Plasma Polyfluoroalkyl Substances Concentrations Research Articles

Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: −0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring.

Plasma per- and polyfluoroalkyl substance mixtures during pregnancy and duration of breastfeeding in the New Hampshire birth cohort study

BackgroundPrior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse. MethodsWe quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010–2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively. ResultsPFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months. ConclusionsIn this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding.

Exploring the impact of prenatal perfluoroalkyl and polyfluoroalkyl substances exposure on blood pressure in early childhood: A longitudinal analysis

Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:β=3.03, 95%CI: (1.01,5.05); second trimester: β=2.35, 95%CI: (0.94,3.75); third trimester: β=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:β=2.55, 95%CI: (0.64,4.45); second trimester: β=2.28, 95%CI: (0.95,3.61); third trimester: β=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (β=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.

Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation.

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.

Abstract P172: Per- and Polyfluoroalkyl Substances (PFASs), Apolipoprotein and the Risk of Coronary Heart Disease: A Case-Control Pilot Study

The association of PFASs with blood lipids, lipoproteins and apolipoproteins, and coronary heart disease (CHD) risk are inconsistent in previous studies. The aim of current study is to examine the potential association between plasma PFASs, blood lipoproteins and their subspecies defined by apolipoproteins, and whether PFASs are associated with CHD risk.A case-control study was conducted in 100 men and 102 women aged 45-70 years. We leveraged 101 participants from HPFS and NHS who were initially free of cardiovascular disease and developed a fatal or non-fatal myocardial infarction during follow-up, and randomly matched controls in a 1:1 ratio for age, smoking status, and date of blood draw. Seven plasma PFASs measurements were examined at baseline, including perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), with all mean CVs <20%. Pearson correlation was applied to study the relationship between PFASs, lipoproteins and subspecies; Conditional logistic regression model was conducted to test the association between PFASs and CHD risk; a mediating effect model was used to assess how blood lipids and apolipoprotein subspecies mediate the association between PFASs and CHD risk.After multivariable adjustments, we did not find significant associations between PFAS and lipids, except for PFHxS and high-density lipoprotein cholesterol (HDL-C) with a significant positive association (r=0.19, p=0.046). For subspecies with apolipoprotein (apo) C-III, we observed non-significant inverse associations between plasma PFAS concentrations and the subspecies of HDL-C, low-density lipoprotein cholesterol (LDL-C) and VLDL-C that contain only apoC-III. For those without ApoC-III, the directions of most associations are positive. Strong associations were demonstrated between PFNA, PFDA and HDL-C with ApoE (r=0.42, p=0.00004; r=0.27, p=0.004, respectively). In addition, elevated PFOS concentrations were associated with higher relative risk of CHD (HR=1.04, p=0.02), especially for branched PFOS (HR=1.18, p=0.003), and these association were largely dose dependent (PFOS: p for linearity = 0.009; brPFOS: 0.0007). Mediation analysis illustrated no mediating effect regarding blood lipids and apolipoprotein subspecies on the association of interest, except for HDL-C on the association between PFOS, nPFOS and CHD risk (%mediated=25%, p=0.03; %mediated=36%, p=0.03, separately).Our results suggest that there is a linear positive dose-response relationship between PFOS and CHD risk, but the association is probably not mediated by subspecies with/without Apo C-III or Apo E.

Gestational per- and polyfluoroalkyl substances exposure and infant body mass index trajectory in the New Hampshire Birth Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months.Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM.Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1–3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RRR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables.In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS.

Per- and polyfluoroalkyl substances (PFAS) and male reproductive function in young adulthood; a cross-sectional study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are a large family of persistent industrial chemicals with endocrine disrupting properties. ObjectivesTo examine biomarkers of reproductive function in young adult males according to current environmental exposure to single and combined PFAS. MethodsThe study population consisted of young men (n = 1041, age 18–21) from the Fetal Programming of Semen Quality (FEPOS) cohort. These men were recruited from pregnancies included in the Danish National Birth Cohort (DNBC) between 1996 and 2002. From 2017 to 2019, participants answered an online questionnaire, completed a clinical examination and provided a blood and a semen sample. Exposure to 15 PFAS was measured in plasma. Six compounds were quantified above the limit of detection in at least 80% of the participants. We applied negative binomial regression and weighted quantile sum (WQS) regression models to assess associations between single and combined exposure to PFAS and measures of semen quality, testicular volume and reproductive hormones among the young men. ResultsWe found no consistent associations between plasma concentrations of PFAS, semen quality and testicular volume. Higher levels of single and combined PFAS were associated with slightly higher levels of follicle-stimulating hormone (FSH) (WQS 4% difference, 95% confidence interval: 0, 9). Perfluorooctanoic acid (PFOA) was the main contributor to this finding with positive signals also from perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). DiscussionWe examined exposure to a range of common PFAS in relation to biomarkers of male reproductive function and found an association with higher levels of FSH among young men from the general population in Denmark. Further studies on especially combined exposure to PFAS are needed to expand our understanding of potential endocrine disruption from both legacy and emerging compounds in relation to male reproductive function.

Per- and Polyfluoroalkyl Substances and Risk of Myocardial Infarction and Stroke: A Nested Case-Control Study in Sweden.

Background:Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been associated with elevated cholesterol levels. However, data on incident cardiovascular disease (CVD) is lacking.Objectives:We investigated the association of exposure to PFAS with risk of myocardial infarction and stroke and, subsidiary, with baseline blood lipids.Methods:This population-based nested case–control study included first incident myocardial infarction and stroke cases with matched controls from two Swedish cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-year-olds (60YO). Baseline blood sampling occurred during 2003–2009 and 1997–1999 with follow-up through 2017 and 2014 for the SMC-C and the 60YO, respectively. Eight plasma PFAS concentrations were measured using targeted liquid chromatography–triple quadrupole mass spectrometry. Five of these were quantifiable in both cohorts; individual values and their standardized sum were categorized into tertiles based on the controls. First incident myocardial infarction () and ischemic stroke () cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Controls were randomly selected from each cohort after matching for age, sex, and sample date. Baseline blood lipids were measured in plasma or serum after overnight fasting.Results:Among the 1,528 case–control subjects, the mean (standard deviation) age was 66 (7.7) y and 67% of them were women. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher cholesterol and lower triglyceride levels among controls at baseline (). The corresponding results were [95% confidence interval (CI): 0.53, 0.93] for CVD, 0.60 (95% CI: 0.39, 0.92) for myocardial infarction, and 0.83 (95% CI: 0.46, 1.50) for stroke.Discussion:This study indicated that exposure to PFAS, although associated with increased cholesterol levels, did not associate with an increased risk of myocardial infarction, stroke, or their composite end point. The findings improve our knowledge on potential health effects of environmental contaminants in the CVD context. https://doi.org/10.1289/EHP9791

Correlates of plasma concentrations of per- and poly-fluoroalkyl substances among reproductive-aged Black women

BackgroundPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. MethodsWe performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23–35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010–2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. ResultsPFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (−34.7; −43.0, −25.1) and PFOA (−33.1; −39.2, −26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (−31.1; −37.8, −23.7), PFHxS (−24.2; −34.5, −12.3), and PFOS (−18.4; −28.3, −7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (−33.1; −39.6, −25.8), PFHxS (−29.3; −39.0, −18.1), PFNA (−25.2; −32.7, −16.8), and PFOS (−18.3; −28.3, −6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (−18.8; −28.3, −8.2), PFOS (−16.4; −24.9, −7.1), PFNA (−10.5; −17.8, −2.6), and PFOA (−10.0; −17.2, −2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4). ConclusionsReproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use).

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

High levels of fluoroalkyl substances and potential disruption of thyroid hormones in three gull species from South Western France

Per- and poly-fluoroalkyl substances (PFAS) raised increasing concerns over the past years due to their persistence and global distribution. Understanding their occurrence in the environment and their disruptive effect on the physiology of humans and wildlife remains a major challenge in ecotoxicological studies. Here, we investigate the occurrence of several carboxylic and sulfonic PFAS in 105 individuals of three seabird species (27 great black-backed gull Larus marinus; 44 lesser black-backed gull Larus fuscus graellsii; and 34 European herring gull Larus argentatus) from South western France. We further estimated the relationship between plasma concentrations of PFAS and i) the body condition of the birds and ii) plasma concentrations of thyroid hormone triiodothyronine (TT3). We found that great and lesser black-backed gulls from South Western France are exposed to PFAS levels comparable to highly contaminated species from other geographical areas, although major emission sources (i.e. related to industrial activities) are absent in the region. We additionally found that PFAS are negatively associated with the body condition of the birds in two of the studied species, and that these results are sex-dependent. Finally, we found positive associations between exposure to PFAS and TT3 in the great black-backed gull, suggesting a potential disrupting mechanism of PFAS exposure. Although only three years of data have been collected, we investigated PFAS trend over the study period, and found that great black-backed gulls document an increasing trend of plasma PFAS concentration from 2016 to 2018. Because PFAS might have detrimental effects on birds, French seabird populations should be monitored since an increase of PFAS exposure may impact on population viability both in the short- and long-term.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β=0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

Cross-Sectional Associations of Plasma Per- and Polyfluoroalkyl Substances with Kidney Function among Pre-Diabetic Adults-Report from the Diabetes Prevention Program

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked with kidney cancer and reduced kidney function, but findings for plasma PFAS concentrations and kidney function are inconsistent. We evaluated cross-sectional associations of plasma concentrations of 6 PFAS [perfluorooctane sulfonate, perfluorooctanoate (PFOA), perfluorohexane sulfonate, N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetate, and perfluorononanoate] with estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among prediabetic adults at risk for kidney disease. Methods: We used baseline data from the Diabetes Prevention Program (enrolled 1996-1999) and applied linear regression to estimate associations between plasma PFAS concentrations (log-2 transformed) with eGFR and ACR. We accounted for sex, age, race, marital status, income, smoking, menopause status, medication use, and diet score in the models, and tested for effect modification by sex and hypertension status. Results: Plasma PFAS concentrations of 925 overweight or obese adults (64.9% female, 57.8% non-Hispanic White) and those among the U.S. population were similar. Mean kidney functions were normal (eGFR: 97.3 ± 15.5 ml/min/1.73m2; ACR: 11.2 ± 30.5). We found no significant associations between PFAS concentrations and eGFR but detected inverse associations of EtFOSAA [β: -3.7 (95% CI: -7.1, -0.3)] and PFOA [(β: -6.4 (95% CI: -12.3, -0.1)] with ACR. We observed potential effect modification by hypertension status (inverse associations among those with hypertension but positive associations among those without hypertension), but none of the effect estimates were statistically significant. Conclusions: We observed weak inverse associations between plasma concentrations of some PFAS with ACR, suggesting higher plasma PFAS concentrations are associated with lower microalbumin ratio in the urine, thus better kidney function. Our main limitation is the potential for reverse causation due to the cross-sectional nature of the data. Longitudinal studies are needed to establish temporality of associations.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers in the Diabetes Prevention Program

Background: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes at baseline using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes.Methods: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanoic sulfate (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction.Results: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β=0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI:-0.03, -0.13] SD). Each doubling in total PFOA and n-PFOA were both associated with -0.13 [95%CI:-0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines.Conclusions: These cross-sectional results suggest that PFAS may increase risk of type 2 diabetes through alterations in amino acid, glycerolipid and glycerophospholipid metabolism pathways, but further prospective research is needed to elucidate mechanisms.

Plasma concentrations of per- and polyfluoroalkyl substances and pubertal timing: A prospective analysis in Project Viva

Background/Aim Exposure to per- and polyfluoroalkyl substances (PFAS) may disrupt pubertal and adrenarchal timing. Animal and human studies have shown associations of prenatal PFAS exposure with delayed puberty in females; fewer studies have investigated childhood exposure. Methods We studied 636 children in Project Viva, a Boston-area prospective pre-birth cohort. We examined associations of plasma concentrations of 6 PFAS measured at mean 7.9 (SD 0.8) years (2006-2010) with markers of pubertal timing. At early adolescence (mean 13.1 (SD 0.8) years), parents reported pubertal signs (a 5-item pubertal development score) and children reported adrenarchal stage (pubic hair Tanner staging pictograph) on questionnaires. We calculated age at peak height velocity using research and clinical measures of height. We used sex-specific linear regression (for pubertal development score and age at peak height velocity) and ordinal logistic regression (for pubic hair staging) models, adjusted for demographic and socioeconomic factors. Results Plasma concentrations were highest for perfluorooctanesulfonic acid (PFOS) [median (IQR) 6.4(5.6) ng/mL], followed by perfluorooctanoate (PFOA) [4.4(3.0) ng/mL] and perfluorodecanoate (PFDA) [0.3(0.3) ng/mL]. Girls had earlier pubertal development than boys [pubertal development score mean (SD) 2.9(0.7) for girls and 2.2(0.7) for boys and age at peak height velocity mean(SD) 11.2(1.0) for girls and 13.1(1.0) for boys]. Girls with greater PFAS concentrations had delayed pubertal timing [e.g., each doubling of PFOA was associated with lower pubertal development score (-0.15 units; 95% CI: -0.29, -0.02) and older age at peak height velocity (0.29 years; 95% CI: 0.06, 0.51)], with strongest associations for PFOA, PFOS, and PFDA. Plasma PFAS concentrations were not associated with pubertal timing in boys or with adrenarchal timing in girls or boys.Conclusions In a large, prospective US cohort, higher plasma PFAS concentrations in mid-childhood were associated with later onset of puberty in girls, which may be a risk factor for infertility and osteoporosis.

Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort.

Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

Associations of Per- and Polyfluoroalkyl Substances (PFAS) With Glucose Tolerance During Pregnancy in Project Viva.

Per- and polyfluoroalkyl substances (PFAS) exposure may alter glucose homeostasis. Research on PFAS exposure and glucose tolerance during pregnancy is limited. The objective of this work is to estimate associations between first-trimester plasma PFAS concentrations and glucose tolerance assessed in late second pregnancy trimester. Pregnant women (n = 1540) enrolled in Project Viva in 1999 to 2002 provided first-trimester plasma samples analyzed for 8 PFAS. At approximately 28 weeks' gestation, women completed 1-hour nonfasting, 50-g oral glucose challenge tests (GCTs); if abnormal, women completed subsequent 3-hour oral glucose tolerance tests (OGTTs) to screen for gestational diabetes mellitus (GDM). We assessed both continuous GCT glucose levels and 4 categories of glucose tolerance (normal glycemia [reference], isolated hyperglycemia, impaired glucose tolerance, GDM). We used multinomial logistic regression to estimate associations of PFAS with glucose tolerance categories. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to assess individual and joint effects of PFAS on continuous GCT glucose levels, respectively. We evaluated effect modification by maternal age and race/ethnicity. PFAS were not associated with glucose tolerance categories. In BKMR analyses, we observed a positive association between ln-perfluorooctane sulfonate (PFOS) and glucose levels (Δ25th to 75th percentile: 6.2 mg/dL, 95% CI, 1.1-11.3) and an inverse-U shaped association between 2-(N-perfluorooctane sulfonamide) acetate and glucose levels. Individual linear regression results were similar. We found suggestive evidence that associations varied by age and racial/ethnic group. Certain PFAS may alter glucose homeostasis during pregnancy, but may not be associated with overt GDM.

Reduced Bone Mineral Density in Children: Another Potential Health Effect of PFAS.

Vol. 128, No. 4 Science SelectionOpen AccessReduced Bone Mineral Density in Children: Another Potential Health Effect of PFASis accompanied byPer- and Polyfluoroalkyl Substance Plasma Concentrations and Bone Mineral Density in Midchildhood: A Cross-Sectional Study (Project Viva, United States) Charles W. Schmidt Charles W. Schmidt Search for more papers by this author Published:20 April 2020CID: 044002https://doi.org/10.1289/EHP6519View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack CitationsCopy LTI LinkHTMLPDF ShareShare onFacebookTwitterLinked InRedditEmail AbstractPer- and polyfluoroalkyl substances (PFAS) are among the most stable industrial compounds ever created.1,2 Used for decades to make nonstick cookware, stain-resistant fabrics, firefighting foam, and other products, they persist indefinitely in the environment and accumulate in the bodies of exposed people.3 A study in adults associated higher PFAS levels in blood with lower bone mineral density, which is a risk factor for osteoporosis.4 Now a study in Environmental Health Perspectives provides new evidence associating the chemicals with lower bone mineral density in children, too.5Bone mass accumulates rapidly during childhood and peaks when individuals reach their late teens and early 20s.6 Therefore, “identifying environmental factors with an influence on bone health during childhood and adolescence can inform preventive interventions with potentially large impacts on fracture risk in later life,” says senior author Abby Fleisch, a pediatric endocrinologist at the Maine Medical Center Research Institute in Portland.Peak bone mineral density in youth strongly predicts an individual’s susceptibility to osteoporosis later in life.8 If evidence bears out that PFAS affects bone mineral density, childhood exposures could have long-term implications for bone health. Image: © iStockphoto/nkbimages.For this study, Fleisch’s team reviewed data from children participating in a long-term study of mothers and their children called Project Viva.7 Sponsored in part by Harvard Medical School, Project Viva recruited just over 2,000 pregnant women between 1999 and 2002 and is still following the mother–child pairs today. Fleisch and her colleagues focused specifically on a subset of 576 children who had undergone bone density scans and provided blood plasma samples for chemical analysis when they were between 6 and 10 years of age. The researchers narrowed their analysis to the six most commonly detected PFAS: summed isomers of perfluorooctanoic acid (PFOA), summed isomers of perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid, N-methyl perfluorooctane sulfonamidoacetic acid, and perfluorononanoic acid. They expressed bone mineral density measures as z-scores normalized for age, sex, race, and height.To generate their results, the authors used linear regression models to see whether lower z-scores (indicating lower bone mineral density) were associated with higher plasma concentrations of individual PFASs. In addition, they used a method called weighted quantile sum (WQS) regression to examine the association of z-scores with the PFAS mixture as a whole.According to the analysis, higher concentrations of each individual PFAS were associated with lower z-scores, with the strongest associations estimated for PFOA, PFOS, and PFDA. A similar association was noted for the PFAS mixture. Specifically, every incremental increase in the WQS index was associated with a corresponding reduction in the z-score for bone mineral density.Most of the children came from relatively high socioeconomic backgrounds and had college-educated mothers. Fleisch acknowledges that could limit the generalizability of the findings to the broader population. She points out that wealthier families may be “more prone to use things that have PFAS, such as carpets and furniture with stain-repellant properties.”Naila Khalil, an associate professor at Wright State University who was not involved in the study, notes, “Researchers tend to focus more on soft-tissue and immune impacts from PFAS exposure. Bone is harder to study, especially in growing children. That makes this paper a robust addition to the limited research on PFAS and its impacts on skeletal health.”Antti Koskela, a physician and researcher who specializes in bone development at the University of Oulu, Finland, points to several strengths of the study. Koskela, who also was not involved in the study, specifically cites the large number of participants, the assessment of a complex PFAS mixture on bone health, and the use of total body dual-energy X-ray absorptiometry for measuring bone density, which is considered the gold standard method. “The data confirm earlier findings and underline concerns about PFAS exposure in children,” he says. “The concern [about potential bone effects] is not just for adults anymore.”Charles W. Schmidt, MS, an award-winning science writer from Portland, ME, writes for Scientific American, Science, Undark, various Nature publications, and many other magazines, research journals, and websites.

Per- and polyfluoroalkyl substances and blood pressure in pre-diabetic adults—cross-sectional and longitudinal analyses of the diabetes prevention program outcomes study

The relationship of plasma concentration of per- and polyfluoroalkyl substances (PFAS) with blood pressure (BP) is uncertain. This study examined cross-sectional and prospective associations of PFAS with BP and hypertension. We quantified plasma PFAS concentrations from 957 participants enrolled in the lifestyle and placebo arms of the Diabetes Prevention Program (DPP), a randomized controlled trial with approximately 15 years of follow-up. We used multivariable linear and logistic regressions to test cross-sectional associations of six PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and perfluorononanoic acid (PFNA), with BP and hypertension prevalence, respectively, at baseline. We used generalized linear mixed models to estimate longitudinal associations between baseline PFAS and the rate of BP changes, and Cox-Proportional hazard models to estimate risk of developing hypertension relative to baseline PFAS. Models were adjusted for baseline age, sex, race/ethnicity, treatment arm, educational attainment, income, marital status, smoking habit, alcohol drinking, and diet. We tested for effect modification by the treatment arm and sex, and accounted for multiple comparisons using the False-Discovery Rate (FDR). PFAS concentrations and hypertension prevalence within the study population (65.3% female, 57.7% White, 65.3% aged 40–59 years) were comparable to the general U.S. population. Cross-sectionally, we found small but statistically significant associations of baseline plasma concentrations of PFOA with systolic BP (β per doubling: 1.49 mmHg, 95% CI: 0.29, 2.70); and MeFOSAA with hypertension (RR = 1.09 per doubling, 95% CI: 1.01, 1.19). Estimates were not statistically significant after FDR adjustment. Longitudinally, we observed null associations in the placebo arm, but some inverse associations of baseline PFOS and MeFOSAA with systolic BP in the lifestyle arm, perhaps due to regression toward the mean. Baseline PFAS concentrations also were not prospectively associated with hypertension risk. Overall, there were modest and mostly null associations of plasma PFAS concentrations with BP and hypertension.

Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography\u2013tandem mass spectrometry

There is evidence of a positive association between per- and polyfluoroalkyl substances (PFASs) and cholesterol levels in human plasma, which may be due to common reabsorption of PFASs and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFASs and BAs in plasma, using 150 μL or 20 μL of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust, and with sufficient linear range to allow reliable determination of both PFASs and BAs. The method detection limits were between 0.01 and 0.06 ng mL−1 for PFASs and between 0.002 and 0.152 ng mL−1 for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng mL−1). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference serum. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs.Graphical