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Major findings

ELEMENT and associated projects (``ELEMENT+`) has generated over 70 original articles in the scientific peer-reviewed literature and has had a major influence on environmental health policy. Among the many research products generated by ELEMENT (see bibliography) have been high-impact publications documenting the impact of maternal environmental lead exposure on risk of spontaneous abortion (LaMadrid-Figuero et al., 2007), newborn birth weight (Gonzalez-Cossio et al., 1997), newborn head circumference and birth length (Hernandez-Avila et al., 2002), newborn genomic methylation (Pilsner et al., 2009), offspring weight gain (Sanin et al., 2001; Afeiche et al., 2011); offspring cognition at age 2 (Gomaa et al., 2002; Tellez-Rojo et al., 2006), and offspring blood pressure at age 4-7 years (Zhang et al., 2011). The availability of biological marker exposure measures at multiple time points, including those taken at each stage of pregnancy, has also enabled the ELEMENT team to explore whether the impact of toxicants has prenatal and postnatal windows of vulnerability (e.g., Hu et al., 2006; Cantonwine et al., 2010; Afeiche et al., 2012; Braun et al., 2012).

The ELEMENT research has also produced many insights into factors that influence the uptake of lead in bone and the mobilization of lead from bone into blood, plasma and breast milk (e.g., Hernandez-Avila et al., 1996; Hu et al., 1998; Hernandez-Avila et al., 1998; Brown et al., 2000; Tellez-Rojo et al., 2002; Smith et al., 2002; Ettinger et al., 2004a,b; 2005). Since the accumulated evidence clearly demonstrates that the mobilization of lead from the maternal skeleton during pregnancy and lactation is a major threat to fetal and infant development, the ELEMENT team conducted two randomized double-blind placebo-controlled trials of dietary calcium supplements in an effort to reduce the mobilization of maternal skeletal lead during pregnancy and lactation. These studies demonstrated that dietary calcium has a beneficial effect (Janakiraman et al., 2003; Hernandez-Avila et al., 2003; Ettinger et al., 2009).

All told, ELEMENT studies on lead exposure and pregnancy formed a major portion of the research base that was evaluated by and influenced the recommendations of a recent Taskforce convened by the U.S. Center for Disease Control, resulting in its recent monograph ``Guidelines for the Identification and Management of Lead Exposure in Pregnant and Lactating Women``

The availability of maternal and offspring DNA, the depth of knowledge on polymorphic genes that encode the enzymes relevant to the uptake, transport, and toxicity of lead and the availability of high-throughput genotyping has also allowed the ELEMENT team to examine a number of gene-environment hypotheses based on biological pathway-driven identification of relevant SNPs (single nucleotide polymorphisms), particularly those related to lipoprotein metabolism (Wright et al, 2003), folate metabolism (Kordas et al., 2009; Pilsner et al., 2010), iron metabolism (Hopkins et al., 2008; Cantonwine et al., 2010), dopamine metabolism (Kordas et al., 2011).

Finally, the research collaboration that resulted in ELEMENT and its associated rich archives of biological samples and data have also served as a platform for an expansion of research to examine the potential impacts on neurobehavioral outcomes of additional toxicants of concern, such as phthalates (Meeker et al., 2009), bisphenol A (Cantonwine et al., 2010), and manganese (Claus Henn et al., 2011). Major new efforts are underway to use the biological samples to address the impacts on neurobehavior of prenatal and postnatal exposure to mercury and fluoride.

Administration of Cohorts 1-3 (Administration of Cohort 4 is conducted by Dr. Robert Wright and colleagues)

Administratively, throughout his transitions from Harvard to the University of Michigan (2006) and, most recently, from the University of Michigan to the University of Toronto (2012), Dr. Hu was and remains the PI of the grant-funded research that created ELEMENT Cohorts 1, 2 and 3. Dr. Peterson was and remains the PI of the grant-funded research that helped support the follow-up of ELEMENT Cohorts 1, 2 and 3 from 2010-2013. Thus, Drs. Hu and Peterson have primary oversight of ELEMENT Cohorts in collaboration with their counterparts at INSP: Dr. Hernandez-Avila (who became the Vice Minister of Health in Mexico from 2007-2012 and then returned to INSP as Director in February of 2012) and Dr. Martha Maria Tellez-Rojo (the Director of the INSP Center for Statistics and Evaluation). These four form the ELEMENT Cohort 1-3 Executive Committee, with the addition of Brisa Sanchez (University of Michigan School of Public Health), Chief Biostatistician for ELEMENT Cohorts 1-3.

In addition, in recognition of the multi-disciplinary nature and history of ELEMENT research, the executive committee consults, as appropriate, with other investigators who are or were the leaders of critical components of the research, including (but limited to), in alphabetical order, Manish Arora (Leader of metals analyses of shed primary teeth funded by K99ES019597); Niladri Basu (Leader of mercury analyses of ELEMENT archived samples funded by start-up funds); Dana Dolinoy (Leader of ELEMENT Cohort 1-3 Epigenetics Data funded by P20 ES018171), Emily Somers (PI of ELEMENT autoantibody assays funded by K01 ES019909), and Robert Wright (co-PI of ELEMENT Cohort 1-3 DNA SNP genotyping funded by ES007821).

The ELEMENT Cohort 1-3 Executive Committee make decisions related to budget, authorship, samples, data, etc.. Each executive committee member may propose a proxy who can represent him/her given the demands of scheduling. In addition, the wider community of ELEMENT investigators and associated trainees participate in biweekly Skype conference calls to discuss works-in-progress, new ideas, laboratory and data base issues, etc.