Salud Ambiental Montevideo

Childhood exposure to metals, pesticides and other neurotoxins can result in irreversible neuropsychological impairments. Whereas metal exposures have declined in the general U.S. population and significant progress has been made in the reduction of certain metals in the environment, other environmental exposures, like pesticides and air pollution, are continuing to be a problem. These exposures often occur in the context of low family resources, poor nutrition, or unsafe neighborhoods.

In many parts of the world, particularly Low and Middle-income Countries (LMIC), the extent of exposure to and harm from multiple chemicals (commonly called mixtures) are only now gaining recognition. The past 5-10 years have ushered an important shift in thinking and methodological advances in the measurement of chemicals to which children are exposed as well statistical approaches to analyzing the effects of the complex mixtures on child growth, health and development. We still do not understand how multiple chemicals affect child health, particularly when the exposures occur at low-level. In the context of LMICs, children’s nutritional status (malnutrition or deficiency of nutrients like iron) may increase children’s vulnerability to the toxicity of chemicals, whereas diet can be a source of exposure to chemicals for children. These questions drive the National Institute of Environmental Health Sciences (NIEHS)-funded research program, Salud Ambiental Montevideo (SAM), led by Dr. Katarzyna Kordas in Uruguay.

Salud Ambiental Montevideo, which stands for Environmental Health Montevideo, has recruited families of first-grade children residing in geographic locations of Uruguay’s capital city with known or suspected sources of environmental metal exposure. Between 2009 and 2019, close to 700 children were enrolled.  Initially, the study focused on toxic metals, but has since expanded exposure assessment to biomarkers of pesticides (chlorpyrifos and pyrethroids) and air pollution (polycyclic aromatic hydrocarbons). Since 2015, the children have been followed up on an annual basis.

Data collection based on questionnaires, neuropsychological tests, home visits, and direct measures was performed. Children’s hair, blood and urine were collected; nutritional status was assessed through measures of height and weight and dietary recalls; a comprehensive battery of neuropsychological tests was administered. The battery included tests of memory, executive functioning, attention, visuo-motor coordination, general cognitive ability, and academic proficiency.  This broad collection of measurements gives SAM the ability to fully evaluate the effect of chemical mixtures on a variety of child developmental outcomes. The study measures are described in more detail on the NIHES-Funded Epidemiology Resources website. Data from SAM participants have contributed to better understanding of the relationship between metal exposures and child cognition and behavior, and to discovering links between diet and metal exposures (see Study Findings below). Several MS and PhD students in the US and Uruguay are using SAM data for their theses and dissertations (see Our Team for examples). SAM also serves as the parent study for some exciting pilot or add-on studies (below).

Rapida-mente:

Dr. Barg is currently leading a pilot study nested within SAM. It is called RÁPIDA-MENTE and its aim is to demonstrate the feasibility of enrolling children into an electrophysiological study and to obtain neural indexes of lead effects in the brain. The study is enrolling 20 boys and 20 girls aged 11-13 years of age to measure their ability to inhibit impulsive responses. We had previously identified difficulties with response inhibition as a problem among children exposed to lead. The study uses behavioral (an experimental go no-go task), electrophysiological (event-related potentials-ERP) and psychometric (questionnaires about daily situations) methods. Our goal is to develop a suitable experimental set up to measure changes in neural activity associated with multiple exposures and to map them in the brain.

Mi Barrio:

Seth Frndak received travel funds from CGHE to conduct a qualitative research study among parents of children enrolled in SAM to understand the neighborhood context of the study families. Neighborhood context plays a role in the behavioral and cognitive development of children. Mi Barrio used semi-structured interviews and photovoice methodology to empower SAM parents to narrate life in Montevideo. Parents were provided with cameras and asked to photograph something important to them in their neighborhood. In subsequent interviews, parents used these photos to tell stories. To date, parents have advocated for cleaner streets, increased safety, enhanced infrastructure, and emphasized the importance of playgrounds. With the help of an anthropology student from the University of the Republic of Uruguay, Yanina Gallo, Seth is analyzing the interviews, building a conceptual framework of positive and negative facets of neighborhoods in Montevideo. The framework will guide future research in SAM on the role of neighborhood context in determining child wellbeing.

Scola-Exposome:

In December 2018, we wrapped up field work to collect exposure information via passive samplers (silicone bands) from 24 children. The children wore the bands for 1 week and we collected paired serum, urine and fecal samples. We are working on analyzing the bands and the biological samples to understand what chemicals children are exposed to and how well the information from the bands correlates with internal exposure metrics. Steve Travis, PhD student in analytical chemistry, is leading method optimization for the analysis of bands and serum samples. This project is a collaboration among the departments of Epidemiology and Environmental Health, Biostatistics, Chemistry, and Toxicology and Pharmacology at the University at Buffalo. Funding was provided by the RENEW Institute at UB and the NIH.

Diet and metal exposures:

• Links Between Diet and Arsenic Exposure - Children consuming rice had higher levels of arsenic in urine than children who did not eat rice.  Concurrently, better detoxification of arsenic was linked to higher arsenic metabolites (%DMA).
• Diet and Cadmium – Children who consumed higher amounts of iron and zinc from their diet had lower concentrations of cadmium in urine. On the other hand, children who consumed more grains had higher levels of cadmium in urine.
• Dietary Predictors of Lead – Children with high dietary calcium intake from milk and other dairy products had lower lead concentrations.  This research lends support to current CDC recommendations for including calcium-rich foods (particularly milk) in the diet of lead-exposed children.

Metal exposures:

• Lead and Water – Overall, lead in water was not related to blood lead or urinary lead levels in children. However, children with high levels of iron were better at removing lead from their bodies.

Metals and oxidative stress:

• Lead Exposure and Oxidative Stress– Blood lead levels were associated with a slight elevation in a marker of lipid peroxidation, thus suggesting that lead exposure increases oxidative stress in children.
• Multiple Metals and Oxidative Stress – A metal mixture of lead, cadmium and arsenic measured in urine was linked with higher levels of oxidative stress (DNA damage) in children. This effect was due to arsenic exposure in particular.

Metals, cognition and behavior:

• Lead and Behavior Problems – Lead was related to poorer ability to inhibit inappropriate behaviors, particularly among girls in Montevideo schools.
• Lead, Manganese, and Cognitive Performance – Blood lead levels in first-graders were linked with poorer cognitive performance profile.
• Low-level Arsenic and IQ – Inorganic arsenic levels in urine were no related to measures of general cognitive ability in children. This study is unique in that very low concentrations of arsenic are observed in Montevideo, most likely linked to dietary exposures rather than water.
• Multiple Metals and Cognition – Arsenic, cadmium and lead were all negatively related to cognitive outcomes in exposed children. Using a quantile regression method allowed for better detection of the detrimental effects of low-level exposure.

We welcome collaborations from colleagues and students that will foster research on the developmental effects of toxicants among children globally. To explore possible collaborations, contact the study PI, Dr. Katarzyna Kordas.