Associations between Maternal Circulating DNA Methylation during Pregnancy and Exposures to Environmental Metals in the National Childrens StudyAbstract Number:2816 Kelly Bakulski*, Jason Feinberg, Shannon Brown, Laura Caulfield, Lynn Goldman, Andrew Feinberg, and Dani Fallin Kelly Bakulski* Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author , Jason Feinberg Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author , Shannon Brown Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author , Laura Caulfield Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author , Lynn Goldman George Washington University, United States, E-mail Address: [email protected] Search for more papers by this author , Andrew Feinberg Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author , and Dani Fallin Johns Hopkins University, United States, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Early life environments can influence later life health outcomes and DNA methylation may represent a persistent mark of these conditions. The relationships between maternal metals exposures in early pregnancy and subsequent DNA methylation measurements in moms and babies are poorly understood.Methods: Blood and urine metals exposures were measured in 138 pregnant women enrolled in the National Children’s Study Vanguard sites during trimester one. Repeated measures of buffy coat genome-wide DNA methylation were assessed on the Illumina 450K array during trimesters one and three as well as from the cord blood in a subset of babies (n=81). We tested for region and site specific associations between DNA methylation and metal exposures, adjusting for cell type composition and other potential confounding factors.Results: In our study population, mean blood cadmium exposure was 0.27 µg/L (95% CI: 0.11-0.62), mean blood manganese was 11.7 µg/L (95% CI: 7.2-19.7), mean blood lead was 0.52 µg/dL (95% CI: 0.18-1.14), mean blood selenium was 178.7 µg/L (95% CI: 143.1-210.3), and mean total blood mercury was 0.99 µg/L (95% CI: 0.11-3.3). Fifteen CpG sites were associated with cadmium exposure in trimester one at a genome-wide significance level of p-value<10-7 and ten of those sites replicated in terms of magnitude and direction in trimester three. Similarly, fifteen sites reached genome-wide significance in trimester one for mercury and fourteen of those replicated in trimester three.Conclusions: We observed maternal DNA methylation differences with trimester one cadmium and mercury exposure levels that persisted to trimester three DNA methylation in a cohort of normal births. The identified regions may act as biomarkers of exposure in cohorts lacking prenatal exposure information. Cord blood methylation and urinary metals exposures will be discussed.