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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R01ES034756&format=word)
| Principal Investigator: Liew, Zeyan | |
|---|---|
| Institute Receiving Award | Yale University |
| Location | New Haven, CT |
| Grant Number | R01ES034756 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 15 May 2024 to 28 Feb 2029 |
| DESCRIPTION (provided by applicant): | 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 relevant to CP. This project will greatly advance environmental and biological insights into CP etiology and the findings may also inform environmental policy and eventually prevention of CP. |
| Science Code(s)/Area of Science(s) |
Primary: 61 - Neurodevelopmental Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | No publications associated with this grant |
| Program Officer | Kimberly Gray |