Assessment of Early Life PFAS Exposure in Perinatal Biospecimens, Infant Formula, and Breastmilk.

项目摘要（摘要） 全氟和多氟烷基物质（PFAS）是一个公共卫生问题，因为它们的环境 持久性、在人体内的长生物半衰期以及相关的健康影响。妊娠期间接触PFAS， 婴儿期和儿童期与低出生体重、先兆子痫、甲状腺功能减退、疫苗减少有关 反应和代谢改变。逐步淘汰传统的全氟辛烷磺酸，主要是全氟辛酸 和全氟辛酸（PFOA）以及全氟辛烷磺酸（PFOS），导致研究不足的全氟辛烷磺酸的生产增加， 其含有较短的C-F链长或支链结构。然而，现有信息有限 关于这些未充分研究的PFAS的暴露程度和毒性。因此，迫切需要 了解未充分研究或替代PFAS对PFAS总暴露量的贡献。这项建议会 填补了我们对人类在发育敏感期暴露于未充分研究的PFAS的知识空白 在两个队列中，使用靶向和非靶向分析方法的组合来评估生命。核心假设 我们的总体目标将通过追求两个具体目标来实现：（1）描述 母体血清、胎盘和脐带内和之间的胎盘、遗留PFAS和研究不足的PFAS的关系 血液样本和（2）定量母乳和配方奶粉中的PFAS、传统PFAS和研究不足的PFAS水平 并确定它们对婴儿血清中PFAS、遗留PFAS和待研究PFAS水平的贡献。 表征暴露于未充分研究的PFAS的程度是风险中的关键需求 评估过程，并将有助于指导未来的研究在选择候选PFAS进行审查。 此外，了解牛奶和配方奶粉如何导致婴儿PFAS身体负担， 在暴露人群中进行母乳喂养指导。这个职业发展奖将延长候选人的先前 在环境工程和环境分析化学方面的培训和研究经验， 提供专家指导和保护时间，以1）获得流行病学研究设计的经验学习 和化学品暴露研究，2）发展非靶向PFAS分析的专业知识，3）熟练掌握 先进的统计数据分析，以及4）发展专业和领导技能。她的主要导师博士。 Joseph Braun（流行病学，化学品暴露），沿着她的指导团队成员Krystal Pollitt博士 （非针对性PFAS分析）和Shelley Liu博士（统计学）将为候选人提供所需的指导 建立一个富有成效的独立研究项目。这将通过实践培训来实现， 包括课程，会议，赠款开发，科学交流和职业发展技能。 在成功完成该资助的培训部分后，预计Manz博士将获得成功 作为一个独立的调查员，并准备建立一个R 01资助的研究计划。

Project Summary (Abstract) Per- and polyfluorinated alkyl substances (PFAS) are a public health concern given their environmental persistence, long biological half-life in humans, and related health effects. Exposure to PFAS during gestation, infancy, and childhood is associated with low birth weight, preeclampsia, hypothyroidism, reduced vaccine response, and metabolic alterations. The phase out of legacy PFAS, most prominently perfluorooctanoic acid and (PFOA) and perfluorooctane sulfonate (PFOS), has led to increased manufacturing of understudied PFAS, which contain shorter C-F chain lengths or branched structures. However, limited information is available regarding the extent of exposure and toxicity of these understudied PFAS. Thus, there is a critical need to understand the contribution of understudied, or replacement, PFAS to total PFAS exposure. This proposal will fill gaps in our knowledge of human exposure to understudied PFAS during developmentally sensitive periods of life using a combination of targeted and untargeted analytical methods in two cohorts. The central hypothesis will be tested and our overall objectives will be accomplished by pursuing two specific aims: (1) Characterize the relations of EOF, legacy PFAS, and understudied PFAS within and between maternal serum, placenta, and cord blood samples and (2) Quantify EOF, legacy PFAS, and understudied PFAS levels in breastmilk and formula and determine their contribution to infant serum EOF, legacy PFAS and understudied PFAS levels. Characterizing the magnitude of exposure to understudied, replacement PFAS is a critical need in the risk assessment process and will help guide future studies in the selection of candidate PFAS to examine. Furthermore, understanding how milk and formula contribute to infant PFAS body burden can help inform breastfeeding guidance in exposed populations. This career development award will extend the candidate’s prior training and research experience in environmental engineering and environmental analytical chemistry by providing expert mentoring and protected time to 1) gain experiential learning in study design for epidemiological and chemical exposure research, 2) develop expertise in untargeted PFAS analysis, 3) acquire proficiency in advanced statistical data analysis, and 4) develop professional and leadership skills. Her primary mentor Dr. Joseph Braun (epidemiology, chemical exposure), along with members of her mentoring team Dr. Krystal Pollitt (untargeted PFAS analysis) and Dr. Shelley Liu (statistics), will provide the needed mentoring for the candidate to establish a productive independent research program. This will be achieved through hands-on training that includes coursework, conferences, grant development, scientific communication, and career development skills. Upon successful completion of the training portion of this grant, it is expected that Dr. Manz will be successful as an independent investigator and prepared to establish a R01 funded research program.