeHg, but adverse effects of postnatal MeHg on different neurocognitive and behavioral functions, and a beneficial impact on neuro-regulation of the heart, demonstrating differential net risks or benefits for these functions that are time and organ-dependent and which therefore may require different public health risk considerations and revisions of documents, such as the National Research Council Report (2002). The proposed study makes innovative use of our well-characterized cohort to determine for the first time whether LCPUFA, that actually have a continuing influence on the CNS across the life span, interact with lifetime and recent postnatal MeHg exposure to modulate its influence on neurocognition and cardiac functions. The results should have immediate and important public health implications for agencies that advise the public about fish consumption. If LCPUFA do not interact with postnatal MeHg exposure, as they do with prenatal MeHg exposure, our findings will suggest that public health risks associated with the two exposures may be different and would have to be differentially considered.