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      Prenatal exposure to persistent organic pollutants and markers of obesity and cardiometabolic risk in Spanish adolescents

      research-article
      a , b , * , c , a , b , d , a , b , d , e , a , b , d , f , g , a , b , d , a , b , d
      Environment International
      Elsevier Science
      Persistent organic pollutants (POPs), Hexachlorobenzene (HCB), Dichlorodiphenyltrichloroethane (p,p’-DDT), Polychlorinated biphenyls (PCBs), Endocrine disruptors, Cardiometabolic syndrome, BMI, body mass index, BP, blood pressure, CM, cardiometabolic, DAG, directed acyclic graph, p,p’-DDE, p,p’-dichlorodiphenyldichloroethane, p,p’-DDT, p,p’-dichlorodiphenyltrichloroethane, EDCs, endocrine-disrupting chemicals, GAM, generalised additive models, GC, gas chromatography, GEE, generalised estimating equations, HCB, hexachlorobenzene, HDL-C, high-density lipoprotein cholesterol (LDL-C), HOMA-IR, homeostatic model assessment of insulin resistance, INMA, Infancia y Medio Ambiente, LDL-C, low-density lipoprotein cholesterol, LOD, limit of detection, LOQ, limit of quantification, MAP, mean arterial pressure, PCBs, polychlorinated biphenyls, POP, persistent organic pollutant, T2D, type II diabetes mellitus, WHO, World Health Organization, WHtR, Waist-to-Height Ratio

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          Highlights

          • We assessed cardiometabolic (CM) effects of prenatal POP exposure into adolescence.

          • Prenatal exposure to POPs (particularly HCB) was positively associated with BMI.

          • p,p’-DDT and HCB were positively associated with other CM markers in adolescence.

          • Prenatal POP exposure may increase the risk of metabolic disorders in adolescence and adult life.

          Abstract

          Background

          Prenatal exposure to persistent organic pollutants (POPs) has been linked to cardiometabolic (CM) risk factors in childhood, but there are no studies evaluating the persistence of these associations into adolescence, a period of relevant changes in endocrine-dependent organ systems and rapid increases in lean and fat mass. We examined the associations of prenatal POP exposures with body mass index (BMI) from age 4 to 18 years, and with other CM risk markers in adolescence.

          Methods

          We analysed 379 children from the Spanish INMA-Menorca birth cohort study with measured cord blood POP concentrations. We calculated BMI z-scores at ages 4, 6, 11, 14 and 18 years using the WHO growth reference. Body fat % was measured at 11 and 18 years and waist-to-height ratio (WHtR) and blood pressure (BP) at 11, 14 and 18 years. We measured CM biomarkers in fasting blood collected at age 14 years and calculated a CM-risk score as the sum of the sex-, and age-specific z-scores for waist circumference, mean arterial BP, homeostatic model assessment of insulin resistance, fasting blood triglycerides, and high-density lipoprotein cholesterol (HDL-C) (n = 217). Generalised estimating equations and multivariate linear regression models assessed the associations with repeated and single time-point measures, respectively.

          Results

          Hexachlorobenzene (HCB) exposure in the third tertile, compared to the first tertile, was associated with higher BMI (β = 0.24; 95% CI: 0.01, 0.47) and WHtR z-score (β = 0.27; 95% CI: 0.04, 0.51). A continuous increase in HCB was associated with an elevated body fat % (β per 10-fold increase = 4.21; 95% CI: 0.51, 7.92), systolic BP (β = 0.32; 95% CI: 0.02, 0.64) and diastolic BP z-score (β = 0.32; 95% CI: 0.02, 0.62) across all ages, and with higher CM-risk score (β = 1.59; 95% CI: 0.02, 3.18) and lipid biomarkers (total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C)) at 14 years. Dichlorodiphenyltrichloroethane (p,p’-DDT) exposure was non-monotonically associated with BMI and systolic BP. p,p’-DDE and Σ-polychlorinated biphenyls (PCBs) (sum of congeners 118, 138, 153, 180) were not associated with adiposity or BP. p,p’-DDT exposure was associated with an increased CM-risk score, and ΣPCBs concentrations with LDL-C in all adolescents and with total cholesterol only in girls ( p-sex interaction = 0.05).

          Conclusion

          This first longitudinal study from 4 to 18 years suggests that the previously reported POP associations with child BMI persist later in adolescence and that prenatal POP exposures are associated with major risk factors for adult CM syndrome.

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          Most cited references57

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          Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls

          Most studies have some missing data. Jonathan Sterne and colleagues describe the appropriate use and reporting of the multiple imputation approach to dealing with them
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            Multicollinearity and misleading statistical results

            Jong Kim (2019)
            Multicollinearity represents a high degree of linear intercorrelation between explanatory variables in a multiple regression model and leads to incorrect results of regression analyses. Diagnostic tools of multicollinearity include the variance inflation factor (VIF), condition index and condition number, and variance decomposition proportion (VDP). The multicollinearity can be expressed by the coefficient of determination (Rh 2) of a multiple regression model with one explanatory variable (Xh ) as the model’s response variable and the others (Xi [i≠h] as its explanatory variables. The variance (σh 2) of the regression coefficients constituting the final regression model are proportional to the VIF ( 1 1 - R h 2 ) . Hence, an increase in Rh 2 (strong multicollinearity) increases σh 2. The larger σh 2 produces unreliable probability values and confidence intervals of the regression coefficients. The square root of the ratio of the maximum eigenvalue to each eigenvalue from the correlation matrix of standardized explanatory variables is referred to as the condition index. The condition number is the maximum condition index. Multicollinearity is present when the VIF is higher than 5 to 10 or the condition indices are higher than 10 to 30. However, they cannot indicate multicollinear explanatory variables. VDPs obtained from the eigenvectors can identify the multicollinear variables by showing the extent of the inflation of σh 2 according to each condition index. When two or more VDPs, which correspond to a common condition index higher than 10 to 30, are higher than 0.8 to 0.9, their associated explanatory variables are multicollinear. Excluding multicollinear explanatory variables leads to statistically stable multiple regression models.
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              Development of a WHO growth reference for school-aged children and adolescents.

              To construct growth curves for school-aged children and adolescents that accord with the WHO Child Growth Standards for preschool children and the body mass index (BMI) cut-offs for adults. Data from the 1977 National Center for Health Statistics (NCHS)/WHO growth reference (1-24 years) were merged with data from the under-fives growth standards' cross-sectional sample (18-71 months) to smooth the transition between the two samples. State-of-the-art statistical methods used to construct the WHO Child Growth Standards (0-5 years), i.e. the Box-Cox power exponential (BCPE) method with appropriate diagnostic tools for the selection of best models, were applied to this combined sample. The merged data sets resulted in a smooth transition at 5 years for height-for-age, weight-for-age and BMI-for-age. For BMI-for-age across all centiles the magnitude of the difference between the two curves at age 5 years is mostly 0.0 kg/m(2) to 0.1 kg/m(2). At 19 years, the new BMI values at +1 standard deviation (SD) are 25.4 kg/m(2) for boys and 25.0 kg/m(2) for girls. These values are equivalent to the overweight cut-off for adults (> or = 25.0 kg/m(2)). Similarly, the +2 SD value (29.7 kg/m(2) for both sexes) compares closely with the cut-off for obesity (> or = 30.0 kg/m(2)). The new curves are closely aligned with the WHO Child Growth Standards at 5 years, and the recommended adult cut-offs for overweight and obesity at 19 years. They fill the gap in growth curves and provide an appropriate reference for the 5 to 19 years age group.
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                Author and article information

                Contributors
                Journal
                Environ Int
                Environ Int
                Environment International
                Elsevier Science
                0160-4120
                1873-6750
                1 June 2021
                June 2021
                : 151
                : 106469
                Affiliations
                [a ]Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain
                [b ]Universitat Pompeu Fabra (UPF), Barcelona, Spain
                [c ]Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States
                [d ]CIBER Epidemiología y Salud Pública (CIBERESP), Spain
                [e ]Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
                [f ]IMIM-Parc Salut Mar, Barcelona, Catalonia, Spain
                [g ]Ib-salut, Area de Salut de Menorca, Menorca, Spain
                Author notes
                [* ]Corresponding autor at: Barcelona Institute for Global Health (ISGlobal), 88 Dr. Aiguader St., 08003 Barcelona, Spain. nuria.guil@ 123456isglobal.org
                Article
                S0160-4120(21)00094-5 106469
                10.1016/j.envint.2021.106469
                7960637
                33711537
                b95fdf63-79f7-4e43-8613-3087ec91e56a
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 16 November 2020
                : 10 February 2021
                : 15 February 2021
                Categories
                Article

                persistent organic pollutants (pops),hexachlorobenzene (hcb),dichlorodiphenyltrichloroethane (p,p’-ddt),polychlorinated biphenyls (pcbs),endocrine disruptors,cardiometabolic syndrome,bmi, body mass index,bp, blood pressure,cm, cardiometabolic,dag, directed acyclic graph,p,p’-dde, p,p’-dichlorodiphenyldichloroethane,p,p’-ddt, p,p’-dichlorodiphenyltrichloroethane,edcs, endocrine-disrupting chemicals,gam, generalised additive models,gc, gas chromatography,gee, generalised estimating equations,hcb, hexachlorobenzene,hdl-c, high-density lipoprotein cholesterol (ldl-c),homa-ir, homeostatic model assessment of insulin resistance,inma, infancia y medio ambiente,ldl-c, low-density lipoprotein cholesterol,lod, limit of detection,loq, limit of quantification,map, mean arterial pressure,pcbs, polychlorinated biphenyls,pop, persistent organic pollutant,t2d, type ii diabetes mellitus,who, world health organization,whtr, waist-to-height ratio

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