摘要：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.
关键词：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
