Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water

Background: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. Objectives: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). Materials and methods: We included all births in Sweden during 2012-2018 of mothers residing >= four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of beta coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. Results: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. Discussions: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation

Presidential Succession and Disability

Background: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear. Methods: In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45-79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression. Results: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99-1.02) or hip fracture (HR 1.02; 95% CI 0.99-1.06) after adjustment for potential confounders. For men consuming >= 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80-1.02) and for hip fracture: 0.89 (95% CI 0.70-1.14). Conclusions: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men

Socio-demographic inequalities influence differences in the chemical exposome among Swedish adolescents

Relatively little is known about the relationship between socio-demographic factors and the chemical exposome in adolescent populations. This knowledge gap hampers global efforts to meet certain UN sustainability goals. The present work addresses this problem in Swedish adolescents by discerning patterns within the chemical exposome and identify demographic groups susceptible to heightened exposures. Enlisting the Riksmaten Adolescents 2016 -17 (RMA) study population (N = 1082) in human-biomonitoring, and using proportional odds ordinal logistic regression models, we examined the associations between concentrations of a diverse array of substances (N = 63) with the determinants: gender, age, participant/maternal birth country income per capita level, parental education levels, and geographic place of living (longitude/ latitude). Participant/maternal birth country exhibited a significant association with the concentrations of 46 substances, followed by gender (N = 41), and longitude (N = 37). Notably, individuals born in high -income countries by high -income country mothers demonstrated substantially higher estimated adjusted means (EAM) concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and per- and polyfluoroalkyl substances (PFASs) compared to those born in low-income countries by low-income country mothers. A reverse trend was observed for cobalt (Co), cadmium (Cd), lead (Pb), aluminium (Al), chlorinated pesticides, and phthalate metabolites. Males exhibited higher EAM concentrations of chromium (Cr), mercury (Hg), Pb, PCBs, chlorinated pesticides, BFRs and PFASs than females. In contrast, females displayed higher EAM concentrations of Mn, Co, Cd and metabolites of phthalates and phosphorous flame retardants, and phenolic substances. Geographical disparities, indicative of north -to -south or west -to -east substance concentrations gradients, were identified in Sweden. Only a limited number of lifestyle, physiological and dietary factors were identified as possible drivers of demographic inequalities for specific substances. This research underscores birth country, gender, and geographical disparities as contributors to exposure differences among Swedish adolescents. Identifying underlying drivers is crucial to addressing societal inequalities associated with chemical exposure and aligning with UN sustainability goals

Risk and benefit assessment of herring and salmonid fish from the Baltic Sea Area

This report is an English translation of a report published in Swedish 2011. The aim of this risk and benefit assessment is to determine the public health consequences of 2 different risk management options: a continuation of the Swedish exemption from maximum limits of dioxins/PCBs for certain fish from the Baltic Sea area, or a cessation of the exemption. The assessment is focused on children and women in childbearing age, important risk groups for negative health effect of dioxin/PCB exposure. Possible health benefits of consumption of fish due to intake of long-chain fatty acids EPA+DHA and vitamin D were also considered. About 6% of women in childbearing age is estimated to consume BS herring twice a month or more, which is related to dioxin/PCB intake above the tolerable weekly intake. When scaled to the total Swedish population, this represents about 100,000 women in the ages of 18-45 with high consumption. About 4-5% of children in Sweden consume BS herring once a month or more, corresponding to about 45,000 children in Sweden. Scenario calculations suggest that a continued exemption from the maximum limits for BS herring can, in the worst case, result in thousands of more children and young women exceeding the TWI than would be the case if Sweden had no exemption. For wild salmonid fish from the Baltic Sea area TWI is exceeded at an average consumption of a few portions a month among women in childbearing ages. Among children the TWI is exceeded already at a regular consumption of less than once a month. A cessation of the exemption would not lead to any limitations of the beneficial intake of nutrients, since BS herring and salmon not complying with the maximum limits would be replaced by BS herring and salmon complying with the limits. In conclusion, a cessation of the exemption from maximum limits would be more beneficial from a public health point-of view than a continued exemption

Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents

While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (& sum;(4)PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10-21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016-17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1-2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and & sum;(4)PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and & sum;(4)PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng & sum;(4)PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW & sum;(4)PFAA concentrations above the maximum limits implemented in Denmark (2 ng & sum;(4)PFAAs/L) and Sweden (4 ng & sum;(4)PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents

Temporal trends, 2000-2017, of perfluoroalkyl acid (PFAA) concentrations in serum of Swedish adolescents

Per- and polyfluoroalkyl substances (PFAS) have been extensively used as surfactants because of their high stability and good water/oil-repellent properties. PFASs, especially perfluoroalkyl acids (PFAAs), have long biological half-lives, and exposure may cause adverse health effects in humans. We assessed temporal trends of concentrations of eight PFAAs in serum of Swedish adolescents (age 16-21 years) from the general population, and estimated the stability of PFAAs and serum samples after 6 years of storage. Repeated cross-sectional sampling was performed on five occasions (covering in total 1213 individuals, 83% males) in southern Sweden between 2000 and 2017. We analyzed serum for perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) using liquid chromatography-tandem mass spectrometry. We assessed time trends using linear regression, long-term stability was assessed by reanalyzing samples collected 2013, and the comparison was done using Pearson correlation and Bland-Altman plots. PFHxS, PFOS, and PFOA decreased by 6.7% (CI: -7.0, -6.3%), 12.6% (CI: -12.9, -12.3%), and 6.5% (CI: -6.8, -6.1%) per year, respectively, and year of sampling explained 48-81% of the variation in concentrations. PFNA and PFDA seemed to increase up to 2009 and decrease thereafter. The trends were consistent after sensitivity analyses excluding women. Strong correlations of 94-97% were observed for concentrations of all compounds, except PFHxS, after storage. The observed trends closely followed the timing of manufacturers' voluntary phaseout initiatives, and of regulatory measures governing the compounds implemented in the EU and USA. This indicates that these actions mitigated the population's exposure to PFHxS, PFOS, and PFOA and, in recent years, to PFNA and PFDA, in southern Sweden. Furthermore, the results suggest that PFAAs remain stable in serum samples after long-term storage

Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study

ABSTRACT: BACKGROUND: Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caffeine. METHODS: Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. RESULTS: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD. CONCLUSION: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee

Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: a cross-sectional study

BACKGROUND: Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure. METHODS: Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996–2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated. RESULTS: In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (β = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and −153) and birth weight was observed in the multivariate model including gestational length (β = −106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls. CONCLUSIONS: Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure

Is the Relationship between Prenatal Exposure to PCB-153 and Decreased Birth Weight Attributable to Pharmacokinetics?

Background: A recent meta-analysis based on data from > 7,000 pregnancies reported an association between prenatal polychlorinated biphenyl (PCB)–153 exposure and reduced birth weight. Gestational weight gain, which is associated negatively with PCB levels in maternal and cord blood, and positively with birth weight, could substantially confound this association. Objective: We sought to estimate the influence of gestational weight gain on the association between PCB-153 exposure and birth weight using a pharmacokinetic model. Methods: We modified a recently published pharmacokinetic model and ran Monte Carlo simulations accounting for variability in physiologic parameters and their correlations. We evaluated the pharmacokinetic model by comparing simulated plasma PCB-153 levels during pregnancy to serial measurements in 10 pregnant women from another study population. We estimated the association between simulated plasma PCB-153 levels and birth weight using linear regression models. Results: The plasma PCB-153 level profiles generated with the pharmacokinetic model were comparable to measured levels in 10 pregnant women. We estimated a 118-g decrease in birth weight (95% CI: –129, –106 g) for each 1-μg/L increase in simulated cord plasma PCB-153, compared with the 150-g decrease estimated based on the previous meta-analysis. The estimated decrease in birth weight was reduced to –6 g (95% CI: –18, 6 g) when adjusted for simulated gestational weight gain. Conclusion: Our findings suggest that associations previously noted between PCB levels and birth weight may be attributable to confounding by maternal weight gain during pregnancy. Citation: Verner MA, McDougall R, Glynn A, Andersen ME, Clewell HJ III, Longnecker MP. 2013. Is the relationship between prenatal exposure to PCB-153 and decreased birth weight attributable to pharmacokinetics? Environ Health Perspect 121:1219–1224; http://dx.doi.org/10.1289/ehp.120645

Determinants of serum concentrations of perfluoroalkyl acids (PFAAs) in school children and the contribution of low-level PFAA-contaminated drinking water

Little is known about the demographic/life-style/physiological determinants explaining the variation of serum perfluoroalkyl acid (PFAA) concentrations in children. We identified significant determinants in children and investigated the influence of low-level PFAA-contaminated drinking water (DW) (&lt;10 ng L−1 of single PFAAs) on serum concentrations. Four perfluorosulfonic acids (PFSAs) and 11 perfluorocarboxylic acids (PFCAs) were analyzed in serum from 5th grade children from 11 Swedish schools (N = 200; average age: 12 years) using liquid chromatography-tandem-mass-spectrometry. Data on demography and life-style/physiological factors were obtained by questionnaires. PFAA concentrations in raw and drinking water (DW) were obtained from the water works supplying DW to the schools. In multiple regression analyses school was the determinant contributing most to the variation in PFAA concentrations, with the lowest contribution for PFHpA (10%) and the highest for PFHxS (81%). Girls had lower adjusted mean concentrations of PFHxS, PFOS, PFNA and PFDA than boys, but a higher concentration of PFHxA. Girls reporting onset of menstruation had lower PFHxS and PFOA concentrations than other girls, suggesting menstrual bleeding elimination. Children born by mothers from less industrialized countries had lower mean concentrations of both PFSAs and PFCAs than children with mothers from highly industrialized countries, suggesting differences in early-life exposure. Life-style factors associated with paternal education levels appeared to influence PFAA concentrations differently than maternal education level. Already at an average DW PFHxS concentration of 2 ng L−1, children had a significantly higher adjusted mean serum PFHxS concentration than at an average DW concentration of &lt;1.6 ng PFHxS L−1. Similar results were observed for PFOS and PFOA. The DW variable explained 16% (PFOA) to 78% (PFHxS) of the variation in serum PFAA concentrations, suggesting that low-level-contaminated DW is a significant source of exposure for children in Sweden. Although some of the associations, especially those with menstruation and maternal birth country, should be interpreted with extra caution due to the small size of the study, the results contribute to future work on identifying populations of children at risk of elevated PFAA exposures