Prenatal & Childhood POP Exposures, Obesity & Cardiovascular Risks in Children -Resubmission-1

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Project Summary A growing body of literature indicates that environmental contaminants, such as persistent organic pollutants, may affect risk of obesity, cardiovascular disease, and other chronic diseases, including renal disease and metabolic syndrome. Laboratory studies suggest that persistent organic pollutants (POPs) such as perfluoroalkylacids (PFAAs), organochlorine pesticides (OCP), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDE) can disrupt developmental endocrine processes and provoke oxidant stress, a major pathophysiologic mechanism underlying cardiovascular and renal risks. While some epidemiological studies have investigated exposure to POPs or related contaminants in relation to obesity and cardiovascular effects, older studies may not reflect the effects of current exposures because they preceded phase-outs of certain POPs and emergence of substitutes. Preliminary analyses suggest associations of PFAAs with sexually dimorphic increases in body mass and reduced glomerular filtration rate (GFR). Past studies have also failed to examine interactions and potential joint effects of multiple low-level POP exposures. Few studies have examined these risks in diverse Latino populations disproportionately affected by obesity, cardiometabolic and renal risks, including not only Mexican Americans but also other subgroups. To examine prenatal and childhood POP exposures as cardiometabolic and renal risks, we will leverage the resources of Starting Early, an established randomized controlled trial of 533 Latino mother-infant pairs funded by the US Department of Agriculture (2011-68001-30207), to examine the association of prenatal and early life POP exposures with the development of preclinical and intermediate endpoints indicative of early metabolic and cardiorenal risks. We will include at least 400 mother-infant pairs from Starting Early and measure prenatal exposure to POP using banked newborn blood spots, while adding prospective urine and blood collection and clinical visits annually at ages 4-7. This study provides a unique opportunity to capitalize on existing resources and an engaged study population to evaluate emerging contaminants of concern to young children. We hypothesize that prenatal and childhood exposure to POPs are associated with body mass, elevated blood pressure, increased arterial stiffness, reduced renal function, and increased oxidant stress biomarkers in childhood. It is possible that alterations detected by such biomarkers can be halted or reversed with modification of risk factors, highlighting the importance of identifying early risk factors and biomarkers of cardiorenal risk in younger populations. With repeated measures of POPs exposure during childhood, our extension of the Starting Early study presents a unique opportunity to evaluate cardiovascular and renal effects of early life exposures.