Faculty Bibliography

There is mounting evidence that bisphenol A (BPA), a chemical used in the production of polycarbonate plastics and the linings of aluminum cans, may have adverse health consequences. The Food and Drug Administration has banned BPA from baby bottles and sippy cups but has deferred further action on other food uses-that is, uses in metal-based food and beverage containers. This article quantifies the potential social costs of childhood obesity and adult coronary heart disease attributable to BPA exposure in the United States in 2008 and models the potential health and economic benefits associated with replacing BPA in all food uses. BPA exposure was estimated to be associated with 12,404 cases of childhood obesity and 33,863 cases of newly incident coronary heart disease, with estimated social costs of $2.98 billion in 2008. Removing BPA from food uses might prevent 6,236 cases of childhood obesity and 22,350 cases of newly incident coronary heart disease per year, with potential annual economic benefits of $1.74 billion (sensitivity analysis: $889 million-$13.8 billion per year). Although more data are needed, these potentially large health and economic benefits could outweigh the costs of using a safer substitute for BPA.

BACKGROUND: Low-grade albuminuria is an indicator of endothelial dysfunction and is associated with an increased risk of cardiovascular disease. A graded level of exposure to bisphenol A was recently identified to be associated with increased risk of low-grade albuminuria in children and adults. Because bisphenol A and phthalates coexist as dietary contaminants, this study investigated whether exposure to phthalates is also associated with low-grade albuminuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were examined from 667 children who participated in the 2009-2010 National Health and Nutrition Examination Survey and who had results for urinary phthalate metabolites and albumin excretion. Urinary albumin and creatinine concentrations were measured in a first morning specimen using a solid-phase fluorescent immunoassay and a Roche/Hitachi Modular P Chemistry Analyzer with an enzymatic method, respectively. Phthalate metabolites were analyzed in a separate spot urine sample from each participant, using high-performance liquid chromatography and tandem mass spectroscopy. RESULTS: For each (roughly) 3-fold increase in metabolites of di-2-ethylhexylphthalate (a high molecular weight phthalate commonly found in foods), a 0.55 mg/g increase in albumin/creatinine ratio (ACR) was identified (P=0.02), whereas a 1.30-fold odds of a higher ACR quartile was also identified for each (roughly) 3-fold increase (P=0.02). Higher ACR was not identified in relationship to metabolites of lower molecular phthalates commonly found in lotions or shampoos, suggesting specificity. CONCLUSIONS: Although reverse causation and unmeasured confounders represent alternative explanations, these findings, in conjunction with our earlier data on bisphenol A, indicate that a wide array of environmental toxins may adversely affect albuminuria and potentially increase the risk of cardiovascular disease. In view of the potential long-term health implications of ongoing exposure in this vulnerable subpopulation, our data support both further study and renewed regulatory efforts to limit exposure during childhood.

Context: Bisphenol A (BPA) is an environmental endocrine disruptor that has been linked to many reproductive disorders in animal models and humans. One such disorder is polycystic ovary syndrome (PCOS), which has been correlated with increased BPA levels in adult women. However, little is known about the role of serum BPA in adolescents with PCOS and its correlation with the metabolic profile. Objectives: To measure BPA levels in adolescent with PCOS as compared to a body mass index (BMI)-matched control group. To correlate serum BPA levels with disease severity, as measured by biochemical and radiologic features. Design: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and controls. Serum BPA was measured and compared between groups and correlated with biochemical (testosterone, insulin resistance) and ovarian ultrasound findings. Setting: Urban tertiary academic medical center. Participants: Study groups included 15 overweight/obese adolescent females with PCOS (mean age 15.27 years, mean BMI 32.84) and 14 BMI-matched female controls (mean age 14.1 years, mean BMI 31). Results: Biochemical data showed a mean free testosterone of 7.06 pg/mL and mean LH:FSH ratio of 1.93 in the PCOS group as compared to mean testosterone of 4.51 pg/mL and mean LH:FSH ratio of 1.12 in the control group (P=0.08 and 0.012, respectively). The index of insulin resistance (HOMA-IR) was 1.65 in the PCOS group and 1.82 in the control group (P=0.75). Serum BPA levels were 0.624 +/-1.29 ng/mL in the PCOS group versus 0.28 +/-0.11 ng/mL in controls (P=0.325). No correlation was found between serum BPA levels and biochemical and radiologic markers of PCOS severity. Conclusions: The results of this exploratory study pose many interesting questions about BPA exposure in adolescents. Although the results are not statistically significant, both adult studies and animal models have shown a strong correlation between serum BPA and severity of PCOS. The weaker relationship in adolescents may be explained in part by shorter duration of exposure to BPA in years. Further studies are warranted to clarify the correlation of PCOS and the endocrine disruptor BPA in a larger setting

BACKGROUND: Di-2-ethylhexylphthalate (DEHP) is an ester of phthalic acid commonly found in processed foods. DEHP may contribute to obesity and insulin resistance in children and adolescents, yet dietary exposures have been not been studied in this vulnerable subpopulation. OBJECTIVE: To assess diet and its relation to urinary phthalates in a nationally representative sample of US children and adolescents. DESIGN: Cross-sectional analysis of 24-h dietary recall and urinary phthalate metabolites from 2743 6-19 year olds participating in the 2003-8 National Health and Nutrition Examination Surveys. Regression analyses examined relationships of food consumption with log-transformed metabolite concentrations, examined as low-molecular weight, high molecular weight and di-2-ethylhexylphthalate categories, controlling for urinary creatinine, age group, body mass index category, race/ethnicity, caloric intake and gender. RESULTS: We identified a -0.04% (95% CI: -0.08, -0.01) increment in di-2-ethylhexylphthalate metabolite concentration/additional gram fruit consumption, a +0.01% increment/additional calorie dietary intake (95% CI: +0.003, +0.02), and a +0.09% (95% CI: +0.02, +0.17) increment/additional gram meat/poultry/fish consumption. Soy consumption (-0.40% increment/additional gram consumed, 95% CI: -0.66, -0.14) was inversely associated with di-2-ethylhexylphthalate, while poultry (+0.23% increment/additional gram consumed, 95% CI: +0.12, +0.35) was positively associated. Findings were robust to examination of metabolite concentrations per unit body mass index and weight, and inclusion of fasting time. CONCLUSIONS: Diet contributes to urinary phthalate concentrations in children and adolescents. Further study is needed to examine the implications of di-2-ethylhexylphthalate exposure, especially earlier in life, when more permanent metabolic changes may occur.

Background: Children's blood lead levels have declined worldwide, especially after the removal of lead in gasoline. However, significant exposure remains, particularly in low- and middle-income countries. To date, there have been no global estimates of the costs related to lead exposure in children in developing countries.Objective: Our main aim was to estimate the economic costs attributable to childhood lead exposure in low- and middle-income countries.Methods: We developed a regression model to estimate mean blood lead levels in our population of interest, represented by each 1-year cohort of children < 5 years of age. We used an environmentally attributable fraction model to estimate lead-attributable economic costs and limited our analysis to the neurodevelopmental impacts of lead, assessed as decrements in IQ points. Our main outcome was lost lifetime economic productivity due to early childhood exposure.Results: We estimated a total cost of $977 billions of international dollars in low- and middle-income countries, with economic losses equal to $134.7 billion in Africa [4.03% of gross domestic product (GDP)], $142.3 billion in Latin America and the Caribbean (2.04% of GDP), and $699.9 billion in Asia (1.88% of GDP). Our sensitivity analysis indicates a total economic loss in the range of $728.6-1162.5 billion.Conclusions: We estimated that, in low- and middle-income countries, the burden associated with childhood lead exposure amounts to 1.20% of world GDP in 2011. For comparison, in the United States and Europe lead-attributable economic costs have been estimated at $50.9 and $55 billion, respectively, suggesting that the largest burden of lead exposure is now borne by low- and middle-income countries.Citation: Attina TM, Trasande L. 2013. Economic costs of childhood lead exposure in low- and middle-income countries. Environ Health Perspect 121:1097-1102; http://dx.doi.org/10.1289/ehp.1206424.

BACKGROUND Di-2-ethylhexylphthalate (DEHP) is an environmental chemical commonly found in processed foods. Phthalate exposures, in particular to DEHP, have been associated with insulin resistance in adults, but have not been studied in adolescents. METHODS: Using cross-sectional data from 766 fasting 12- to 19-year-olds in the 2003-2008 NHANES, we examined associations of phthalate metabolites with continuous and categorical measures of homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: Controlling for demographic and behavioral factors, diet, continuous age, BMI category, and urinary creatinine, for each log (roughly threefold) increase in DEHP metabolites, a 0.27 increase (95% confidence interval 0.14-0.40; P < .001) in HOMA-IR was identified. Compared with the first tertile of DEHP metabolite in the study population (14.5% insulin resistant), the third tertile had 21.6% prevalence (95% confidence interval 17.2%-26.0%; P = .02). Associations persisted despite controlling for bisphenol A, another endocrine-disrupting chemical commonly found in foods, and HOMA-IR and insulin resistance were not significantly associated with metabolites of lower molecular weight phthalates commonly found in cosmetics and other personal care products. CONCLUSIONS: Urinary DEHP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. This study cannot rule out the possibility that insulin-resistant children ingest food with higher phthalate content, or that insulin-resistant children excrete more DEHP.

OBJECTIVE: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates-low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)-based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels. RESULTS: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension. CONCLUSIONS: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention.

Objectives:To assess associations of caesarean section with body mass from birth through adolescence.Design:Longitudinal birth cohort study, following subjects up to 15 years of age.Setting and participants:Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219).Outcome measures:Primary outcome: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI >/=85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years.Results:Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak.Conclusion:Caesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.International Journal of Obesity advance online publication, 14 May 2013; doi:10.1038/ijo.2013.49.

BACKGROUND: Phthalates have antiandrogenic effects and may disrupt lipid and carbohydrate metabolism. Racial/ethnic subpopulations have been documented to have varying urinary phthalate concentrations and prevalences of childhood obesity. OBJECTIVE: We examined associations between urinary phthalate metabolites and body mass outcomes in a nationally representative sample of US children and adolescents. METHODS: We performed stratified and whole-sample cross-sectional analyses of 2,884 children 6-19 years of age who participated in the 2003-2008 National Health and Nutrition Examination Survey. Multivariable linear and logistic analyses of body mass index Z-score, overweight, and obesity were performed against molar concentrations of low-molecular weight (LMW), high-molecular weight (HMW) and di-2-ethylhexylphthalate (DEHP) metabolites, controlling for gender, television watching, caregiver education, caloric intake, poverty-income ratio, race/ethnicity, serum cotinine, and age group. Sensitivity analysis examined robustness of results to removing sample weighting, normalizing phthalate concentrations for molecular weight and examination of different dietary intake covariates. RESULTS: In stratified, multivariable models, each log unit (roughly threefold) increase in LMW metabolites was associated with 21% and 22% increases in odds (95% CIs 1.05-1.39 and 1.07-1.39, respectively) of overweight and obesity, and a 0.090 SD unit increase in BMI Z-score (95% CI 0.003-0.18), among non-Hispanic blacks. Significant associations were not identified in any other racial/ethnic subgroup or in the study sample as a whole after controlling for potential confounders, associations were not significant for HMW or DEHP metabolites, and results did not change substantially with sensitivity analysis. CONCLUSIONS: We identify a race/ethnicity-specific association of phthalates with childhood obesity in a nationally representative sample. Further study is needed to corroborate the association, and evaluate genetic/epigenomic predisposition and/or increased phthalate exposure as possible explanations for differences among racial/ethnic subgroups.