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Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight.Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions.Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20–484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 50–1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): –250, –50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: –18, 4 g).Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.

Current smoking in adult life moderately impairs the semen quality. It is well known that semen quality is associated to fecundity. Therefore, it would be sensible to advise men to abstain from smoking to avoid decreased fecundity.

Background: Perfluorinated alkyl acids (PFAAs), persistent chemicals with unique water-, dirt-, and oil-repellent properties, are suspected of having endocrine-disrupting activity. The PFAA compounds perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are found globally in humans; because they readily cross the placental barrier, in utero exposure may be a cause for concern.Objectives: We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels.Methods: We recruited 169 male offspring (19–21 years of age) from a pregnancy cohort established in Aarhus, Denmark, in 1988–1989, corresponding to 37.6% of the eligible sons. Each man provided a semen sample and a blood sample. Semen samples were analyzed for sperm concentration, total sperm count, motility, and morphology, and blood samples were used to measure reproductive hormones. As a proxy for in utero exposure, PFOA and PFOS were measured in maternal blood samples from pregnancy week 30.Results: Multivariable linear regression analysis suggested that in utero exposure to PFOA was associated with lower adjusted sperm concentration (ptrend = 0.01) and total sperm count (ptrend = 0.001) and with higher adjusted levels of luteinizing hormone (ptrend = 0.03) and follicle-stimulating hormone (ptrend = 0.01). PFOS did not appear to be associated with any of the outcomes assessed, before or after adjustment.Conclusions: The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.

BackgroundSome legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures.ObjectivesWe assessed associations between multiple correlated biomarkers of environmental exposure and birth weight.MethodsWe evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.ResultsTwo phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL).ConclusionsThis study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.CitationLenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP, Heederik D, Rylander L, Vermeulen R. 2016. Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: multi-pollutant models based on elastic net regression. Environ Health Perspect 124:365–372; http://dx.doi.org/10.1289/ehp.1408933

Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.

BACKGROUNDMore than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders.OBJECTIVE AND RATIONALEThe aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism.SEARCH METHODSA systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data.OUTCOMESThe literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder.WIDER IMPLICATIONSThe current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in th...

Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function.Objectives: We assessed the associations between exposure to phthalate metabolites and pregnancy loss.Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother.Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5, 369.5).Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.