Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC study.

study questionWhat is the effect of maternal exposure to perfluorooctane sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) on female fecundity? SUMMARY ANSWER: Increasing concentrations of PFOA or PFHxS in maternal plasma were associated with reduced fecundability and infertility. WHAT IS KNOWN ALREADY: Perfluorinated chemicals (PFCs) are a group of synthetic compounds used in industrial production. There is a concern about the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although some recent studies suggest that increasing concentrations of PFCs may decrease fecundity, divergence in the methodological approaches used to evaluate this association have prevented firm conclusions being reached. STUDY DESIGN, SIZE, DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. PARTICIPANTS/MATERIALS, SETTING,

methodsA questionnaire was administered and medical chart data and biospecimens were collected from participants. After excluding women who withdrew, those for whom data were incomplete, those whose pregnancies followed birth control failure, and accounting for male fertility, 1743 participants remained. TTP was defined as the number of months of unprotected intercourse needed to become pregnant in the current pregnancy, as self-reported in the first trimester of pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first trimester were considered as a surrogate of preconception exposure. Fecundability odds ratios (FORs) were estimated using Cox proportional hazard models for discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The odds of infertility (TTP > 12 months or infertility treatment in the index pregnancy) were estimated using logistic regression. Each chemical concentration (ng/ml) was log-transformed and divided by its SD. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42 (95% confidence interval (CI) 0.40-0.45), 0.81 (95% CI 0.79-0.83) and 0.90 (95% CI 0.89-0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61-1.71), 4.59 (95% CI 4.46-4.72) and 1.01 (95% CI 0.97-1.05), respectively. After adjustment for potential confounders, PFOA and PFHxS were associated with a 11 and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83-0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86-0.97; P = 0.002 for PFHxS), while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91-1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11-1.53; P = 0.001) and by 27% per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09-1.48; P = 0.003), while no significant association was observed for PFOS (OR = 1.14; 95% CI 0.98-1.34; P = 0.09). LIMITATIONS, REASONS FOR CAUTION: Women with the highest concentrations of PFCs might have been excluded from the study if there is a causal association with infertility. The MIREC study did not assess concentrations of PFCs in males, semen quality, menstrual cycle characteristics or intercourse frequency. WIDER IMPLICATIONS OF THE

findingsOur results add to the evidence that exposure to PFOA and PFHxS, even at lower levels than previously reported, may reduce fecundability. STUDY FUNDING/COMPETING INTERESTS: The MIREC study is supported by the Chemicals Management Plan of Health Canada, the Canadian Institutes for Health Research (CIHR, grant no. MOP - 81285) and the Ontario Ministry of the Environment. M.P.V. was supported by a CIHR Fellowship Award, and a CIHR-Quebec Training Network in Perinatal Research (QTNPR) Ph.D. scholarship. W.D.F. is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.