Mercury Vapor from Amalgam and Methylmercury Co-Exposure on Neurodevelopment

描述（由申请人提供）：汞（Hg）蒸气和一甲基汞（MeHg）分别是强效神经毒素。牙齿汞合金修复体由大约50%的金属汞组成，是人类接触汞蒸气的主要来源，而大多数接触甲基汞来自食用鱼类。两种形式的汞都会穿过胎盘和血脑屏障，使发育中的胎儿暴露于危险之中。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影响的数据很少，而且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通过加性或协同机制提高风险。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，该研究是一项纵向队列研究，旨在研究产前接触甲基汞、营养状况和发育之间的关系。塞舌尔居民使用汞合金享受免费牙科保健，并食用大量海鱼。scdn儿童已经评估了8次，迄今为止他们的营养和发育状况已经得到了很好的描述。迄今为止，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抽样来确定的，孕妇在怀孕期间的牙齿状况是通过分娩后的口腔检查来确定的。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/存在/丢失的汞合金修复体作为出生后汞蒸气暴露的测量，并分析头发作为出生后甲基汞暴露的测量。神经发育测试将在72和96个月时进行。来自先前塞舌尔队列的初步数据表明，当汞蒸气暴露（通过妊娠期间母体汞合金测量）纳入分析时，存在不利关联。该项目的目的是利用已经被充分表征的SCDNS队列的可用性，量化产前和产后共同暴露于汞蒸气和甲基汞的不良神经发育结果的风险水平。将检验三个假设：1)同时暴露于汞蒸气和甲基汞会加重神经发育不良后果的风险水平；2)产前暴露的影响会因产后暴露而加重；3)总体暴露效应会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.