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Particulate Air Pollutants and Autism Risk: Exposure Characteristics, Indicators of Susceptibility, and Mechanistic Pathways

颗粒空气污染物和自闭症风险：暴露特征、易感性指标和机制途径

基本信息

批准号：
10424413
负责人：
ROB S MCCONNELL
金额：
$ 63.27万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10424413
关键词：
2-butenal Address Affect Age Air Pollutants Algorithms Animals Archives Asthma Autism Diagnosis Bacterial Infections Behavioral Biological Biological Assay Biological Markers Biometry Birth Blood Caliber California Case-Control Studies Characteristics Child Childhood Communities Complex Computerized Medical Record Development Diabetes Mellitus Disease Environmental Epidemiology Environmental Exposure Epidemiology Exposure to Family Fetus Future Goals Homocysteine Human Inflammatory Iron Knowledge Life Link Lipid Peroxidation Low Birth Weight Infant Maternal-fetal medicine Metals Methods Mothers Neonatal Neurobiology Obesity Outcome Oxidative Stress Oxidative Stress Pathway Participant Particulate Particulate Matter Pathway interactions Phenotype Placenta Play Population Population Study Pre-Eclampsia Predisposition Pregnancy Prevalence Reactive Oxygen Species Reporting Resolution Resources Risk Risk Factors Role Sample Size Sampling Serum Albumin Source Spottings Standardization Suggestion Sulfonic Acids Toddler Ultrafine Virus Diseases Workplace adduct ambient air pollution ambient particle autism spectrum disorder autistic behaviour base boys cohort comorbidity disorder risk early life exposure economic cost epidemiology study exposure pathway fetal fine particles immune activation in utero male maternal comorbidity modifiable risk multidisciplinary neurodevelopmental effect neuropsychiatric disorder neurotoxic novel offspring particle postnatal prenatal prenatal exposure prenatal risk factor prepregnancy obesity residence screening sex social systematic review systemic inflammatory response trait

项目摘要

PROJECT SUMMARY/ABSTRACT Autism spectrum disorder (ASD) imposes large lifetime social and economic costs on families and communities. Causes, differentially affecting boys, likely are multifactorial. In search of modifiable risk factors, several studies have found associations of ASD risk with prenatal ambient air pollution exposure; evidence from human epidemiological and animal studies is converging on the neurotoxic effects of fine particulate matter less than 2.5 µm in diameter (PM2.5). Recently, early life exposure to currently unregulated ultrafine PM0.1 was shown to cause autism-like behavioral traits specific to males, but methods have not been available to examine effects of PM0.1 or of components of the complex PM mixture likely to be causal. We hypothesize that ASD will be associated with novel PM2.5 and PM0.1 exposure estimates with high temporal and spatial resolution at maternal residences and workplaces during pregnancy (Aim 1a), and that associations will be driven by specific PM components (Aim 1b). We will assess this hypothesis in a pregnancy-birth cohort of 400,000 mother-offspring pairs followed through Kaiser Permanente Southern California (KPSC), a population resource with standardized algorithms for systematic screening and diagnosis of ASD and gestational risk factors, available through an exceptionally high quality electronic medical record. Maternal immune activation (MIA) has been proposed as a common mechanism linking prenatal risk factors, including diverse viral and bacterial infections, asthma, pre-pregnancy obesity, diabetes, to subsequent ASD risk. Because prenatal PM exposure, and ASD phenotype, have in common pro-inflammatory and oxidative stress pathways, we hypothesize that MIA-related maternal comorbidities will increase fetal susceptibility to neurodevelopmental effects of PM exposure leading to ASD (Aim 2). This novel hypothesis can only be studied in large population studies such as the KPSC cohort with sufficient power for assessing interactions that together could explain a much larger proportion of ASD than single risk factor epidemiology. Finally, ASD epidemiology has been limited by the lack of biological markers both of environmental exposures and of pathways of effects. Using a novel assay for electrophilic adducts to human serum albumin in neonatal archived dried blood spots from 420 children selected from the cohort based on exposure, we will examine biological markers for PM exposure and oxidative stress. We hypothesize that PM2.5 will be associated with a targeted panel of adducts reflecting exposure and with adducts reflecting oxidative stress (Aim 3a). We hypothesize that these targeted biological markers of exposures and pathways, and additional ones identified in an untargeted HSA “adductome”, will be associated with an abnormal Checklist for Autism in Toddlers (CHAT)1 administered at ages 18 and 24 months to all participants in the KPSC cohort (Aim 3b). The study will address critical gaps in knowledge of effects of PM and PM composition, and ASD susceptibility, and will provide clues to biological pathways underlying PM effects on ASD.

项目总结/文摘

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ambient air pollution and COVID-19 incidence during four 2020-2021 case surges.

DOI：
10.1016/j.envres.2022.112758
发表时间：
2022-05-15
期刊：
Environmental research
影响因子：
8.3
作者：
Sidell MA;Chen Z;Huang BZ;Chow T;Eckel SP;Martinez MP;Lurmann F;Thomas DC;Gilliland FD;Xiang AH
通讯作者：
Xiang AH

Diabetes in Pregnancy for Mothers and Offspring: Reflection on 30 Years of Clinical and Translational Research: The 2022 Norbert Freinkel Award Lecture.