Methyl Mercury Effect on Adolescent Development Renewal

甲基汞对青少年发育更新的影响

• 批准号: 8274446
• 负责人: PHILIP W DAVIDSON
• 金额: $ 76.89万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274446
• 关键词: 21 year old; Adolescence; Adolescent Development; Adult; Adverse effects; Affect; Age-Years; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Attention; Attenuated; Behavioral; Benefits and Risks; Biological Markers; Blood Pressure; Brain; C-reactive protein; Cardiac; Cardiovascular system; Child Development; Cognition; Cognitive; Cohort Studies; Complex; Consumption; Coupled; Data; Development; Diet; Discrimination Learning; Eating; Evaluation; Exposure to; Fishes; Funding; Grant; Health; Heart; Homeostasis; Hypertension; Impaired cognition; Impairment; Impulsivity; Inflammation; Ion Channel; Lead; Life; Literature; Longevity; Mammals; Measurement; Measures; Medial; Mercury; Modification; Morbidity - disease rate; Mothers; Myocardium; National Research Council; Neuraxis; Neurocognition; Neurocognitive; Nutrient; Nutritional status; Organ; Outcome; Pattern; Polychlorinated Biphenyls; Polyunsaturated Fatty Acids; Population; Pregnancy; Psychomotor Performance; Public Health; Regulation; Reporting; Research; Resources; Risk; Risk Factors; Scientist; Sea; Sentinel; Seychelles; Social Behavior; Staging; Study Subject; Testing; Thick; Time; Tissues; Toxic effect; Universities; Vascular Endothelium; arterial stiffness; blood pressure regulation; cognitive function; cohort; emerging adult; exposed human population; fetal; follow-up; heart function; heart rate variability; improved; indexing; innovation; insight; lead exposure; member; model design; neurocognitive test; postnatal; prenatal; prenatal exposure; prenatal influence; programs; public health relevance; relating to nervous system; response; stem; toxicant; young adult

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.

描述（由申请人提供）：本申请是题为“甲基汞对青少年发展的影响”的补助金5-R01ES008442的竞争性更新。塞舌尔儿童发展研究（SCDS）一直在检验一种假设，即食用富含鱼类的饮食中接触甲基汞与不良健康后果有关。从食用鱼类中暴露于甲基汞被认为会损害认知和心脏的神经调节。自1989年以来，我们一直在跟踪一组779名研究对象，这些母亲在怀孕期间平均每周吃12顿鱼餐。研究对象现在都快21岁了。研究人员对受试者的认知和行为发展进行了评估。2006年，该项目得到了一个竞争性补充项目的资助，扩大到包括对心脏自主调节的测量。受试者自己习惯性地食用富含鱼类的食物。鱼类含有甲基汞和包括长链多不饱和脂肪酸（LCPUFA）在内的营养物质，对大脑发育和心脏功能有益。初步数据表明，产前和产后暴露于鱼类中MeHg和LCPUFA的组合可能与不同的结果模式有关。然而，关于产后暴露的信息有限。我们将检查大约21岁和23岁的SCDS队列，以评估产后MeHg暴露的净累积风险和最近的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，旨在确定产后共同暴露对这些终点的影响，调整产前甲基汞暴露，和/或终生累积（产前和产后）暴露于甲基汞，以及最近暴露于LCPUFA，以确定这些暴露所伴随的单独风险。塞舌尔人口与美国人口有许多相似之处，因此可以作为鱼类消费风险和收益的哨兵。低随访损失提供了一个独特的机会，可以继续研究这个非常有特征的队列，并区分产前和产后MeHg的影响，因为它的成员从青春期到青年期。随着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，这项研究的结果将是重要的。这项研究还应该澄清食用鱼类与神经认知和心脏疾病的关系的风险和益处，这些疾病可能直到成年后期才会在临床表现出来。