Early-life Phthalate Exposures and Adolescent Obesity and Cardiometabolic Health

Abstract

Background: Phthalates may act as metabolic disruptors, altering body composition and glucose and lipid metabolism. Phthalate exposure is ubiquitous among pregnant women and young children who may be more susceptible to adverse health effects. Previous studies are primarily cross-sectional or do not evaluate cardiometabolic outcomes during adolescence. Objectives: Investigate associations of repeated urinary phthalate metabolite concentrations during gestation and childhood with 1) body composition, 2) insulin resistance, and 3) lipid levels at 12 years of age. Methods: We used data from a prospective pregnancy and birth cohort that enrolled pregnant women from Cincinnati, OH from 2003-2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed: 1) fat and lean mass of the whole body, android and gynoid sub regions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores (N=206), 2) insulin and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR) (N=183), and 3) triglycerides, high-density (HDL), and low-density (LDL) lipoprotein cholesterol in fasting serum samples (N=183). Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. Results: In Specific Aim 1, prenatal and later childhood urinary concentrations of mono-n-butyl (MnBP), mono-isobutyl (MiBP), and mono-benzyl (MBzP) phthalate were associated with lower whole-body fat and lean body mass index z-scores. In Specific Aim 2, most early-life phthalate biomarkers were not associated with 12-year measures of insulin resistance. In Specific Aim 3, some urinary phthalate biomarkers, particularly low-molecular weight phthalates, were inversely associated with lipid levels at age 12 years. Conclusions: Prenatal and childhood phthalate exposures may be associated with body composition, particularly lean mass, and lipid levels at 12-years age, with exposure-period and sex-specific differences

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