Urinary phthalates are associated with higher blood pressure in childhood.

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.

[1]  M. Iida,et al.  Differential effects of phthalate esters on transcriptional activities via human estrogen receptors α and β, and androgen receptor , 2005 .

[2]  T. Meinertz,et al.  Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease , 2001, Circulation.

[3]  F. Greenway,et al.  Prevalence of risk factors for metabolic syndrome in adolescents: National Health and Nutrition Examination Survey (NHANES), 2001-2006. , 2009, Archives of pediatrics & adolescent medicine.

[4]  Bernhard Liebl,et al.  Intake of phthalates and di(2-ethylhexyl)adipate: results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data. , 2007, Environment international.

[5]  T. Schettler,et al.  Human exposure to phthalates via consumer products. , 2006, International journal of andrology.

[6]  Ivan Rusyn,et al.  Modes of Action and Species-Specific Effects of Di-(2-ethylhexyl)Phthalate in the Liver , 2006, Critical reviews in toxicology.

[7]  B. Rosner,et al.  The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents , 2004 .

[8]  Kyungho Choi,et al.  Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with "Temple Stay" participants. , 2010, Environmental research.

[9]  N. Lee,et al.  Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells , 2012, Environmental health perspectives.

[10]  D. Christakis,et al.  International Journal of Behavioral Nutrition and Physical Activity Television Viewing, Computer Use, Obesity, and Adiposity in Us Preschool Children , 2022 .

[11]  S. Larsen,et al.  Monophthalates promote IL-6 and IL-8 production in the human epithelial cell line A549. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[12]  S. Daniels,et al.  Youth With Obesity and Obesity-Related Type 2 Diabetes Mellitus Demonstrate Abnormalities in Carotid Structure and Function , 2009, Circulation.

[13]  Michael P. Jones Indicator and stratification methods for missing explanatory variables in multiple linear regression , 1996 .

[14]  Kelly K Ferguson,et al.  Urinary phthalate metabolites in relation to biomarkers of inflammation and oxidative stress: NHANES 1999-2006. , 2011, Environmental research.

[15]  Timothy D. Dye,et al.  Phthalate Metabolites are Positively Associated With Waist Circumference and Insulin Resistance in Adult US Males , 2007 .

[16]  P. Yoon,et al.  Prevalence of Cardiovascular Disease Risk Factors Among US Adolescents, 1999−2008 , 2012, Pediatrics.

[17]  L. Trasande,et al.  Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States , 2012, Kidney international.

[18]  T. Gourlay,et al.  Inflammatory response of rat and human neutrophils exposed to di-(2-ethyl-hexyl)-phthalate-plasticized polyvinyl chloride. , 2003, Artificial organs.

[19]  R. Alexander Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. , 1995, Hypertension.

[20]  Antonia M. Calafat,et al.  Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. , 2012, Environmental research.

[21]  Ronald P. Brown,et al.  Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity. , 2011, Toxicology.

[22]  Antonia M. Calafat,et al.  Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age , 2004, Environmental health perspectives.

[23]  Elizabeth E Hatch,et al.  Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002 , 2008, Environmental health : a global access science source.

[24]  Lester R Curtin,et al.  Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. , 2002, Pediatrics.

[25]  D. Coffin,et al.  Di-n-butyl-and Di-2-ethylhexyl phthalate in human adipose tissue , 1974, Bulletin of environmental contamination and toxicology.

[26]  S. Daniels,et al.  Increased arterial stiffness is found in adolescents with obesity or obesity-related type 2 diabetes mellitus , 2010, Journal of hypertension.

[27]  T. Paus,et al.  Sex Differences in the Contributions of Visceral and Total Body Fat to Blood Pressure in Adolescence , 2012, Hypertension.

[28]  Robert Bonner,et al.  Association between oxidative stress and masked hypertension in a multi-ethnic population of obese children and adolescents. , 2011, The Journal of pediatrics.

[29]  Béatrice Desvergne,et al.  PPAR-mediated activity of phthalates: A link to the obesity epidemic? , 2009, Molecular and Cellular Endocrinology.

[30]  T. Cole,et al.  Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials , 2001, The Lancet.

[31]  N. Skakkebaek,et al.  High urinary phthalate concentration associated with delayed pubarche in girls. , 2012, International journal of andrology.

[32]  Dana B Barr,et al.  Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. , 2003, Environmental health perspectives.

[33]  D. Baird,et al.  Reproducibility of urinary phthalate metabolites in first morning urine samples. , 2002, Environmental health perspectives.

[34]  K. Flegal,et al.  Prevalence of high body mass index in US children and adolescents, 2007-2008. , 2010, JAMA.

[35]  L. Trasande,et al.  Environmental Health Perspectives Environmental Health Perspectives Race/ethnicity-specific Associations of Urinary Phthalates with Childhood Body Mass in a Nationally Representative Sample Race/ethnicity-specific Associations of Urinary Phthalates with Childhood Body Mass in a Nationally Representa , 2022 .

[36]  S. Sathyanarayana Phthalates and children's health. , 2008, Current problems in pediatric and adolescent health care.

[37]  Se-Young Oh,et al.  Community level exposure to chemicals and oxidative stress in adult population. , 2009, Toxicology Letters.

[38]  R. Henning,et al.  Microalbuminuria and Endothelial Dysfunction: Emerging Targets for Primary Prevention of End-organ Damage , 2006, Journal of Cardiovascular Pharmacology.

[39]  Louis Richer,et al.  Functional Variation in the Androgen-Receptor Gene Is Associated With Visceral Adiposity and Blood Pressure in Male Adolescents , 2010, Hypertension.

[40]  Samuel P. Caudill,et al.  Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements , 2004, Environmental health perspectives.

[41]  R. Newbold,et al.  Developmental exposure to endocrine disruptors and the obesity epidemic. , 2007, Reproductive toxicology.

[42]  P E Shrout,et al.  The effects of measurement errors on some multivariate procedures. , 1977, American journal of public health.

[43]  N. Skakkebaek,et al.  Metabolism of phthalates in humans. , 2007, Molecular nutrition & food research.

[44]  S. Daniels,et al.  Tobacco Smoke Exposure Is Associated With the Metabolic Syndrome in Adolescents , 2005, Circulation.