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

项目摘要 人类普遍暴露于金属和全氟烷基和多氟烷基物质（PFAS），这些物质是 在实验和人群环境中确定或疑似神经毒物。接触这些化学物质 在胎儿大脑发育的关键时期子宫内尤其有害。存在四大文献空白： 1)子宫内暴露于这些化学物质和儿童神经发育障碍风险的前瞻性研究 (NDs)在美国是有限的，大多数研究来自主要是白色，欧洲人群; 2）尽管 越来越多的证据表明，这些化学品可能会影响多种ND和系统，大多数研究仅限于 不考虑合并症的单一ND结局; 3）暴露很少单独发生，但合并 不同化学品类别之间的接触仍然不清楚，更不用说化学品与营养的相互作用了（营养可能 修改化学毒性）; 4）大多数儿童环境健康研究侧重于确定风险因素， 很少有人使用或开发可以直接为公共卫生行动提供信息的面向解决方案的分析方法。填补 这些关键的差距，崔博士建议调查金属和PFAS与临床医生诊断的ND 考虑合并症，同时检查可能减轻化学毒性的营养调节剂， 通过模拟对化学品和营养的干预效应，产生与政策相关的效应估计。到 为了实现这一总体目标，她将利用丰富的现有资源（生物标本数据和临床 在波士顿出生队列中，一项大型前瞻性出生 这一群体中有大量未被充分研究的低收入少数群体。在K99中，崔博士将估计 产后24-72小时母血中金属元素及PFAS与ND的关系， 后代的合并症（目标1）。将采用聚类分析考虑合并症，以评价是否 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， 暴露。她将接受ND和合并症，化学营养，研究 翻译，和先进的统计方法（即，聚类分析，混合分析，因果推理）从一个 多学科指导团队，并通过额外的培训活动，包括课程，研讨会，工作 针对非专业受众和政策背景的研究传播活动， 国际研讨会或会议。在R00中，她将评估有害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 如果在怀孕期间对化学品和营养进行干预， 化学品和营养（目标3）。K99/R00将使Choi博士成为一名创新的独立研究人员 在环境流行病学方面，在ND和合并症、化学营养相互作用 研究翻译和先进的方法。我们的研究结果和活动将提高公众认识， 作为未来环境或营养政策的科学依据，以减少ND的负担。

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.