Maternal exposure to chemicals and offspring neurodevelopmental disabilities: informing public health actions by understanding nutritional modifiers and simulating interventions

母亲接触化学品和后代神经发育障碍：通过了解营养调节剂和模拟干预措施为公共卫生行动提供信息

• 批准号: 10723459
• 负责人: Giehae Choi
• 金额: $ 9.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-14 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723459
• 关键词: Address; Affect; Allergic; Attention deficit hyperactivity disorder; Awareness; Biological Markers; Biometry; Birth; Blood; Boston; Brain; Chemical Exposure; Chemical Modifier; Chemicals; Child; Child Health; Child Mental Health; Cluster Analysis; Communication; Conduct Disorder; Data; Development; Developmental Delay Disorders; Diagnosis; Dietary Intervention; Dietary Practices; Economic Burden; Educational Intervention; Educational workshop; Electronic Health Record; Environment; Environmental Epidemiology; Environmental Health; Epidemiologist; European; Exposure to; Folic Acid; Foundations; Future; Goals; Health; Health Care Costs; Heavy Metals; Heterogeneity; Human; Individual; International; Intervention; Joints; Lead; Link; Literature; Longevity; Low income; Maternal Exposure; Medical; Mentorship; Metabolic Diseases; Metal exposure; Metals; Methods; Minority; Modeling; Multivitamin; Neurodevelopmental Disability; Neurodevelopmental Disorder; Neurotoxins; Nutrition Assessment; Nutritional; Outcome; Personal Satisfaction; Phenotype; Policies; Policy Maker; Poly-fluoroalkyl substances; Population; Positioning Attribute; Postpartum Period; Pregnancy; Problem behavior; Prospective Studies; Public Health; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Science; Solid; Statistical Methods; System; Technical Expertise; Time; Toxic effect; Training; Training Activity; Translational Research; Translations; Vitamin B 12; Vitamin D; analytical method; autism spectrum disorder; career; chemical reduction; clinical diagnosis; cohort; comorbidity; critical period; ethnic diversity; fetal; gastrointestinal; improved; in utero; innovation; intervention effect; multidisciplinary; neurotoxic; neurotoxicity; nutrition; offspring; phenome; prenatal exposure; prevent; prospective; racial diversity; research data dissemination; skills; symposium; working group

Project summary Humans are ubiquitously exposed to metals and per-and polyfluoroalkyl substances (PFAS), which are either established or suspected neurotoxicants in experimental and population settings. Exposure to these chemicals can be particularly harmful in utero, a critical period of fetal brain development. Four major literature gaps exist: 1) prospective studies of in utero exposure to these chemicals and child risk of neurodevelopmental disorders (NDs) are limited in the U.S, with most studies from predominantly White, European populations; 2) despite growing evidence that these chemicals may affect multiple NDs and systems, most studies are limited to a single ND outcome without consideration of comorbidities; 3) exposures rarely occur in isolation, yet combined exposure across different chemical classes remain unclear let alone chemical-nutrition interplay (nutrition may modify chemical toxicities); 4) most children’s environmental health studies focus on identifying risk factors with few that use or develop solution-oriented analytic methods that can directly inform public health actions. To fill these critical gaps, Dr. Choi proposes to investigate metals and PFAS in relation to clinician-diagnosed NDs considering comorbidities, while examining nutritional modifiers that may mitigate chemical toxicities and generating policy-relevant effect estimates via simulating intervention effects on chemicals and nutrition. To address this overarching goal, she will leverage rich existing resources (biospecimen data and clinical diagnoses of NDs and comorbidities across the lifespan) in the Boston Birth Cohort, a large prospective birth cohort with a significant representation of understudied low-income minorities. In K99, Dr. Choi will estimate the relations of metals and PFAS in maternal blood collected 24-72hours postpartum with NDs and comorbidities in offspring (Aim 1). Comorbidities will be considered with cluster analysis, to evaluate whether children with certain NDs and comorbidities are more vulnerable to the toxic effects of gestational chemical exposures. She will receive interdisciplinary training across NDs & comorbidities, chemical-nutrition, research translation, and advanced statistical methods (i.e., cluster analysis, mixtures analysis, causal inference) from a multidisciplinary mentorship team and via additional training activities including coursework, seminars, working groups, research dissemination activities targeted at lay audiences and policy settings, and national and international workshops or conferences. In R00, she will evaluate nutritional modifiers of the adverse chemical- ND relations identified in Aim 1 (Aim 2) and simulate intervention effects by estimating the number of NDs that could have been prevented had there been pregnancy interventions on chemicals, nutrition, and both chemicals and nutrition (Aim 3). This K99/R00 will position Dr. Choi as an innovative, independent researcher in environmental epidemiology, with a unique niche in NDs and comorbidities, chemical-nutrition interplay, research translation, and advanced methods. Our findings and activities will increase public awareness and serve as scientific evidence for future policies on the environment or nutrition to reduce the burdens of NDs.

项目摘要 人类无处不在地暴露于金属和每种多氟烷基物质（PFAS）中，它们是 在实验和人群环境中建立或怀疑的神经毒性。暴露于这些化学物质 在子宫内可能特别有害，这是胎儿脑发育的关键时期。存在四个主要的文献差距： 1）对这些化学物质和儿童神经发育障碍的风险的前瞻性研究 （NDS）在美国受到限制，大多数研究主要来自白人，欧洲人口； 2）领先 越来越多的证据表明这些化学物质可能影响多个ND和系统，大多数研究仅限于 单一的结果，没有考虑合并症； 3）暴露很少孤立地发生，但合并 跨不同化学类别的暴露尚不清楚，更不用说化学养育相互作用了（营养可能 修改化学毒性）； 4）大多数儿童的环境健康研究都专注于确定风险因素 很少有人使用或开发以解决方案为导向的分析方法可以直接为公共卫生行动提供信息。填充 这些关键的差距，Choi博士的提议研究金属和PFA与临床诊断的NDS有关 考虑合并症，同时检查营养修饰剂，以减轻化学毒性和 通过模拟对化学物质和营养的效果来产生与政策相关的效果。到 解决这个总体目标，她将利用丰富的现有资源（双期数据和临床） 在波士顿出生队列中的整个生命周期中的ND和合并症的诊断 同类众所周知的低收入少数族裔。在K99中，崔博士将估计 产后24-72小时与ND和ND和 后代合并症（AIM 1）。合并症将通过聚类分析考虑，以评估是否 具有某些ND和合并症的儿童更容易受到妊娠化学物质的毒性作用 暴露。她将在NDS＆合并症，化学养育，研究中接受跨学科培训 翻译和高级统计方法（即聚类分析，混合分析，因果推断） 多学科心态团队，并通过其他培训活动，包括课程，半手，工作 群体，针对外行受众和政策环境的研究传播活动以及国家以及 国际讲习班或会议。在R00中，她将评估不良化学的营养修饰符 在AIM 1（AIM 2）中确定的ND关系，并通过估计ND的数量来模拟干预效果 如果对化学物质，营养以及两者都有怀孕干预，则可以预防 化学和营养（目标3）。这款K99/R00将把崔博士定位为创新的独立研究人员 在环境流行病学中，具有独特的NDS和合并症，化学生相互作用， 研究翻译和高级方法。我们的发现和活动将提高公众意识，并 作为对环境或营养的未来政策的科学证据，以减少NDS的燃烧。