Emerging data point to significant effects of arsenic during the vulnerable window of fetal development and early childhood. Altered immunity is among the key pathways identified in experimental studies and in highly exposed populations. But such studies do not exist in the US at levels relevant to our population. Infectious diseases are responsible for the majority of early childhood deaths worldwide. In the US, infections are the most common causes of illnesses in children, and allergy and atopy have become a widespread source of childhood morbidity. Our study builds on an established cohort study to determine whether common exposure levels of arsenic and other contaminants influence children’s immune response including risk of infection, allergy/atopy, vaccine response and intestinal microbial acquisition. The cohort comprises 1,000 mother-infant dyads who are residents of New Hampshire and obtain household water from private wells, a potential source of arsenic exposure in the region. We now have compelling preliminary data both from animal studies and early epidemiologic data from our cohort that indicate aberrant immune function and clinical phenotypes related to arsenic exposure that support our hypotheses. Further, recent discoveries are beginning to uncover the fundamental role that the establishment of microbiome early in life plays on immune development and competency as well as in metal biotransformation. Our team has acquired the expertise to evaluate environmental influences on the developing microbiome and are poised to translate recent experimental findings on As and intestinal microbial composition during the critical neonatal period.

To our knowledge this is among the first prospective molecular epidemiologic studies of As and child health in the US, and among the only children’s cohorts with detailed childhood infection information along with other immune-related variables. Thus, using a state-of-the-art, multidisciplinary approach, we have a unique opportunity to relate both clinical and biologic markers of immune function with multiple routes of As exposure (i.e., via water and food) using biomarker measurements (maternal As exposure during pregnancy via urine and toenails, and infants exposure during their first five years of life via nails, urine) in collaboration with Project 2, along with mechanistic changes (e.g., placental epigenetics, gene expression profiles) in collaboration with Project 3.

Emerging evidence suggests that exposure to high concentrations of arsenic in drinking water can adversely impact prenatal growth and childhood cognitive development. Much less is known about the child health effects of arsenic at the lower doses that are commonly consumed through drinking water in the U.S. Moreover, recent research suggests that diet may be the most significant source of arsenic exposure for the general U.S. population– though relatively little is known about dietary sources of arsenic. Understanding arsenic exposure through both diet and water is important to assessing exposure risk, especially in young children who are rapidly developing and may be the most vulnerable to contaminants.

The goal of this study is to quantify children’s exposure to arsenic via both drinking water and food, and to evaluate whether this exposure affects physical growth and neurological development. Our study focuses on the New Hampshire Birth Cohort (NHBC), which recruits from a population where about 15% of households have private wells with arsenic concentrations above the current maximum contaminant level of 10 µg/L. We will characterize pathways of early life arsenic exposure by assessing how biomarkers of exposure (e.g., urine and toenail arsenic levels during pregnancy, infancy, and early childhood) are related to dietary assessments during infancy and childhood. We will then evaluate how these arsenic exposure biomarkers are related to growth and adiposity during the first five years of life, as well as behavioral skills, cognitive ability and motor proficiency between the ages of 3 and 5 years.

Thus, this innovative work will combine detailed longitudinal assessment of early life arsenic exposure and subsequent physical and neurological development to better understand the exposure sources and children’s health impacts of this common contaminant in a U.S. population.

There is mounting evidence that the environment experienced by a pregnant woman can have a profound influence on the health of her child both at birth and throughout that child’s life. Our project is focused on trying to understand, at the molecular level, how environmental signals and exposures during this short period of development can impart these lifelong impacts. We are specifically examining the importance of the placenta in delivering these environmental signals to the developing child and how the environment can alter the way the placenta functions.

The placenta is the first complex organ to form and serves as a critical interface between the developing infant and his or her mother. This organ facilitates the passage of nutrients, water, gases, and waste between mother and infant, but also plays other important roles during development. The placenta produces specific hormones, growth factors, and neuropeptides which direct fetal development, and also through production of various enzymes, receptors, and transporters, controls the types of chemicals and exposures that can pass from mother to infant.

We believe that environmental factors, like arsenic exposure from food or water, effect the way the placenta performs these important functions, and that alterations to these functions can lead to changes in the health and development of the infant. Our study specifically looks at alterations to the expression of key development genes and arsenic associated pathways, to demonstrate the functional effects of arsenic exposure on the placenta.

We are also examining the epigenetic regulation of genes in the placenta by utilizing genome-wide studies of DNA methylation. These studies will pinpoint critical genes and pathways altered by arsenic and other environmental exposures and can ultimately be linked to growth and neurobehavioral outcomes in the child. Studies such as ours, will allow us to better understand the molecular mechanisms at work mediating the maternal environment’s role in child health. Such findings, we believe, could eventually be translated into novel targets for therapeutic intervention or applied as molecular diagnostics to identify children at risk at birth so that appropriate and useful interventional strategies can be initiated.

The importance of combining state-of-the-art research with the translation of this work to the community has been an integral component of the Children's Environmental Health and Disease Prevention Research Centers program since its inception by the EPA and NIEHS 15 years ago. Here at the Dartmouth Center we aim to engage a wide range of stakeholders to protect the environmental health and wellbeing of children in a sustainable manner. Key members of our community are the mothers who are participants in our Birth Cohort study, the health care community, and parents. Given our researchers focus on mechanisms and effects of early life exposure to metals, in particular arsenic in food and water, the COTC seeks to explore ways to incorporate these findings into clinical care and public health practice.

Our Partnerships and Projects

The Dartmouth Northern New England Primary Care Cooperative, also known as the "Dartmouth CO-OP".

We are collaborating with this practice based research network of rural primary care practices in New Hampshire, Vermont and Maine. In our current research study, we are working with selected practices in regions where there are a high percentage of families on private water systems to identify best practices for integrating well water testing into routine pediatric preventive care. This involves both education of the parents as well as the health care team on the basics of drinking water safety and testing, with particular emphasis on the regional importance of natural arsenic contamination. Our team's use of GIS mapping of arsenic contamination in relationship to the location of these regional primary care practices has been used to raise awareness of this issue among health care providers and for recruitment of practices to the well water testing study. Results of this study will be disseminated to other regional practitioners.

The DALI Project: Arsenic in our Food Supply and What You Can Do About It- A Digital Story and Educational Tool

Our Center was selected as a project site for the "Dali Lab"- a group of talented computer science students and their faculty mentors within the Department of Computer Science at Dartmouth College. Students in the Dali project worked with Dr. Carolyn Murray to bring to life in a digital format the "story" of how arsenic enters our food supply. These undergraduates translated the Center's research findings about sources of arsenic in the diet and converted them to a visually pleasing and interactive format to engage and empower the public, particularly parents.

New Hampshire Birth Cohort Participants

Participants in our birth cohort study that now numbers over 1,200 are a high priority community for our Center. We have been conducting focus groups within the NHBCS. Through these focus groups and future surveys we are seeking input on how best to communicate well water testing results, how best to design educational materials, and to better understand where mothers obtain the environmental health information they use to make decisions about their own health and that of their children. We will then use this information to inform the development of educational resources, both written and web based, to support the informational needs of our stakeholders and provide a platform for our scientists to share their findings.

Vermont Law School Center for Agriculture and Food Systems

This newly created Center in one of this country's premier law schools for Environmental Law underscores the burgeoning interest in food, food policy and the relationship between our food systems and human health. We meet regularly with Center leaders to identify how our scientific findings can help inform their efforts in addressing regulatory initiatives aimed at improving the health and safety of our food supplies. We are both working with the Dartmouth DALI lab (see below) on exciting projects to share our research findings with stakeholders in innovative ways.