Prenatal Maternal Phthalate Exposures and Trajectories of Childhood Adiposity from Four to Twelve Years

Abstract

BACKGROUND AND AIM: Trajectories of child adiposity have lifelong consequences for future cardiometabolic risk. Prenatal phthalate exposures may affect processes that pre-program later childhood adiposity, but findings from studies examining these associations are conflicting. We examined associations between individual phthalate exposure biomarkers and total phthalate mixture during pregnancy with child adiposity trajectories. METHODS: Data were from 514 mother-child pairs in the PROGRESS cohort of Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine samples and created an average pregnancy measure using the geometric mean. We evaluated the 15 metabolites as nine biomarkers, including four metabolite molar sums. We measured child BMI z-score, bioimpedance-based fat mass index (FMI), and waist-to-height ratio (WHtR) at three visits between four and twelve years of age. We identified trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We then estimated associations of phthalate biomarkers with class membership using multinomial logistic regression. We used quantile g-computation to estimate the effect of the total phthalates mixture and assessed effect modification by sex. RESULTS:We detected three trajectories of child adiposity, “low-stable” remained stable at low adiposity (n=260), “low-high” started low then increased to high (n=147), and “high-high” started high and remained high (n=107). A doubling of the sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), was associated with greater odds of being in the “high-high” trajectory (adjusted odds ratio [OR] = 1.53 [1.08, 2.19]; p = 0.02) in comparison to the “low-stable” group, whereas a doubling in mono(carboxy-isononyl) phthalate (MCNP) was associated with lower odds of being in the “low-high” trajectory (adjusted OR = 0.66 [0.45, 97]; p = 0.03). No sex-specific or total mixtures associations were detected. CONCLUSIONS:Pregnancy urinary concentrations of ΣDEHP metabolites and MCNP were associated with trajectories of child adiposity in opposing directions. KEYWORDS: Phthalates, Children's environmental health, Environmental epidemiology, Mixtures analysis