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3858513 
Journal Article 
Early-life exposure to perfluoroalkyl substances and childhood metabolic function 
Fleisch, AF; Rifas-Shiman, SL; Mora, AM; Calafat, AM; Ye, X; Luttmann-Gibson, H; Gillman, MW; Oken, E; Sagiv, SK 
2017 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE 
RES TRIANGLE PK 
125 
481-487 
English 
BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited.

METHODS: We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex.

RESULTS: Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring.

CONCLUSIONS: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303. 
Public Health And Safety; Studies; Insulin resistance; Health risk assessment; Rodents; United States--US 
PFAS
• Additional PFAS (formerly XAgency)
     Literature Search November 2019
          Other Sources
               Reference list review of included studies
               TEDX
     Screened Studies
          Included
               Include (TIAB)
          Excluded
               Exclude (Full Text)
• Expanded PFAS SEM (formerly PFAS 430)
     Litsearch: September 2019
          PubMed
          Web of Science
          ToxNet
          Other Sources
               PFAS TOX Database
     Screened Studies
          Excluded
               Exclude (TIAB)
     Not prioritized for screening
     Perfluorooctane
     Potassium perfluorooctanoate
     Sodium perfluorooctanoate
     9-H-Perfluorononanoic acid
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               Pubmed
               WOS
     PFDA (335-76-2)
          Literature Search
               Pubmed
               WOS
     PFNA (375-95-1)
          Literature Search
               Pubmed
               WOS
     PFHxS (355-46-4)
          Literature search
               Pubmed
               WOS
• PFAS 150
     Literature Search Update December 2020
          PubMed
          WOS
     Literature Search August 2019
          PubMed
          Web of Science
          Other sources
               Reference list review of included studies
               PFAS TOX Database
     Screened Studies
          Excluded
               Exclude (TIAB)
     Ammonium perfluorooctanoate
     Perfluorinated compounds
     Perfluorohexanesulfonic acid
     Perfluorononanoic acid
     Perfluorooctane
     Perfluorooctanesulfonic acid
     Perfluorooctanoic acid
• PFDA
     Literature Search
          Pubmed
          WOS
     Scopus: April 2021
     Screening Results
          Human/Epi studies
               Developmental tox
               Other
     Title and Abstract Screening
          Full Text Screening
               Studies Meeting PECO
                    Human health effect studies
     June 2022 Pelch Database
     Literature Searches (through April 2023 update and post-public comment/peer review)a    
          Other
               Published PFAS SEMs
          Title & Abstract Screening
               Tagged as Supplemental
                    Full Text Screening
                         Studies Meeting PECO
                              Human health effects studies
• PFHxS
     Database searches
          Pubmed
          Toxline
          WOS
          Scopus
          Pelch PFAS SEM
     Inclusion
          TiAb
          Full Text
               Human Study
• PFNA
     Literature Search (August 2017)
          Pubmed
     Litsearch Update 2017-2018
          PFAS Untag
     PFNA Literature Search pre-2019
          Pubmed
          WOS
     Literature Search
          Pubmed
          Toxline
          WOS
     PFNA May 2019 Update
          Pubmed
          Toxnet
          Web of Science
     Screening Results
          Human/Epi studies
               Developmental tox
               Other
     PFNA HAWC Readout
          Human
     Title and Abstract Screening
          Full Text Screening
               Studies Meeting PECO
                    Human health effects studies
     June 2022 Pelch Database
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          Pubmed
          WOS
     Screening Results
          Human/Epi studies
               Developmental tox
     Literature Search Update (2013-2019)
          PubMed
          WOS
• PFOA and PFOS OW MCLG Approaches
     Cited in White Papers