Plasma Perfluoroalkyl Substances Research Articles

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies

BackgroundWomen with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. ObjectiveTo estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. MethodsOur study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. ResultsUsing quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. ConclusionsThe first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

A co-twin control study of in utero exposure to poly- and perfluoroalkyl substances and associations with neonatal thyroid-stimulating hormone

Research quantifying associations between early-life exposure to poly- and perfluoroalkyl substances (PFAS) and neonatal thyroid hormone levels is limited and reports inconsistent results. This study aimed to examine the associations of in utero PFAS exposure with neonatal thyroid-stimulating hormone (TSH), and to verify whether genetic and familial factors contribute to these associations. Within Wuhan Twin Birth Cohort study, we included 148 mother-twin pairs recruited between March 2016 and January 2018. Maternal plasma PFAS concentrations were measured at three different trimesters and averaged. Additionally, we measured cord plasma PFAS concentrations for twin newborns and retrieved their TSH levels from the medical system. Multivariable linear regression, generalized estimation equation, and linear mixed models were used to examine the covariate-adjusted associations. For maternal PFAS analyses, a 2-fold increment of average maternal perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) concentrations was linked with a 15% (95% CI: 2.5%, 28%) and 14% (95% CI: 2.4%, 28%) increase in neonatal TSH, respectively. For twin newborns discordant for PFAS exposure, a 2-fold increment of cord plasma PFOA, PFDA, perfluoroundecanoic acid (PFUdA), and perfluorohexanesulfonic acid (PFHxS) concentrations was related to a 7.1% (95% CI: 0.31%, 14%), 12% (95% CI: 4.8%, 20%), 7.5% (95% CI: 0.30%, 15%), and 8.5% (95% CI: 3.0%, 14%) increase in TSH among twins as individuals, respectively. Although these associations were mainly observed between twin pairs, certain PFAS exposure might have an independent association with increased TSH. Our present study suggests that higher maternal and cord plasma PFAS concentrations are associated with increased neonatal TSH, and genetic and familial factors contribute to these associations.

Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles

BackgroundPerfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.ObjectiveWe aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.MethodsWe measured concentrations of cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein subclasses, as well as fatty acid and different phospholipid measures, using serum proton nuclear magnetic resonance (1H-NMR), and four plasma PFAS using liquid chromatography-mass spectrometry (UHPLC-MS/MS). Measurements were available for 493 participants (all aged 50 years, 50% female). Multivariable linear regression was used to estimate the association of four PFAS with 43 different 1H-NMR measures, with adjustment for body mass index (BMI), smoking, education, and physical activity.ResultsWe found that perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), but not perfluorohexanesulfonate (PFHxS), concentrations were consistently positively associated with concentrations of cholesterol in lipoprotein subfractions, apolipoproteins, as well as composite fatty acid- and phospholipid profiles. The most consistent associations were found for the relationship of PFAS with total cholesterol in intermediate-density lipoprotein (IDL), across all low-density lipoprotein (LDL) subfractions and small high-density lipoprotein (HDL). Moreover, we found weak to null evidence for an association of any of the measured 13 triglyceride lipoprotein subfractions with PFAS.ConclusionsOur results suggest that plasma PFAS concentrations are associated with cholesterol in small HDL, IDL and all LDL subfractions, as well as apolipoproteins and composite fatty acid and phospholipid profiles but to a lesser extent with triglycerides in lipoproteins. Our findings draw attention to the need for more detailed measurements of lipids across various lipoprotein subfractions and subclasses in assessing the role of PFAS in lipid metabolism.ImpactBy performing an in-depth characterization of circulating cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein, fatty acid, and phospholipid concentrations, this study has expanded upon the limited literature available on the associations of plasma PFAS concentrations beyond clinical routine laboratory testing for lipids.

Role of bioavailability and protein binding of four anionic perfluoroalkyl substances in cell-based bioassays for quantitative in vitro to in vivo extrapolations

Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. The QIVIVE ratio is the ratio of nominal (Cnom) or freely dissolved concentration (Cfree) in human blood to Cnom or Cfree in the bioassays. Considering that the concentrations of PFAS in human plasma and in vitro bioassays may vary by orders of magnitude, we tested the hypothesis that anionic PFAS bind to proteins concentration-dependently and therefore the binding differs substantially between human plasma and bioassays, which has an impact on QIVIVE. Solid phase microextraction (SPME) with C18-coated fibers served to quantify the Cfree of four anionic PFAS (perfluorobutanoate (PFBA), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)) in the presence of proteins and lipid, medium components, cells and human plasma over five orders of magnitude in concentrations. The C18-SPME method was used to quantify the non-linear binding to proteins, human plasma and medium, and the partition constants to cells. These binding parameters were used to predict Cfree of PFAS in cell bioassays and human plasma by a concentration-dependent mass balance model (MBM). The approach was illustrated with a reporter gene assay indicating activation of the peroxisome proliferator-activated receptor gamma (PPARγ-GeneBLAzer). Blood plasma levels were collected from literature for occupational exposure and the general population. The QIVIVEnom ratios were higher than the QIVIVEfree ratios due to the strong affinity to proteins and large differences in protein contents between human blood and bioassays. For human health risk assessment, the QIVIVEfree ratios of many in vitro assays need to be combined to cover all health relevant endpoints. If Cfree cannot be measured, they can be estimated with the MBM and concentration-dependent distribution ratios.

Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort

ObjectivesExperimental models have demonstrated a link between exposure to perfluoroalkyl substances (PFAS) and decreased fertility and fecundability; however, human studies are scarce. We assessed the associations between preconception plasma PFAS concentrations and fertility outcomes in women. MethodsIn a case-control study nested within the population-based Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), we measured PFAS in plasma collected in 2015–2017 from 382 women of reproductive age trying to conceive. Using Cox proportional hazards regression (fecundability ratios [FRs]) and logistic regression (odds ratios [ORs]) models, we assessed the associations of individual PFAS with time-to-pregnancy (TTP), and the likelihoods of clinical pregnancy and live birth, respectively, over one year of follow-up, adjusting for analytical batch, age, education, ethnicity, and parity. We used Bayesian weighted quantile sum (BWQS) regression to assess the associations of the PFAS mixture with fertility outcomes. ResultsWe found a 5–10 % reduction in fecundability per quartile increase of exposure to individual PFAS (FRs [95 % CIs] for clinical pregnancy = 0.90 [0.82, 0.98] for PFDA; 0.88 [0.79, 0.99] for PFOS; 0.95 [0.86, 1.06] for PFOA; 0.92 [0.84, 1.00] for PFHpA). We observed similar decreased odds of clinical pregnancy (ORs [95 % CIs] = 0.74 [0.56, 0.98] for PFDA; 0.76 [0.53, 1.09] for PFOS; 0.83 [0.59, 1.17] for PFOA; 0.92 [0.70, 1.22] for PFHpA) and live birth per quartile increases of individual PFAS and the PFAS mixture (ORs [95 % CIs] = 0.61 [0.37, 1.02] for clinical pregnancy, and 0.66 [0.40, 1.07] for live birth). Within the PFAS mixture, PFDA followed by PFOS, PFOA, and PFHpA were the biggest contributors to these associations. We found no evidence of association for PFHxS, PFNA, and PFHpS and the fertility outcomes examined. ConclusionsHigher PFAS exposures may be associated with decreased fertility in women. The potential impact of ubiquitous PFAS exposures on infertility mechanisms requires further investigation.

Maternal plasma perfluoroalkyl substances concentrations in early pregnancy and cardiovascular development in offspring: A prospective cohort study

BackgroundHigh maternal plasma perfluoroalkyl substances (PFAS) concentrations has been associated with adverse birth outcomes, but data on early childhood cardiovascular health is limited. This study aimed to assess the potential association between maternal plasma PFAS concentrations during early pregnancy and cardiovascular development in offspring. Material and methodsCardiovascular development was assessed through blood pressure measurement, echocardiography and carotid ultrasound examinations among 957 children from the Shanghai Birth Cohort aged at 4 years old. Maternal plasma concentrations of PFAS were measured at mean gestational age of 14.4 (SD:1.8) weeks. The joint associations between PFAS mixture concentrations and cardiovascular parameters were analyzed using a Bayesian kernel machine regression (BKMR). The potential association of individual PFAS chemicals concentrations was explored using multiple linear regression. ResultsIn BKMR analyses, carotid intima media thickness (cIMT), interventricular septum thickness in diastole and systole, posterior wall thicknesses in diastole and systole, and relative wall thickness were significantly lower when all log10-transformed PFAS were fixed at 75th percentile in comparison to at their 50th percentile[Estimated overall Risk:-0.31 (95%CI: −0.42, −0.20), −0.09 (95%CI: −0.11, −0.07), −0.21 (95%CI: −0.26, −0.16), −0.09 (95%CI: −0.11, −0.07), −0.07 (95%CI: −0.10, −0.04) and −0.005 (95%CI: −0.006, −0.004)].Furthermore, maternal plasma concentrations of individual short-chain PFAS was associated with a decrease in left ventricular wall thickness, intraventricular septum thickness and enlarged chamber volume, and long-chain with a decrease in cIMT. ConclusionsOur findings suggest that maternal plasma PFAS concentrations during early pregnancy was adversely associated with cardiovascular development in offspring, including thinner cardiac wall thickness and cIMT.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case–control study in Chinese population

BackgroundPerfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population.MethodsParticipants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer.ResultsPerfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21).ConclusionsOverall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort

Background & AimsExposure to poly- and perfluoroalkyl substances (PFAS), a class of persistent organic pollutants, is ubiquitous. Animal studies suggest that PFAS may increase risk of fatty liver and hepatocellular carcinoma (HCC) via impacts on hepatic lipid, amino acid, and glucose metabolism, but human data is lacking. We examined associations between PFAS exposure, altered metabolic pathways, and risk of non-viral HCC.MethodsIn this nested case-control study, pre-diagnostic plasma PFAS and metabolomics were measured in 50 incident HCC cases and 50 individually matched controls from the Multiethnic Cohort (MEC) study. Cases/controls were matched by age, sex, race, and study area. PFAS exposure and risk of HCC were examined using conditional logistic regression. A metabolome-wide association study and pathway enrichment analysis was performed for PFAS exposure and HCC risk, and key metabolites/metabolic pathways were identified using a meet in the middle approach.ResultsHigh perfluorooctane sulfonic acid (PFOS) levels (90th percentile from NHANES; >55 μg/L) were associated with 4.5-fold increased risk of HCC (odds ratio 4.5, 95% CI 1.2-16.0). Pathway enrichment analysis showed that PFOS exposure was associated with alterations in amino acid and glycan biosynthesis pathways, which were also associated with HCC risk. We identified 4 metabolites linking PFOS exposure with HCC, including glucose, butyric acid (a short-chain fatty acid), α-ketoisovaleric acid (a branched-chain α-keto acid), and 7α-hydroxy-3-oxo-4-cholestenoate (a bile acid), each of which was positively associated with PFOS exposure and risk of HCC.ConclusionThis proof-of-concept analysis shows that exposure to high PFOS levels was associated with increased risk of non-viral HCC, likely via alterations in glucose, amino acid, and bile acid metabolism. Larger studies are needed to confirm these findings.Lay summaryPer- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they are difficult to break down and stay in the human body for years, are extremely common and can cause liver damage. In a first of its kind study, we found that exposure to high levels of perfluorooctanesulfonic acid, one of the most common PFAS chemicals, was linked to increased risk of hepatocellular carcinoma in humans. Hepatocellular carcinoma is difficult to treat and is one of the most common forms of liver cancer, and these findings may provide new avenues for helping to prevent this disease.

Poly- and perfluoroalkyl substances (PFAS) exposure through infant feeding in early life.

Per- and polyfluoroalkyl substances (PFAS) are non-degradable, man-made-chemicals with an elimination half-life of multiple years, causing accumulation in the environment and humans with potential harmful effects. However, longitudinal PFAS levels in human milk, daily PFAS intake and the association with infant plasma PFAS levels have never been reported. We investigated longitudinal PFOA and PFOS levels in human milk and the daily PFAS intake through infant feeding in the first 3months of life, the most important determinants and the correlation with PFAS plasma levels at age 3months and 2years. In 372 healthy term-born Dutch infants, we determined PFOA and PFOS levels in human milk given at age 1 and 3months, in 6 infant formula brands and in infant plasma at 3months and 2years, using liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry(LC-ESI-MS/MS). We studied the associations between daily PFAS intake and predictive characteristics by multiple regression models. PFOA and PFOS levels in human milk decreased between 1 and 3months after delivery, regardless whether breastfeeding was given exclusively(EBF) or in combination with formula feeding. PFOA and PFOS could not be detected in any formula feeding. Daily PFAS intake(ng/kg) was highest in EBF-infants. Higher amount of human milk, older maternal age, lower parity and first-time breastfeeding were associated with higher daily intake. Daily PFAS intake in early life was strongly correlated with PFAS plasma levels at age 3months and 2years(R=0.642-0.875, p<0.001). Human milk contains PFOA and PFOS, in contrast to formula feeding. Daily PFOA and PFOS intake in early life is highest in exclusively breastfed infants and it is highly correlated with infant's plasma levels throughout infancy. Our findings show that breastfeeding is an important PFAS exposure pathway in the first months of life, with unknown but potential adverse effects. Knowing the important health benefits of breastfeeding, our findings warrant more research about the health outcomes in later life.

Longitudinal poly- and perfluoroalkyl substances (PFAS) levels in Dutch infants.

Per- and polyfluoroalkyl substances (PFAS) are a potential hazard for public health. These man-made-chemicals are non-degradable with an elimination half-life of multiple years, causing accumulation in the environment and humans. Rodent studies demonstrated that PFAS are harmful, especially when present during the critical window in the first months of life. Because longitudinal data during infancy are limited, we investigated longitudinal plasma levels in infants aged 3months and 2years and its most important determinants. In 369 healthy term-born Dutch infants, we determined plasma PFOS, PFOA, PFHxS, PFNA and PFDA levels at age 3months and 2years, using liquid chromatography-electrospray-ionization-tandem-mass-spectrometry (LC-ESI-MS/MS). We studied the associations with maternal and child characteristics by multiple regression models. At age 3months, median plasma levels of PFOS, PFOA, PFHxS, PFNA and PFDA were 1.48, 2.40, 0.43, 0.23 and 0.07ng/mL, resp. Levels decreased slightly until age 2years to 1.30, 1.81, 0.40, 0.21 and 0.08ng/mL, resp. Maternal age, first born, Caucasian ethnicity and exclusive breastfeeding were associated with higher infant's plasma levels at age 3months. Levels at 3months were the most important predictor for PFAS levels at age 2years. Infants with exclusive breastfeeding during the first 3months of life (EBF) had 2-3 fold higher levels throughout infancy compared to infants with exclusive formula feeding (EFF), with PFOA levels at 3months 3.72ng/mL versus 1.26ng/mL and at 2years 3.15ng/mL versus 1.22ng/mL, respectively. Plasma PFAS levels decreased only slightly during infancy. Higher levels at age 3months were found in Caucasian, first-born infants from older mothers and throughout infancy in EBF-infants. Our findings indicate that trans-placental transmission and breastfeeding are the most important determinants of PFAS exposure in early life.

Perfluoroalkyl substances and risk of myocardial infarction and stroke

BACKGROUND AND AIM: Perfluoroalkyl substances (PFAS) are widespread persistent pollutants and its exposure in humans relates to elevated cholesterol. However, the potential to impact public health globally by increasing risk of cardiovascular disease remains unexplored. Therefore, we investigated associations of PFAS exposure with risk of myocardial infarction and/or stroke and subsidiary, with baseline blood lipids. METHODS: A nested case-control study with first incident myocardial infarction and stroke and matched controls from two Swedish cohorts (Swedish Mammography Cohort-Clinical and Cohort of 60-year-olds) was used. Baseline blood sampling occurred during 2003-2009 and 1997-1999 with follow-up through 2017 and 2014 for the cohorts, respectively. Eight plasma PFAS´ concentrations were measured using targeted liquid chromatography-triple quadrupole mass spectrometry. Individual values and the standardized sum of five quantifiable PFAS were categorized into tertiles based on the controls. First incident myocardial infarction (n=345) and ischemic stroke (n=354) cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Control individuals, matched for age, sex and sample date, were randomly selected from each cohort. Baseline blood lipids were measured after overnight fasting. RESULTS:We investigated 1528 case-control subjects with mean [SD] age of 66 [7.7] years, 67% women and PFAS levels around or slightly below established benchmark doses. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher total cholesterol and lower triglyceride levels amongst controls at baseline (n=631), but not with increased risk of cardiovascular disease (OR=0.70, 95% CI=0.53, 0.93), myocardial infarction (OR=0.60, 95% CI=0.39, 0.92) or stroke (OR=0.83, 95% CI=0.46-1.50). CONCLUSIONS:This study indicated that PFAS exposure, although associated with increased cholesterol levels, did not associate with increased risk of myocardial infarction, stroke or their composite endpoint. The findings improve our knowledge on cardiovascular health effects of environmental factors and suggest disturbances in pathways unrelated to cholesterol. KEYWORDS: Cardiovascular diseases, PFAS, Environmental Epidemiology

Prenatal Exposure to Perfluoroalkyl Substances and Mental Health in Childhood

BACKGROUND AND AIM: Epidemiological studies have evaluated the effect of prenatal exposure to perfluoroalkyl substances (PFAS) on neurobehavioral and cognitive endpoints in childhood, but a research focus on mental health is lacking. We evaluated the associations between prenatal PFAS exposure and mental health including depressive symptoms, physical or emotional stress, and psychosis-like experience in children at age 11. METHODS: Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002 (N=2,250), we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child self-report mental health outcomes using validated questionnaires. Binary classifications (with or without moderate/severe symptoms) for each of the outcomes and continuous outcome variables were analyzed. We used unconditional logistic regressions to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the binary outcomes according to log2-transformed PFAS concentrations and PFAS tertiles. PFAS mixture by using the weighted-quantile-sum index was conducted. Analyses were repeated using negative binomial regressions for continuous count outcome variables. Sex-specific analyses were conducted. RESULTS:The highest exposure tertile for perfluorooctanoic acid (OR=1.34, 95% CI: 1.06, 1.71), perfluorohexane sulfonate (OR=1.43, 95% CI: 1.06, 1.92) and perfluoroheptane sulfonate (OR=1.37, 95% CI: 1.02, 1.84) were associated with elevated physical or emotional stress in childhood. The WQS index for PFAS mixture was also positively associated with stress in childhood (OR=1.21, 95% CI: 1.05, 1.40). There were no consistent associations found for these PFAS compounds and depressive symptoms or psychosis-like experience. Findings from negative binomial regressions were similar. There were also no apparent differences in analyses stratified by sex. CONCLUSIONS:Higher prenatal levels of three PFAS compounds and PFAS mixtures might influence physical and emotional stress in childhood. More research of fetal exposures to environmental pollutants and mental health risk in the offspring would be needed. KEYWORDS: PFAS, Mental health outcomes, Children's environmental health, Environmental epidemiology

Association between gestational PFAS exposure and Children's adiposity in a diverse population

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4–8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (β = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (β = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (β = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

Perfluoroalkyl Substances in Plasma of Smallmouth Bass from the Chesapeake Bay Watershed.

Smallmouth bass Micropterus dolomieu is an economically important sportfish and within the Chesapeake Bay watershed has experienced a high prevalence of external lesions, infectious disease, mortality events, reproductive endocrine disruption and population declines. To date, no clear or consistent associations with contaminants measured in fish tissue or surface water have been found. Therefore, plasma samples from two sites in the Potomac River and two in the Susquehanna River drainage basins, differing in land-use characteristics, were utilized to determine if perfluoroalkyl substances were present. Four compounds, perfluorooctane sulphonic acid (PFOS), perfluoroundecanoic acid (PFUnA), perfluorodecanoic acid (PFDA) and perfluorododecanoic acid (PFDoA), were detected in every fish. Two additional compounds, perfluorooctane sulphonamide (PFOSA) and perfluorononanoic acid (PFNA), were less commonly detected at lower concentrations, depending on the site. Concentrations of PFOS (up to 574 ng/mL) were the highest detected and varied significantly among sites. No seasonal differences (spring versus fall) in plasma concentrations were observed. Concentrations of PFOS were not significantly different between the sexes. However, PFUnA and PFDoA concentrations were higher in males than females. Both agricultural and developed land-use appeared to be associated with exposure. Further research is needed to determine if these compounds could be affecting the health of smallmouth bass and identify sources.

Parental plasma concentrations of perfluoroalkyl substances and InVitro fertilization outcomes.

Perfluoroalkyl substances (PFAS) are known to be endocrine-disrupting compounds, but are nevertheless widely used in consumer and industrial products and have been detected globally in human and wildlife. Data from animal and epidemiological studies suggest that PFAS may affect human fertility. This led us to consider whether maternal or paternal plasma PFAS had effects on invitro fertilization (IVF) outcomes. The study population consisted of 96 couples who underwent IVF treatment in 2017 due to tubal factor infertility. The concentrations of 10 PFAS in blood samples from both male and female partners were measured. Poisson regression with log link was performed to evaluate the association between the tertiles of PFAS concentrations and numbers of retrieved oocytes, mature oocytes, two-pronuclei (2PN) zygotes, and good-quality embryos, while multiple linear regression models were used to investigate the correlation between plasma PFAS and semen parameters. Multivariable logistic regression was used to evaluate the association between the tertiles of PFAS concentrations and clinical outcomes. It was found that maternal plasma concentrations of perfluorooctanoic acid (PFOA) were negatively associated with the numbers of retrieved oocytes (ptrend=0.023), mature oocytes (ptrend=0.015), 2PN zygotes (ptrend=0.014), and good-quality embryos (ptrend=0.012). Higher paternal plasma PFOA concentrations were found to be significantly associated with reduced numbers of 2PN zygotes (ptrend=0.047). None of the maternal or paternal PFAS were significantly associated with the probability of implantation, clinical pregnancy, or live birth. To our knowledge, the present study is the first to assess the association between parental exposure to PFAS and IVF outcomes. Our results suggest the potential reproductive effects of PFAS on both men and women, and that exposure to PFAS may negatively affect IVF outcomes. Future studies, particularly with large sample size cohorts, are needed to confirm these findings.

Prenatal Exposure to Perfluoroalkyl Substances and Dysmorphic Facial Features at age 5

Background: Perfluoroalkyl substances (PFAS) are widespread persistent pollutants suggested to induce developmental neurotoxicity in animals, but evidence from human studies remains inconclusive. Epidemiological studies have focused on neurobehavioral and psychological evaluations but other measures such as facial features anomalies have never been investigated. Facial dysmorphia is known to accompany impaired development in the central nervous system and part of the diagnosis of the Fetal Alcohol Syndrome. Objective: To investigate the association between prenatal PFAS exposures and facial features measured at age 5. Methods: We analyzed standardized digital facial photographs taken from 670 children enrolled in the Danish National Birth Cohort (DNBC) at age 5 and three facial features (palpebral fissure length (PFL), philtrum groove, and upper lip thickness) using the Facial Photographic Analysis Software. The features were classified as short or normal PFL as binary outcomes, while philtrum (grooved or smooth versus normal) and upper lip (thick or thin versus normal) were classified in three groups. Six types of prenatal PFAS in maternal plasma collected in early pregnancy (median, 8 gestational weeks) were studied. We conducted logistic regression analysis and estimated the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS level (ng/mL), adjusting for potential confounders including maternal alcohol intake, smoking and age. Results: We found that all six types of prenatal PFAS levels were correlated with higher odds for having a short PFL (e.g. OR ranging from 1.38 to 2.23) with the association being the strongest for perfluorodecanoic acid (PFDA, OR: 2.23, 95% CI: 1.21, 4.11). There were no associations between any of the PFAS and philtrum smoothness or upper lip thickness. Conclusion: Maternal pregnancy PFAS serum levels were associated with shorter PFL in the offspring. Our findings are novel and warrant further research.

Prenatal exposure to perfluoroalkyl substances and behavioral difficulties in childhood at 7 and 11 years

Background: Perfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive. Objective: The study aimed to assess the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and evaluated the potential mediating role of maternal thyroid hormones in these associations. Methods: Using pooled samples in the Danish National Birth Cohort, we evaluated the associations between concentrations of six types of PFAS in maternal plasma collected in early pregnancy (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n=2,421), and by parents (n=2,070) and children at 11 years (n=2,071). Behavioral difficulties were defined as having composite SDQ scores of the total, externalizing and internalizing behaviors above the 90th percentile. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS exposure. The possible mediating effect of maternal TSH and fT4 level in the association between prenatal PFAS and SDQ scores were also evaluated. Results: Prenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR=1.40, 95% CI: 1.14-1.73 for age 7; OR=1.27, 95% CI: 1.05-1.53 for age 11) or children (OR=1.32, 95% CI: 1.11-1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of indirect effects via maternal TSH and fT4 level were observed for total and externalizing behaviors at 7 years reported by parents only. Discussion: Prenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.

A case-control study of perfluoroalkyl substances and the risk of breast cancer in Taiwanese women

Breast cancer (BC) is a common cancer in women worldwide; however, the incidence of BC is increasing in younger women, possibly associated with the environment. Perfluoroalkyl substances (PFAS) are one of endocrine disruptors that accumulate in environment and impact human health. This study aimed to investigate whether the PFAS and BC are associated. We enrolled 120 BCE patients and 119 controls at National Taiwan University Hospital (NTUH) and also collected bio-specimen and questionnaire from 2013 to 2015. All subjects’ plasma PFAS levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionization (UHPLC-ESI-MS/MS). A logistic regression model was used to estimate the association between PFAS and BC. In the ≤50 years age group, the adjusted odds ratio (OR) was 2.34 (95% CI = 1.02, 5.38) for perfluorooctane sulfonate (PFOS) exposure per natural log unit increase. After stratifying the estrogen receptor (ER) status and age group, we obtained a positive association for PFHxS and PFOS concentrations with respect to the risk of ER positive tumors for ≤50 years age group. In conclusion, we found that PFAS were associated with the BC risk of ER positive tumors in young Taiwanese women. Further studies are needed to follow and explore whether these associations are causal.

Perfluoroalkyl substances exposure in early pregnancy and preterm birth in singleton pregnancies: a prospective cohort study

BackgroundPreterm birth (PTB, < 37 completed weeks’ gestation) is one of the global public health concerns. Epidemiologic evidence on the potential impact of perfluoroalkyl substances (PFAS) on PTB is still limited and inconsistent. We aimed to investigate the associations between prenatal PFAS exposure and PTB among singleton live births.MethodsWe studied 2849 mother-infant pairs in the Shanghai Birth Cohort (SBC) from 2013 to 2016. Ten PFAS in maternal plasma in early pregnancy (gestational age, median (interquartile range): 15 (13–16) weeks) were measured. Primary outcomes were duration of gestation, PTB, spontaneous PTB and clinically indicated PTB. A linear regression model was used to assess the associations between ln-transformed PFAS and duration of gestation (in weeks). Logistic regression models were applied to estimate the relative risks of these outcomes.ResultsThe incidence of overall PTB was 4.8% (95% confidence limit: 4.0–5.6%, n = 136) in this study population. In the linear regression analyses, PFAS were not associated with the duration of gestation after controlling for potential confounders. In the multiple logistic models, no significant associations were observed between PFAS and overall PTB, spontaneous or indicated PTB.ConclusionIn this prospective cohort study, we did not observe significant associations between maternal plasma PFAS concentrations in early pregnancy and gestational length, overall PTB, spontaneous or indicated PTB.

Pelagic vs Coastal-Key Drivers of Pollutant Levels in Barents Sea Polar Bears with Contrasted Space-Use Strategies.

In the Barents Sea, pelagic and coastal polar bears are facing various ecological challenges that may explain the difference in their pollutant levels. We measured polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers in fat, and perfluoroalkyl substances in plasma in pelagic and coastal adult female polar bears with similar body condition. We studied polar bear feeding habits with bulk stable isotope ratios of carbon and nitrogen. Nitrogen isotopes of amino acids were used to investigate their trophic position. We studied energy expenditure by estimating field metabolic rate using telemetry data. Annual home range size was determined, and spatial gradients in pollutants were explored using latitude and longitude centroid positions of polar bears. Pollutant levels were measured in harp seals from the Greenland Sea and White Sea-Barents Sea as a proxy for a West-East gradient of pollutants in polar bear prey. We showed that pelagic bears had higher pollutant loads than coastal bears because (1) they feed on a higher proportion of marine and higher trophic level prey, (2) they have higher energy requirements and higher prey consumption, (3) they forage in the marginal ice zones, and (4) they feed on prey located closer to pollutant emission sources/transport pathways.