Association of Prenatal Urinary Concentrations of Phthalates and Bisphenol A and Pubertal Timing in Boys and Girls

Background: Animal studies suggest that phthalates and bisphenol A (BPA), endocrine-disrupting chemicals found in many consumer products, may impact the timing of puberty. Objectives: We aimed to determine the association of prenatal exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys and girls participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study. Methods: We quantified urinary concentrations of eight phthalate metabolites and BPA at two time points during pregnancy among participating mothers (n=338) and conducted clinical Tanner staging of puberty on their children every 9 months between 9 and 13 y of age. We conducted accelerated failure time models and examined the role of child overweight/obese status in this association. Results: The sum of urinary metabolites of di(2-ethylhexyl) phthalate (∑DEHP), monobenzyl phthalate (MBzP), and BPA were associated with later onset of at least one of the three outcomes assessed in girls (thelarche, pubarche, or menarche) and with earlier onset of at least one of the two outcomes assessed in boys (gondarche and pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and menarche mostly among normal-weight girls but not overweight/obese girls. MBzP was associated with later thelarche in all girls, and ∑DEHP was associated with later thelarche and menarche in all girls. BPA and all phthalate biomarkers were associated with earlier gonadarche and pubarche in all boys as well as in overweight/obese boys when stratified by weight. Among normal-weight boys, associations with BPA were also inverse, whereas associations with phthalate metabolites were close to the null or positive. Conclusions: Several high-molecular-weight phthalates and BPA were associated with later puberty in girls and earlier puberty in boys included in the CHAMACOS cohort study. Childhood overweight/obesity may modify these associations. https://doi.org/10.1289/EHP3424

[1]  H. Koch,et al.  Pre-pubertal exposure with phthalates and bisphenol A and pubertal development , 2017, PloS one.

[2]  Stephen Rauch,et al.  Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity , 2017, Pediatric Research.

[3]  Chunhua Wu,et al.  Urine bisphenol A and pubertal development in boys. , 2017, International journal of hygiene and environmental health.

[4]  A. Calafat,et al.  Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls. , 2017, Reproductive toxicology.

[5]  W. Liu,et al.  DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice. , 2016, Toxicology and applied pharmacology.

[6]  A. Zota,et al.  Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010 , 2016, Environmental health perspectives.

[7]  A. Papadimitriou.  Timing of Puberty and Secular Trend in Human Maturation , 2016 .

[8]  W. Kiess,et al.  Contemporary Trends in Onset and Completion of Puberty, Gain in Height and Adiposity. , 2016, Endocrine development.

[9]  A. Calafat,et al.  Environmental phenols and pubertal development in girls. , 2015, Environment international.

[10]  X. Fang,et al.  Could exposure to phthalates speed up or delay pubertal onset and development? A 1.5-year follow-up of a school-based population. , 2015, Environment international.

[11]  C. Hsiung,et al.  The effects of phthalate and nonylphenol exposure on body size and secondary sexual characteristics during puberty. , 2015, International journal of hygiene and environmental health.

[12]  Yan Zhao,et al.  Elevated phthalates' exposure in children with constitutional delay of growth and puberty , 2015, Molecular and Cellular Endocrinology.

[13]  G. Ellison,et al.  Urinary bisphenol A and age at menarche among adolescent girls: evidence from NHANES 2003-2010. , 2015, Environmental research.

[14]  L. Liang,et al.  Serum Bisphenol A Concentration and Premature Thelarche in Female Infants Aged 4-month to 2-year , 2015, The Indian Journal of Pediatrics.

[15]  J. Meeker,et al.  In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. , 2014, Environmental research.

[16]  J. Meeker,et al.  Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys. , 2014, Reproductive toxicology.

[17]  Haiying Wu,et al.  [Impact of neonatal exposure to different doses of bisphenol A on puberty in female rats]. , 2014, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[18]  A. Calafat,et al.  Phthalate exposure and pubertal development in a longitudinal study of US girls. , 2014, Human reproduction.

[19]  Jay S Kaufman,et al.  The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. , 2014, Preventive medicine.

[20]  R. Emsley,et al.  PARAMED: Stata module to perform causal mediation analysis using parametric regression models , 2013 .

[21]  A. Calafat,et al.  Prenatal and Postnatal Bisphenol A Exposure and Body Mass Index in Childhood in the CHAMACOS Cohort , 2013, Environmental health perspectives.

[22]  M. Marcovecchio,et al.  Obesity and growth during childhood and puberty. , 2013, World review of nutrition and dietetics.

[23]  D. Buttke,et al.  Exposures to Endocrine-Disrupting Chemicals and Age of Menarche in Adolescent Girls in NHANES (2003–2008) , 2012, Environmental health perspectives.

[24]  H. Patisaul,et al.  Disrupted Organization of RFamide Pathways in the Hypothalamus Is Associated with Advanced Puberty in Female Rats Neonatally Exposed to Bisphenol A1 , 2012, Biology of reproduction.

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

[26]  B. Rubin,et al.  Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects , 2011, The Journal of Steroid Biochemistry and Molecular Biology.

[27]  Johannes Textor,et al.  DAGitty: a graphical tool for analyzing causal diagrams. , 2011, Epidemiology.

[28]  M. Park,et al.  Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice , 2011, Clinical and experimental reproductive medicine.

[29]  A. Schecter,et al.  Bisphenol A (BPA) in U.S. food. , 2010, Environmental science & technology.

[30]  Christopher R McCartney,et al.  Obesity and the pubertal transition in girls and boys. , 2010, Reproduction.

[31]  J. Toppari,et al.  Trends in puberty timing in humans and environmental modifiers , 2010, Molecular and Cellular Endocrinology.

[32]  Arnold Schecter,et al.  Dietary Intake Is Associated with Phthalate Body Burden in a Nationally Representative Sample , 2010, Environmental health perspectives.

[33]  R. Hiatt,et al.  Investigation of Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in Girls , 2010, Environmental health perspectives.

[34]  L Earl Gray,et al.  Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[35]  D. Dunger,et al.  Childhood obesity and the timing of puberty , 2009, Trends in Endocrinology & Metabolism.

[36]  Yen-Yin Chou,et al.  Phthalate Exposure in Girls During Early Puberty , 2009, Journal of pediatric endocrinology & metabolism : JPEM.

[37]  Tyler J. VanderWeele,et al.  Conceptual issues concerning mediation, interventions and composition , 2009 .

[38]  A. Calafat,et al.  Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. , 2008, Environmental research.

[39]  S. Swan,et al.  Examination of US Puberty-Timing Data from 1940 to 1994 for Secular Trends: Panel Findings , 2008, Pediatrics.

[40]  A. Calafat,et al.  Temporal Variability and Predictors of Urinary Bisphenol A Concentrations in Men and Women , 2007, Environmental health perspectives.

[41]  A. Calafat,et al.  Quantification of 22 phthalate metabolites in human urine. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[42]  Laura N. Vandenberg,et al.  Human exposure to bisphenol A (BPA). , 2007, Reproductive toxicology.

[43]  Stuart C Sealfon,et al.  These authors contributed equally to this manuscript. , 2007 .

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

[45]  Reiko Kishi,et al.  Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[46]  Li-xing Zheng,et al.  [Study on the level of environmental endocrine disruptors in serum of precocious puberty patients]. , 2006, Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine].

[47]  A. Calafat,et al.  Automated on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine. , 2005, Analytical chemistry.

[48]  Evelyn P. Whitlock,et al.  Screening and Interventions for Childhood Overweight: A Summary of Evidence for the US Preventive Services Task Force , 2005, Pediatrics.

[49]  J. Cerhan,et al.  Epidemiologic evaluation of measurement data in the presence of detection limits. , 2005, Environmental health perspectives.

[50]  J. Cerhan,et al.  Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits , 2004, Environmental Health Perspectives.

[51]  M. A. Mohd,et al.  Assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol A and nonylphenol. , 2003, Toxicology letters.

[52]  A. Siega-Riz,et al.  A Diet Quality Index for Pregnancy detects variation in diet and differences by sociodemographic factors , 2002, Public Health Nutrition.

[53]  J. Furr,et al.  Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[54]  Kristina A. Thayer,et al.  Environmental toxins: Exposure to bisphenol A advances puberty , 1999, Nature.

[55]  J. Stoker,et al.  The Department of Health and Human Services. , 1999, Home healthcare nurse.

[56]  G Block,et al.  Comparison of two dietary questionnaires validated against multiple dietary records collected during a 1-year period. , 1992, Journal of the American Dietetic Association.

[57]  J. Tanner,et al.  1 Normal growth and techniques of growth assessment , 1986 .

[58]  J M Tanner,et al.  Normal growth and techniques of growth assessment. , 1986, Clinics in endocrinology and metabolism.