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.

项目摘要/摘要自闭症谱系障碍（ASD）不可能对家庭的终身社会和经济成本进行巨大的社会和经济成本，社区。原因，对男孩的影响不同，可能是多因素的。寻找可修改的风险因素，几项研究发现，ASD风险与产前环境空气污染暴露的关联。证据来自人类流行病学和动物研究正在融合精细特定的神经毒性作用物质直径小于2.5 µm（PM2.5）。最近，生命早期暴露于当前不受监管的超级铁 PM0.1被证明会引起自闭症类似于男性的行为特征，但没有可用的方法检查PM0.1或复杂PM混合物的成分的影响可能是因果关系。我们假设 ASD将与新型PM2.5和PM0.1估计相关，并具有高临时和空间怀孕期间的物质住宅和工作场所的解决方案（AIM 1A），该关联将为由特定的PM组件驱动（AIM 1B）。我们将在怀孕的同类中评估这一假设 40万个母亲源对乘以人口的Kaiser Permanente南加州（KPSC）具有标准化算法的资源，用于系统筛查和诊断ASD和妊娠风险的诊断因素，可通过异常高质量的电子病历获得。母体免疫激活（MIA）已被认为是关联产前风险因素的一种常见机制，包括多元化病毒和细菌感染，哮喘，妊娠前肥胖，糖尿病，随后的ASD风险。因为产前PM 暴露和ASD表型具有常见的促炎和氧化应激途径，我们假设与MIA相关的母校合并症将增加胎儿对神经发育的敏感性导致ASD的PM暴露的影响（AIM 2）。这个新颖的假设只能在大量人群中研究诸如KPSC队列等研究具有足够的能力来评估相互作用，这可以解释一个可以解释的与单个危险因素流行病学相比，ASD的比例要大得多。最后，ASD流行病学一直是受环境暴露和效果途径的生物标记不足的限制。使用新生儿存档的干血点420 我们根据暴露从同类中选出的儿童，我们将检查PM暴露和氧化应激。我们假设PM2.5将与反映的靶向加合物相关联暴露以及反映氧化应激的加合物（AIM 3A）。我们假设这些针对的生物学曝光和途径的标记，以及在未靶向的HSA“加合物”中确定的其他标记，将是与18岁和24个月的幼儿（CHAT）1中自闭症的异常清单相关给KPSC队列的所有参与者（AIM 3B）。该研究将解决有关影响的关键差距 PM和PM组成以及ASD敏感性，并将为PM下面的生物途径提供线索对ASD的影响。

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.