# Environmental Chemical Exposures and Biologic Markers for Cerebral Palsy (EXPOSE CP)

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $737,299

## Abstract

PROJECT SUMMARY
Cerebral palsy (CP) is the most common and severe lifelong neuromotordisability in childhood, affecting
1
in
345 newborns in
the
United States each year. Asphyxia at birth, a presumed cause of CP, is present in less than
10% of all cases. The causes for most CP cases remain unexplained. Fetal brain development is vulnerable to
exposure from chemical contaminants that are endocrine-disruptive and/or neurotoxic. Yet worldwide few
resources exist to study potential environmental exposure effects on CP. Here, we propose to conduct a powerful
study in California (CA) that will generate rich prenatal environmental, hormonal, and metabolomic data for CP,
and examine whether multiple environmental neurotoxicants affect CP development and elucidate exposure-
induced disease mechanisms. Guided by our preliminary studies, we have identified per- and poly-fluoroalkyl
substances (PFAS), polybrominated
chemicals
preterm
diphenyl ethers (PBDE)
can disrupt biologic/neurotoxicity pathways, including the thyroid system, and clinical factors, such as
birth, that are highly relevant to CP etiology.
and selected pesticide groups as our focus. These
We will use several unique resources in CA, including the
prenatal and neonatal blood samples from the CA biobank, the statewide diagnostic and treatment system for
CP, and the pesticide use reporting system (PUR) in CA. Since 2016, we have utilized these resources to
establish the first-ever environmental CP study (PESCP) in CA that has identified CP cases statewide and linked
them to the birth records. We will leverage the PESCP and select 450 congenital CP cases, 450 population and
85 preterm controls without CP, and retrieve maternal serum and newborn dried blood-spot samples from the
biobanks (2005-2016) to derive prenatal exposure (PFAS and PBDE) and metabolomic markers. We have
previously modeled agricultural pesticide exposure in PESCP using the PUR records and our sophisticated GIS-
based Residential Ambient Pesticide Exposure System (GRAPES). In aim 1, we will estimate
effects
joint/mixture effects of multiple pollutants (sub-aim 1). PFAS
while
coatings
at prenatal screening are predictive of CP.
neurodevelopment,
the independent
and pesticide groups and CP risk. Additionally, we will
and pesticides were selected based on prior results
PBDE were chosen because they are extremely widespread in CA due to the state's laws on fire-resistant
and their strong effects on neurodevelopment. In aim 2 , we will test
It is well known that maternal thyroid abnormalities can affect fetal
but a well-powered study of CP does not exist. Finally, our team
of prenatal exposure toPFAS, PBDE, explore the
,
whether maternal thyroid hormones
will apply a high-resolution
untargeted metabolomics approach that we pioneered in studies of autism and childhood cancer in CA in aim 3
to investigate biologic responses to exposure and uncover mechanisms through metabolomic profiles in paired
maternal and newborn sera that are rel...

## Key facts

- **NIH application ID:** 10801968
- **Project number:** 1R01ES034756-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Zeyan Liew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $737,299
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801968

## Citation

> US National Institutes of Health, RePORTER application 10801968, Environmental Chemical Exposures and Biologic Markers for Cerebral Palsy (EXPOSE CP) (1R01ES034756-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10801968. Licensed CC0.

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