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。

基本信息

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
项目类别：
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

项目摘要

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.

项目概要（摘要）全氟和多氟烷基物质 (PFAS) 因其环境影响而成为公共卫生问题持久性、人体生物半衰期长以及妊娠期间接触 PFAS 的相关健康影响。婴儿期和儿童期与低出生体重、先兆子痫、甲状腺功能减退、疫苗接种减少有关反应和代谢改变的淘汰。 (PFOA) 和全氟辛烷磺酸 (PFOS)，导致未充分研究的 PFAS 的生产增加，其含有较短的 C-F 链长度或支链结构但是，可用的信息有限。因此，迫切需要了解这些未充分研究的 PFAS 的暴露程度和毒性。了解未充分研究的 PFAS 或替代 PFAS 对 PFAS 总暴露量的贡献。填补我们对人类在发育敏感时期接触未充分研究的 PFAS 的认识空白中心假设是在两个队列中结合使用有针对性和无针对性的分析方法。将受到考验，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、胎盘和脐带内部和之间的 EOF、遗留 PFAS 和待研究的 PFAS 的关系血液样本和 (2) 量化母乳和配方奶粉中的 EOF、传统 PFAS 和未充分研究的 PFAS 水平并确定它们对婴儿血清 EOF、遗留 PFAS 和未充分研究的 PFAS 水平的贡献。表征未充分研究的替代 PFAS 的暴露程度是风险中的关键需求评估过程，并将有助于指导未来研究选择候选 PFAS 进行检查。此外，了解牛奶和配方奶粉如何导致婴儿 PFAS 身体负担有助于了解该职业发展奖将延长候选人的先前资格。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受保护的时间，以 1) 在流行病学研究设计中获得体验式学习和化学品暴露研究，2) 培养非目标 PFAS 分析方面的专业知识，3) 熟练掌握高级统计数据分析，以及 4) 培养专业和领导技能。 Joseph Braun（流行病学、化学品暴露）和她的指导团队成员 Krystal Pollitt 博士（非针对性 PFAS 分析）和 Shelley Liu 博士（统计）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计划，这将通过实践培训来实现。包括课程作业、会议、资助开发、科学交流和职业发展技能。成功完成这笔赠款的培训部分后，预计 Manz 博士将取得成功作为一名独立研究者，准备建立 R01 资助的研究计划。