Use of NHANES Data to Link Chemical Exposures to Chronic Diseases: A Cautionary Tale

Background: The National Health and Nutrition Examination Survey (NHANES) is one example of cross-sectional datasets that have been used to draw causal inferences regarding environmental chemical exposures and adverse health outcomes. Our objectives were to analyze four NHANES datasets using consistent a priori selected methods to address the following questions: Is there a consistent association between urinary bisphenol A (BPA) measures and diabetes, coronary heart disease (CHD), and/or heart attack across surveys? Is NHANES an appropriate dataset for investigating associations between chemicals with short physiologic half-lives such as BPA and chronic diseases with multi-factorial etiologies? Data on urinary BPA and health outcomes from 2003-2004, 2005-2006, 2007-2008, and 2009-2010 were available. Methodology and Findings: Regression models were adjusted for creatinine, age, gender, race/ethnicity, education, income, smoking, heavy drinking, BMI, waist circumference, calorie intake, family history of heart attack, hypertension, sedentary time, and total cholesterol. Urinary BPA was not significantly associated with adverse health outcomes for any of the NHANES surveys, with ORs (95% CIs) ranging from 0.996 (0.951-1.04) to 1.03 (0.978-1.09) for CHD, 0.987 (0.941-1.04) to 1.04 (0.996-1.09) for heart attack, and 0.957 (0.899-1.02) to 1.01 (0.980-1.05) for diabetes. Conclusions: Using scientifically and clinically supportable exclusion criteria and outcome definitions, we consistently found no associations between urinary BPA and heart disease or diabetes. These results do not support associations and causal inferences reported in previous studies that used different criteria and definitions. We are not drawing conclusions regarding whether BPA is a risk factor for these diseases. We are stating the opposite-that using cross-sectional datasets like NHANES to draw such conclusions about short-lived environmental chemicals and chronic complex diseases is inappropriate. We need to expend resources on appropriately designed epidemiologic studies and toxicological explorations to understand whether these types of chemicals play a causal role in chronic diseases.