Factors Modifying the Toxicity of Methylmercury in a Fish-Eating Population

改变甲基汞对吃鱼人群的毒性的因素

• 批准号: 7785157
• 负责人: PHILIP W DAVIDSON
• 金额: $ 73.55万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-21 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7785157
• 关键词: Address; Adverse effects; Affect; Age; Age-Months; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Behavior; Benefits and Risks; Biological Assay; Brain; Child; Child Development; Communication; Complex; Consumption; Coupled; Data; Data Set; Development; Diet; Dietary intake; Eating; Emotional; Enrollment; Equilibrium; Exposure to; Fishes; Food; Funding; Grant; Hair; Health Planning; Health Policy; Human; Infant; Intake; Language; Life; Linear Regressions; Literature; Masks; Maternal Exposure; Measures; Mercury; Methylmercury Compounds; Modeling; Mothers; Neurologic; Neurotoxins; Nutrient; Nutritional; Nutritional status; Oceans; Outcome; Performance; Perinatal Exposure; Phase; Policies; Polyunsaturated Fatty Acids; Population; Pregnancy; Pregnant Women; Principal Investigator; Public Health; Publishing; Recruitment Activity; Reproduction; Rodent; Role; Safety; Selenium; Sensory; Seychelles; Source; Statistical Models; Testing; Tocopherols; Tocotrienols; Toxic effect; United States Food and Drug Administration; Vitamin E; base; cohort; communication behavior; exposed human population; fatty acid oxidation; good diet; improved; in utero; in vitro Model; innovation; maternal serum; member; neurodevelopment; neurotoxic; neurotoxicity; novel; nutrition; oxidative damage; palm oil; prenatal; prenatal exposure; public health relevance; response; social; social communication; stem

DESCRIPTION (provided by principal investigator): This application is the first resubmission of a competing renewal of the Seychelles Child Development and Nutrition Study (SCDNS), initially funded in 2000 to examine the hypothesis that maternal nutritional and dietary status during pregnancy might modify the toxicity of MeHg when exposure stems from consumption of a diet high in fish. During the initial period of the SCDNS, prenatal exposure to MeHg and selected nutrients were measured and neurodevelopment of cohort of 229 children was evaluated through the first 30 months of life. We found no evidence of independent adverse effects of prenatal MeHg on developmental outcomes within the range of MeHg exposure studied (1-18 ppm in maternal hair). However, there was an adverse effect of prenatal MeHg exposure on psychomotor ability when statistical models were adjusted for maternal dietary intake and nutritional status. This effect was due to maternal serum levels of )-3 and )-6 long-chain polyunsaturated fatty acids (LCPUFA). )-3 LCPUFA levels had a beneficial influence on psychomotor development while both MeHg and )-6 LCPUFA adversely affected psychomotor development. Thus, LCPUFA might have a direct impact on developmental endpoints and modify the MeHg effect. It is also likely that other nutritional covariates might further modify the toxicity of MeHg. Our aim is to extend the SCDNS to pursue an innovate study to test in more depth the parameters of our recently published novel finding showing an apparent modulation of MeHg neurotoxicity by LCPUFA. The initial study measured a limited number of candidate nutrients present in fish and enrolled a cohort based on power estimates from our earlier studies. In retrospect, we underestimated the complexity of nutrient effects on neurotoxicity and development. Using a larger more powerful cohort (n~1,500) being recruited by the Seychelles Ministry of Health, we plan to confirm the main effects found to date and test interactions between MeHg and LCPUFA. Our plan also includes assaying vitamin E and selenium status in pregnancy as possible modifiers of the combined effects of MeHg and LCPUFA on development. The new cohort will be assessed for development using measures that showed an association between either MeHg alone, LCPUFA alone or the combination of both in our initial study. Measures of social communication and behavior will be added to increase the scope of the assessment Continuing the SCDNS utilizing a larger cohort and focusing specifically on the role of LCPUFA in relation to MeHg neurotoxic exposures and child development should allow us to efficiently pursue the scientific questions raised by our first five years of study. It will also contribute to establishing the risks and benefits of fish consumption during pregnancy. In addition we will begin to study the broader question of how diet may interact with MeHg exposure. These results should enable regulators to promulgate scientifically based advisories concerning safety of consuming fish during pregnancy. PUBLIC HEALTH RELEVANCE: Public Health Significance Human exposure to MeHg is almost exclusively from fish consumption and all fish contain some MeHg. Fish also provide other nutrients such as Long chain Polyunsaturated Fatty Acids (LCPUFA) that are essential for brain development and exert a beneficial influence on child development. Our results to date suggest that the beneficial influence of LCPUFA on neurodevelopment may modulate adverse effects of MeHg. The proposed study will determine if other dietary nutrients can reduce the neurotoxicity of MeHg and increment the effects of LCPUFA. The results should have immediate and important public health implications not only for agencies that advise the public about fish consumption, but also for public health policies regarding nutrient intake during pregnancy.

描述（由首席研究员提供）：本申请是塞舌尔儿童发育和营养研究 (SCDNS) 竞争性更新的首次重新提交，该研究最初于 2000 年资助，旨在检验这样的假设：怀孕期间母亲的营养和饮食状况可能会改变因食用高鱼饮食而接触甲基汞的毒性。在 SCDNS 的初始阶段，测量了产前甲基汞和选定营养素的暴露情况，并评估了 229 名儿童在出生后前 30 个月的神经发育情况。我们没有发现证据表明产前甲基汞对发育结果产生独立的不利影响，在研究的甲基汞暴露范围内（母亲头发中的浓度为 1-18 ppm）。然而，当根据母亲饮食摄入量和营养状况调整统计模型时，产前甲基汞暴露会对精神运动能力产生不利影响。这种效应是由于母体血清中 )-3 和 )-6 长链多不饱和脂肪酸 (LCPUFA) 水平所致。 )-3 LCPUFA 水平对精神运动发育具有有益影响，而 MeHg 和 )-6 LCPUFA 则对精神运动发育产生不利影响。因此，LCPUFA 可能对发育终点产生直接影响并改变甲基汞效应。其他营养协变量也可能进一步改变甲基汞的毒性。我们的目标是扩展 SCDNS 进行一项创新研究，更深入地测试我们最近发表的新发现的参数，该发现显示 LCPUFA 对 MeHg 神经毒性有明显的调节作用。最初的研究测量了鱼类中存在的有限数量的候选营养素，并根据我们早期研究的功率估计招募了一个队列。回想起来，我们低估了营养物质对神经毒性和发育影响的复杂性。我们计划利用塞舌尔卫生部招募的更大、更强大的队列（n~1,500）来确认迄今为止发现的主要影响，并测试 MeHg 和 LCPUFA 之间的相互作用。我们的计划还包括测定妊娠期维生素 E 和硒的状况，作为 MeHg 和 LCPUFA 对发育的综合影响的可能调节剂。在我们的初步研究中，将使用显示单独的 MeHg、单独的 LCPUFA 或两者的组合之间的关联的措施来评估新队列的发育。将增加社会沟通和行为的衡量标准，以扩大评估范围。继续利用更大的队列进行 SCDNS，并特别关注 LCPUFA 在甲基汞神经毒性暴露和儿童发育方面的作用，应该使我们能够有效地解决我们前五年研究中提出的科学问题。它还将有助于确定怀孕期间食用鱼类的风险和益处。此外，我们将开始研究饮食如何与甲基汞暴露相互作用的更广泛的问题。这些结果将使监管机构能够发布有关怀孕期间食用鱼类安全的科学建议。 公共卫生相关性：公共卫生意义 人类接触甲基汞几乎完全来自鱼类消费，所有鱼类都含有一定程度的甲基汞。鱼还提供其他营养物质，例如长链多不饱和脂肪酸 (LCPUFA)，它们对大脑发育至关重要，并对儿童发育产生有益影响。我们迄今为止的结果表明，LCPUFA 对神经发育的有益影响可能会调节甲基汞的不利影响。拟议的研究将确定其他膳食营养素是否可以降低甲基汞的神经毒性并增加 LCPUFA 的作用。研究结果不仅对向公众提供鱼类消费建议的机构，而且对有关怀孕期间营养摄入的公共卫生政策产生直接和重要的公共卫生影响。