NYU School of Medicine, Erasmus University Medical Center and New York State Department of Health respond to PA-12-185, proposing to study prenatal and childhood phthalate and bisphenol A (BPA) exposures in relationship to fetal growth, body mass, insulin resistance, fat mass and blood pressure in childhood. Di-2- ethylhexylphthalate (DEHP) is a high-molecular weight phthalate ester commonly found in processed foods, and mono-(2-ethylhexyl) phthalate increases expression of three peroxisome proliferator- , a DEHP metabolite, activated receptors which play key roles in lipid and carbohydrate metabolism, providing biological plausibility for DEHP metabolites in childhood obesity and insulin resistance. BPA, which is used to manufacture polycarbonate resin used to coat food and beverage containers, has been found to produce molecular hallmarks of obesity, and insulin resistance. Past studies of these chemical exposures and obesity have been cross-sectional and of older children and adolescents, whereas DEHP metabolites and BPA are more likely to disrupt developmental endocrine processes earlier in life and produce the chronic caloric imbalance that leads to obesity. We propose to analyze samples from three timepoints in pregnancy and two in childhood from 1431 mother-infant pairs in Generation R, a prospective, longitudinal multi-ethnic birth cohort study which has longitudinally followed 9,778 pregnancies with birth dates between 2002-2006. BPA (adjusted median 1.6 ?g/g Cr) and total DEHP metabolites (adjusted median 88.4 ?g/g Cr) in the study population are consistent with NHANES samples, increasing applicability of study findings to the US context. The PI, L. Trasande, is a nationally renowned expert in children's environmental health and first author on the first study to identify an association of an environmental chemical with childhood obesity in a nationally representative sample. The proposed study also benefits from strong support from Generation R, including the Director (V. Jaddoe), an experienced pediatric and perinatal epidemiologist with a strong record in studying early determinants of cardiovascular disease and A. Burdorf, who has developed standardized fetal growth curves for the study population. A major strength of this proposal is analysis of urine samples from three timepoints in pregnancy, which will permit examination of period-specific associations of phthalate metabolites and BPA with body mass, insulin resistance and cardiovascular risks. Analyses will be performed by K. Kannan at Wadsworth Laboratories of the New York State Department of Health, who has deep experience with precise measurement of phthalate and BPA biomarkers in urine. The proposed work endeavors to challenge existing clinical practice paradigms that obesity prevention should focus only on improved energy balance to an approach that also recognizes the role of chemical factors in the environment that may impart risk independently.

Public Health Relevance

Unhealthy diet and reduced physical activity in childhood are the leading suspected causes of increases in childhood obesity, diabetes, and blood pressure, but increasingly synthetic chemicals are being recognized for potential independent contributions. We propose to study prenatal and child exposures to phthalates and BPA in a large multiethnic Dutch cohort which has carefully characterized other risk factors for obesity, in utero and postnatal trajectories of growth, fat mass, insulin resistance and blood pressure. Significant associations identified here could be the basis for randomized control trials that focu on interventions to reduce exposures at time periods identified to be important.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Kidney, Nutrition, Obesity and Diabetes (KNOD)
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Heindel, Jerrold
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New York University
Schools of Medicine
New York
United States
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Philips, Elise M; Jaddoe, Vincent W V; Trasande, Leonardo (2017) Effects of early exposure to phthalates and bisphenols on cardiometabolic outcomes in pregnancy and childhood. Reprod Toxicol 68:105-118
Kataria, Anglina; Levine, Dov; Wertenteil, Sara et al. (2017) Exposure to bisphenols and phthalates and association with oxidant stress, insulin resistance, and endothelial dysfunction in children. Pediatr Res 81:857-864
Trasande, Leonardo; Vandenberg, Laura N; Bourguignon, Jean-Pierre et al. (2016) Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals. J Epidemiol Community Health 70:1051-1056
Farzan, Shohreh F; Chen, Yu; Trachtman, Howard et al. (2016) Urinary polycyclic aromatic hydrocarbons and measures of oxidative stress, inflammation and renal function in adolescents: NHANES 2003-2008. Environ Res 144:149-157
Trasande, L; Zoeller, R T; Hass, U et al. (2016) Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis. Andrology 4:565-72
Trasande, Leonardo; Attina, Teresa M (2015) Association of exposure to di-2-ethylhexylphthalate replacements with increased blood pressure in children and adolescents. Hypertension 66:301-8
Kataria, Anglina; Trachtman, Howard; Malaga-Dieguez, Laura et al. (2015) Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents. Environ Health 14:89
Attina, Teresa M; Trasande, Leonardo (2015) Association of Exposure to Di-2-Ethylhexylphthalate Replacements With Increased Insulin Resistance in Adolescents From NHANES 2009-2012. J Clin Endocrinol Metab 100:2640-50
Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard (2015) The effects of environmental chemicals on renal function. Nat Rev Nephrol 11:610-25