Mercury Vapor from Amalgam and Methylmercury Co-Exposure on Neurodevelopment

描述(由申请人提供)：汞(汞)蒸气和甲基汞(甲基汞)分别是有效的神经毒素。牙科汞齐修复体由大约50%的金属汞组成，是人体接触汞蒸气的主要来源，而接触甲基汞的大部分来自鱼类消费。这两种形式的汞都会穿过胎盘和血脑屏障，暴露在发育中的胎儿身上。值得关注的是，人类胎儿似乎特别容易受到甲基汞的影响。关于产前汞蒸气暴露对发育的影响的数据很少，也没有关于汞蒸气和甲基汞联合暴露的数据，尽管人们担心联合暴露可能会通过相加或协同机制增加风险。拟议的研究将建立在塞舌尔儿童发育营养研究(SCDNS)的基础上，这是一项纵向队列研究，旨在研究产前暴露于甲基汞、营养状况和发育之间的关系。塞舌尔的居民使用汞齐提供免费的牙科护理，并消费大量的海鱼。SCDNS儿童已经接受了八次评估，到目前为止，他们的营养和发育状况得到了很好的描述。到目前为止，产前和产后接触甲基汞的情况是通过对母亲/孩子的头发进行定期采样来确定的，孕妇怀孕期间的牙齿状况是通过分娩后的口腔检查确定的。在拟议的研究中，我们将对儿童进行常规牙科检查，记录放置/呈现/丢失的汞合金修复体作为出生后汞蒸气暴露的衡量标准，以及头发分析作为出生后甲基汞暴露的衡量标准。神经发育测试将在72个月和96个月时进行。来自塞舌尔先前队列的初步数据表明，当分析中包括汞蒸气暴露(根据怀孕期间存在的孕妇汞齐测量)时，存在不利的关联。拟议项目的目的是利用已经具有良好特征的SCDNS队列的可用性，以量化产前和出生后共同暴露于汞蒸气和甲基汞造成不利神经发育后果的风险水平。将检验三个假设：1)汞蒸气和甲基汞的联合暴露将加剧不良神经发育结果的风险水平；2)出生前暴露的影响将因出生后暴露而加剧；3)总体暴露影响将受到产前营养因素的调节。

DESCRIPTION (provided by applicant): Mercury (Hg) vapor and monomethylmercury (MeHg) are separately potent neurotoxins. Dental amalgam restorations, which are composed of approximately 50% metallic Hg, are the principal source of human exposure to Hg vapor, while most exposure to MeHg comes from fish consumption. Both forms of Hg cross the placental and blood-brain barriers, exposing the developing fetus. Of significant concern, the human fetus appears especially vulnerable to MeHg. There is a paucity of data on the developmental effects of prenatal Hg vapor exposure, and no data on the combined exposure to Hg vapor and MeHg exposure, despite concerns that combined exposure may elevate risk via additive or synergistic mechanisms. The proposed study will build on the strength of the Seychelles Child Development Nutrition Study (SCDNS), a longitudinal cohort study examining the association between prenatal exposure to MeHg, nutritional status, and development. Residents of the Seychelles have free dental care using amalgams and consume large quantities of ocean fish. SCDNS children have been evaluated eight times and their nutritional and developmental status to date has been well characterized. Prenatal and postnatal exposure to MeHg to date has been determined by periodic sampling of the mother's/child's hair and maternal dental status during pregnancy was established by oral examinations following delivery. In the proposed study, we will conduct routine dental exams in children recording amalgam restorations placed/present/lost as a measure of postnatal Hg vapor exposure and hair analysis as a measure of postnatal MeHg exposure. Neurodevelopmental testing will occur at 72 and 96 months. Preliminary data from a prior Seychelles cohort suggests an adverse association when Hg vapor exposure (as measured by maternal amalgams present during gestation) is included in analyses. The aim of the proposed project is to capitalize on the availability of the already well-characterized SCDNS cohort to quantify the level of risk for adverse neurodevelopmental outcomes attributable to prenatal and postnatal co-exposure to Hg vapor and MeHg. Three hypotheses will be tested: 1) The level of risk for adverse neurodevelopmental outcomes will be accentuated by combined exposure to Hg vapor and MeHg; 2) Effects of prenatal exposure will be accentuated by postnatal exposure; and 3) Overall exposure effects will be modulated by prenatal nutritional factors.