Relating phthalate and BPA exposure to metabolism in peripubescence: The role of exposure timing, sex, and puberty

Abstract

Context: Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis. Objective: To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis. Design: Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring. Setting: Public maternity hospitals in Mexico City. Patients or Other Participants: Women recruited during pregnancy; offspring recruited for follow- up at age 8â€"14 years (n = 250). Interventions: None. Main Outcome Measures: Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance. Results: Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8â€"14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P = .02) and higher leptin among girls (P = .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P = .01). Conclusions: Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.