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BACKGROUND: Increasingly, risk of bias tools are used to evaluate epidemiologic studies as part of evidence synthesis (evidence integration), often involving meta-analyses. Some of these tools consider hypothetical randomized controlled trials (RCTs) as gold standards. METHODS: We review the strengths and limitations of risk of bias assessments, in particular, for reviews of observational studies of environmental exposures, and we also comment more generally on methods of evidence synthesis. RESULTS: Although RCTs may provide a useful starting point to think about bias, they do not provide a gold standard for environmental studies. Observational studies should not be considered inherently biased vs. a hypothetical RCT. Rather than a checklist approach when evaluating individual studies using risk of bias tools, we call for identifying and quantifying possible biases, their direction, and their impacts on parameter estimates. As is recognized in many guidelines, evidence synthesis requires a broader approach than simply evaluating risk of bias in individual studies followed by synthesis of studies judged unbiased, or with studies given more weight if judged less biased. It should include the use of classical considerations for judging causality in human studies, as well as triangulation and integration of animal and mechanistic data. CONCLUSIONS: Bias assessments are important in evidence synthesis, but we argue they can and should be improved to address the concerns we raise here. Simplistic, mechanical approaches to risk of bias assessments, which may particularly occur when these tools are used by nonexperts, can result in erroneous conclusions and sometimes may be used to dismiss important evidence. Evidence synthesis requires a broad approach that goes beyond assessing bias in individual human studies and then including a narrow range of human studies judged to be unbiased in evidence synthesis.

Exposures to persistent organohalogen chemicals during pregnancy are associated with adverse health effects. Low-income, minority women with pre-existing co-morbidities may be particularly vulnerable to these exposures, but have historically been understudied. We aimed to characterize exposures to multiple chemical classes among a sample of ethnically diverse, lower income, overweight or obese pregnant women. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly-and perfluoroalkyl substances (PFASs) were measured in 98 pregnant women (California; 2011-2013). Aggregate exposures were evaluated using correlational clustering, a "chemical burden" score, and PCA. Associations between sociodemographic characteristics and individual and aggregate exposures were evaluated using multivariable linear regression. Clustering and PCA both produced four groupings: (PC1) PBDEs/ OH-PBDEs, (PC2) PCBs, (PC3) PFNA/PFOA/PFDeA, (PC4) PFHxS/PFOS. Race/ethnicity and prepregnancy BMI were associated with PBDEs, OH-PBDEs and PC1. Maternal age was associated with PCBs and PC2. Parity was associated with PBDEs, OH-PBDEs and PC2. Poverty was negatively associated with PCBs, whereas food insecurity was positively associated with PFOS. We observed variations in sociodemographic profiles of exposures by chemical class and weak across-class correlations. These findings have implications for epidemiologic studies of chemical mixtures and for exposure reduction strategies.