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The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lead is a known neurotoxicant with many detrimental health effects, including neurocognitive deficits and cardiovascular and metabolic disorders. However, few studies have tested the association between lead exposure and the physiological stress response, which in and of itself may act as a precursor to and/or underlying mechanism of detrimental health outcomes. The purpose of this study was to examine the influence of early childhood and early adolescent low-level lead exposure on early adolescent heart rate variability, a widely-used measure of physiological stress. Participants were 408 children from Jintan, China for whom blood lead levels were measured between 3 and 5 years (early childhood) and again at 12 years (early adolescence). Heart rate variability was assessed at 12 years while participants underwent an induced stress task utilizing the ratio of low to high frequency (LF/HF) ECG measures. Mean blood lead levels in the cohort were 6.63 mcg/dl and 3.10 mcg/dl at 3-5 years and 12 years, respectively. Blood lead levels at 3-5 years of age (β 0.06, p = 0.027), but not at age 12 (β -0.05, p = 0.465), were significantly associated with LF/HF measures while controlling for multiple sociodemographic variables, potentially reflecting a dysregulated stress response with a shift towards sympathetic dominance. These findings suggest that early childhood lead exposure may have a detrimental influence on early adolescent autonomic responses to acute stress, which holds implications for cardiovascular health and overall growth and development., (Copyright © 2021 Elsevier Inc. All rights reserved.)