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

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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.