The goal of this study is to examine the effect of prenatal and early life metals exposure on the developing brain, cognitive and adaptive function, and autism spectrum disorder (ASD). The unfolding of autistic behaviors across the first few years of childhood is accompanied by age-specific brain changes that differ between children with ASD and those with typical developmental trajectories. Infant siblings of children with ASD are at a nearly 5-fold increased risk for ASD, and nearly 60% experience neurodevelopmental delay, making a high familial risk (HR) model of ASD infants an attractive approach for studying early brain development and characterizing early life behavior. However, the initial goal of many existing populations with a wealth of neuroimaging, cognitive, behavior, and ASD data has not often included the effect of the environment. New methods of environmental exposure assessment are needed to leverage these existing valuable populations. Using the developmental properties of shed deciduous teeth and laser-based sampling methods, we can measure both the intensity and timing of exposure from the second trimester to the first year of life for metals exposure. Heavy metals are both established neurotoxicants and essential nutrients. Here we propose to examine the relationship between prenatal and early life metals exposure and longitudinal measures of brain development, cognitive and adaptive function, and ASD risk in the Autism Spectrum Disorder Enriched Risk (ASD-ER) Environmental Influences on Children's Health Outcomes (ECHO) cohort (OD023342). ASD-ER consists of 13 sites, each having enrolled HR infants with longitudinal follow-up through 36 months of age. These participants were then contacted and asked to provide shed deciduous teeth.
The Specific Aims of this study are to: (1) examine the effect of prenatal and early life metals exposure on the development of ASD and dimensional ASD phenotypes; (2) evaluate the effect of prenatal and early life metals exposure on the early trajectory of cognitive development and adaptive function; and (3) investigate the effect of prenatal and early life metals exposure on early longitudinal brain development. Because exposure to neurotoxic metals can be mitigated and that to essential nutrients be augmented, the potential public health impact of this study is large. Additionally, identification of a risk factor in very young children provides the opportunity for early intervention where reduction of risk for disordered development is still possible.

Public Health Relevance

This study will examine the effect of prenatal and early life metals exposure on the developing brain, cognitive and adaptive function, and risk for autism spectrum disorder (ASD) and related traits. We will integrate novel tooth-based biomarkers of metals exposure into the Autism Spectrum Disorder Enriched Risk (ASD-ER) cohort, a unique collaborative of 13 prospective high familial risk for ASD populations. Because exposure to metals is common and our study is conducted in very young children there is great potential for intervention and broad public health impact.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES029511-01A1
Application #
9884990
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Lawler, Cindy P
Project Start
2020-03-01
Project End
2024-12-31
Budget Start
2020-03-01
Budget End
2020-12-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205