Bisphenol A and cardiometabolic risk factors in obese children Naila Khalil a, ⁎ ,1 , James R. Ebert b,1 , Lei Wang c , Scott Belcher d , Miryoung Lee e , Stefan A. Czerwinski f , Kurunthachalam Kannan c a 3123 Research Blvd, Suite #200, Center for Global Health, Department of Community Health, Boonshoft School of Medicine, Wright State, University, Dayton, OH, USA b The Pediatric Lipid Clinic, the Children's Medical Center of Dayton, One Children's Plaza, Dayton, OH 45404, USA c Wadsworth Center, New York State Department of Health and Department of Environmental Health Sciences, State University of New York, Albany, NY 12201-0509, USA d 231 Albert Sabin Way, University of Cincinnati, Cincinnati, OH 45267-0575, USA e Community Health and Pediatrics, Wright State University, 3171 Research Blvd. Dayton, OH 45420-4006, USA f Community Health, Wright State University, 3171 Research Blvd. Dayton, OH 45420, USA HIGHLIGHTS • Cross sectional study of 39 obese and overweight children aged 3–8 years • Urinary BPA (u-BPA) measured by liquid chromatography-tandem mass spectrometry • Association between u-BPA and obesity analyzed by linear regression, spline analyses • U-BPA concentration in male obese children was associated with adverse liver and metabolic effects and high diastolic blood pressure abstract article info Article history: Received 11 July 2013 Received in revised form 26 September 2013 Accepted 26 September 2013 Available online xxxx Editor: Frank Riget Keywords: Bisphenol A Endocrine disruptor Non-monotonic dose response Childhood obesity Nonalcoholic fatty liver disease Spline analysis Background and objective: Bisphenol-A (BPA) is an endocrine disruptor (ED) that has been associated with obesity and metabolic changes in liver in humans. Non-alcoholic fatty liver disease (NAFLD) affects 40% of all obese children in the United States. Association of BPA with NAFLD in children is poorly understood. We investigated if BPA might play a role. Methods: In a cross sectional study of 39 obese and overweight children aged 3–8 years enrolled from the Children Medical Center of Dayton, Ohio, anthropometric, clinical and biochemical assessment of serum samples were conducted. Urinary BPA was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and was adjusted for urinary creatinine BPA (creatinine) using linear regression and spline analyses. Results: Higher urinary BPA (creatinine) concentration in overweight and obese children was associated with in- creasing free thyroxine. In male children BPA (creatinine) decreased with age, and was associated with elevated liver enzyme aspartate aminotransferase and diastolic blood pressure. The association of BPA (creatinine) persisted even after adjusting for age and ethnicity. Also in males, BPA concentration unadjusted for creatinine was significantly associated with serum fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) showing non-monotonic exposure–response relationship. Conclusion: Urinary BPA in obese children, at least in males is associated with adverse liver and metabolic effects, and high diastolic blood pressure. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Obesity in children is a major public health concern. Early life obesity not only tracks to adulthood, increasing the risk of metabolic and car- diovascular disease (CVD) but also is associated with liver abnormalities including non-alcoholic fatty liver disease (NAFLD). NAFLD affects 40% of obese children (Schwimmer et al., 2006). In addition to lifestyle factors, environmental chemicals acting as endocrine disruptors have been thought to play a role in childhood obesity (Newbold et al., 2009; DiVall, 2013) and NAFLD (Polyzos et al., 2012). Bisphenol A (BPA), a high production industrial chemical and com- ponent of polycarbonate plastics is ubiquitous in the environment (CDC, 2013). BPA is considered an endocrine-disrupting chemical (EDC) with estrogenic and thyroid hormone effects observed in experi- mental and epidemiological studies (Melzer et al., 2010; Moriyama et al., 2002; Vandenberg et al., 2009). According to 2003–2004 National Science of the Total Environment 470–471 (2014) 726–732 ⁎ Corresponding author. Tel.: +1 937 258 5559; fax: +1 937 258 5544. E-mail addresses: naila.khalil@wright.edu (N. Khalil), James.Ebert@wright.edu (J.R. Ebert), Scott.Belcher@uc.edu (S. Belcher), miryoung.lee@wright.edu (M. Lee), stefan.czerwinski@wright.edu (S.A. Czerwinski), kkannan@wadsworth.org (K. Kannan). 1 Both authors contributed equally to the manuscript. 0048-9697/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.scitotenv.2013.09.088 Contents lists available at ScienceDirect Science of the Total Environment journal homepage: www.elsevier.com/locate/scitotenv