Search

Background: Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive., Objectives: We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities., Methods: Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression)., Results: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease., Discussion: Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Martyn Kirk worked part-time for the Australian Government Department of Health between 2020 and 2022 on the Australian national COVID-19 response., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental chemical contamination is a recognised risk factor for psychological distress, but has been seldom studied in the context of per- and polyfluoroalkyl substances (PFAS) contamination. We examined psychological distress in a cross-sectional study of three Australian communities exposed to PFAS from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities without environmental contamination., Methods: Participation was voluntary following recruitment from a PFAS blood-testing program (exposed) or random selection (comparison). Participants provided blood samples and completed a survey on their exposure history, sociodemographic characteristics, and four measures of psychological distress (Kessler-6, Distress Questionnaire-5, Patient Health Questionnaire-15, and Generalised Anxiety Disorder-7). We estimated prevalence ratios (PR) of clinically-significant psychological distress scores, and differences in mean scores: (1) between exposed and comparison communities; (2) per doubling in PFAS serum concentrations in exposed communities; (3) for factors that affect the perceived risk of living in a community exposed to PFAS; and (4) in relation to self-reported health concerns., Results: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher levels of self-reported psychological distress in exposed communities than in comparison communities (e.g., Katherine compared to Alice Springs, Northern Territory: clinically-significant anxiety scores, adjusted PR = 2.82, 95 % CI 1.16-6.89). We found little evidence to suggest that psychological distress was associated with PFAS serum concentrations (e.g., Katherine, PFOS and anxiety, adjusted PR = 0.85, 95 % CI 0.65-1.10). Psychological distress was higher among exposed participants who were occupationally exposed to firefighting foam, used bore water on their properties, or were concerned about their health., Conclusion: Psychological distress was substantially more prevalent in exposed communities than in comparison communities. Our findings suggest that the perception of risks to health, rather than PFAS exposure, contribute to psychological distress in communities with PFAS contamination., Competing Interests: Declaration of competing interest MDK worked part-time for the Australian Government Department of Health between 2020 and 2022 on the Australian national COVID-19 response team. The other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Environmental chemicals have been implicated in the etiology of impaired fetal growth. However, few studies have assessed the effects of chemical mixtures or considered the possibility of non-monotonic exposure-response relationships for chemicals that act through the endocrine system., Methods: We assessed exposure to polybrominated diphenyl ethers, organochlorine pesticides, metals, and perfluorinated alkyl substances in blood and urine samples collected approximately two weeks prior to delivery in 166 non-smoking pregnant women, and subsequent birth weight, length, and head circumference of neonates who were part of the Australian Maternal Exposures to Toxic Substances (AMETS) study. We used Bayesian structured additive regression models with spike-slab priors to estimate mixture effects, identify important exposures, and model non-linearity in exposure-response relationships., Results: Mixtures of polybrominated diphenyl ethers, organochlorine pesticides, metals, and perfluorinated alkyl substances were not associated with fetal growth outcomes. Estimated change in fetal growth outcomes for an increase in exposure from the 25th to 75th percentile suggested no meaningful associations; the strongest evidence was for a small inverse association between birth weight and cesium exposure measured in whole blood (-124 g, 90% credible interval: -240 to -3 g). We identified several chemicals that may be associated with fetal growth non-linearly; however, 90% credible intervals contained small values consistent with no meaningful association., Conclusions: Using a Bayesian penalized regression method, we assessed the shapes of exposure-response relationships, controlled for confounding by co-exposure, and estimated the single and combined effects of a large mixture of correlated environmental chemicals on fetal growth. Our findings, based on a small sample of mother-neonate pairs, suggest that mixtures of persistent chemicals are not associated with birth weight, length, and head circumference. The potential for non-monotonic relationships between environmental chemicals and fetal growth outcomes warrants further study., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Statistical methods for identifying harmful chemicals in a correlated mixture often assume linearity in exposure-response relationships. Nonmonotonic relationships are increasingly recognized (eg, for endocrine-disrupting chemicals); however, the impact of nonmonotonicity on exposure selection has not been evaluated. In a simulation study, we assessed the performance of Bayesian kernel machine regression (BKMR), Bayesian additive regression trees (BART), Bayesian structured additive regression with spike-slab priors (BSTARSS), generalized additive models with double penalty (GAMDP) and thin plate shrinkage smoothers (GAMTS), multivariate adaptive regression splines (MARS), and lasso penalized regression. We simulated realistic exposure data based on pregnancy exposure to 17 phthalates and phenols in the US National Health and Nutrition Examination Survey using a multivariate copula. We simulated data sets of size N = 250 and compared methods across 32 scenarios, varying by model size and sparsity, signal-to-noise ratio, correlation structure, and exposure-response relationship shapes. We compared methods in terms of their sensitivity, specificity, and estimation accuracy. In most scenarios, BKMR, BSTARSS, GAMDP, and GAMTS achieved moderate to high sensitivity (0.52-0.98) and specificity (0.21-0.99). BART and MARS achieved high specificity (≥0.90), but low sensitivity in low signal-to-noise ratio scenarios (0.20-0.51). Lasso was highly sensitive (0.71-0.99), except for quadratic relationships (≤0.27). Penalized regression methods that assume linearity, such as lasso, may not be suitable for studies of environmental chemicals hypothesized to have nonmonotonic relationships with outcomes. Instead, BKMR, BSTARSS, GAMDP, and GAMTS are attractive methods for flexibly estimating the shapes of exposure-response relationships and selecting among correlated exposures., (© 2020 John Wiley & Sons Ltd.)

Background: Prenatal exposures to endocrine-disrupting chemicals (EDCs) during critical developmental windows have been implicated in the etiologies of a wide array of adverse perinatal and pediatric outcomes. Epidemiological studies have concentrated on the health effects of individual chemicals, despite the understanding that EDCs act together via common mechanisms, that pregnant women are exposed to multiple EDCs simultaneously, and that substantial toxicological evidence of adverse developmental effects has been documented. There is a move toward multipollutant models in environmental epidemiology; however, there is no current consensus on appropriate statistical methods., Objectives: We aimed to review the statistical methods used in these studies, to identify additional applicable methods, and to determine the strengths and weaknesses of each method for addressing the salient statistical and epidemiological challenges., Methods: We searched Embase, MEDLINE, and Web of Science for epidemiological studies of endocrine-sensitive outcomes in the children of mothers exposed to EDC mixtures during pregnancy and identified alternative statistical methods from the wider literature., Discussion: We identified 74 studies and analyzed the methods used to estimate mixture health effects, identify important mixture components, account for nonmonotonicity in exposure–response relationships, assess interactions, and identify windows of exposure susceptibility. We identified both frequentist and Bayesian methods that are robust to multicollinearity, performing shrinkage, variable selection, dimension reduction, statistical learning, or smoothing, including methods that were not used by the studies included in our review., Conclusions: Compelling motivation exists for analyzing EDCs as mixtures, yet many studies make simplifying assumptions about EDC additivity, relative potency, and linearity, or overlook the potential for bias due to asymmetries in chemical persistence. We discuss the potential impacts of these choices and suggest alternative methods to improve analyses of prenatal exposure to EDC mixtures. https://doi.org/10.1289/EHP2207.