Early-life exposure to perfluoroalkyl substances in relation to serum adipokines in a longitudinal birth cohort

Shih, Yuh-Chuan; Blomberg, Annelise J.; Jørgensen, Louise Helskov; Weihe, Pál; Grandjean, Philippe

doi:10.1016/j.envres.2021.111905

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…Although some animal experiments [83] and observations in humans [84,85] found negative associations between PFAS and Leptin concentrations, often positive associations were observed. Experimental evidence for induction of higher leptin concentrations by PFAS was observed in human cells in vitro [86] and in animals [87][88][89][90] and also observations on humans showed positive associations between internal exposure to PFAS and leptin serum concentrations [91][92][93]. Specially relevant in relation to our findings concerning cognition in elderly people is the observation of Ding et al [94] who found that, in women aged 45-56, higher PFAS concentrations were associated with higher leptin and free leptin values.…”

Section: Difference In Impact Between Adolescents and Older Adultssupporting

confidence: 51%

Per- and polyfluoroalkyl substances (PFAS) and neurobehavioral function and cognition in adolescents (2010–2011) and elderly people (2014): results from the Flanders Environment and Health Studies (FLEHS)

et al. 2022

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Background PFAS are persistent, bioaccumulative compounds repelling water, oil and stains which are widely used. There is mounting evidence linking exposure to a range of adverse health outcomes including renal, hepatic, immunotoxic, reproductive, endocrine disrupting and carcinogenic effects. PFAS possibly also induce neurobehavioral and developmental effects. Within Flanders Environment and Health Studies (FLEHS) internal exposure to PFAS and relevant health effects are assessed since 2008. Results Adolescents 14–15 y (2010–2011) living in an industrially contaminated area (without known PFAS contamination) and adults 50–65 y (2014) randomly sampled from the general Flemish population using a stratified clustered multi-stage design, were recruited. For the adolescents perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in serum, for the adults PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS). In adolescents the Neurobehavioral Evaluation System (NES3) computerized battery of tests developed to study the neurological effects of an exposure to environmental agents was applied. The adults did the Stroop test, the NES3 Continuous Performance Test and the NES3 Digit Span Test. In adolescents sleepiness, masculinity and femininity were assessed via the Epworth Sleepiness Scale and Personal Attributes Questionnaires, respectively. In adolescents PFOA was associated with significantly increased somnolence, and PFOS with a significant inverse association with boys’ femininity and with girls’ masculinity. In adolescents, PFAS were also associated with a marginal decrease in sustained attention (PFOS) and cognitive performance (PFOA) and a significant decrease in short-term memory (PFOS). However, in older adults PFOS was associated with a significant increase in the capacity to pay attention and PFHxS with a significant increase in sustained attention. Conclusion Our observations point to neurobehavioral and cognitive effects of PFAS. The neurobehavioral effects might in part result from the changes in sex hormone levels that have been reported to be associated with internal exposure to PFAS. Interestingly, whereas in relation to cognition some adverse effects were recorded for adolescents, for elderly persons our observations rather suggest possible weak positive effects with respect to cognition. Our observations might be in line with the view that PFAS have many, sometimes contrasting health effects.

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Section: Difference In Impact Between Adolescents and Older Adultssupporting

confidence: 51%

Per- and polyfluoroalkyl substances (PFAS) and neurobehavioral function and cognition in adolescents (2010–2011) and elderly people (2014): results from the Flanders Environment and Health Studies (FLEHS)

et al. 2022

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“…This results in the production of the pro-inflammatory cytokines IL-1β and IL-18, and in case of chronic activation potentially can be linked to the development of diseases such as type-2 diabetes. Further, adipocyte secretion may affect immune responses, and it is therefore of interest that developmental PFAS exposures seem to be associated with changes in serum-adipokine concentrations [ 145 ].…”

Section: Resultsmentioning

confidence: 99%

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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Background Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. Objective The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. Methods A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. Conclusions Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

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“…13 Similarly, in a study of 490 mother-child pairs in the Faroe Islands, PFAS biomarker concentrations at 18 months and 5 and 9 years were associated with decreased leptin at age nine. 53 A unique strength of this study is that LPA enabled us to identify two distinct longitudinal PFAS exposure groups that differed by covariates such as breastfeeding, which may contribute to higher PFAS exposure in children. [54][55][56] This has implications for policy-directed research: LPA may help researchers concisely characterize longitudinal exposure patterns, describe potential routes and related risk factors, and estimate the impact of longitudinal exposure to chemical mixtures on health.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluating the association between longitudinal exposure to a PFAS mixture and adolescent cardiometabolic risk in the HOME Study

Fleury,

Kuiper,

Buckley

et al. 2024

Environmental Epidemiology

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Background: Exposure to per- and polyfluoroalkyl substances (PFAS) throughout gestation and childhood may impact cardiometabolic risk. Methods: In 179 HOME Study participants (Cincinnati, OH; recruited 2003–2006), we used latent profile analysis to identify two distinct patterns of PFAS exposure from serum concentrations of four PFAS measured at birth and ages 3, 8, and 12 years. We assessed the homeostatic model of insulin resistance, triglycerides-to-high-density lipoprotein cholesterol ratio, leptin-to-adiponectin ratio, systolic blood pressure, visceral fat, and hemoglobin A1c levels at age 12 years. We used multivariable linear regression to assess the association of membership in the longitudinal PFAS mixture exposure group with a summary measure of overall cardiometabolic risk and individual components. Results: One PFAS exposure profile (n = 66, 39%) had higher geometric means of all PFAS across all visits than the other. Although adjusted associations were null in the full sample, child sex modified the association of longitudinal PFAS mixture exposure group with overall cardiometabolic risk, leptin-to-adiponectin ratio, systolic blood pressure, and visceral fat (interaction term P values: 0.02–0.08). Females in the higher exposure group had higher cardiometabolic risk scores (ß = 0.43; 95% CI = −0.08, 0.94), systolic blood pressures (ß = 0.6; 95% CI = 0.1, 1.1), and visceral fat (ß = 0.44; 95% CI = −0.13, 1.01); males had lower cardiometabolic risk scores (ß = −0.52; 95% CI = −1.06, −0.06), leptin-to-adiponectin ratios (ß = −0.7; 95% CI = −1.29, −0.1), systolic blood pressures (ß = −0.14; 95% CI = −0.7, 0.41), and visceral fat (ß = −0.52; 95% CI = −0.84, −0.19). Conclusions: Exposure to this PFAS mixture throughout childhood may have sex-specific effects on adolescent cardiometabolic risk.

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Early-life exposure to perfluoroalkyl substances in relation to serum adipokines in a longitudinal birth cohort

Cited by 15 publications

References 41 publications

Per- and polyfluoroalkyl substances (PFAS) and neurobehavioral function and cognition in adolescents (2010–2011) and elderly people (2014): results from the Flanders Environment and Health Studies (FLEHS)

Per- and polyfluoroalkyl substances (PFAS) and neurobehavioral function and cognition in adolescents (2010–2011) and elderly people (2014): results from the Flanders Environment and Health Studies (FLEHS)

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Evaluating the association between longitudinal exposure to a PFAS mixture and adolescent cardiometabolic risk in the HOME Study

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