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      Prenatal metal concentrations and childhood cardio-metabolic risk using Bayesian Kernel Machine Regression to assess mixture and interaction effects.

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          Abstract

          Background:

          Trace metal concentrations may affect cardio-metabolic risk, but the role of prenatal exposure is unclear. We examined: 1) the relationship between blood metal concentrations during pregnancy and child cardio-metabolic risk factors; 2) overall effects of metals mixture (essential vs. nonessential); and 3) interactions between metals.

          Methods:

          We measured 11 metals in maternal 2 nd trimester whole blood in a prospective birth cohort in Mexico City. In children 4–6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N=609); and plasma hemoglobin A1C (HbA1c) , non-high density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N=411). We constructed cardio-metabolic component scores using age- and sex-adjusted z-scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z-scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions.

          Results:

          Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β=−1.01 z-score units per 1 unit ln(Se), 95%CI = −1.84; −0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = −0.32 and 95% CI: −0.61, −0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardio-metabolic risk than were nonessential metals.

          Conclusions:

          Low essential metals during pregnancy were associated with increased cardio-metabolic risk factors in childhood.

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          Most cited references33

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          Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures.

          Because humans are invariably exposed to complex chemical mixtures, estimating the health effects of multi-pollutant exposures is of critical concern in environmental epidemiology, and to regulatory agencies such as the U.S. Environmental Protection Agency. However, most health effects studies focus on single agents or consider simple two-way interaction models, in part because we lack the statistical methodology to more realistically capture the complexity of mixed exposures. We introduce Bayesian kernel machine regression (BKMR) as a new approach to study mixtures, in which the health outcome is regressed on a flexible function of the mixture (e.g. air pollution or toxic waste) components that is specified using a kernel function. In high-dimensional settings, a novel hierarchical variable selection approach is incorporated to identify important mixture components and account for the correlated structure of the mixture. Simulation studies demonstrate the success of BKMR in estimating the exposure-response function and in identifying the individual components of the mixture responsible for health effects. We demonstrate the features of the method through epidemiology and toxicology applications.
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            Lipid screening and cardiovascular health in childhood.

            This clinical report replaces the 1998 policy statement from the American Academy of Pediatrics on cholesterol in childhood, which has been retired. This report has taken on new urgency given the current epidemic of childhood obesity with the subsequent increasing risk of type 2 diabetes mellitus, hypertension, and cardiovascular disease in older children and adults. The approach to screening children and adolescents with a fasting lipid profile remains a targeted approach. Overweight children belong to a special risk category of children and are in need of cholesterol screening regardless of family history or other risk factors. This report reemphasizes the need for prevention of cardiovascular disease by following Dietary Guidelines for Americans and increasing physical activity and also includes a review of the pharmacologic agents and indications for treating dyslipidemia in children.
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              The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20–40 Months of Age: Evidence from Rural Bangladesh

              Background: Exposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects. Objectives: We aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children’s neurodevelopment. Methods: We employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother–child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry. Results: Analyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18 μ g / dl ], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile ( As ≥ 0.7 μ g / dl , Mn ≥ 6.6 μ g / dl , Pb ≥ 4.2 μ g / dl ) compared to the median ( As = 0.5 μ g / dl , Mn = 5.8 μ g / dl , Pb = 3.1 μ g / dl ). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of − 0.3 ( − 0.5 , − 0.1 ) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity. Conclusions: Employing a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614
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                Author and article information

                Journal
                9009644
                1090
                Epidemiology
                Epidemiology
                Epidemiology (Cambridge, Mass.)
                1044-3983
                1531-5487
                24 January 2019
                March 2019
                01 March 2020
                : 30
                : 2
                : 263-273
                Affiliations
                [1 ]Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
                [2 ]Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [3 ]National Institute of Perinatology, Mexico City, Mexico
                [4 ]Center for Research on Nutrition and Health, National Institute of Public Health, Cuernavaca, Morelos, Mexico
                [5 ]Department of Epidemiology, Brown University, Providence, Rhode Island
                [6 ]Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
                Author notes
                Corresponding Author: Allison Kupsco, 520-240-7893, ak4181@ 123456cumc.columbia.edu , Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
                Article
                PMC6402346 PMC6402346 6402346 nihpa1008121
                10.1097/EDE.0000000000000962
                6402346
                30720588
                2babf45e-78b2-44b0-a998-68ff300e8906
                History
                Categories
                Article

                Metabolic Diseases,Environmental health,Metals,Complex Mixtures,Pediatric Obesity,Prenatal Exposure Delayed Effects,Cardiovascular Diseases

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