Isabella Rosato1, Maryam Zare Jeddi2, Caterina Ledda3, Elisa Gallo1, Tony Fletcher4, Gisella Pitter5, Erich Batzella1, Cristina Canova6. 1. Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy. 2. RIVM-National Institute for Public Health and the Environment, Bilthoven, the Netherlands. 3. Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy; Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. 4. Screening and Health Impact Assessment Unit, Azienda Zero-Veneto Region, Padova, Italy. 5. London School of Hygiene and Tropical Medicine, London, United Kingdom. 6. Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy. Electronic address: cristina.canova@unipd.it.
Abstract
BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.
BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.
Authors: Jigen Na; Huiting Chen; Hang An; Nan Li; Lailai Yan; Rongwei Ye; Zhiwen Li Journal: Int J Environ Res Public Health Date: 2022-01-04 Impact factor: 3.390
Authors: Erich Batzella; Maryam Zare Jeddi; Gisella Pitter; Francesca Russo; Tony Fletcher; Cristina Canova Journal: Int J Environ Res Public Health Date: 2022-09-29 Impact factor: 4.614
Authors: Elizabeth G Radke; J Michael Wright; Krista Christensen; Cynthia J Lin; Alexandra E Goldstone; Courtney Lemeris; Kristina A Thayer Journal: Environ Health Perspect Date: 2022-09-30 Impact factor: 11.035