Leonardo Trasande, MD, MPP Teresa Attina, MD, PhD, MPH Jan Blustein, MD, PhD

1. Association Between Urinary Bisphenol A Concentration and Obesity Prevalence in Children and Adolescents Leonardo Trasande, MD, MPP Teresa Attina, MD, PhD, MPH Jan Blustein, MD, PhD

2. Bisphenol A (BPA) • Used to manufacture polycarbonate resin • Found in canned food, polycarbonate bottled liquids and other consumer products • Breakdown product of coatings intended to prevent metal corrosion in food and beverage containers • Recently banned from baby bottles and sippy cups by US Food and Drug Administration • Comprehensive, cross-sectional study of dust, indoor and outdoor air, and solid and liquid food in preschool age children suggested that dietary sources constitute 99% of BPA exposure Discovered by Aleksandr Dianin, 1891 Schecter et al. Environ Sci Technol. 2010;44(24):9425-9430 Wilson et al. Environ Res. Jan 2007;103(1):9-20. Tavernise S. New York Times, 17 July 2012 edition.

3. BPA in humans • Exposure is ubiquitous • Studies suggest brief half-life (4-43 hours) • But BPA also detected in fat • Urinary levels of BPA do not decline rapidly with fasting time, suggesting accumulation in body tissues Stahlhut et al. Environ Health Perspect. 2009;117(5):784-789. Volkel et al.Chem Res Toxicol. 2002;15(10):1281-1287. Fernandez et al. Reprod Toxicol. Aug-Sep 2007;24(2):259-264.

4. BPA and obesity • Laboratory studies suggest that BPA disrupts multiple metabolic mechanisms, • Occurs at exposure levels commonly seen in US population • Urinary BPA concentration has been associated with: • Adult obesity • Adult diabetes, cardiovascular diagnoses and abnormalities in liver function • Increased frequency of later coronary artery disease in later life • Differences in heart rate variability and blood pressure in elderly Masuno et al. J Lipid Res. 2002;43(5):676-684 Sakurai K et al. Br J Pharmacol. 2004;141(2):209-214 Carwile JL, Michels KB. Environ Res. 2011;111(6):825-830 Lang al. JAMA. 2008;300(11):1303-1310 Melzer et al. PLoS One. 2010;5(1):e8673 Melzer et al. Circulation. 2012;125(12):1482-1490 Bae et al. Hypertension 2012;60:786-793

5. BPA and childhood obesity? • Children are known to be uniquely vulnerable to environmental chemicals • Yet no studies to date connecting environmental chemical exposures to obesity • We examined associations of urinary BPA concentration with body mass in 6-19 year olds in NHANES 2003-8. • NHANES is a federal survey of the nation’s health, conducted nationally through mobile testing sites. • Sample was 2838 US children, representative of the US

6. Quantifying BPA and body mass BPA • Urinary concentrations from Centers for Disease Control and Prevention (CDC)’s laboratories • We transformed the concentrations in two ways: • Divided the sample into fourths based on BPA concentration (lowest to highest) • Also looked at linear BPA concentration (expressed as the logarithm to normalize the distribution) Body mass • Height and weight measured by CDC’s trained staff • We transformed these in two ways • Standardized BMI (weight in kilograms divided by height in meters squared) for age and gender into Z-scores • Classified overweight as at/above 85th percentile for age and gender (obese at/above 95th percentile)

7. Other factors that were considered • Simultaneously examined other factors associated with obesity • Age group (6-11 and 12-19 years) • Gender • Racial/ethnic group • Socioeconomic status • Caregiver education • Serum cotinine level (tobacco smoke exposure) • Television watching • Caloric intake • Urinary dilution (creatinine)

8. Key characteristics of the sample • Median BPA: 2.8 ng/mL • Caloric intake and television watching not associated with BPA, but BPA was associated with overweight and obesity 34.1% overweight 17.8% obese

9. Main (multivariable) results *p<0.05; **p<0.01; ***p<0.001

10. Specificity of association • We also examined chemically similar environmental phenols used in sunscreens and soaps • Urinary concentrations of these similar phenols were not associated with obesity

11. Race-specific effects • Associations of BPA concentration with obesity (but not BMI Z-score) were isolated to whites, and were absent in Hispanics and Blacks. • If obese whites have unique dietary behaviors that predispose them to increases in urinary BPA, then this could explain our results, though there is no evidence to support this. • A difference in genetic or other predisposition is another plausible explanation.

12. Caveats • Reverse causation is possible • Obese children ingest more foods that contain BPA • Urinary BPA represents more recent exposure, rather than the chronic exposure that is more likely to lead to obesity • BPA may disrupt metabolism earlier in life than in the childhood and adolescent years we studied

13. Nonlinear association • Consistent with biological activity of many hormones • Duplicated in many studies • Dr. Linda Birnbaum (NIEHS Director) has emphasized that regulatory policymakers should include information about non-linear associations, when they deliberate. Vandenberg LN et al. Endocr Rev. Jun 2012;33(3):378-455. Birnbaum Environ Health Perspect. Apr 2012;120(4):A143-144.

14. Summary • First report of an association of an environmental chemical exposure with childhood obesity in a nationally representative sample • Association evident when exposure and outcome are modeled in a number of different ways • Adjusted prevalence of obesity of 22.3% (among children in the highest uBPA quartile, compared with a 10.3% prevalence among those in the lowest uBPA quartile.

15. L Trasande and coauthors Association Between Urinary Bisphenol A Concentration and Obesity Prevalence in Children and Adolescents