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)
CH3
OH
HO
Discovered by
Aleksandr Dianin, 1891
CH3
• 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
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)
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
• Median BPA: 2.8 ng/mL
• Caloric intake and television
watching not associated with
BPA, but BPA was
associated with overweight
and obesity
17.8% obese
Main (multivariable) results
Quartile (Percentile)
Prevalence
Odds Ratio
BMI Z-score
1 (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.
L Trasande and coauthors
Association Between Urinary Bisphenol A
Concentration and Obesity Prevalence in
Children and Adolescents
Available at www.jama.com