Identifying windows of susceptibility to endocrine disrupting chemicals in relation to gestational weight gain among pregnant women attending a fertility clinic

Background: Exposure to endocrine disrupting chemicals (EDC), such as phthalates and phenols, during preg-nancy may be associated with excessive gestational weight gain (GWG), an important predictor of future health of the mother and the offspring. There is however a paucity of literature examining this association, and no study has accounted for the complex nature of EDCs exposure as a time-varying mixture of chemicals. Objective: We examined the association between trimester-specific EDCs mixture and GWG in pregnant women attending a fertility clinic, to identify windows of susceptibility to such exposures, and assess the individual contribution of each chemical over pregnancy. Methods: We included 243 pregnant women from the Environment and Reproductive Health (EARTH) Study, who provided up to 3 urine samples (one per trimester), and with available data on GWG. Urinary concentrations of 7 phthalate metabolites, bisphenol A, and 2 parabens, corrected for specific gravity, were included in the analysis. The association between trimester-specific EDCs mixture and GWG was evaluated using multiple regression models - categorizing exposures into concentration quartiles- and with Bayesian Kernel Machine Regression (BKMR), while adjusting for potential confounders. Hierarchical BKMR (hBKMR) was used to account for the time-varying nature of chemical concentrations over pregnancy, identifying the most important trimester and most important EDC within each trimester. Results: During 1st trimester, higher GWG was observed at higher sum of metabolites of di (2-ethylhexyl) phthalate (Sigma DEHP) from both multiple regression (e.g. comparing the 4th quartile with the 1st: beta = 2.36 kg, 95% CI: 0.47, 5.19) and BKMR. During 2nd and 3rd trimesters, positive associations with mono-n-butyl phthalate and propylparaben, and negative with Sigma DEHP and methylparaben were observed. When evaluating exposures as a time-varying mixture with hBKMR, 1st trimester was the most important exposure window when evaluating prenatal urinary EDCs in relation to GWG. Within the 1st trimester, urinary Sigma DEHP, mono-isobutyl phthalate and propylparaben had the highest contribution in the positive association between the mixture and GWG. Conclusion: We observed positive associations between urinary EDCs during pregnancy, especially DEHP me-tabolites, and GWG. Our results suggest the 1st trimester of pregnancy as the time window of highest suscep-tibility to the effects of EDCs on GWG, with potential indication for the design of public health interventions, informing prevention strategies for reducing sources of exposure at specific time points.

Automated summary

Exposure to endocrine disrupting chemicals during pregnancy, particularly in the 1st trimester, is associated with excessive gestational weight gain. This highlights the importance of considering the timing and specific chemicals in EDC exposure for maternal and offspring health.