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

Bisphenol A (BPA) Used to manufacture polycarbonate resin Discovered by Aleksandr Dianin, 1891 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 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.

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.

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

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

Quantifying BPA and body mass 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)

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)

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

Main (multivariable) results Quartile (Percentile) Prevalence Odds Ratio BMI Z-score 1 (0-24%) 10.3% Reference 2 (25-49%) 20.1% 2.24 *** 0.12 3 (50-74%) 19.0% 2.08 *** 0.16 * 4 (≥75%) 22.3% 2.57 *** 0.22 * *p<0.05; **p<0.01; ***p<0.001

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

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.

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

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.

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.

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