The Navigation Guide - evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth

Environ Health Perspect. 2014 Oct;122(10):1015-27. doi: 10.1289/ehp.1307177. Epub 2014 Jun 25.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Birth Weight / drug effects*
  • Caprylates / toxicity*
  • Environmental Health
  • Environmental Pollutants / toxicity
  • Evidence-Based Medicine
  • Female
  • Fetal Development / drug effects*
  • Fluorocarbons / toxicity*
  • Mice
  • Pregnancy


  • Caprylates
  • Environmental Pollutants
  • Fluorocarbons
  • perfluorooctanoic acid