Faculty Bibliography

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.

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.

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.

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.

The impact of air pollution on fetal growth remains controversial, in part, because studies have been limited to sub-regions of the United States with limited variability. No study has examined air pollution impacts on neonatal health care utilization. We performed descriptive, univariate and multivariable analyses on administrative hospital record data from 222,359 births in the 2000, 2003 and 2006 Kids Inpatient Database linked to air pollution data drawn from the US Environmental Protection Agency's Aerometric Information Retrieval System. In this study, air pollution exposure during the birth month was estimated based on birth hospital address. Although air pollutants were not individually associated with mean birth weight, a three-pollutant model controlling for hospital characteristics, demographics, and birth month identified 9.3% and 7.2% increases in odds of low birth weight and very low birth weight for each mug/m(3) increase in PM(2.5) (both P<0.0001). PM(2.5) and NO(2) were associated with -3.0% odds/p.p.m. and +2.5% odds/p.p.b. of preterm birth, respectively (both P<0.0001). A four-pollutant multivariable model indicated a 0.05 days/p.p.m. NO(2) decrease in length of the birth hospitalization (P=0.0061) and a 0.13 days increase/p.p.m. CO (P=0.0416). A $1166 increase in per child costs was estimated for the birth hospitalization per p.p.m. CO (P=0.0002) and $964 per unit increase in O(3) (P=0.0448). A reduction from the 75th to the 25th percentile in the highest CO quartile for births predicts annual savings of $134.7 million in direct health care costs. In a national, predominantly urban, sample, air pollutant exposures during the month of birth are associated with increased low birth weight and neonatal health care utilization. Further study of this database, with enhanced control for confounding, improved exposure assessment, examination of exposures across multiple time windows in pregnancy, and in the entire national sample, is supported by these initial investigations.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 January 2013; doi:10.1038/jes.2012.124.

Urinary bisphenol A (BPA), a widely used biomarker of exposure to BPA, has been associated with cardiometabolic derangements in laboratory studies and with low-grade albuminuria in Chinese adults. Despite the known unique vulnerability of children to environmental chemicals, no studies have examined associations of urinary BPA with albuminuria in children. As exposure to BPA is widespread in the United States population, we examined data from 710 children in the 2009-10 National Health and Nutrition Examination Survey with urinary BPA measurements and first morning urine samples with creatinine values. Controlled for a broad array of sociodemographic and environmental risk factors as well as insulin resistance and elevated cholesterol, children with the highest compared with the lowest quartile of urinary BPA had a significant 0.91 mg/g higher albumin-to-creatinine ratio, adjusted for the urinary BPA concentration. When the multivariable model was reprised substituting continuous measures of BPA, a significant 0.28 mg/g albumin-to-creatinine ratio increase was identified for each log unit increase in urinary BPA. Thus, an association of BPA exposure with low-grade albuminuria is consistent with previous results found in Chinese adults and documents this in children in the United States. Our findings broaden the array of adverse effects of BPA to include endothelial dysfunction as evidenced by the low-grade albuminuria and support proactive efforts to prevent harmful exposures.Kidney International advance online publication, 9 January 2013; doi:10.1038/ki.2012.422.

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.

OBJECTIVE: Prior research on the physical health of children exposed to the World Trade Center (WTC) attacks has largely relied on parental report via questionnaire. We examined the impact of clinically-reported exposures on the physical health of children who lived and/or attended school in downtown Manhattan on September 11, 2001. STUDY DESIGN: We performed a cross-sectional study of 148 patients who presented to the WTC Environmental Health Center/Survivors Health Program, and were /=1day in their home between September 11 and 18, 2001; and 25.7% reported home dust exposure. New-onset nasal/sinus congestion was reported in 52.7%, while nearly one-third reported new gastroesophageal reflux (GERD) symptoms. Prehypertension or hypertension was identified in 45.5%. Multivariable regression with exposure variables, body mass index category, and age as covariates identified strongest associations of dust cloud with spirometry (17.1% decrease in maximum midexpiratory flow). Younger children experienced increased peripheral eosinophils (+0.098% per year, p=0.023), while older children experienced more new-onset GERD (OR 1.17, p=0.004), headaches (OR 1.10, p=0.011), and prehypertension (OR 1.09, p=0.024). Home dust exposure was associated with reduced high-density lipoprotein (-10.3mg/dL, p=0.027) and elevated triglycerides (+36.3mg/dL, p=0.033). CONCLUSIONS: While these findings cannot be assumed to generalize to all children exposed to the WTC attacks, they strongly suggest the need for more extensive study of respiratory, metabolic, and cardiovascular consequences.