First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis

Background: Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP). Methods: Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results: In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites. Conclusions: We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.