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      Prenatal Exposure to Perfluorooctanoate and Risk of Overweight at 20 Years of Age: A Prospective Cohort Study

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          Abstract

          Background: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring.

          Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans.

          Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988–1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up ( n = 665), and biomarkers of adiposity were quantified in a subset ( n = 422) of participants.

          Results: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m 2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m 2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years.

          Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

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          Most cited references38

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          The Danish National Birth Cohort--its background, structure and aim.

          It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000. a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.
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            Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008.

            Since 2002, practices in manufacturing polyfluoroalkyl chemicals (PFCs) in the United States have changed. Previous results from the National Health and Nutrition Examination Survey (NHANES) documented a significant decrease in serum concentrations of some PFCs during 1999-2004. To further assess concentration trends of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA), we analyzed 7876 serum samples collected from a representative sample of the general U.S. population ≥12 years of age during NHANES 1999-2008. We detected PFOS, PFOA, PFNA, and PFHxS in more than 95% of participants. Concentrations differed by sex regardless of age and we observed some differences by race/ethnicity. Since 1999-2000, PFOS concentrations showed a significant downward trend, because of discontinuing industrial production of PFOS, but PFNA concentrations showed a significant upward trend. PFOA concentrations during 1999-2000 were significantly higher than during any other time period examined, but PFOA concentrations have remained essentially unchanged during 2003-2008. PFHxS concentrations showed a downward trend from 1999 to 2006, but concentrations increased during 2007-2008. Additional research is needed to identify the environmental sources contributing to human exposure to PFCs. Nonetheless, these NHANES data suggest that sociodemographic factors may influence exposure and also provide unique information on temporal trends of exposure.
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              Waist circumference as a measure for indicating need for weight management.

              To test the hypothesis that a single measurement, waist circumference, might be used to identify people at health risk both from being overweight and from having a central fat distribution. A community derived random sample of men and women and a second, validation sample. North Glasgow. 904 men and 1014 women (first sample); 86 men and 202 women (validation sample). Waist circumference, body mass index, waist:hip ratio. Waist circumference > or = 94 cm for men and > or = 80 cm for women identified subjects with high body mass index (> or = 25 kg/m2) and those with lower body mass index but high waist:hip ratio (> or = 0.95 for men, > or = 0.80 women) with a sensitivity of > 96% and specificity > 97.5%. Waist circumference > or = 102 cm for men or > or = 88 cm for women identified subjects with body mass index > or = 30 and those with lower body mass index but high waist:hip ratio with a sensitivity of > 96% and specificity > 98%, with only about 2% of the sample being misclassified. Waist circumference could be used in health promotion programmes to identify individuals who should seek and be offered weight management. Men with waist circumference > or = 94 cm and women with waist circumference > or = 80 cm should gain no further weight; men with waist circumference > or = 102 cm and women with waist circumference > or = 88 cm should reduce their weight.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                03 February 2012
                May 2012
                : 120
                : 5
                : 668-673
                Affiliations
                [1 ]Center for Fetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
                [2 ]Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
                [3 ]Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland
                [4 ]Department of Public Health, Section for Epidemiology, Aarhus University, Denmark
                [5 ]Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway
                [6 ]Department of Analytical Chemistry, University of Oslo, Oslo, Norway
                [7 ]Department of Paediatrics, Aarhus University Hospital, Skejby, Denmark
                [8 ]Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
                Author notes
                Address correspondence to T.I. Halldorsson, Center for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Orestads Boulevard 5, Building 206, 2300 Copenhagen, Denmark. Telephone: 4532688692. Fax: 4532683165. E-mail: lur@ 123456ssi.dk
                Article
                ehp.1104034
                10.1289/ehp.1104034
                3346773
                22306490
                0e691d65-45d3-4f02-bf2e-ea996f010312
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 June 2011
                : 03 February 2012
                Categories
                Research

                Public health
                perfluoroalkyl compounds,pregnancy,prenatal exposure,pfoa,overweight,offspring obesity
                Public health
                perfluoroalkyl compounds, pregnancy, prenatal exposure, pfoa, overweight, offspring obesity

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