Perfluorinated Compounds and Subfecundity in Pregnant Women

Department of Health and Human Services, National Institute for Environmental Health Sciences, National Institutes of Health, Durham, NC 27709, USA.
Epidemiology (Cambridge, Mass.) (Impact Factor: 6.2). 11/2011; 23(2):257-63. DOI: 10.1097/EDE.0b013e31823b5031
Source: PubMed


Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds-perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA).
This case-control analysis included 910 women enrolled in the Norwegian Mother and Child Cohort Study in 2003 and 2004. Around gestational week 17, women reported their time to pregnancy and provided blood samples. Cases consisted of 416 women with a time to pregnancy greater than 12 months, considered subfecund. Plasma concentrations of perfluorinated compounds were analyzed using liquid chromatography-mass spectrometry. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each pollutant quartile using logistic regression. Estimates were further stratified by parity.
The median plasma concentration of PFOS was 13.0 ng/mL (interquartile range [IQR] = 10.3-16.6 ng/mL) and of PFOA was 2.2 ng/mL (IQR = 1.7-3.0 ng/mL). The relative odds of subfecundity among parous women was 2.1 (95% CI = 1.2-3.8) for the highest PFOS quartile and 2.1 (1.0-4.0) for the highest PFOA quartile. Among nulliparous women, the respective relative odds were 0.7 (0.4-1.3) and 0.5 (0.2-1.2).
Previous studies suggest that the body burden of perfluorinated compounds decreases during pregnancy and lactation through transfer to the fetus and to breast milk. Afterward, the body burden may increase again. Among parous women, increased body burden may be due to a long interpregnancy interval rather than the cause of a long time to pregnancy. Therefore, data from nulliparous women may be more informative regarding toxic effects of perfluorinated compounds. Our results among nulliparous women did not support an association with subfecundity.

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    • "A study using data from the LIFE study indicated that increased serum concentration of FOSA, a fluorochemical residual, in females was significantly associated with reduced couple fecundity, as assessed by a prolonged TTP, though serum concentrations of this fluorochemical residual were below the LOD in 90% of females (Buck Louis et al., 2013). On the other hand, a case-control study of 910 women from the Norwegian Mother and Child Cohort suggested the post-pregnancy re-accumulation of PFASs as a possible explanation for the association between PFASs and subfecundity, given that a long interpregnancy interval among parous women may increase the body burden of PFASs (Whitworth et al., 2012). In a case-cohort study of 156 cerebral palsy cases from the Danish National Birth Cohort during 1996–2002, high maternal plasma PFOS and PFOA levels in early or midpregnancy were associated with an increased risk of cerebral palsy in boys (Liew et al., 2014). "
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    ABSTRACT: Select persistent environmental chemicals have been associated with a reduction in the secondary sex ratio (SSR), or the ratio of male to female live births. We evaluated preconception maternal, paternal, and couple serum concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in relation to the SSR, given the absence of previous investigation. Two hundred thirty-three couples from Michigan and Texas were enrolled prior to conception and prospectively followed through delivery of a singleton birth, 2005-2009. Maternal and paternal serum concentrations (ngmL(-1)) were measured at baseline for seven PFASs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a male birth, after adjusting for potential confounders. When maternal and paternal PFAS concentrations were modeled jointly, five of the seven PFASs, including the two most prominent PFASs, perfluorooctane sulfonic acid and perfluorooctanoic acid, were not significantly associated with the SSR. However, paternal N-methyl-perfluorooctane sulfonamidoacetic acid (MeFOSAA) and perfluorononanoic acid (2nd versus 1st tertile, OR, 0.43, 95% CI, 0.21-0.88) were significantly associated with an excess of female births. Meanwhile, a dose-response relation was observed only for paternal MeFOSAA (2nd versus 1st tertile, OR, 0.53, 95% CI, 0.26-1.10; 3rd versus 1st tertile, OR, 0.34, 95% CI, 0.13-0.89). This study suggests a possible dose-response relation between a less prevalent PFAS and a reversal in the SSR, though the underlying mechanisms remain unknown and the findings await corroboration to eliminate other explanations including chance. Copyright © 2015 Elsevier Ltd. All rights reserved.
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    • "A recent analysis of the MoBa cohort, using the discrete-time Cox proportional hazard model, also reported diminished fecundability at increasing concentrations of PFOA (FOR 0.83; 95% CI 0.75 –0.91) (Ding et al., 2014). In the study by Whitworth et al. (2012), however, the authors considered that "
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    • "Two other pregnancy studies are worth mentioning despite not being directly comparable to research with individual chemical concentrations and TTP. Whitworth et al. (2012) assessed plasma PFOA and PFOS concentrations in 910 pregnant women participating in the Norwegian Mother and Child (MoBA) cohort study with retrospectively collected TTP dichotomized as requiring O12 months for pregnancy vs %12 months. Parous but not nulliparous women in the highest quartiles of PFOA and PFOS had a significant twofold higher odds of a TTP O12 months in comparison to women with lower concentrations. "
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    ABSTRACT: Speculation has arisen that human fecundity may be declining, possibly a function of exposure to persistent environmental chemicals that resist degradation resulting in various pathways for human exposure. In contrast to considerable animal evidence suggesting adverse effects of such chemicals on reproduction, limited human research has been undertaken. To date, available data stem largely from 10 unique study cohorts that have quantified individual chemical exposures in relation to time-to-pregnancy (TTP), which is a measure of couple fecundity. Diminished fecundability odds ratios (FORs) indicative of longer TTP were observed in all but two studies, though not all findings achieved statistical significance. Persistent chemicals associated with reduced couple fecundity as measured by a longer TTP included β-HCH, cadmium, lead, mercury, p,p'-DDE, TCCD dioxin, and select PBDEs, PCBs and PFCs. Important methodologic limitations need to be considered in weighing the evidence: 1) reliance on pregnant women, which may exclude women with the highest exposures if related to the inability to conceive; 2) retrospectively reported TTP, which may be associated with bi-directional reporting errors and 3) limited attention to male partners or couples' exposures. While current evidence is not inconsistent with animal evidence, concerted efforts to address lingering data gaps should include novel strategies for recruiting couples, the longitudinal measurement of TTP and the continued enrollment of couples across successive pregnancies. This latter strategy will provide a more complete understanding of the toxicokinetics of chemicals during sensitive windows and their implications for fecundity and its related impairments.
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