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

项目摘要/摘要 在生命早期接触神经毒性金属与不良神经发育结局相关 妨碍儿童充分发挥其潜能的能力。婴儿在子宫中吸收金属，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 预防战略和流行病学研究。铅(铅)、镉(Cd)、砷(As)、锰 (锰)、汞(汞)和其他具有神经毒性的金属可以在各种类型的标本中检测到，但只能在头发中检测到 提供易于获取的、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向远端出现。人的头发长到~1 厘米/月，记录前几周到几个月的暴露；新生儿头发理论上记录了前几周的暴露 至~28周孕期。头发的化学成分有助于从全身循环中吸收金属， 头发中的含量往往高于其他介质(如血液、尿液)中的含量。头发也很稳定，很轻， 不需要特殊的存储，收集它是非侵入性的，这是儿科研究非常理想的特征。 传统上，金属是在大量头发样本中测量的，但这种方法缺乏时间分辨率。 最近，激光消融与电感耦合等离子体质谱(LA-ICPMS)相结合已经被 开发用于生成高度空间分辨率和灵敏的头发中金属的测量方法，用于法医和 其他应用，但该技术尚未广泛应用于环境健康。 我们寻求利用肯尼亚内罗毕400对母婴的新出生队列来开发和测试 LA-ICP-MS法测量新生儿和婴儿头发中时间分辨的金属暴露。《ABC(空气)》 儿童早期生活中的污染暴露与大脑发育)研究于2020年启动，以 描述出生前和出生后暴露于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。此分项研究的目标是 建立了测定头发中铅、镉、锰、砷和汞的LA-ICPMS方法，并用中国人的头发进行了验证。 30-40名ABC婴儿的亚样本。我们将评估收集ABC婴儿出生时头发的可行性 (请妈妈们自己剪一剪)，并在为期6周、6个月和12个月的正常儿童探视期间 (学习护士会收集它)。我们将优化激光扫描以捕捉神经发育的关键窗口 以及量化和最小化分析变异性的测试策略。我们将在5个月内测量目标金属- 每个窗口中每个婴儿的10根头发，并比较他们在不同窗口的时间分布。这 这项工作将产生一种经过验证的方法，用于量化在 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，并有助于建立头发作为有效的，非侵入性的生物标志物 金属在生命早期就会暴露。

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.