Urinary Bisphenol A and Obesity in US Children
Urinary Bisphenol A and Obesity in US Children
We examined the association between increasing levels of urinary BPA and obesity in children aged 6–18 years who participated in NHANES in 3 study cycles, 2003–2004, 2005–2006, and 2007–2008, where BPA measurements were available. NHANES is a cross-sectional study using a stratified, multistage probability sample, representative of noninstitutionalized civilians in the United States. A detailed description of the NHANES study design and methods is available elsewhere. NHANES was approved by the National Center for Health Statistics Research Ethics Review Board. Written child assent was obtained from children aged 7–11 years; written informed consent was obtained from children 12 years or older; and written parental consent was obtained for those younger than 18 years.
A random one-third subset of NHANES participants 6 years or older was selected for the measurement of urinary BPA levels. The current study sample consists of 2,664 children (6–18 years) from this subset. As recommended by the National Center for Health Statistics, specific sample weights for this BPA subsample were used when analyzing the data, to avoid potential selection bias.
We further excluded participants with missing data (n = 464) on covariates included in the multivariable model, including body mass index, age, sex, race/ethnicity, parent/guardian education, physical activity, serum cotinine, and urinary creatinine. This resulted in the final sample of 2,200 participants (48.5% girls), 17.7% of whom were obese.
Measures of BPA concentration included BPA parent compound and conjugated metabolites. Urinary BPA was measured by using solid-phase extraction coupled on-line to high-performance liquid chromatography and tandem mass spectrometry. Rigorous quality assurance and quality control ensured that samples were not contaminated during collection, handling, and analysis.
Standing height was measured in centimeters to the nearest 0.1 cm by using an electronic stadiometer. Weight was measured in kilograms to the nearest 0.1 kg by using a Toledo self-zeroing weight scale (Seritex, Carlstadt, New Jersey). Body mass index was calculated (weight (kg)/height (m)). The Centers for Disease Control and Prevention (CDC) classifies the weight status categories used with children and teens according to percentile ranking relative to their age and sex. Following these guidelines, we defined obesity in children as age- and sex-specific body mass index greater than or equal to the 95th percentile.
Serum cotinine was measured in nanograms per milliliter by isotope dilution–high performance liquid chromatography. Urinary creatinine concentrations, a measure of urinary dilution, were collected from specimens by the clean-catch technique and measured in milligrams per deciliter. Information on other covariates, such as age, sex, race/ethnicity, parent/guardian education, and physical activity, was gathered from a standardized questionnaire.
The outcome variable, obesity, was defined as body mass index levels greater than or equal to the 95th percentile for age and gender. The main exposure of interest, urinary BPA, was categorized into quartiles (<1.5 ng/mL, 1.5–2.7 ng/mL, 2.8–5.4 ng/mL, >5.4 ng/mL) and also analyzed as a continuous variable, after log transformation due to skewed distribution. The odds ratio with 95% confidence interval of obesity for BPA was calculated by taking the lowest quartile (quartile 1) as the referent using multivariable logistic regression models. We used 2 models: the age- and sex-adjusted model and the multivariable-adjusted model, additionally adjusting for race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and others), parent/guardian education (below high school, high school, above high school), urinary creatinine (mg/dL), serum cotinine (ng/mL), and moderate physical activity (absent, present). Linear trends in the odds ratio of obesity across increasing urinary BPA quartiles were determined by modeling BPA as an ordinal variable. We performed subgroup analysis by gender and race/ethnicity and tested for statistical interaction (α = 0.10) by including multiplicative cross-product interaction terms between BPA quartiles and these stratifying variables in regression models. Sample weights that account for the unequal probabilities of selection, oversampling, and nonresponse were applied for all analyses by using SAS, version 9.3, software (SAS Institute, Inc., Cary, North Carolina); standard error values were estimated by using the Taylor series linearization method.
Materials and Methods
We examined the association between increasing levels of urinary BPA and obesity in children aged 6–18 years who participated in NHANES in 3 study cycles, 2003–2004, 2005–2006, and 2007–2008, where BPA measurements were available. NHANES is a cross-sectional study using a stratified, multistage probability sample, representative of noninstitutionalized civilians in the United States. A detailed description of the NHANES study design and methods is available elsewhere. NHANES was approved by the National Center for Health Statistics Research Ethics Review Board. Written child assent was obtained from children aged 7–11 years; written informed consent was obtained from children 12 years or older; and written parental consent was obtained for those younger than 18 years.
A random one-third subset of NHANES participants 6 years or older was selected for the measurement of urinary BPA levels. The current study sample consists of 2,664 children (6–18 years) from this subset. As recommended by the National Center for Health Statistics, specific sample weights for this BPA subsample were used when analyzing the data, to avoid potential selection bias.
We further excluded participants with missing data (n = 464) on covariates included in the multivariable model, including body mass index, age, sex, race/ethnicity, parent/guardian education, physical activity, serum cotinine, and urinary creatinine. This resulted in the final sample of 2,200 participants (48.5% girls), 17.7% of whom were obese.
Measures of BPA concentration included BPA parent compound and conjugated metabolites. Urinary BPA was measured by using solid-phase extraction coupled on-line to high-performance liquid chromatography and tandem mass spectrometry. Rigorous quality assurance and quality control ensured that samples were not contaminated during collection, handling, and analysis.
Standing height was measured in centimeters to the nearest 0.1 cm by using an electronic stadiometer. Weight was measured in kilograms to the nearest 0.1 kg by using a Toledo self-zeroing weight scale (Seritex, Carlstadt, New Jersey). Body mass index was calculated (weight (kg)/height (m)). The Centers for Disease Control and Prevention (CDC) classifies the weight status categories used with children and teens according to percentile ranking relative to their age and sex. Following these guidelines, we defined obesity in children as age- and sex-specific body mass index greater than or equal to the 95th percentile.
Serum cotinine was measured in nanograms per milliliter by isotope dilution–high performance liquid chromatography. Urinary creatinine concentrations, a measure of urinary dilution, were collected from specimens by the clean-catch technique and measured in milligrams per deciliter. Information on other covariates, such as age, sex, race/ethnicity, parent/guardian education, and physical activity, was gathered from a standardized questionnaire.
Statistical Analysis
The outcome variable, obesity, was defined as body mass index levels greater than or equal to the 95th percentile for age and gender. The main exposure of interest, urinary BPA, was categorized into quartiles (<1.5 ng/mL, 1.5–2.7 ng/mL, 2.8–5.4 ng/mL, >5.4 ng/mL) and also analyzed as a continuous variable, after log transformation due to skewed distribution. The odds ratio with 95% confidence interval of obesity for BPA was calculated by taking the lowest quartile (quartile 1) as the referent using multivariable logistic regression models. We used 2 models: the age- and sex-adjusted model and the multivariable-adjusted model, additionally adjusting for race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and others), parent/guardian education (below high school, high school, above high school), urinary creatinine (mg/dL), serum cotinine (ng/mL), and moderate physical activity (absent, present). Linear trends in the odds ratio of obesity across increasing urinary BPA quartiles were determined by modeling BPA as an ordinal variable. We performed subgroup analysis by gender and race/ethnicity and tested for statistical interaction (α = 0.10) by including multiplicative cross-product interaction terms between BPA quartiles and these stratifying variables in regression models. Sample weights that account for the unequal probabilities of selection, oversampling, and nonresponse were applied for all analyses by using SAS, version 9.3, software (SAS Institute, Inc., Cary, North Carolina); standard error values were estimated by using the Taylor series linearization method.
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