Export to Word
(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R21ES035485&format=word)
| Principal Investigator: Liew, Zeyan | |
|---|---|
| Institute Receiving Award | Yale University |
| Location | New Haven, CT |
| Grant Number | R21ES035485 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 10 Jul 2024 to 30 Jun 2026 |
| DESCRIPTION (provided by applicant): | PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) is the most common life-long neuromotor physical mobility. CP affects about1 in 345 newborns each year condition that permanently affects children's in the United States. The etiology of CP is complex and multifactorial. We know that CP is caused by lesions occurring in the developing brain, but what risk factors trigger the developing brain damage remain largely unknown. Newborn asphyxia at delivery only presents in less than 10% of cases. While ambient/household environmental risk factors for CP have long been suspected and discussed, few studies have been conducted to evaluate environmental exposure effects on CP development. Recently, a seasonal pattern of CP occurrence was observed in our California study, where air pollution exposure was suspected to play an important role. Air pollution is one of the most widespread environmental pollutants, and the literature has consistently suggested maternal exposure to ambient air pollution during pregnancy can affect major perinatal predictors of CP, including maternal preeclampsia, preterm birth, and Apgar scores. Moreover, emerging research shows air pollution affects cognitive, neurobehavioral, and motor function deficits in childhood, as well as increases the risk for white matter injury and thinning of the cerebral cortex in the developing brain which are highly relevant to CP etiology. The collective set of scientific evidence points toward a need to thoroughly examine whether air pollution exposure poses a risk to CP development. Our proposed study is novel and will be the first and largest population-based study of CP and air pollution to date. We will use records from the California Department of Developmental Services (DDS) to identify children who were born during 2000-2015 and diagnosed with CP in California. We expect to identify ~10,000 CP cases and we will utilize a case-cohort design and select 20% of births in California during the study period (N=~1.6M births) as the population controls. We will apply a sibling-matched analysis to triangulate the main results. We will utilize a newly developed land-use-regression (LUR) model with a high temporal (daily) and spatial resolution (100m X 100m) to estimate gestational exposures to three major ambient air pollutants (PM2.5, NO2, and O3), study the associations between maternal pregnancy exposures and CP risk using single and multi- pollutant analyses, and explore the critical time window of exposure. Moreover, we will perform causal mediation analyses to examine to what extent the racial/social disparities of CP in California may be explained by environmental disparities in exposure to air pollution, and whether a specific pregnancy complication or adverse birth outcome mediates the association between air pollution exposures and CP risk. Findings from this project will advance our knowledge of suspected environmental risk factors of CP, and possibly inform risk identification and primary prevention of CP. Results from this project will be critical for future research strategies to examine environmental hypotheses of CP, possibly using an approach integrating biomarkers and active data collection. |
| 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 |