Development of a novel laser ablation-ICP-MS method for time-resolved measurement of neurotoxic metals in newborn and infant hair

开发一种新型激光烧蚀-ICP-MS 方法，用于新生儿和婴儿头发中神经毒性金属的时间分辨测量

• 批准号: 10705132
• 负责人: Anne Riederer
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705132
• 关键词: Ablation; Age; Age Months; Air Pollution; Arsenic; Back; Biological Markers; Birth; Blood; Body Burden; Brain; Cadmium; Chemicals; Child; Circulation; Clinic Visits; Consent; Data; Data Aggregation; Detection; Development; Distal; Enrollment; Environment; Environmental Health; Exposure to; Forensic Medicine; Future; Hair; Hair shaft structure; Head; Head circumference; Hospitals; Human; Individual; Inductively Coupled Plasma Mass Spectrometry; Infant; Instruction; Kenya; Lasers; Lead; Length; Life; Link; Manganese; Measurement; Measures; Medical Records; Mercury; Metal exposure; Metals; Methods; Mothers; Neurotoxins; Newborn Infant; Nurses; Oral cavity; Outcome; Parents; Pediatric Research; Pregnancy; Prevention; Prevention strategy; Protocols documentation; Research; Research Personnel; Resources; Sampling; Scanning; Schedule; Series; Source; Specimen; Techniques; Testing; Third Pregnancy Trimester; Time; Universities; Urine; Well Child Visits; Work; absorption; abstracting; analytical method; cohort; detection limit; early life exposure; epidemiology study; in utero; infancy; insight; light weight; neonatal period; neurodevelopment; neurotoxic; novel; postnatal; prenatal; prenatal exposure; prospective; recruit; temporal measurement; tool; uptake

PROJECT SUMMARY/ABSTRACT Exposure to neurotoxic metals in early life is associated with adverse neurodevelopmental outcomes that hinder children's ability to reach their full potential. Infants absorb metals in utero and as they start crawling, mouthing, and exploring their environments. Understanding these exposures is important for developing prevention strategies and for epidemiological research. Lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), mercury (Hg) and other neurotoxic metals can be measured in a variety of specimen types but only hair provides a readily-accessible, time-resolved exposure record, with recent exposure appearing in the proximal end of the hair shaft and past exposure appearing sequentially toward the distal end. Human hair grows ~1 cm/month, recording exposures back weeks to months; newborn hair theoretically chronicles exposures back to ~28 weeks gestation. Hair's chemical make-up facilitates metals uptake from the general circulation, and levels in hair tend to be higher than those in other media (e.g., blood, urine). Hair is also stable, lightweight, requires no special storage, and collecting it is non-invasive, a highly desirable feature for pediatric research. Traditionally, metals have been measured in bulk hair samples, but this approach lacks temporal resolution. More recently, laser ablation linked with inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed to generate highly spatially-resolved and sensitive measurements of metals in hair for forensic and other applications, but the technique is not yet widely used in environmental health. We seek to leverage a new birth cohort of 400 mother-infant pairs in Nairobi, Kenya to develop and test an LA-ICP-MS method for measuring time-resolved metals exposures in newborn and infant hair. The ABC (Air Pollution Exposures in Early Life and Brain Development in Children) study was launched in 2020 to characterize the variability and magnitude of pre- and postnatal exposures to key environmental neurotoxicants and assess their impact on child neurodevelopment up to age three years. The objective of this sub-study is to develop an LA-ICP-MS method for measuring Pb, Cd, Mn, As, and Hg in hair and validate it using hair from a sub-sample of 30-40 ABC babies. We will assess the feasibility of collecting hair from the ABC babies at birth (asking moms themselves to snip a tuft) and during the scheduled 6-week, 6- and 12-month well-child visits (the study nurse will collect it). We will optimize the laser scans to capture key windows of neurodevelopment and test strategies for quantifying and minimizing analytical variability. We will measure the target metals in 5- 10 hair strands from each infant in each window, and compare their temporal profiles across windows. This work will produce a validated method for quantifying time-resolved exposures to neurotoxic metals during the critical first year of neurodevelopment. We will also gain insight on the incremental value of measuring exposures across multiple time points in infancy, and help establish hair as a valid, non-invasive biomarker of metals exposures in early life.

项目概要/摘要 生命早期接触神经毒性金属与神经发育不良结果相关， 阻碍儿童充分发挥潜力的能力。婴儿在子宫内吸收金属，当他们开始爬行时， 嘴巴，并探索他们的环境。了解这些暴露对于开发非常重要 预防策略和流行病学研究。铅（Pb）、镉（Cd）、砷（As）、锰 (Mn)、汞 (Hg) 和其他神经毒性金属可以在多种样本类型中进行测量，但仅限于头发 提供易于访问的、时间分辨的暴露记录，最近的暴露出现在近端 毛干的末端和过去的暴露顺序出现在远端。人的头发长~1 厘米/月，记录几周至几个月的暴露情况；理论上，新生儿的头发记录了暴露的过程 至妊娠约 28 周。头发的化学成分有利于从全身循环中吸收金属，并且 头发中的含量往往高于其他介质（例如血液、尿液）中的含量。头发也稳定、轻盈， 不需要特殊的存储，并且收集它是非侵入性的，这是儿科研究非常理想的功能。 传统上，金属是在大块头发样本中测量的，但这种方法缺乏时间分辨率。 最近，激光烧蚀与电感耦合等离子体质谱 (LA-ICP-MS) 相结合 开发用于对头发中的金属进行高度空间分辨率和灵敏的测量，用于法医和 其他应用，但该技术尚未广泛应用于环境健康领域。 我们寻求利用肯尼亚内罗毕 400 对母婴的新生队列来开发和测试 LA-ICP-MS 方法用于测量新生儿和婴儿头发中时间分辨金属暴露。 ABC（航空 生命早期的污染暴露和儿童大脑发育）研究于 2020 年启动，旨在 描述产前和产后接触关键环境神经毒物的变异性和程度 并评估它们对三岁以下儿童神经发育的影响。这项子研究的目的是 开发一种 LA-ICP-MS 方法来测量头发中的 Pb、Cd、Mn、As 和 Hg，并使用来自 30-40 个 ABC 婴儿的子样本。我们将评估在 ABC 婴儿出生时收集头发的可行性 （要求妈妈们自己剪掉一簇绒毛）以及在预定的 6 周、6 个月和 12 个月的儿童健康检查期间 （研究护士将收集它）。我们将优化激光扫描以捕获神经发育的关键窗口 以及量化和最小化分析变异性的测试策略。我们将在 5 天内测量目标金属 每个窗口中每个婴儿的 10 根头发，并在各个窗口中比较它们的时间轮廓。这 这项工作将产生一种经过验证的方法，用于量化神经毒性金属的时间分辨暴露 神经发育的关键第一年。我们还将深入了解测量的增量价值 婴儿期多个时间点的暴露，并帮助将头发确立为有效的、非侵入性的生物标志物 早年接触金属。