Children in the US are exposed to various neurotoxicants that can damage their developing brains. We have
recently shown that the long-known negative impact of low SES on cognitive development is mediated by
differences in brain structure. Specifically, the association between brain structure and SES is more
pronounced in the poorest children, those who are often the most exposed to neurotoxic metals, such as lead
(Pb). Here, we aim to better understand the impact of perinatal Pb exposure on brain, cognitive and behavioral
development longitudinally using a novel tooth dentine assay. This novel measure allows quantification of
prenatal and postnatal Pb exposure beginning with the 2nd trimester in utero and ultimately until the tooth is
shed during later childhood; dentine develops over time, much like rings of a tree, trapping earlier exposures
beneath the next “ring” of dentine to form, allowing temporal measurements of Pb in consecutive rings of
dentine. The effects of Pb exposure may be exacerbated in the context of low SES, but this important aspect of
brain development in the environmental setting has received little research attention. In this proposal, we will
leverage substantial existing funding by investigating Pb exposure among a subset of ~500 participants of the
Adolescent Brain Cognitive Development (ABCD) study who have donated shed deciduous (baby) teeth. We
will also leverage recent funding from the Children's Health Exposure Analysis Resource (CHEAR: Project
#2017-1920; now HHEAR) to cover the costs of tooth analysis at three distinct developmental periods: the 2nd
trimester and 3rd trimester of fetal development and the 1st year of life. Notably, the ABCD cohort of over
11,800 participants varies considerably on race and ethnicity, geographic location, family income, and parent
education, and nearly 4,000 participants have donated teeth. This will allow a strategic selection of participants
who are matched by Pb risk measures (based on publicly available risk maps of Pb exposure geocoded to
each participant's home address) while controlling for SES and race factors that could be confounded by risk of
Pb exposure. Pb risk may increase the likelihood of exposure, but it is clear that some at high risk could have
low exposure whereas some at low risk may have high exposure. While our preliminary studies show that Pb
risk status is associated with brain, cognition, and behavior as a function of SES in the ABCD cohort, only by
measuring endogenous Pb levels within groups of individuals matched on SES by risk status can we determine
how and where to focus future efforts to reduce remediable Pb risk factors and improve the health of children
in the US. In this proposal, we will assess (1) associations between dentine Pb levels on structural brain
development during childhood and determine if associations vary as a function of level of exposure at 3
developmental time points, (2) associations between dentine Pb levels and cognitive and behavioral
development along with sex differences on these associations, and (3) the moderating or mediating effects of
SES on brain-cognitive-behavioral development in the context of perinatal Pb exposure.
