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.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

BACKGROUND: Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE: To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS: In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS: Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION: Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.