# Prenatal exposure to metals and risk for Autism Spectrum Disorder in MARBLES and EARLI

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $595,594

## Abstract

Autism Spectrum Disorder (ASD) is a major public health burden in the US, with current prevalence
estimates of 1 in 68 children and economic costs exceed $60 billion per year. Identification of causes that can
inform prevention and policy is the most efficient way to stem the tide of this rising prevalence. Most research
to date has focused on identifying genetic causes of autism, however, recent twin and population-scale studies
have shown that both genes and environmental exposures contribute equally to ASD risk and etiology.
Evidence suggests the critical exposure window is most likely during in utero development, and thus focus on
prenatal risk factors is extremely important. Environmental epidemiology has long recognized the neurotoxic
effects of exposure to heavy metals, and some air pollution studies have specifically implicated exposure to
metals during pregnancy as a risk factor for ASD. However, further assessment of risk due to prenatal metals
exposure has been limited by (1) lack of prospective data from pregnancy; (2) lack of direct measures of
biologically effective dose; (3) lack of consideration of maternal or child genetic susceptibility; (4) lack of fully
characterized ASD phenotypes. Here we propose the first prospective, longitudinal study examining the
contribution of prenatal exposure to lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese
(Mn) on ASD risk, while accounting for potential genetic modification of metal exposure-ASD associations,
using data from 456 mother-child dyads from the two largest enriched risk, prospective, longitudinal pregnancy
autism cohorts in the US: Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in
Bablies Learning the Early Signs (MARBLES). Our aims are to: (1) estimate prospective associations between
direct measures of perinatal Pb, Cd, Hg, Se, and Mn levels, and ASD outcomes, including ASD-related
quantitative neurodevelopmental phenotypes; (2) Incorporate maternal and child genetic susceptibility into
analyses that estimate this risk; (3) Examine the role of DNA methylation (DNAm) in any detected metals
associations, either as a birth biomarker of prenatal exposure, or as a mediator of risk effects. This study is
likely to impact the field of autism and contribute to the advancement of human public health because it will: a)
establish the relevance of prenatal metal exposures to ASD risk; b) determine whether prenatal metal
exposure susceptibility differs based on underlying maternal or child genetic structure; c) potentially inform
pathways and biological mechanisms, i.e. epigenetics, involved in disease and/or prenatal exposure
processes; and d) generate unified GWAS, epigenetic, and metal measurement data across the 2 largest US
longitudinal pregnancy autism cohorts that can be used in future investigations of health outcomes and/or
additional exposure domains.

## Key facts

- **NIH application ID:** 10013202
- **Project number:** 5R01ES025531-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** HEATHER E VOLK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $595,594
- **Award type:** 5
- **Project period:** 2016-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013202

## Citation

> US National Institutes of Health, RePORTER application 10013202, Prenatal exposure to metals and risk for Autism Spectrum Disorder in MARBLES and EARLI (5R01ES025531-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10013202. Licensed CC0.

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