Gestational exposure to organophosphate esters (OPEs) and adiposity during middle childhood in the MIREC Cohort

Toxicological evidence suggests that organophosphate esters (OPEs) may disrupt metabolic processes involved in energy balance and adiposity, yet epidemiological findings remain inconsistent. Among 283 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort, we examined associations between gestational urinary OPE metabolites, including bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), and diphenyl phosphate (DPHP), measured at 6-13 and 16-21 weeks of gestation, and seven indicators of adiposity in children aged 7-11 years. We employed adjusted linear and modified Poisson regressions for metabolite-specific estimates and quantile g-computation for joint mixture effects. Associations varied by gestational window. At 6-13 weeks gestation, each doubling in BCIPP concentration was associated with an increased risk of overweight/obesity (aRR=1.05; 95% CI: 1.02, 1.08) and higher body fat percentage (β=0.41; 95% CI: 0.35, 0.47). Similarly, each doubling in DNBP was positively associated with waist-to-height (WHtR) Z-scores (β=0.07; 95% CI: 0.05, 0.09) and body fat percentage (β=0.39; 95% CI: 0.34, 0.44), whereas doubling of DPHP was associated with higher fat mass index (FMI) Z-scores (β=0.04; 95% CI: 0.01, 0.07). At 16-21 weeks, BCIPP doubling remained associated with increased risk of overweight/obesity (aRR=1.03; 1.01, 1.05). Additionally, BDCIPP (β=0.03; 0.01, 0.05) and DNBP (β=0.03; 0.01, 0.05) doubling were associated with higher FMI Z-scores, and DNBP was associated with increased waist circumference (WC) Z-scores (β=0.04; 0.01, 0.06). While the overall mixture effect was null, BCIPP and DNBP were identified as the primary positive contributors to the joint effects. Findings support gestational OPEs as potential obesogens.