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      Determining Prenatal, Early Childhood and Cumulative Long-Term Lead Exposure Using Micro-Spatial Deciduous Dentine Levels

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          Abstract

          The aim of this study was to assess the validity of micro-spatial dentine lead (Pb) levels as a biomarker for accurately estimating exposure timing over the prenatal and early childhood periods and long-term cumulative exposure to Pb. In a prospective pregnancy cohort sub-sample of 85 subjects, we compared dentine Pb levels measured using laser ablation-inductively coupled plasma mass spectrometry with Pb concentrations in maternal blood collected in the second and third trimesters, maternal bone, umbilical cord blood, and childhood serial blood samples collected from the ages of 3 months to ≥6 years. We found that Pb levels (as 208Pb:43Ca) in dentine formed at birth were significantly associated with cord blood Pb (Spearman ρ = 0.69; n = 27; p<0.0001). The association of prenatal dentine Pb with maternal patella Pb (Spearman ρ = 0.48; n = 59; p<0.0001) was stronger than that observed for tibia Pb levels (Spearman ρ = 0.35; n = 41; p<0.03). When assessing postnatal exposure, we found that Pb levels in dentine formed at 3 months were significantly associated with Pb concentrations in children’s blood collected concurrently (Spearman ρ = 0.64; n = 55; p<0.0001). We also found that mean Pb concentrations in secondary dentine (that is formed from root completion to tooth shedding) correlated positively with cumulative blood lead index (Spearman ρ = 0.38; n = 75; p<0.0007). Overall, our results support that micro-spatial measurements of Pb in dentine can be reliably used to reconstruct Pb exposure timing over the prenatal and early childhood periods, and secondary dentine holds the potential to estimate long-term exposure up to the time the tooth is shed.

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          Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development

          Background The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. Objective We studied prenatal lead exposure’s impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. Methods We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose. Results Maternal lead levels were moderately high with a first-trimester blood lead mean (± SD) value of 7.1 ± 5.1 μg/dL and 14% of values ≥10 μg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores. Conclusions Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.
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            Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.

            The skeleton contains the majority of the body's lead burden in both children and adults. The half-life of lead in bone is in the range of years to decades, depending on bone type, metabolic state, and subject age, among other things. Measurement of skeletal lead has benefited greatly from the recent development of X-ray fluorescence (XRF) instruments that can make rapid, safe, accurate, and relatively precise measurements of lead in bone. Two types of XRF technologies exist, LXRF and KXRF; this paper focuses on KXRF, which has been the most widely validated and used. KXRF is proving to be a powerful analytical methodology for evaluating bone lead levels as a measure of time-integrated (i.e., cumulative) lead dose in epidemiologic studies of the effects of chronic lead exposure. However, insufficient attention has been given to conceptualizing the paradigms by which bone lead levels reflect lead exposure and by which the skeleton serves as an endogenous source of lead. Consideration of these paradigms, which rely on bone lead kinetics, is necessary for the proper development of a priori hypotheses involving bone lead accumulation and release, the selection of bone sites for measurement by KXRF, and the design of epidemiologic studies involving bone lead dynamics. We discuss and present supporting evidence for a conceptual model that distinguishes two major paradigms of skeletal lead, including 1) bone lead as an indicator of cumulative lead exposure (bone lead as repository), and 2) bone lead as a source of body lead burden that is mobilizable into the circulation (bone lead as source). These two roles are not mutually exclusive. Instead, they are components of the processes controlling lead accumulation into and release from bone over time. Developing successful strategies for distinguishing these two processes in epidemiologic studies will require separate measurements of lead in cortical and trabecular bone and additional measurement of specific markers of bone mineral turnover and resorption. It may also involve developing accurate methods for evaluating lead in labile compartments of the circulation, such as plasma, as a potentially useful and responsive measure of bone lead release, of the partitioning of circulatory lead, and of the toxicological significance of lead released from bone to other target organs. Images Figure 1 Figure 2 Figure 3
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              Barium distributions in teeth reveal early life dietary transitions in primates

              Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations 1,2 . Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth 3 . Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation 4 . Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                19 May 2014
                : 9
                : 5
                : e97805
                Affiliations
                [1 ]Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
                [2 ]Faculty of Dentistry, University of Sydney, Sydney, Australia
                [3 ]Office of the Director, National Institute of Public Health, Cuernavaca, Morelos, México
                [4 ]Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
                [5 ]Division of Statistics, Center for Evaluation Research and Surveys, National Institute of Public Health, Cuernavaca, Morelos, México
                Stony Brook University, Graduate Program in Public Health, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MA CA BS MH-A HH ROW MMT-R. Performed the experiments: MA CA BS. Analyzed the data: MA CA HH ROW MMT-R. Contributed reagents/materials/analysis tools: MA CA BS MH-A HH ROW MMT-R. Wrote the paper: MA CA BS MH-A HH ROW MMT-R.

                Article
                PONE-D-13-53210
                10.1371/journal.pone.0097805
                4026445
                24841926
                fb39ce3a-04da-443a-8019-fd908d598b78
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 December 2013
                : 23 April 2014
                Page count
                Pages: 8
                Funding
                This study was supported by funding from NIEHS grants R00ES019597 (Arora), P42ES05947 (Hu), R01ES07821 (Hu), P42ES00000 (Hu), R01ES07821 (Hu, Wright) R01ES013744 (Wright), R01ES014930 (Wright), and Australian NHMRC grant APP1028372 (Arora). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Toxicology
                Toxic Agents
                Medicine and Health Sciences
                Epidemiology
                Biomarker Epidemiology
                Environmental Epidemiology
                Health Care
                Environmental Health
                Pediatrics
                Child Health
                Public and Occupational Health

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                Uncategorized

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