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.

项目概要 人类普遍接触金属和全氟烷基物质和多氟烷基物质 (PFAS)，它们要么 在实验和人群环境中暴露于这些化学物质中已确定或可疑的神经毒物。 在子宫内尤其有害，这是胎儿大脑发育的关键时期，存在四个主要文献空白： 1) 子宫内接触这些化学物质与儿童神经发育障碍风险的前瞻性研究 (ND) 在美国有限，大多数研究主要针对白人、欧洲人群 2) 越来越多的证据表明这些化学品可能影响多种 ND 和系统，但大多数研究仅限于 单一 ND 结果，不考虑合并症；3) 暴露很少单独发生，而是组合发生 不同化学类别的暴露仍不清楚，更不用说化学与营养之间的相互作用了（营养可能 4) 大多数儿童环境健康研究侧重于识别风险因素 很少有人使用或开发能够直接为公共卫生行动提供信息的以解决方案为导向的分析方法。 对于这些关键差距，Choi 博士建议研究金属和 PFAS 与临床医生诊断的 ND 的关系 考虑合并症，同时检查可能减轻化学毒性的营养调节剂和 通过模拟对化学品和营养的干预效果，生成与政策相关的效果估计。 为了实现这一总体目标，她将利用丰富的现有资源（生物样本数据和临床数据） 波士顿出生队列中的 ND 和整个生命周期的合并症的诊断，这是一个大型的预期出生 Choi 博士将在 K99 中估计，该群体中有大量未被充分研究的低收入少数群体。 产后 24-72 小时采集的母血中金属和 PFAS 与 ND 的关系 后代的合并症（目标 1）将通过聚类分析来考虑，以评估是否存在合并症。 患有某些 ND 和合并症的儿童更容易受到妊娠化学品的毒性作用 她将接受跨学科培训，涉及 ND 和合并症、化学营养、研究。 翻译和高级统计方法（即聚类分析、混合物分析、因果推断） 多学科指导团队并通过额外的培训活动，包括课程作业、研讨会、工作 团体、针对非专业受众和政策制定以及国家和地区的研究传播活动 在 R00 中，她将评估不良化学物质的营养调节剂。 目标 1（目标 2）中确定的 ND 关系，并通过估计以下 ND 的数量来模拟干预效果： 如果对化学品、营养等方面进行妊娠干预，本可以避免这种情况 化学品和营养（目标 3）。K99/R00 将使 Choi 博士成为一名创新、独立的研究员。 在环境流行病学领域，在新城疫和合并症、化学营养相互作用方面具有独特的优势， 研究翻译和先进方法将提高公众意识和 作为未来环境或营养政策的科学证据，以减少新发现的负担。