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. ExpandCollapse Abstract