The Association Between Per- And Polyfluoroalkyl Substances Exposure With Childhood Obesity: An Umbrella Review

The Association Between Per- And Polyfluoroalkyl Substances Exposure With Childhood Obesity: An Umbrella Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review The Association Between Per- And Polyfluoroalkyl Substances Exposure With Childhood Obesity: An Umbrella Review Randy Howard Brataatmaja, Cindy Fitria Notari, Alexander Kam, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6886652/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Oct, 2025 Read the published version in Discover Public Health → Version 1 posted 11 You are reading this latest preprint version Abstract Objectives: This umbrella review aimed to synthesize and critically evaluate the available evidence regarding the association between exposure to per- and polyfluoroalkyl substances (PFAS) and childhood obesity. Methods: A comprehensive literature search was conducted in PubMed, ScienceDirect, Biomed Central, and ProQuest databases for systematic reviews and meta-analyses published between 2016 and 2025. Eligible studies included individuals aged 0–20 years. Article screening followed the PRISMA Flow Diagram methodology, and the review protocol was registered with PROSPERO (CRD42024537809). Quality assessment was performed using the Joanna Briggs Institute (JBI) checklist for systematic reviews and meta-analyses. Results: Five systematic reviews, including four meta-analyses, were identified. Three studies reported a positive association between perfluorooctanoic acid (PFOA) exposure and childhood obesity, with one study noting increased risk among children older than three years. Two studies found a negative association. For perfluorooctane sulfonate (PFOS), findings were heterogeneous: three studies indicated a negative association between PFOS exposure and obesity, while one study yielded inconclusive results. Conclusions: Current evidence regarding the impact of PFOA and PFOS exposure on childhood obesity is inconsistent. Further high-quality longitudinal research is required to clarify these associations. Adolescent Childhood Exposure Obesity Per- and Polyfluoroalkyl Substances Prenatal Figures Figure 1 Figure 7 INTRODUCTION Childhood obesity represents a complex multifactorial condition characterized by excessive body fat accumulation that poses significant health risks [ 1 ]. The World Health Organization (WHO) defines childhood obesity using age-specific body mass index (BMI) percentiles, with obesity classified as BMI above the 95th percentile for age and sex [ 2 ]. This condition has emerged as one of the most serious public health challenges of the 21st century, with alarming global prevalence rates that continue to rise across both developed and developing countries [ 3 ]. The etiology of childhood obesity extends beyond the traditional paradigm of energy imbalance resulting from excessive caloric intake and insufficient physical activity. Contemporary research increasingly recognizes the potential contribution of environmental exposures, particularly endocrine-disrupting chemicals, to metabolic dysregulation and adiposity development during critical developmental windows. Among these chemical exposures, per- and polyfluoroalkyl substances (PFAS) have garnered significant scientific attention due to their persistence, bioaccumulative properties, and potential metabolic effects [ 4 ]. PFAS comprise a diverse group of synthetic chemicals characterized by strong carbon-fluorine bonds that confer exceptional stability, heat resistance, and water and oil repellency [ 5 ]. These properties have led to their widespread industrial applications in consumer products, including food packaging, textiles, non-stick cookware, and firefighting foams [ 6 ]. Consequently, PFAS have become ubiquitous environmental contaminants, with biomonitoring studies consistently detecting these compounds in human serum across global populations, including pregnant women and children [ 7 ]. Emerging evidence suggests that PFAS exposure, particularly during critical developmental periods, may interfere with metabolic programming and adipogenesis through multiple biological mechanisms [ 8 , 9 ]. These include disruption of thyroid hormone homeostasis, peroxisome proliferator-activated receptor (PPAR) signaling, mitochondrial function, and adipocyte differentiation pathways [ 10 ]. Despite the biological plausibility of PFAS-induced metabolic effects, epidemiological studies investigating associations between PFAS exposure and childhood obesity have yielded inconsistent results, with reports of positive, negative, and null associations [ 11 , 12 ]. The scientific literature exploring PFAS-obesity associations has grown substantially in recent years, resulting in several systematic reviews and meta-analyses attempting to synthesize available evidence. However, these reviews have employed varying methodological approaches, inclusion criteria, and analytical techniques, potentially contributing to their divergent conclusions. Furthermore, most reviews have focused predominantly on the two most extensively studied PFAS compounds—perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)—despite the environmental prevalence of numerous other PFAS congeners with potential metabolic effects [ 9 , 11 , 13 – 15 ]. Given these knowledge gaps and contradictory findings, this umbrella review aims to comprehensively evaluate and synthesize evidence from existing systematic reviews and meta-analyses regarding the association between PFAS exposure and childhood obesity. By systematically assessing the methodological quality, consistency, and strength of evidence across reviews, this study seeks to provide a critical appraisal of current knowledge and identify key research priorities to advance understanding of PFAS-related metabolic health effects in children. The specific objectives of this review include: To evaluate the methodological quality of existing systematic reviews and meta-analyses examining PFAS exposure and childhood obesity associations. To synthesize evidence regarding associations between specific PFAS compounds and various adiposity measures in children and adolescents. To assess consistency and heterogeneity of findings across different studies, populations, and exposure assessment methodologies. To identify knowledge gaps and methodological limitations in the current literature to inform future research directions. Understanding the potential contribution of PFAS exposure to childhood obesity has significant public health implications, particularly for environmental health policy, clinical practice guidelines for pediatric obesity prevention, and targeted interventions for vulnerable populations. This umbrella review aims to provide a comprehensive evaluation of the current evidence base to inform these important public health applications. METHODS Protocol Registration This umbrella review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42024537809) to ensure transparency and avoid duplication. Search Strategy We conducted a comprehensive literature search across four major electronic databases: PubMed, ScienceDirect, Biomed Central, and ProQuest. The search period encompassed publications from January 2016 to January 2025. We employed a structured search strategy using carefully selected keywords and controlled vocabulary terms related to PFAS, obesity, and pediatric populations. The following search string was adapted for each database: (“PFAS” OR “Per- and Polyfluoroalkyl Substances” OR “PFOS” OR “PFOA”) AND (“Obesity” OR “Hyperlipidemia” OR “Overweight” OR “Adiposity”) AND (“Juvenile” OR “Young” OR “Adolescent” OR “Childhood” OR “Children” OR “Child”) Eligibility Criteria Inclusion Criteria This umbrella review included systematic reviews and meta-analyses that met the following criteria: Examined associations between PFAS exposure and obesity-related outcome Focused on pediatric populations (age 0–20 years) Published in English language Published between January 2016 and March 2025 Included systematic search strategies and explicit methodologies Exclusion Criteria Studies were excluded if they: Were narrative reviews without systematic methodologies Focused exclusively on adult populations Did not specifically address obesity-related outcomes Examined only non-PFAS environmental contaminants Were conference abstracts, editorials, or commentaries without full methodological details Study Selection The study selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers screened titles and abstracts of identified articles against the eligibility criteria. Full-text articles of potentially eligible studies were then retrieved and independently assessed. Discrepancies in study selection were resolved through discussion and consensus, with consultation from a third reviewer when necessary. Data Extraction Data extraction was performed independently by two reviewers (RHB and NS) using a standardized form developed a priori. The following information was extracted from each included review: Publication details (authors, year, journal) Review characteristics (objectives, inclusion/exclusion criteria, number of included studies) Participant characteristics (age range, sample size, geographic region) Exposure assessment methods (PFAS compounds measured, biological matrices, analytical techniques) Outcome measures (obesity definitions, anthropometric parameters) Main findings (reported associations, effect estimates, heterogeneity measures) Risk of bias assessment (methods and results) Authors' conclusions and limitations Quality Assessment The methodological quality of included reviews was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews and Meta-analyses [ 16 ]. This instrument evaluates 11 domains including research question clarity, inclusion criteria appropriateness, search strategy comprehensiveness, critical appraisal methods, data extraction procedures, and statistical analysis methods. Two independent reviewers (RHB and NS) conducted quality assessments, with disagreements resolved through discussion or consultation with a third reviewer (CI). Data Synthesis Due to the anticipated heterogeneity across reviews in terms of included study designs, exposure assessments, outcome measures, and analytical approaches, we employed a narrative synthesis approach. We organized findings according to specific PFAS compounds examined and obesity-related outcomes measured. Where multiple reviews reported on the same associations, we compared their findings, considering methodological quality, recency, and comprehensiveness. We also examined potential sources of heterogeneity, including differences in exposure timing, outcome definitions, confounding adjustment, and population characteristics. RESULTS Study Selection The initial database search yielded 1024 potentially relevant articles. After removing duplicates (n = 4), 1020 articles underwent title and abstract screening. Of these, 1013 were excluded for not meeting the eligibility criteria. The remaining 7 articles proceeded to full-text assessment, resulting in the final inclusion of 5 systematic reviews, 4 of which included meta-analyses. The PRISMA flow diagram details the complete selection process (Fig. 1 ). Characteristics of Included Reviews The five included systematic reviews were published between 2018 and 2024. Collectively, these reviews synthesized evidence from 46 unique primary studies, encompassing both cross-sectional and longitudinal designs. Sample sizes in the primary studies ranged from 44 to 2,423 participants. The reviews primarily examined associations between prenatal or early childhood PFAS exposure and various measures of adiposity, including BMI, weight-for-height z-scores, overweight/obesity status, and waist circumference (Table 1 ). Quality Assessment Based on the JBI Critical Appraisal Checklist, the methodological quality of included reviews varied. All five reviews clearly specified their research questions and inclusion criteria. Four reviews employed comprehensive search strategies across multiple databases. All reviews conducted formal quality assessments of included primary studies, though the specific tools varied. The most common methodological limitations included inadequate exploration of publication bias and incomplete assessment of heterogeneity sources. Synthesis of Evidence The relationship between PFAS exposure and childhood obesity showed considerable variation across reviews and specific compounds. Regarding perfluorooctanoic acid (PFOA), two reviews reported positive associations with obesity measures [ 14 , 15 ], with one meta-analysis finding a statistically significant pooled effect size (OR = 1.25, 95% CI: 1.04–1.50) for children older than three years [ 14 ]. Conversely, one review reported no association between PFOA exposure and childhood BMI [ 13 ], one review reported no association between prenatal PFOA exposure and childhood BMI, with inverse association being found between postnatal PFOA exposure and obesity [ 11 ], and one review reported an inconclusive result [ 12 ]. For perfluorooctane sulfonate (PFOS), the second most extensively studied PFAS compound, three reviews indicated negative associations with adiposity measures [ 9 , 11 , 13 ], while one review reported inconsistent findings across included studies [ 14 ]. Meta-analyses examining PFOS-obesity associations generally found non-significant pooled effect estimates, suggesting weak or null relationships. Less consistent data were available for other PFAS compounds, including perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDA). Two reviews examining these compounds reported predominantly null associations, with isolated findings of negative associations for specific compounds and subpopulations. Several reviews identified potential effect modification by sex, with some studies reporting stronger associations among female participants. Additionally, timing of exposure emerged as a potentially important factor, with prenatal exposure frequently showing different associations compared to childhood exposure measurements. DISCUSSION This umbrella review synthesized evidence from five systematic reviews examining associations between PFAS exposure and obesity in children and adolescents. Our findings reveal substantial heterogeneity in both the methodological approaches and conclusions of existing reviews, highlighting the complexity of this research area and the challenges in drawing definitive conclusions about PFAS-obesity relationships. The inconsistent findings regarding PFOA exposure—with both positive and negative associations reported across different reviews—warrant careful interpretation. Several biological mechanisms could potentially explain positive associations, including PFOA's documented effects on peroxisome proliferator-activated receptors (PPARs), which play crucial roles in adipocyte differentiation and lipid metabolism [ 17 ]. Additionally, PFOA has been associated with altered thyroid hormone levels, which could indirectly influence energy metabolism and weight regulation [ 18 ]. However, the negative associations reported in some reviews suggest more complex dose-response relationships or potential confounding by factors not consistently addressed across primary studies. For PFOS, the predominance of negative associations with obesity measures appears somewhat more consistent across reviews. These findings contrast with toxicological evidence suggesting PFOS may promote adipogenesis through PPAR pathways similar to PFOA. This discrepancy highlights the importance of considering species differences in PFAS metabolism and the limitations of extrapolating from in vitro and animal studies to human populations. Several methodological considerations may contribute to the heterogeneous findings across reviews. First, the timing of exposure assessment varied considerably across primary studies, with some focusing on prenatal exposure and others on childhood measurements. Given the potentially distinct developmental windows of susceptibility to environmental obesogens, these differences in exposure timing may partially explain inconsistent results. Second, the specific obesity-related outcomes examined varied across studies, from BMI z-scores to categorical overweight/obesity classifications, potentially affecting the detection and interpretation of associations. Third, approaches to confounding adjustment differed substantially, with varying consideration of critical factors such as maternal BMI, socioeconomic status, dietary patterns, and co-exposure to other environmental chemicals. The potential for effect modification by sex observed in some reviews merits further investigation. Sex differences in PFAS-obesity associations could stem from hormone-dependent mechanisms, as PFAS compounds have demonstrated interactions with estrogen receptors and sex hormone-binding globulin [ 19 ]. Additionally, sex-specific differences in PFAS toxicokinetics, including elimination half-lives and volume of distribution, could contribute to differential susceptibility. While this umbrella review provides a comprehensive synthesis of current evidence, several limitations must be acknowledged. First, a significant limitation of the existing literature is the heavy reliance on studies conducted in high-income countries. There is a critical gap in research from low- and middle-income countries (LMICs), where environmental exposures and nutritional status may differ significantly, potentially influencing the relationship between PFAS and obesity [ 20 ]. Factors such as varying dietary patterns, levels of PFAS exposure from contaminated water sources, and differences in genetic susceptibility within diverse populations could all play a role [ 21 ]. Addressing this gap is essential for a comprehensive understanding of the global impact of PFAS on childhood obesity. Second, our review was restricted to systematic reviews and meta-analyses published in English, potentially missing relevant evidence published in other languages. Third, the included reviews predominantly focused on PFOA and PFOS, with limited data on newer PFAS compounds that have increasingly replaced these legacy compounds following regulatory restrictions. Fourth, the overlap of primary studies across multiple reviews presents challenges for interpreting the body of evidence, as the same primary data may contribute disproportionately to apparent consistency or inconsistency in findings. CONCLUSION This umbrella review demonstrates that current evidence regarding associations between PFAS exposure and childhood obesity remains inconclusive. While some reviews report positive associations, particularly for PFOA exposure and among specific subpopulations, others indicate negative or null relationships. These inconsistencies highlight the complex nature of PFAS-obesity relationships and underscore the need for more rigorous research addressing critical methodological challenges. Future research should prioritize prospective cohort studies with repeated measures of both PFAS exposure and adiposity outcomes throughout childhood and adolescence in LMICs. Such longitudinal designs would better capture critical windows of susceptibility and allow for examination of temporal trends in associations. Additionally, more comprehensive assessment of multiple PFAS compounds, including emerging short-chain replacements, would provide a more complete understanding of the overall PFAS burden and potential mixture effects. Standardization of outcome measures, confounding adjustment strategies, and effect modification analyses would facilitate more meaningful comparisons across studies and enhance the reliability of future systematic reviews. Integrating mechanistic biomarkers into epidemiological studies could also help elucidate biological pathways linking PFAS exposure to metabolic perturbations. From a public health perspective, the potential contribution of PFAS exposure to childhood obesity, even if modest at the individual level, could have significant population-level implications given the ubiquity of these compounds in the environment. Therefore, precautionary approaches to PFAS regulation and exposure reduction may be warranted while research continues to clarify these relationships. Declarations Funding declaration : This study did not receive any funding from any entity. Clinical trial number : not applicable Human Ethics and Consent to Participate declarations : not applicable Consent to Publish declaration : not applicable Conflicts of Interest: The authors have no conflicts of interest associated with the material presented in this paper. Author Contribution R.H.B. and C.I. contributed to conceptualizing the review and developing the review protocol. R.H.B. contributed to conducting comprehensive literature searches and writing the initial draft of the review. R.H.B. and C.F.N. contributed to extracting data from studies and synthesizing the findings. N.S. contributed to verifying the methodology. C.I., N.S., A.K., and R.L. contributed to critically reviewing and editing the manuscript. C.I. contributed to the overall supervision of the project .All authors contributed to reading and reviewing the manuscript. Acknowledgements: The author acknowledges the institutional support from the Faculty of Medicine, Universitas Andalas. References Kansra AR, Lakkunarajah S, Jay MS. Childhood and adolescent obesity: a review. Front Pediatr. 2021;8:581461. Wang Y. Epidemiology of childhood obesity—methodological aspects and guidelines: what is new? Int J Obes. 2004;28(Suppl 3):S21–8. Karnik S, Kanekar A. Childhood obesity: a global public health crisis. Int J Prev Med. 2012;3(1). Kim JT, Lee HK. Childhood obesity and endocrine disrupting chemicals. Ann Pediatr Endocrinol Metab. 2017;22(4):219–25. Dias D, Bons J, Kumar A, Kabir M, Liang H. Forever chemicals, per-and polyfluoroalkyl substances (PFAS), in lubrication. Lubricants. 2024;12(4):114. Herzke D, Olsson E, Posner S. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) in consumer products in Norway – A pilot study. Chemosphere. 2012;88(8):980–7. Qi W, Clark JM, Timme-Laragy AR, Park Y. Per- and polyfluoroalkyl substances and obesity, type 2 diabetes and non-alcoholic fatty liver disease: a review of epidemiologic findings. Toxicol Environ Chem. 2020;102(1–4):1–36. Lewis N, Abdulkadir A, Kandel S, Rosby R, Hossain E. Per- and Polyfluoroalkyl Substances (PFAS) as Emerging Obesogens: Mechanisms, Epidemiological Evidence, and Regulatory Challenges. Physiologia. 2024;4(4):517–67. Lee YJ, Jung HW, Kim HY, Choi YJ, Lee YA. Early-Life Exposure to Per- and Poly-Fluorinated Alkyl Substances and Growth, Adiposity, and Puberty in Children: A Systematic Review. Front Endocrinol. 2021;12:683297. Obregon MJ. Adipose tissues and thyroid hormones. Front Physiol. 2014;5:479. Frangione B, Birk S, Benzouak T et al. Exposure to perfluoroalkyl and polyfluoroalkyl substances and pediatric obesity: a systematic review and meta-analysis. Int J Obes. 2005. 2024;48(2):131–146. Liu Y, Wosu AC, Fleisch AF, et al. Associations of Gestational Perfluoroalkyl Substances Exposure with Early Childhood BMI z-Scores and Risk of Overweight/Obesity: Results from the ECHO Cohorts. Environ Health Perspect. 2023;131(6):067001. Stratakis N, Rock S, La Merrill MA, et al. Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies. Obes Rev. 2022;23(Suppl 1):e13383. Frigerio G, Ferrari CM, Fustinoni S. Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses. Environ Health. 2023;22(1):56. Liu P, Yang F, Wang Y, Yuan Z. Perfluorooctanoic Acid (PFOA) Exposure in Early Life Increases Risk of Childhood Adiposity: A Meta-Analysis of Prospective Cohort Studies. Int J Environ Res Public Health. 2018;15(10):2070. Martin J. © Joanna Briggs Institute 2017 Critical Appraisal Checklist for Systematic Reviews and Research Syntheses [Internet]. Published online 2017 [cited 2025 Apr 25]. Pederick JL, Frkic RL, McDougal DP, Bruning JB. A structural basis for the activation of peroxisome proliferator-activated receptor gamma (PPARγ) by perfluorooctanoic acid (PFOA). Chemosphere. 2024;354:141723. Coperchini F, Croce L, Ricci G, et al. Thyroid Disrupting Effects of Old and New Generation PFAS. Front Endocrinol. 2021;11:612320. Xie X, Weng X, Liu S, et al. Perfluoroalkyl and Polyfluoroalkyl substance exposure and association with sex hormone concentrations: Results from the NHANES 2015–2016. Environ Sci Eur. 2021;33(1):69. Zhou X, Wang X, Ou T, Huang L, He B. Association between family economic situation and serum PFAS concentration in American adults with hypertension and hyperlipemia. Sci Rep. 2024;14:20799. Ford ND, Patel SA, Narayan KMV. Obesity in Low- and Middle-Income Countries: Burden, Drivers, and Emerging Challenges. Annu Rev Public Health. 2017;38:145–64. Tables Table 1. Characteristics of systematic reviews and meta-analyses examining the association between the exposure to PFAS and persistent organic pollutants (POPs) and adipose tissue level in children Author Database Search Period Included Studies Total Sample Biological Matrix Dependent Variable Independent Variable Study Assessment Quality* Results Frangione, et al. (2023) 11 MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Cochrane Central 2000 – 2022 13 studies 20,812 Maternal serum BMI, waist circumference PFOA, PFOS, PFHxS, PFNA, PFDA, PFUA, and PFDoA High Quality Overall, prenatal exposure to four (4) types of PFAS compounds was not associated with changes in BMI or waist circumference; An inverse relationship was found between postnatal exposure to three (3) types of PFAS compounds, namely PFOA, PFOS, and PFHxS, and changes in BMI (β (95% CI) = -0.16 (-0.22, -0.10)). Liu, et al. (2018) 15 EMBASE, Web of Science, PubMed 1986 – 2011 10 studies 6,076 Maternal postpartum serum, maternal prenatal serum, maternal prenatal plasma, umbilical cord blood BMI z-score, childhood overweight PFOA High Quality There is a substantial effect (RR or OR) between PFOA exposure and overweight in children, with an effect size of 1.25 (95% CI: 1.04 to 1.50); There is also a significant positive association between PFOA exposure and the z-score of BMI (β = 0.10, 95% CI: 0.03 to 0.17) Stratakis, et al. (2022) 13 PubMed, EMBASE Studies up to 2021 59 studies Total sample is not reported Maternal serum, umbilical cord blood BMI, waist circumference PFOA, PFOS, PBDE, DDE, HCB High Quality No association was found between PFOS exposure and children's IMT z-score (β [95% CI = 0 (-0.01, 0.01)]). A positive but non-significant association was observed between PFOA exposure and children's IMT z-score (β [95% CI = 0.03 (-0.02, 0.08)]). Frigerio, et al. (2023) 14 PubMed, EMBASE 2000 – 2022 30 studies 49,255 Maternal blood and neonatal blood BMI, waist circumference PFOA, PFOS, PFHxS, PFNA, PFDA, PFUA, and PFDoA High Quality A positive association was found between PFOA concentration and BMI in children over the age of 3 years, as well as between prenatal PFNA exposure and BMI in boys over 3 years of age. A negative association was observed between prenatal PFOS exposure and BMI in children under 3 years of age, and between PFHxS exposure and overweight status. Lee, et al. (2021) MEDLINE, EMBASE, Web of Science, Scopus 2007 – 2021 90 studies Total sample is not reported Maternal blood, umbilical cord blood, and neonatal blood Waist circumference, body fat percentage, and BMI PFOA, PFOS, PFNA, and PFHxS High Quality The evidence remains inconclusive regarding the association between exposure to PFAS compounds and obesity. *Each review article is assessed using the Joanna Briggs Institute (JBI) Checklist for Systematic Reviews and Research Syntheses DDE: Dichlorodiphenyldichloroethylene; HCB: Hexachlorobenzene; PFOA: Perfluorooctanoic acid; PFOS: Perfluorooctane Sulfate; PFNA: Perfluorononanoic Acid; PFHxS: Perfluorohexanesulfonic Acid; PFDA: Perfluorodecanoic Acid; PFUnDA: Perfluoroundecanoic Acid; PFDoA: Perfluorododecanoic Acid; PFBS: Perfluorobutanesulfonic Acid Additional Declarations No competing interests reported. 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06:53:16","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2550260,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialsBrataatmajaetal..docx","url":"https://assets-eu.researchsquare.com/files/rs-6886652/v1/fb3d8369e5888c55bbf7e341.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe Association Between Per- And Polyfluoroalkyl Substances Exposure With Childhood Obesity: An Umbrella Review\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eChildhood obesity represents a complex multifactorial condition characterized by excessive body fat accumulation that poses significant health risks [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The World Health Organization (WHO) defines childhood obesity using age-specific body mass index (BMI) percentiles, with obesity classified as BMI above the 95th percentile for age and sex [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This condition has emerged as one of the most serious public health challenges of the 21st century, with alarming global prevalence rates that continue to rise across both developed and developing countries [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe etiology of childhood obesity extends beyond the traditional paradigm of energy imbalance resulting from excessive caloric intake and insufficient physical activity. Contemporary research increasingly recognizes the potential contribution of environmental exposures, particularly endocrine-disrupting chemicals, to metabolic dysregulation and adiposity development during critical developmental windows. Among these chemical exposures, per- and polyfluoroalkyl substances (PFAS) have garnered significant scientific attention due to their persistence, bioaccumulative properties, and potential metabolic effects [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePFAS comprise a diverse group of synthetic chemicals characterized by strong carbon-fluorine bonds that confer exceptional stability, heat resistance, and water and oil repellency [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These properties have led to their widespread industrial applications in consumer products, including food packaging, textiles, non-stick cookware, and firefighting foams [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Consequently, PFAS have become ubiquitous environmental contaminants, with biomonitoring studies consistently detecting these compounds in human serum across global populations, including pregnant women and children [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEmerging evidence suggests that PFAS exposure, particularly during critical developmental periods, may interfere with metabolic programming and adipogenesis through multiple biological mechanisms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These include disruption of thyroid hormone homeostasis, peroxisome proliferator-activated receptor (PPAR) signaling, mitochondrial function, and adipocyte differentiation pathways [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Despite the biological plausibility of PFAS-induced metabolic effects, epidemiological studies investigating associations between PFAS exposure and childhood obesity have yielded inconsistent results, with reports of positive, negative, and null associations [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe scientific literature exploring PFAS-obesity associations has grown substantially in recent years, resulting in several systematic reviews and meta-analyses attempting to synthesize available evidence. However, these reviews have employed varying methodological approaches, inclusion criteria, and analytical techniques, potentially contributing to their divergent conclusions. Furthermore, most reviews have focused predominantly on the two most extensively studied PFAS compounds\u0026mdash;perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)\u0026mdash;despite the environmental prevalence of numerous other PFAS congeners with potential metabolic effects [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven these knowledge gaps and contradictory findings, this umbrella review aims to comprehensively evaluate and synthesize evidence from existing systematic reviews and meta-analyses regarding the association between PFAS exposure and childhood obesity. By systematically assessing the methodological quality, consistency, and strength of evidence across reviews, this study seeks to provide a critical appraisal of current knowledge and identify key research priorities to advance understanding of PFAS-related metabolic health effects in children.\u003c/p\u003e \u003cp\u003eThe specific objectives of this review include:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo evaluate the methodological quality of existing systematic reviews and meta-analyses examining PFAS exposure and childhood obesity associations.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo synthesize evidence regarding associations between specific PFAS compounds and various adiposity measures in children and adolescents.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo assess consistency and heterogeneity of findings across different studies, populations, and exposure assessment methodologies.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo identify knowledge gaps and methodological limitations in the current literature to inform future research directions.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e Understanding the potential contribution of PFAS exposure to childhood obesity has significant public health implications, particularly for environmental health policy, clinical practice guidelines for pediatric obesity prevention, and targeted interventions for vulnerable populations. This umbrella review aims to provide a comprehensive evaluation of the current evidence base to inform these important public health applications.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol Registration\u003c/h2\u003e \u003cp\u003eThis umbrella review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42024537809) to ensure transparency and avoid duplication.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eWe conducted a comprehensive literature search across four major electronic databases: PubMed, ScienceDirect, Biomed Central, and ProQuest. The search period encompassed publications from January 2016 to January 2025. We employed a structured search strategy using carefully selected keywords and controlled vocabulary terms related to PFAS, obesity, and pediatric populations. The following search string was adapted for each database:\u003c/p\u003e \u003cp\u003e(\u0026ldquo;PFAS\u0026rdquo; OR \u0026ldquo;Per- and Polyfluoroalkyl Substances\u0026rdquo; OR \u0026ldquo;PFOS\u0026rdquo; OR \u0026ldquo;PFOA\u0026rdquo;) AND (\u0026ldquo;Obesity\u0026rdquo; OR \u0026ldquo;Hyperlipidemia\u0026rdquo; OR \u0026ldquo;Overweight\u0026rdquo; OR \u0026ldquo;Adiposity\u0026rdquo;) AND (\u0026ldquo;Juvenile\u0026rdquo; OR \u0026ldquo;Young\u0026rdquo; OR \u0026ldquo;Adolescent\u0026rdquo; OR \u0026ldquo;Childhood\u0026rdquo; OR \u0026ldquo;Children\u0026rdquo; OR \u0026ldquo;Child\u0026rdquo;)\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eInclusion Criteria\u003c/p\u003e \u003cp\u003eThis umbrella review included systematic reviews and meta-analyses that met the following criteria:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExamined associations between PFAS exposure and obesity-related outcome\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFocused on pediatric populations (age 0\u0026ndash;20 years)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePublished in English language\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePublished between January 2016 and March 2025\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eIncluded systematic search strategies and explicit methodologies\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eExclusion Criteria\u003c/p\u003e \u003cp\u003eStudies were excluded if they:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eWere narrative reviews without systematic methodologies\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFocused exclusively on adult populations\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDid not specifically address obesity-related outcomes\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExamined only non-PFAS environmental contaminants\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eWere conference abstracts, editorials, or commentaries without full methodological details\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003e The study selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers screened titles and abstracts of identified articles against the eligibility criteria. Full-text articles of potentially eligible studies were then retrieved and independently assessed. Discrepancies in study selection were resolved through discussion and consensus, with consultation from a third reviewer when necessary.\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eData extraction was performed independently by two reviewers (RHB and NS) using a standardized form developed a priori. The following information was extracted from each included review:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePublication details (authors, year, journal)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eReview characteristics (objectives, inclusion/exclusion criteria, number of included studies)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eParticipant characteristics (age range, sample size, geographic region)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExposure assessment methods (PFAS compounds measured, biological matrices, analytical techniques)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eOutcome measures (obesity definitions, anthropometric parameters)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eMain findings (reported associations, effect estimates, heterogeneity measures)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eRisk of bias assessment (methods and results)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAuthors' conclusions and limitations\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eQuality Assessment\u003c/h2\u003e \u003cp\u003eThe methodological quality of included reviews was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews and Meta-analyses [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This instrument evaluates 11 domains including research question clarity, inclusion criteria appropriateness, search strategy comprehensiveness, critical appraisal methods, data extraction procedures, and statistical analysis methods. Two independent reviewers (RHB and NS) conducted quality assessments, with disagreements resolved through discussion or consultation with a third reviewer (CI).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Synthesis\u003c/h3\u003e\n\u003cp\u003e Due to the anticipated heterogeneity across reviews in terms of included study designs, exposure assessments, outcome measures, and analytical approaches, we employed a narrative synthesis approach. We organized findings according to specific PFAS compounds examined and obesity-related outcomes measured. Where multiple reviews reported on the same associations, we compared their findings, considering methodological quality, recency, and comprehensiveness. We also examined potential sources of heterogeneity, including differences in exposure timing, outcome definitions, confounding adjustment, and population characteristics.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Selection\u003c/h2\u003e\n \u003cp\u003eThe initial database search yielded 1024 potentially relevant articles. After removing duplicates (n\u0026thinsp;=\u0026thinsp;4), 1020 articles underwent title and abstract screening. Of these, 1013 were excluded for not meeting the eligibility criteria. The remaining 7 articles proceeded to full-text assessment, resulting in the final inclusion of 5 systematic reviews, 4 of which included meta-analyses. The PRISMA flow diagram details the complete selection process (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eCharacteristics of Included Reviews\u003c/h2\u003e\n \u003cp\u003eThe five included systematic reviews were published between 2018 and 2024. Collectively, these reviews synthesized evidence from 46 unique primary studies, encompassing both cross-sectional and longitudinal designs. Sample sizes in the primary studies ranged from 44 to 2,423 participants. The reviews primarily examined associations between prenatal or early childhood PFAS exposure and various measures of adiposity, including BMI, weight-for-height z-scores, overweight/obesity status, and waist circumference (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ch2 align=\"left\" class=\"colspec\"\u003eQuality Assessment\u003c/h2\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003cp\u003eBased on the JBI Critical Appraisal Checklist, the methodological quality of included reviews varied. All five reviews clearly specified their research questions and inclusion criteria. Four reviews employed comprehensive search strategies across multiple databases. All reviews conducted formal quality assessments of included primary studies, though the specific tools varied. The most common methodological limitations included inadequate exploration of publication bias and incomplete assessment of heterogeneity sources.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eSynthesis of Evidence\u003c/h2\u003e\n \u003cp\u003eThe relationship between PFAS exposure and childhood obesity showed considerable variation across reviews and specific compounds. Regarding perfluorooctanoic acid (PFOA), two reviews reported positive associations with obesity measures [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e], with one meta-analysis finding a statistically significant pooled effect size (OR\u0026thinsp;=\u0026thinsp;1.25, 95% CI: 1.04\u0026ndash;1.50) for children older than three years [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Conversely, one review reported no association between PFOA exposure and childhood BMI [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e], one review reported no association between prenatal PFOA exposure and childhood BMI, with inverse association being found between postnatal PFOA exposure and obesity [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e], and one review reported an inconclusive result [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eFor perfluorooctane sulfonate (PFOS), the second most extensively studied PFAS compound, three reviews indicated negative associations with adiposity measures [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e], while one review reported inconsistent findings across included studies [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Meta-analyses examining PFOS-obesity associations generally found non-significant pooled effect estimates, suggesting weak or null relationships.\u003c/p\u003e\n \u003cp\u003eLess consistent data were available for other PFAS compounds, including perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDA). Two reviews examining these compounds reported predominantly null associations, with isolated findings of negative associations for specific compounds and subpopulations.\u003c/p\u003e\n \u003cp\u003eSeveral reviews identified potential effect modification by sex, with some studies reporting stronger associations among female participants. Additionally, timing of exposure emerged as a potentially important factor, with prenatal exposure frequently showing different associations compared to childhood exposure measurements.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis umbrella review synthesized evidence from five systematic reviews examining associations between PFAS exposure and obesity in children and adolescents. Our findings reveal substantial heterogeneity in both the methodological approaches and conclusions of existing reviews, highlighting the complexity of this research area and the challenges in drawing definitive conclusions about PFAS-obesity relationships.\u003c/p\u003e \u003cp\u003eThe inconsistent findings regarding PFOA exposure\u0026mdash;with both positive and negative associations reported across different reviews\u0026mdash;warrant careful interpretation. Several biological mechanisms could potentially explain positive associations, including PFOA's documented effects on peroxisome proliferator-activated receptors (PPARs), which play crucial roles in adipocyte differentiation and lipid metabolism [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Additionally, PFOA has been associated with altered thyroid hormone levels, which could indirectly influence energy metabolism and weight regulation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, the negative associations reported in some reviews suggest more complex dose-response relationships or potential confounding by factors not consistently addressed across primary studies.\u003c/p\u003e \u003cp\u003eFor PFOS, the predominance of negative associations with obesity measures appears somewhat more consistent across reviews. These findings contrast with toxicological evidence suggesting PFOS may promote adipogenesis through PPAR pathways similar to PFOA. This discrepancy highlights the importance of considering species differences in PFAS metabolism and the limitations of extrapolating from in vitro and animal studies to human populations.\u003c/p\u003e \u003cp\u003eSeveral methodological considerations may contribute to the heterogeneous findings across reviews. First, the timing of exposure assessment varied considerably across primary studies, with some focusing on prenatal exposure and others on childhood measurements. Given the potentially distinct developmental windows of susceptibility to environmental obesogens, these differences in exposure timing may partially explain inconsistent results. Second, the specific obesity-related outcomes examined varied across studies, from BMI z-scores to categorical overweight/obesity classifications, potentially affecting the detection and interpretation of associations. Third, approaches to confounding adjustment differed substantially, with varying consideration of critical factors such as maternal BMI, socioeconomic status, dietary patterns, and co-exposure to other environmental chemicals.\u003c/p\u003e \u003cp\u003eThe potential for effect modification by sex observed in some reviews merits further investigation. Sex differences in PFAS-obesity associations could stem from hormone-dependent mechanisms, as PFAS compounds have demonstrated interactions with estrogen receptors and sex hormone-binding globulin [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additionally, sex-specific differences in PFAS toxicokinetics, including elimination half-lives and volume of distribution, could contribute to differential susceptibility.\u003c/p\u003e \u003cp\u003eWhile this umbrella review provides a comprehensive synthesis of current evidence, several limitations must be acknowledged. First, a significant limitation of the existing literature is the heavy reliance on studies conducted in high-income countries. There is a critical gap in research from low- and middle-income countries (LMICs), where environmental exposures and nutritional status may differ significantly, potentially influencing the relationship between PFAS and obesity [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Factors such as varying dietary patterns, levels of PFAS exposure from contaminated water sources, and differences in genetic susceptibility within diverse populations could all play a role [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Addressing this gap is essential for a comprehensive understanding of the global impact of PFAS on childhood obesity. Second, our review was restricted to systematic reviews and meta-analyses published in English, potentially missing relevant evidence published in other languages. Third, the included reviews predominantly focused on PFOA and PFOS, with limited data on newer PFAS compounds that have increasingly replaced these legacy compounds following regulatory restrictions. Fourth, the overlap of primary studies across multiple reviews presents challenges for interpreting the body of evidence, as the same primary data may contribute disproportionately to apparent consistency or inconsistency in findings.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis umbrella review demonstrates that current evidence regarding associations between PFAS exposure and childhood obesity remains inconclusive. While some reviews report positive associations, particularly for PFOA exposure and among specific subpopulations, others indicate negative or null relationships. These inconsistencies highlight the complex nature of PFAS-obesity relationships and underscore the need for more rigorous research addressing critical methodological challenges.\u003c/p\u003e \u003cp\u003eFuture research should prioritize prospective cohort studies with repeated measures of both PFAS exposure and adiposity outcomes throughout childhood and adolescence in LMICs. Such longitudinal designs would better capture critical windows of susceptibility and allow for examination of temporal trends in associations. Additionally, more comprehensive assessment of multiple PFAS compounds, including emerging short-chain replacements, would provide a more complete understanding of the overall PFAS burden and potential mixture effects.\u003c/p\u003e \u003cp\u003eStandardization of outcome measures, confounding adjustment strategies, and effect modification analyses would facilitate more meaningful comparisons across studies and enhance the reliability of future systematic reviews. Integrating mechanistic biomarkers into epidemiological studies could also help elucidate biological pathways linking PFAS exposure to metabolic perturbations.\u003c/p\u003e \u003cp\u003eFrom a public health perspective, the potential contribution of PFAS exposure to childhood obesity, even if modest at the individual level, could have significant population-level implications given the ubiquity of these compounds in the environment. Therefore, precautionary approaches to PFAS regulation and exposure reduction may be warranted while research continues to clarify these relationships.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding declaration\u003c/strong\u003e: This study did not receive any funding from any entity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e: not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e: not applicable\u003c/p\u003e\u003ch2\u003eConflicts of Interest:\u003c/h2\u003e \u003cp\u003eThe authors have no conflicts of interest associated with the material presented in this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eR.H.B. and C.I. contributed to conceptualizing the review and developing the review protocol. R.H.B. contributed to conducting comprehensive literature searches and writing the initial draft of the review. R.H.B. and C.F.N. contributed to extracting data from studies and synthesizing the findings. N.S. contributed to verifying the methodology. C.I., N.S., A.K., and R.L. contributed to critically reviewing and editing the manuscript. C.I. contributed to the overall supervision of the project .All authors contributed to reading and reviewing\u0026nbsp;the\u0026nbsp;manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eThe author acknowledges the institutional support from the Faculty of Medicine, Universitas Andalas.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKansra AR, Lakkunarajah S, Jay MS. Childhood and adolescent obesity: a review. Front Pediatr. 2021;8:581461.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y. Epidemiology of childhood obesity\u0026mdash;methodological aspects and guidelines: what is new? Int J Obes. 2004;28(Suppl 3):S21\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarnik S, Kanekar A. Childhood obesity: a global public health crisis. Int J Prev Med. 2012;3(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JT, Lee HK. Childhood obesity and endocrine disrupting chemicals. Ann Pediatr Endocrinol Metab. 2017;22(4):219\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDias D, Bons J, Kumar A, Kabir M, Liang H. Forever chemicals, per-and polyfluoroalkyl substances (PFAS), in lubrication. Lubricants. 2024;12(4):114.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHerzke D, Olsson E, Posner S. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) in consumer products in Norway \u0026ndash; A pilot study. Chemosphere. 2012;88(8):980\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQi W, Clark JM, Timme-Laragy AR, Park Y. Per- and polyfluoroalkyl substances and obesity, type 2 diabetes and non-alcoholic fatty liver disease: a review of epidemiologic findings. Toxicol Environ Chem. 2020;102(1\u0026ndash;4):1\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewis N, Abdulkadir A, Kandel S, Rosby R, Hossain E. Per- and Polyfluoroalkyl Substances (PFAS) as Emerging Obesogens: Mechanisms, Epidemiological Evidence, and Regulatory Challenges. Physiologia. 2024;4(4):517\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee YJ, Jung HW, Kim HY, Choi YJ, Lee YA. Early-Life Exposure to Per- and Poly-Fluorinated Alkyl Substances and Growth, Adiposity, and Puberty in Children: A Systematic Review. Front Endocrinol. 2021;12:683297.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObregon MJ. Adipose tissues and thyroid hormones. Front Physiol. 2014;5:479.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrangione B, Birk S, Benzouak T et al. Exposure to perfluoroalkyl and polyfluoroalkyl substances and pediatric obesity: a systematic review and meta-analysis. Int J Obes. 2005. 2024;48(2):131\u0026ndash;146.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Wosu AC, Fleisch AF, et al. Associations of Gestational Perfluoroalkyl Substances Exposure with Early Childhood BMI z-Scores and Risk of Overweight/Obesity: Results from the ECHO Cohorts. Environ Health Perspect. 2023;131(6):067001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStratakis N, Rock S, La Merrill MA, et al. Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies. Obes Rev. 2022;23(Suppl 1):e13383.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrigerio G, Ferrari CM, Fustinoni S. Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses. Environ Health. 2023;22(1):56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu P, Yang F, Wang Y, Yuan Z. Perfluorooctanoic Acid (PFOA) Exposure in Early Life Increases Risk of Childhood Adiposity: A Meta-Analysis of Prospective Cohort Studies. Int J Environ Res Public Health. 2018;15(10):2070.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin J. \u0026copy; Joanna Briggs Institute 2017 Critical Appraisal Checklist for Systematic Reviews and Research Syntheses [Internet]. Published online 2017 [cited 2025 Apr 25].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePederick JL, Frkic RL, McDougal DP, Bruning JB. A structural basis for the activation of peroxisome proliferator-activated receptor gamma (PPARγ) by perfluorooctanoic acid (PFOA). Chemosphere. 2024;354:141723.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoperchini F, Croce L, Ricci G, et al. Thyroid Disrupting Effects of Old and New Generation PFAS. Front Endocrinol. 2021;11:612320.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie X, Weng X, Liu S, et al. Perfluoroalkyl and Polyfluoroalkyl substance exposure and association with sex hormone concentrations: Results from the NHANES 2015\u0026ndash;2016. Environ Sci Eur. 2021;33(1):69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou X, Wang X, Ou T, Huang L, He B. Association between family economic situation and serum PFAS concentration in American adults with hypertension and hyperlipemia. Sci Rep. 2024;14:20799.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFord ND, Patel SA, Narayan KMV. Obesity in Low- and Middle-Income Countries: Burden, Drivers, and Emerging Challenges. Annu Rev Public Health. 2017;38:145\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Characteristics of systematic reviews and meta-analyses examining the association between the exposure to PFAS and persistent organic pollutants (POPs) and adipose tissue level in children\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9.9626%;\"\u003eAuthor\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 11.208%;\"\u003eDatabase\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 7.721%;\"\u003eSearch Period\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.7173%;\"\u003eIncluded Studies\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 9.2154%;\"\u003eTotal Sample\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 11.7061%;\"\u003eBiological Matrix\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.193%;\"\u003eDependent Variable\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6986%;\"\u003eIndependent Variable\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12.9514%;\"\u003eStudy Assessment Quality*\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 7.2946%;\"\u003eResults\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5.5067%;\"\u003e\n \u003cp\u003eFrangione, et al. (2023)\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.0074%;\"\u003e\n \u003cp\u003eMEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Cochrane Central\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.2195%;\"\u003e\n \u003cp\u003e2000 \u0026ndash; 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.8631%;\"\u003e\n \u003cp\u003e13 studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.6485%;\"\u003e\n \u003cp\u003e20,812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7928%;\"\u003e\n \u003cp\u003eMaternal serum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2231%;\"\u003e\n \u003cp\u003eBMI, waist circumference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.2934%;\"\u003e\n \u003cp\u003ePFOA, PFOS, PFHxS, PFNA, PFDA, PFUA, and PFDoA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.4352%;\"\u003e\n \u003cp\u003eHigh Quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2946%;\"\u003e\n \u003cp\u003eOverall, prenatal exposure to four (4) types of PFAS compounds was not associated with changes in BMI or waist circumference;\u003cbr\u003e\u0026nbsp;An inverse relationship was found between postnatal exposure to three (3) types of PFAS compounds, namely PFOA, PFOS, and PFHxS, and changes in BMI (\u0026beta; (95% CI) = -0.16 (-0.22, -0.10)).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5.5067%;\"\u003e\n \u003cp\u003eLiu, et al. (2018)\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.0074%;\"\u003e\n \u003cp\u003eEMBASE, Web of Science, PubMed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.2195%;\"\u003e\n \u003cp\u003e1986 \u0026ndash; 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.8631%;\"\u003e\n \u003cp\u003e10 studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.6485%;\"\u003e\n \u003cp\u003e6,076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7928%;\"\u003e\n \u003cp\u003eMaternal postpartum serum, maternal prenatal serum, maternal prenatal plasma, umbilical cord blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2231%;\"\u003e\n \u003cp\u003eBMI z-score, childhood overweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.2934%;\"\u003e\n \u003cp\u003ePFOA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.4352%;\"\u003e\n \u003cp\u003eHigh Quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2946%;\"\u003e\n \u003cp\u003eThere is a substantial effect (RR or OR) between PFOA exposure and overweight in children, with an effect size of 1.25 (95% CI: 1.04 to 1.50);\u003c/p\u003e\n \u003cp\u003eThere is also a significant positive association between PFOA exposure and the z-score of BMI (\u0026beta; = 0.10, 95% CI: 0.03 to 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5.5067%;\"\u003e\n \u003cp\u003eStratakis, et al. (2022)\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.0074%;\"\u003e\n \u003cp\u003ePubMed, EMBASE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.2195%;\"\u003e\n \u003cp\u003eStudies up to 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.8631%;\"\u003e\n \u003cp\u003e59 studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.6485%;\"\u003e\n \u003cp\u003eTotal sample is not reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7928%;\"\u003e\n \u003cp\u003eMaternal serum, umbilical cord blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2231%;\"\u003e\n \u003cp\u003eBMI, waist circumference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.2934%;\"\u003e\n \u003cp\u003ePFOA, PFOS, PBDE, DDE, HCB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.4352%;\"\u003e\n \u003cp\u003eHigh Quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2946%;\"\u003e\n \u003cp\u003eNo association was found between PFOS exposure and children\u0026apos;s IMT z-score (\u0026beta; [95% CI = 0 (-0.01, 0.01)]).\u003c/p\u003e\n \u003cp\u003eA positive but non-significant association was observed between PFOA exposure and children\u0026apos;s IMT z-score (\u0026beta; [95% CI = 0.03 (-0.02, 0.08)]).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5.5067%;\"\u003e\n \u003cp\u003eFrigerio, et al. (2023)\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.0074%;\"\u003e\n \u003cp\u003ePubMed, EMBASE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.2195%;\"\u003e\n \u003cp\u003e2000 \u0026ndash; 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.8631%;\"\u003e\n \u003cp\u003e30 studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.6485%;\"\u003e\n \u003cp\u003e49,255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7928%;\"\u003e\n \u003cp\u003eMaternal blood and neonatal blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2231%;\"\u003e\n \u003cp\u003eBMI, waist circumference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.2934%;\"\u003e\n \u003cp\u003ePFOA, PFOS, PFHxS, PFNA, PFDA, PFUA, and PFDoA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.4352%;\"\u003e\n \u003cp\u003eHigh Quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2946%;\"\u003e\n \u003cp\u003eA positive association was found between PFOA concentration and BMI in children over the age of 3 years, as well as between prenatal PFNA exposure and BMI in boys over 3 years of age.\u003c/p\u003e\n \u003cp\u003eA negative association was observed between prenatal PFOS exposure and BMI in children under 3 years of age, and between PFHxS exposure and overweight status.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5.5067%;\"\u003e\n \u003cp\u003eLee, et al. (2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.0074%;\"\u003e\n \u003cp\u003eMEDLINE, EMBASE, Web of Science, Scopus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.2195%;\"\u003e\n \u003cp\u003e2007 \u0026ndash; 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.8631%;\"\u003e\n \u003cp\u003e90 studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.6485%;\"\u003e\n \u003cp\u003eTotal sample is not reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7928%;\"\u003e\n \u003cp\u003eMaternal blood, umbilical cord blood, and neonatal blood\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2231%;\"\u003e\n \u003cp\u003eWaist circumference, body fat percentage, and BMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.2934%;\"\u003e\n \u003cp\u003ePFOA, PFOS, PFNA, and PFHxS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.4352%;\"\u003e\n \u003cp\u003eHigh Quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2946%;\"\u003e\n \u003cp\u003eThe evidence remains inconclusive regarding the association between exposure to PFAS compounds and obesity.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Each review article is assessed using the Joanna Briggs Institute (JBI) Checklist for Systematic Reviews and Research Syntheses\u003c/p\u003e\n\u003cp\u003eDDE: Dichlorodiphenyldichloroethylene; HCB: Hexachlorobenzene; PFOA: Perfluorooctanoic acid; PFOS: Perfluorooctane Sulfate; PFNA: Perfluorononanoic Acid; PFHxS: Perfluorohexanesulfonic Acid; PFDA: Perfluorodecanoic Acid; PFUnDA: Perfluoroundecanoic Acid; PFDoA: Perfluorododecanoic Acid; PFBS: Perfluorobutanesulfonic Acid\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Public Health](https://link.springer.com/journal/12982)","snPcode":"12982","submissionUrl":"https://submission.springernature.com/new-submission/12982/3","title":"Discover Public Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adolescent, Childhood, Exposure, Obesity, Per- and Polyfluoroalkyl Substances, Prenatal","lastPublishedDoi":"10.21203/rs.3.rs-6886652/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6886652/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives:\u003c/h2\u003e \u003cp\u003eThis umbrella review aimed to synthesize and critically evaluate the available evidence regarding the association between exposure to per- and polyfluoroalkyl substances (PFAS) and childhood obesity.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA comprehensive literature search was conducted in PubMed, ScienceDirect, Biomed Central, and ProQuest databases for systematic reviews and meta-analyses published between 2016 and 2025. Eligible studies included individuals aged 0\u0026ndash;20 years. Article screening followed the PRISMA Flow Diagram methodology, and the review protocol was registered with PROSPERO (CRD42024537809). Quality assessment was performed using the Joanna Briggs Institute (JBI) checklist for systematic reviews and meta-analyses.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eFive systematic reviews, including four meta-analyses, were identified. Three studies reported a positive association between perfluorooctanoic acid (PFOA) exposure and childhood obesity, with one study noting increased risk among children older than three years. Two studies found a negative association. For perfluorooctane sulfonate (PFOS), findings were heterogeneous: three studies indicated a negative association between PFOS exposure and obesity, while one study yielded inconclusive results.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eCurrent evidence regarding the impact of PFOA and PFOS exposure on childhood obesity is inconsistent. 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