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

围产期生物样本、婴儿配方奶粉和母乳中生命早期 PFAS 暴露的评估。

• 批准号: 10723660
• 负责人: Katherine Elizabeth Manz
• 金额: $ 15.89万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723660
• 关键词: Active Learning; Address; Analytical Chemistry; Behavior; Biological; Biological Monitoring; Biometry; Blood specimen; Body Burden; Breast Feeding; Chemical Exposure; Chemicals; Child Health; Childhood; Communication; Consumption; Data; Data Analyses; Developed Countries; Development; Environment; Environmental Engineering technology; Epidemiology; Exposure to; Fluorine; Food; Funding; Future; Goals; Grant; Guidelines; Half-Life; Health; Human; Human Milk; Hypothyroidism; Individual; Infant; Infant formula; K-Series Research Career Programs; Knowledge; Leadership; Length; Life; Link; Low Birth Weight Infant; Measures; Mentored Research Scientist Development Award; Mentors; Metabolic; Methodology; Methods; Milk; Mothers; Outcome; Outcome Study; Perinatal; Phase; Placenta; Poly-fluoroalkyl substances; Population; Pre-Eclampsia; Predisposition; Pregnancy; Process Assessment; Production; Productivity; Property; Public Health; Research; Research Design; Research Personnel; Rhode Island; Risk Assessment; Sampling; Serum; Source; Statistical Data Interpretation; Structure; Techniques; Testing; Time; Toxic effect; Toxicity Tests; Training; Umbilical Cord Blood; Vulnerable Populations; analytical method; candidate selection; career; career development; cohort; computerized data processing; critical period; early life exposure; experience; exposed human population; infancy; innovation; manufacture; maternal serum; member; next generation; perfluorooctane sulfonate; perfluorooctanoic acid; post pregnancy; postnatal; prevent; programs; skill acquisition; skills; statistics; substance use; symposium; thyroid disruption; vaccine response

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.

项目摘要（摘要） 鉴于其环境 持久性，人类的长生物学半衰期以及相关的健康影响。妊娠期间暴露于PFA， 婴儿期和童年与低出生体重，先兆子痫，甲状腺功能减退，疫苗降低有关 反应和代谢改变。遗产PFA的阶段，最突出的全氟辛酸酸 （PFOA）和全氟辛烷磺酸盐（PFO），导致已知PFA的生产增加， 包含较短的C-F链长或分支结构。但是，有限的信息可用 关于这些理解的PFA的暴露和毒性程度。那是迫切需要的 了解理解或替代PFA对PFA总暴露的贡献。该提议将 填补我们对人类暴露在发展敏感时期中了解PFA的知识的空白 在两个队列中使用靶向和非目标分析方法的组合。中心假设 将经过测试，我们的整体目标将通过追求两个具体目标来实现：（1）表征 EOF的关系，传统PFA和Mater血清，胎盘和绳索之间的PFA 血液样本和（2）量化母乳和配方中的EOF，传统PFA和PFAS水平 并确定它们对婴儿血清EOF，Legacy PFA和PFAS水平的贡献。 替代PFA是特征的幅度，PFA是风险的迫切需求 评估过程，将有助于指导未来的研究候选PFA进行检查。 此外，了解牛奶和配方奶对婴儿PFAS身体的贡献如何有助于告知 裸露人群的母乳喂养指导。该职业发展奖将扩大候选人的先验 通过 提供专家的心理和受保护时间1）获得流行病学研究设计的经验学习经验 和化学暴露研究，2）在未靶向的PFA分析方面发展专业知识，3）熟练程度 高级统计数据分析，以及4）发展专业和领导能力。她的主要导师博士 约瑟夫·布劳恩（Joseph Braun）（流行病学，化学曝光），以及她的指导团队Krystal Pollitt博士 （未靶向的PFA分析）和Shelley Liu博士（统计）将为候选人提供所需的心理 建立独立研究计划。这将通过动手培训来实现 包括课程，会议，赠款发展，科学沟通和职业发展技能。 成功完成了这笔赠款的培训部分后，预计曼兹博士将成功 作为独立研究者，并准备建立R01资助的研究计划。