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Lifestyle and Environment · Environmental Exposures

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

Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ

Environmental health perspectives, 2014
DOI 10.1289/ehp.1307893 PMID 24968388 PMC PMC4181929

RRM Academy Synopsis

Higher PFOA exposure is associated with lower birth weight

Higher PFOA exposure before or during pregnancy was associated with lower birth weight in a systematic review of observational studies in people. A meta-analysis of 9 studies and 4,149 births found an 18.9-gram lower birth weight for each 1-ng/mL rise in PFOA. The authors rated the evidence moderate in quality and sufficient in strength.

Key Findings

  • A meta-analysis of 9 studies and 4,149 births estimated a birth weight difference of –18.9 g (95% CI: –29.8, –7.9) for each 1-ng/mL increase in serum or plasma PFOA.
  • Adding one estimate from a study the authors flagged for exposure-assessment bias risk gave –15.4 g (95% CI: –26.5, –4.3). I2 rose from 38% to 72%.
  • A meta-analysis using only unadjusted estimates gave –30.9 g (95% CI: –49.3, –12.5) per ng/mL, a larger and less precise estimate than the adjusted one.
  • Higher PFOA was also associated with shorter birth length. Ponderal index and head circumference had confidence intervals that included zero.
  • The authors found generally low risk of bias across studies, rated the body of evidence moderate in quality, and rated the strength of human evidence sufficient.

Interpretation

The review pools observational studies and served as the first case study of the Navigation Guide method. The studies measured or estimated exposure to PFOA, an industrial chemical found in products that resist fire and stains, and compared it with birth measurements. The authors judged that chance, bias and confounding were reasonably excluded as explanations. They note that reverse causation, in which slower fetal growth reduces PFOA clearance in pregnancy, cannot be disproved.

RRM Context

Restorative reproductive medicine looks for root causes, and the setting where a pregnancy develops belongs to that search. Fetal growth is one outcome through which an environmental exposure can show up, and every delivery records a birth weight. The Navigation Guide pairs a written protocol with graded evidence ratings. Reviewers in any field can use that structure to weigh exposure research openly.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method.

Objective

We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans.

Methods

We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence.

Results

We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a -18.9 g (95% CI: -29.8, -7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a "moderate" quality rating to the overall body of human evidence.

Conclusion

On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is "sufficient" human evidence that developmental exposure to PFOA reduces fetal growth.

Topics

By this author

Related research

Lifestyle and Environment › Environmental Exposures › Persistent Organic Pollutants · Research Methods › Evidence Synthesis › Systematic Reviews
Paula I Johnson, Patrice Sutton, Dylan S Atchley, Erica Koustas, Juleen Lam, Saunak Sen, Karen A Robinson, Daniel A Axelrad, Tracey J Woodruff
P Johnson, P Sutton, D Atchley, E Koustas, J Lam, S Sen, K Robinson, Dan Axelrad, Danny Axelrad, D Axelrad, T Woodruff
PMID 24968388 24968388 DOI 10.1289/ehp.1307893 10.1289/ehp.1307893 Johnson et al. 2014, Johnson 2014

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