The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

Koustas, Erica; Lam, Juleen; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

doi:10.1289/ehp.1307177

Cited by 349Per- and polyfluoroalkyl substances researchToxic Organic Pollutants ImpactEffects and risks of endocrine disrupting chemicals

The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

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Koustas, Erica, Lam, Juleen, Sutton, Patrice, Johnson, Paula I., Atchley, Dylan S., Sen, Saunak, Robinson, Karen A., Axelrad, Daniel A. +1 more·2014·Environmental Health Perspectives

DOI 10.1289/ehp.1307177PMC PMC4181920

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Abstract

Abstract Background: In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action. Objectives: We applied the Navigation Guide systematic review method to answer the question “Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?” and to rate the strength of the experimental animal evidence. Methods: We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence. Results: Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of –0.023 g (95% CI: –0.029, –0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as “moderate” and “low” quality, respectively. Conclusion: Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals. Citation: Koustas E, Lam J, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1015–1027; http://dx.doi.org/10.1289/ehp.1307177

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PFAS are recognized developmental toxicants.
“In utero exposure to per- and polyfluoroalkyl substances (PFAS), which are recognized developmental toxicants, potentially leads to decreased anthropometric measures in infants at birth.”
From Associations between in utero exposure of per- and polyfluoroalkyl substances (PFAS) mixture and anthropometry measures at birth (2025) · cites this paper as Koustas et al., 2014
The Discussion (‘Animal Evidence for PFOA and Fetal Growth’; page unavailable) finds sufficient evidence that developmental exposure to PFOA or its salts reduces fetal growth in animals. That supports a developmental effect for one PFAS compound, but not the broader claim that PFAS as a class are recognized developmental toxicants. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Systematic review methods have only recently been developed and utilized in environmental health sciences.
“such methods have only recently been developed and utilized in environmental health sciences [23–30].”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [24]
The observation that author cooperation was necessary to complete the meta-analysis is consistent with the authors' previous systematic reviews.
“This observation is consistent with our previous systematic reviews, [24, 27, 28, 30]”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [24]

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The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth
Johnson, P. I., Sutton, P., Atchley, D. S., Koustas, E., Lam, J., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307893 · Cited by 449 · see citing works
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The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth
Lam, J., Koustas, E., Sutton, P., Johnson, P. I., Atchley, D. S., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307923 · Cited by 214 · see citing works
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The Navigation Guide Systematic Review Methodology Proof of Concept: PFOA and Fetal Growth
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The Navigation Guide - Evidence-Based Medicine Meets Environmental Health: PFOA and Fetal Growth
Johnson, P., Sutton, P., Atchley, D. S., Koustas, E., Lam, J., Sen, Ś., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2013) · ISEE Conference Abstracts · doi:10.1289/isee.2013.p-1-32-20 · Cited by 2 · see citing works
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TITLE The Navigation Guide — Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth
(2015)

Authors: Koustas, E., Lam, J., Sutton, P., Johnson, P. I., Atchley, D. S., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J.
Affiliations: Environmental Protection Agency (US)
University of California, San Francisco (US)
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
Johns Hopkins University (US)
Corresponding author: Koustas, Erica
ORCID: Lam, Juleen
Johnson, Paula I.
Robinson, Karen A.
Axelrad, Daniel A.
Woodruff, Tracey J.
Venue: Environmental Health Perspectives
Publisher: American Chemical Society (ACS)
Published: 2014-06-25
Volume: 122
Issue: 10
Pages: 1015-1027
ISSN: 0091-6765 (ISSN-L)
1552-9924
DOI: 10.1289/ehp.1307177
PMC: PMC4181920
OpenAlex: W1969835924
Cited by: 349
References: 121
Citations by year: 2026: 5 · 2025: 14 · 2024: 14 · 2023: 30 · 2022: 25 · 2021: 41 · 2020: 60 · 2019: 31 · 2018: 30 · 2017: 42 · 2016: 24 · 2015: 22 · 2014: 10
FWCI: 3.08
Type: journal article
Language: en
Open access: gold
doi.org
Licence: public-domain
creativecommons.org/licenses/by/4.0/ (vor, 1283 d)
Locations: Environmental Health Perspectives (publishedVersion, public-domain)
PubMed Central (publishedVersion, public-domain)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute of Environmental Health Sciences (ES018135, P01ES022841, ES022841, P20ES018135)
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords: perfluorooctanoic acid, fetal growth, prenatal exposure, animal studies, birth weight, evidence synthesis, perfluorinated compounds, developmental toxicity
MeSH terms: Animals, Birth Weight, Caprylates, Environmental Health, Environmental Pollutants, Female, Fluorocarbons, Pregnancy, Evidence-Based Medicine, Fetal Development, Mice

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The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

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