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

项目总结 人类无处不在地接触到金属和全氟烷基和多氟烷基物质(PFAS)，它们是 在实验和人群环境中确定或怀疑有神经毒物。暴露在这些化学品中 尤其是在胎儿大脑发育的关键时期--宫内。存在四个主要的文学鸿沟： 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 (NDS)在美国有限，大多数研究来自以白人为主的欧洲人群；2)尽管 越来越多的证据表明，这些化学物质可能会影响多种NDS和系统，大多数研究仅限于 不考虑合并症的单一ND结果；3)单独暴露很少发生，但合并 不同化学类别的暴露仍然不清楚，更不用说化学-营养相互作用了(营养可能 修改化学毒性)；4)大多数儿童的环境健康研究侧重于确定危险因素 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面向解决方案的分析方法。填满 这些关键的差距，崔博士建议调查金属和全氟辛烷磺酸与临床医生诊断的NDS的关系 考虑到共病，同时检查可能减轻化学毒性和 通过模拟对化学品和营养的干预效果来生成与政策相关的效果估计。至 为了实现这一首要目标，她将利用丰富的现有资源(生物质学数据和临床 波士顿出生队列中NDS和终生合并症的诊断)，一个大的预期出生 研究不足的低收入少数群体中有大量代表的队列。在K99中，崔博士将估计 产后24~72小时母血中金属元素和全氟辛烷磺酸与NDS和 后代的合并症(目标1)。合并症将通过聚类分析加以考虑，以评估是否 患有某些NDS和合并症的儿童更容易受到妊娠化学物质的毒性影响 曝光。她将接受NDS和合并症、化学营养、研究等领域的跨学科培训 翻译，以及高级统计方法(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环境的研究传播活动，以及国家和 国际研讨会或会议。在R00中，她将评估有害化学物质的营养改良剂- 目标1(目标2)中确定的ND关系，并通过估计符合以下条件的NDS数量来模拟干预效果 如果有关于化学物质、营养和两者的怀孕干预，本可以预防的 化学品和营养(目标3)。这款K99/R00将把崔博士定位为一位创新的独立研究员 在环境流行病学方面，NDS和共病、化学-营养相互作用、 研究翻译，先进的方法。我们的发现和活动将提高公众的意识和 作为未来环境或营养政策的科学证据，以减轻NDS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.