Early life fluoride exposure, neurodevelopment and childhood sleep patterns

生命早期氟化物暴露、神经发育和儿童睡眠模式

• 批准号: 10703494
• 负责人: Ashley Malin
• 金额: $ 24.87万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-12 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703494
• 关键词: Accelerometer; Adolescent; Adult; Age; Archives; Biology; Biometry; Birth; Body part; Calcium; Chemicals; Child; Childhood; Chronic; Cities; Clinical; Clinical Research; Data Reporting; Dental; Dental caries; Developed Countries; Development; Disease; Endocrine; Endocrine Disruptors; Endocrine disruption; Ensure; Environment; Environmental Exposure; Environmental Health; Epidemiology; Equilibrium; Exposure to; Faculty; Fatigue; Fluorides; Funding; Goals; Growth; Health; Health Benefit; Histopathology; Hormones; Human; Hydroxide Ion; Hydroxyapatites; Knowledge acquisition; Life; Longevity; Maintenance; Measures; Mediating; Medical center; Melatonin; Mentors; Mexico; Modern 1601-history; National Research Council; Neurosecretory Systems; New York; North America; Obesity; Oral health; Pathology; Patient Self-Report; Phase; Physiological; Pineal gland; Play; Population; Positioning Attribute; Pregnancy; Preventive; Production; Psychologist; Public Health; Questionnaires; Recommendation; Regulation; Reporting; Research; Research Personnel; Resources; Risk Factors; Role; Saliva; Salivary; Science; Scientist; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Solid; Symptoms; System; Time; Titrations; Tooth structure; Toxic Environmental Substances; Toxicology; Training; Training Programs; Translating; Urine; Water; Water fluoridation; Work; Youth; actigraphy; appropriate dose; bone; calcification; career; clinically relevant; cohort; cost effective; dental agent; design; early childhood; epidemiology study; evidence base; fluorapatite; improved; innovation; interest; nervous system disorder; neurodevelopment; neurotoxic; novel; prevent; prospective; public health priorities; response; risk minimization; saliva sample; skill acquisition; skills; sleep pattern; sleep quality; sleep regulation; social stress; standard measure; tenure track; tool; urinary

PROJECT SUMMARY I am a clinical psychologist interested in understanding the role of environmental exposures in neuro-endocrine development. The goal of this proposal is to receive training to acquire the skills needed to continue my academic career by examining the role of child fluoride exposure in sleep patterns and melatonin production. In this proposal, I plan to train with an expert mentoring team with transdisciplinary expertise covering exposure biology, sleep disorders, toxicology, epidemiology and biostatistics. Specifically, I will train in 1) exposure science with Dr. Manish Arora 2) clinical sleep research with Dr. Michael Thorpy, and 3) toxicology with Dr. Robert Wright. I will also acquire expertise in epidemiology and the epidemiological assessment of pediatric sleep with Drs. Rosalind Wright, Emily Oken and Kristie Ross, as well as biostatistics with Dr. Chris Gennings. The proposed formal coursework and training with my mentors, advisors and collaborators will enable me to acquire the knowledge and skills necessary to become an independent transdisciplinary researcher. Further, it will enable me to achieve my long-term career goal of becoming an environmental health scientist investigating the role of environmental toxicants in sleep and neuro-endocrine development. I propose to leverage biospecimens and collected measures, including urine, saliva, Actigraphy data, and self- reported daytime fatigue from an existent prospective birth cohort, the Programming Research in Obesity, Growth Environment and Social Stress study. I also aim to conduct an in-depth clinical study examining associations of urine fluoride with gold standard measures of sleep among adolescents. This work will address the following aims: 1.) Determine whether childhood urinary fluoride concentrations (CUF) at 4-5 and 6-7 years predict sleep and wake time, sleep duration and sleep efficiency (measured via accelerometry) and daytime fatigue (measured via a validated self-report questionnaire) at later ages; 2.) Examine whether salivary melatonin rhythms at 6-7 years mediate the association between CUF and sleep patterns/daytime fatigue among children as assessed in Aim 1; 3.) Determine whether urinary fluoride levels are associated with physiological sleep parameters and symptoms of sleep apnea among adolescents assessed at the Sleep- Wake Disorders Center at Montefiore Medical Center. The proposed research represents the first study to examine whether early childhood fluoride exposure predicts changes in childhood sleep patterns, daytime fatigue or melatonin rhythms. As such, it will advance the field of pediatric sleep research by providing valuable information regarding a modifiable potential risk factor for pediatric sleep disturbances. It will also help to inform titration of the appropriate dose of fluoride to maximize dental health efficacy and minimize risk. I will conduct this study in a cost-effective manner by levering available resources from a previously funded cohort. Lastly, I will translate the research and training in this proposal to position myself as an independent investigator with a tenure track faculty position.

项目概要 我是一名临床心理学家，有兴趣了解环境暴露在神经内分泌中的作用 发展。该提案的目标是接受培训以获得继续我的工作所需的技能 通过研究儿童氟化物暴露在睡眠模式和褪黑激素产生中的作用来促进学术生涯。 在这个提案中，我计划与一个具有跨学科专业知识的专家指导团队一起进行培训，涵盖 暴露生物学、睡眠障碍、毒理学、流行病学和生物统计学。具体来说，我将在1）中进行训练 Manish Arora 博士的暴露科学 2) Michael Thorpy 博士的临床睡眠研究，以及 3) 毒理学 与罗伯特·赖特博士。我还将获得流行病学和流行病学评估方面的专业知识 儿科睡眠与博士。 Rosalind Wright、Emily Oken 和 Kristie Ross，以及 Chris 博士的生物统计学 杰宁斯。拟议的与我的导师、顾问和合作者一起进行的正式课程和培训将 使我能够获得成为独立的跨学科人员所需的知识和技能 研究员。此外，它将使我能够实现成为一名环保人士的长期职业目标 健康科学家研究环境毒物在睡眠和神经内分泌发育中的作用。 我建议利用生物样本和收集的测量数据，包括尿液、唾液、体动记录数据和自我检测数据。 现有的预期出生队列“肥胖编程研究”报告了白天疲劳， 成长环境和社会压力研究。我还打算进行深入的临床研究 尿氟化物与青少年睡眠金标准测量的关联。这项工作将解决 目标如下： 1.) 确定 4-5 岁和 6-7 岁时儿童尿氟化物浓度 (CUF) 是否 预测睡眠和醒来时间、睡眠持续时间和睡眠效率（通过加速度测量）以及白天 晚年时的疲劳（通过经过验证的自我报告问卷进行测量）； 2.) 检查唾液是否 6-7 岁褪黑激素节律介导 CUF 与睡眠模式/日间疲劳之间的关联 在目标 1 中评估的儿童中； 3.) 确定尿氟水平是否与以下因素相关： 睡眠监测中心评估青少年的生理睡眠参数和睡眠呼吸暂停症状 蒙蒂菲奥里医疗中心的唤醒障碍中心。 拟议的研究代表了第一项研究幼儿期氟化物暴露是否 预测儿童睡眠模式、白天疲劳或褪黑激素节律的变化。如此一来，将会推进 儿科睡眠研究领域提供有关可改变的潜在风险的有价值的信息 儿童睡眠障碍的因素。它还将有助于告知滴定适当剂量的氟化物 最大限度地提高牙齿健康功效并最大限度地降低风险。我将以具有成本效益的方式进行这项研究 利用先前资助的群体的可用资源。最后，我将把研究和培训转化为 这个提案将我自己定位为一名具有终身教职的独立调查员。