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

项目概要/摘要 在生命早期暴露于神经毒性金属与不利的神经发育结果有关， 阻碍儿童充分发挥潜力。婴儿在子宫内吸收金属，当他们开始爬行时， 做口型，探索环境。了解这些曝光对于开发 预防战略和流行病学研究。铅（Pb）、镉（Cd）、砷（As）、锰 (Mn)汞（Hg）和其他神经毒性金属可以在各种标本类型中测量，但只有头发 提供了一个易于访问的，时间分辨的曝光记录，最近的曝光出现在近端 发干末端和过去暴露顺序地朝向远端出现。人类头发生长~1 厘米/月，记录数周至数月的暴露量;新生儿头发理论上记录了暴露量 妊娠28周。头发的化学组成有助于从全身循环中吸收金属， 毛发中的水平往往高于其它介质中的水平（例如，血液、尿液）。头发也很稳定，重量轻， 不需要特殊的存储，并且收集它是非侵入性的，这是儿科研究非常期望的特征。 传统上，金属已被测量散装头发样本，但这种方法缺乏时间分辨率。 最近，与电感耦合等离子体质谱法（LA-ICP-MS）相关联的激光烧蚀已经被应用于质谱分析。 开发用于对头发中的金属进行高度空间分辨率和灵敏度的测量，用于法医和 其他应用，但该技术尚未广泛用于环境卫生。 我们试图利用肯尼亚内罗毕一个新的400对母婴出生队列来开发和测试一种 LA-ICP-MS方法用于测量新生儿和婴儿头发中时间分辨的金属暴露。ABC（Air） 早期生活中的污染暴露和儿童大脑发育）研究于2020年启动， 描述出生前后暴露于关键环境神经毒物的可变性和程度 并评估它们对三岁以下儿童神经发育的影响。本子研究的目的是 开发了一种LA-ICP-MS法测定人发中Pb、Cd、Mn、As和Hg的方法，并使用来自 30-40个ABC婴儿的子样本。我们将评估从出生时的ABC婴儿收集头发的可行性 （要求妈妈们自己剪一簇头发），在预定的6周、6个月和12个月的健康儿童访问期间， (the研究护士将收集它）。我们将优化激光扫描以捕捉神经发育的关键窗口 以及用于量化和最小化分析可变性的测试策略。我们将在5- 每个窗口中每个婴儿的10根头发，并比较它们在各个窗口中的时间分布。这 工作将产生一个有效的方法，用于量化时间分辨暴露于神经毒性金属期间， 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 在婴儿期的多个时间点暴露，并帮助建立头发作为一个有效的，非侵入性的生物标志物， 早期生活中的金属接触。

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.