ASSOCIATION BETWEEN URINARY BISPHENOL A CONCENTRATION AND OBESITY PREVALENCE IN CHILDREN AND ADOLESCENTS

Leonardo Trasande, MD, MPPTeresa Attina, MD, PhD, MPHJan Blustein, MD, PhD

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

CH3

CH3

OHOH

Schecter et al. Environ Sci Technol. 2010;44(24):9425-9430Wilson et al. Environ Res. Jan 2007;103(1):9-20.Tavernise S. New York Times, 17 July 2012 edition.

Discovered by Aleksandr Dianin, 1891

BPA in humans

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):676-684Sakurai K et al. Br J Pharmacol. 2004;141(2):209-214Carwile JL, Michels KB. Environ Res. 2011;111(6):825-830 Lang al. JAMA. 2008;300(11):1303-1310Melzer et al. PLoS One. 2010;5(1):e8673Melzer et al. Circulation. 2012;125(12):1482-1490Bae 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 massBPA•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

• 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

Main (multivariable) results

Quartile (Percentile) Prevalence Odds Ratio BMI Z-score1 (0-24%) 10.3% Reference 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.

Available at www.jama.com

L Trasande and coauthors

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