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.

项目摘要/摘要 早期生活中神经毒性金属的暴露与不良神经发育结果有关 阻碍孩子们发挥全部潜力的能力。婴儿在子宫内吸收金属，随着他们开始爬行， 介绍并探索他们的环境。了解这些暴露对于发展很重要 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测量，但只有头发 提供了易于访问的，时间分辨的曝光记录，最近出现在近端 头发轴的末端和过去的曝光依次向远端出现。人头发长大〜1 CM/月，记录曝光会回溯到几周到几个月；从理论上讲，新生的头发记载了曝光 妊娠约28周。头发的化学构成有助于一般循环中的金属吸收，并且 头发的水平往往高于其他培养基（例如血液，尿液）。头发也稳定，轻巧， 不需要特殊的存储，收集它是无创的，这是儿科研究的非常理想的特征。 传统上，金属是在散装头发样品中测量的，但是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）相关的激光消融已有 开发是为了产生高度空间分辨和敏感的金属的敏感测量，用于法医和法医 其他应用程序，但该技术尚未在环境健康中广泛使用。 我们试图利用肯尼亚内罗毕的400对母亲的新出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的时间分辨金属暴露。 ABC（空气 儿童早期生命和大脑发育的污染暴露）研究于2020年启动至 表征了关键环境神经毒性的产前和产后暴露的变异性和大小 并评估他们对三岁以下的儿童神经发育的影响。这个子研究的目的是 开发一种LA-ICP-MS方法，用于测量头发中的PB，CD，MN AS和HG，并使用来自A的头发进行验证 30-40个ABC婴儿的子样本。我们将评估出生时从ABC婴儿中收集头发的可行性 （要求妈妈自己剪簇），在预定的6周，6个月和12个月的夫妇访问中 （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 和测试策略，以量化和最小化分析可变性。我们将在5-中测量目标金属 每个窗口中的每个婴儿的10束束，并在窗户上比较其时间轮廓。这 工作将产生一种经过验证的方法，用于量化时间分辨为神经毒性金属的暴露 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 在婴儿期的多个时间点接触，并帮助将头发确立为有效的，无创的生物标志物 金属在早期暴露。