Prenatal urinary phthalates and postpartum metabolic health in Women from Mexico City

Abstract

Studies have reported associations between phthalates, a family of ubiquitous environmental contaminants, and metabolic complications of pregnancy, but no study has considered these outcomes beyond pregnancy. We examined associations of prenatal phthalates exposure with postpartum metabolic health biomarkers in the PROGRESS cohort.The longitudinal PROGRESS cohort includes 948 pregnant women recruited during the second trimester from 2007 to 2011. We quantified 15 phthalate metabolites from spot urines collected during the second and third trimesters. Maternal metabolic health biomarkers were fasting blood measures of glycemia [glucose, insulin, %glycated hemoglobin (HbA1C%)] and lipids (total, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) cholesterol, and triglycerides], collected at 48 and 72 months postpartum. We used linear mixed models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to estimate associations of geometric mean urinary phthalate metabolite concentrations (between 2nd/3rd trimesters) and metabolic health biomarkers.In multivariable-adjusted linear mixed models, each doubling of mean urinary mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) was associated with 0.12 uIU/L greater plasma insulin (95%CI: 0.0, 0.25) and 0.06% greater HbA1C% (95%CI: 0.03, 0.09). Mixtures analyses indicated that phthalate mixtures were positively associated with plasma insulin and HbA1c% and MECPTP and diisobutyl phthalate metabolites were the primary drivers. Mediation analyses found that greater gestational weight retention (GWR) mediated 29% of the observed association between urinary MECPTP and plasma insulin. No mediation by GWR was observed for HbA1C%.We found that prenatal MECPTP concentrations were positively associated with plasma insulin and HbA1C% up to 72 months postpartum. In previous analyses of this cohort, we found that prenatal MECPTP was associated with greater GWR and blood pressure. Collectively, these findings suggest that exposure to di-2-ethylhexyl terephthalate, parent compound of MECPTP, may contribute to poorer metabolic health among women. GWR may be one mediator of later metabolic dysfunction; other underlying mechanisms and clinical implications are unknown.