Review Article | Published:

Early-life exposure to EDCs: role in childhood obesity and neurodevelopment

Nature Reviews Endocrinology volume 13, pages 161173 (2017) | Download Citation

Abstract

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during gestation, infancy and childhood. The fetus, infant and child might have enhanced sensitivity to environmental stressors such as EDCs due to their rapid development and increased exposure to some EDCs as a consequence of development-specific behaviour, anatomy and physiology. In this Review, I discuss epidemiological studies examining the relationship between early-life exposure to bisphenol A (BPA), phthalates, triclosan and perfluoroalkyl substances (PFAS) with childhood neurobehavioural disorders and obesity. The available epidemiological evidence suggest that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehaviour (BPA and phthalates) and excess adiposity or increased risk of obesity and/or overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability and elucidating the presence and nature of sexually dimorphic EDC effects would enable stronger inferences to be made from epidemiological studies than currently possible. Ultimately, improved estimates of the causal effects of EDC exposures on child health could help identify susceptible subpopulations and lead to public health interventions to reduce these exposures.

Key points

  • Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood neurodevelopmental disorders or obesity by disrupting hormone-mediated processes during critical periods of development

  • The developing fetus, infant and child might have enhanced sensitivity to environmental stressors such as EDCs and increased exposure to some EDCs due to developmentally appropriate behaviour, anatomy and physiology

  • The available epidemiological evidence suggest that prenatal bisphenol A and phthalate exposure is associated with adverse neurobehavioural outcomes in children, but not excess adiposity or risk of obesity or being overweight

  • Epidemiological studies show that prenatal PFAS exposure is associated with reduced fetal growth, excess adiposity and risk of being overweight or obese, but not neurobehavioural outcomes

  • Improving EDC exposure measurement, reducing confounding bias, identifying discrete periods of vulnerability and sexually dimorphic associations, and quantifying the effects of EDC mixtures will enhance inferences made from epidemiological studies

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References

  1. 1.

    Sir Richard Doll Lecture. Developmental origins of chronic disease. Public Health 126, 185–189 (2012).

  2. 2.

    et al. Developmental origins of health and disease: integrating environmental influences. Endocrinology 156, 3416–3421 (2015).

  3. 3.

    et al. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ. Health Perspect. 113, 894–899 (2005).

  4. 4.

    , , & Dose-response relationship of prenatal mercury exposure and IQ: an integrative analysis of epidemiologic data. Environ. Health Perspect. 115, 609–615 (2007).

  5. 5.

    et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N. Engl. J. Med. 365, 1304–1314 (2011).

  6. 6.

    , & Lead and PCBs as risk factors for attention deficit/hyperactivity disorder. Environ. Health Perspect. 118, 1654–1667 (2010).

  7. 7.

    , & 60- and 72-month follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol: cognitive and language assessment. J. Dev. Behav. Pediatr. 13, 383–391 (1992).

  8. 8.

    , , & Endocrine-disrupting chemicals and obesity development in humans: a review. Obes. Rev. 12, 622–636 (2011).

  9. 9.

    , & Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Front. Psychol. 1, 223 (2010).

  10. 10.

    , & Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int. J. Obes. 32, 201–210 (2008).

  11. 11.

    et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 153, 4097–4110 (2012).

  12. 12.

    , , & What can epidemiological studies tell us about the impact of chemical mixtures on human health? Environ. Health Perspect. 124, A6–A9 (2016). This article provides an overview and discussion of the types of questions that epidemiological studies of chemical mixtures can address.

  13. 13.

    , & Environmental chemicals in pregnant women in the United States: NHANES 2003–2004. Environ. Health Perspect. 119, 878–885 (2011).

  14. 14.

    et al. The pregnancy exposome: multiple environmental exposures in the INMA–Sabadell Birth Cohort. Environ. Sci. Technol. 49, 10632–10641 (2015).

  15. 15.

    , , , & Environmental pollutants and child health — a review of recent concerns. Int. J. Hyg. Environ. Health 219, 331–342 (2016). This article reviews the health effects of a variety of EDCs, including banned organochlorine chemicals.

  16. 16.

    et al. Differences between children and adults: implications for risk assessment at California EPA. Int. J. Toxicol. 21, 403–418 (2002).

  17. 17.

    , & Identifying critical windows of exposure for children's health. Environ. Health Perspect. 108 (Suppl. 3), 451–455 (2000).

  18. 18.

    & Breastfeeding and the weanling's dilemma. Am. J. Public Health 94, 1075 (2004).

  19. 19.

    Onset of xenobiotic metabolism in children: toxicological implications. Food Addit. Contam. 15 (Suppl.), 45–51 (1998).

  20. 20.

    , & Developmental expression of cytochrome P450 enzymes in human liver. Pharmacol. Toxicol. 82, 209–217 (1998).

  21. 21.

    & Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ. Health Perspect. 108 (Suppl. 3), 511–533 (2000).

  22. 22.

    & Ontogeny of the human central nervous system: what is happening when? Early Hum. Dev. 82, 257–266 (2006).

  23. 23.

    & Epigenetics and environmental chemicals. Curr. Opin. Pediatr. 21, 243–251 (2009).

  24. 24.

    , , , & Elucidating the links between endocrine disruptors and neurodevelopment. Endocrinology 156, 1941–1951 (2015). This article discusses both animal and epidemiological studies examining the neurotoxic effects of EDCs.

  25. 25.

    , & Endocrine disruptors and obesity. Nat. Rev. Endocrinol. 11, 653–661 (2015). This article provides an overview of animal and human studies of environmental obesogens.

  26. 26.

    & Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J. Neuroendocrinol. 16, 809–818 (2004).

  27. 27.

    , , & Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why? Clin. Endocrinol. 79, 152–162 (2013).

  28. 28.

    et al. Maternal mild thyroid hormone insufficiency in early pregnancy and attention-deficit/hyperactivity disorder symptoms in children. JAMA Pediatr. 169, 838–845 (2015).

  29. 29.

    et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann. Neurol. 74, 733–742 (2013).

  30. 30.

    et al. Maternal thyroid function during pregnancy and behavioral problems in the offspring: the generation R study. Pediatr. Res. 69, 454–459 (2011).

  31. 31.

    , & Neurodevelopment in infants and preschool children with congenital hypothyroidism: etiological and treatment factors affecting outcome. J. Pediatr. Psychol. 17, 187–213 (1992).

  32. 32.

    & Attention problems in adolescents with congenital hypothyroidism: a multicomponential analysis. J. Int. Neuropsychol. Soc. 7, 734–744 (2001).

  33. 33.

    & Dissociating attention deficits in children with ADHD and congenital hypothyroidism using multiple CPTs. J. Child Psychol. Psychiatry 42, 1049–1056 (2001).

  34. 34.

    , & The influence of etiology and treatment factors on intellectual outcome in congenital hypothyroidism. J. Dev. Behav. Pediatr. 22, 376–384 (2001).

  35. 35.

    Early infancy as a critical period for development of obesity and related conditions. Nestle Nutr. Workshop Ser. Pediatr. Program. 65, 13–20 (2010).

  36. 36.

    Prenatal origin of obesity and their complications: gestational diabetes, maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia. Reprod. Toxicol. 32, 205–212 (2011).

  37. 37.

    , & Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod. Toxicol. 20, 345–352 (2005).

  38. 38.

    Developmental origins of chronic disease. Public Health 126, 185–189 (2012).

  39. 39.

    The developmental origins of adult disease. J. Am. Coll. Nutr. 23 (6 Suppl.), 588S–595S (2004).

  40. 40.

    et al. Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter? Am. J. Clin. Nutr. 89, 1383–1392 (2009).

  41. 41.

    et al. Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis. Paediatr. Perinat. Epidemiol. 26, 19–26 (2012).

  42. 42.

    & Rapid growth in infancy and childhood and obesity in later life — a systematic review. Obes. Rev. 6, 143–154 (2005).

  43. 43.

    et al. Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children. J. Clin. Endocrinol. Metab. 99, 2557–2566 (2014).

  44. 44.

    et al. Infant growth and later body composition: evidence from the 4-component model. Am. J. Clin. Nutr. 87, 1776–1784 (2008).

  45. 45.

    et al. Association between birth weight and visceral fat in adults. Am. J. Clin. Nutr. 92, 347–352 (2010).

  46. 46.

    et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109, 433–438 (2004).

  47. 47.

    & Obesity and insulin resistance. J. Clin. Invest. 106, 473–481 (2000).

  48. 48.

    Pathophysiology of insulin resistance in human disease. Physiol. Rev. 75, 473–486 (1995).

  49. 49.

    et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

  50. 50.

    , , , & Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort. Am. J. Clin. Nutr. 95, 633–639 (2012).

  51. 51.

    The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Prog. Brain Res. 153, 57–73 (2006).

  52. 52.

    , , , & The role of gut hormones and the hypothalamus in appetite regulation. Endocr. J. 57, 359–372 (2010).

  53. 53.

    , , & Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring) 22, 1865–1871 (2014).

  54. 54.

    et al. Attention-deficit/hyperactive disorder is related to decreased weight in the preschool period and to increased rate of overweight in school-age boys. J. Child Adolesc. Psychopharmacol. 25, 691–700 (2015).

  55. 55.

    , , , & Prevalence of overweight and obesity in children and adolescents with ADHD: the significance of comorbidities and pharmacotherapy. J. Atten. Disord. (2015).

  56. 56.

    et al. Cognitive performance and BMI in childhood: shared genetic influences between reaction time but not response inhibition. Obesity (Silver Spring) 22, 2312–2318 (2014).

  57. 57.

    , , , & Dietary restraint and impulsivity modulate neural responses to food in adolescents with obesity and healthy adolescents. Obesity (Silver Spring) 23, 2183–2189 (2015).

  58. 58.

    et al. The stomach-derived hormone ghrelin increases impulsive behavior. Neuropsychopharmacology 41, 1199–1209 (2015). This rodent study demonstrates that the adipocytokine, ghrelin, can affect impulsive behaviour.

  59. 59.

    et al. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ. Health Perspect. 118, 565–571 (2010).

  60. 60.

    et al. Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age. Environ. Health Perspect. 120, 290–295 (2012).

  61. 61.

    et al. Endocrine disruptors and childhood social impairment. Neurotoxicology 32, 261–267 (2011).

  62. 62.

    et al. Prenatal exposure to phthalates and infant development at 6 months: prospective Mothers and Children's Environmental Health (MOCEH) study. Environ. Health Perspect. 119, 1495–1500 (2011).

  63. 63.

    et al. Persistent associations between maternal prenatal exposure to phthalates on child IQ at age 7 years. PLoS ONE 9, e114003 (2014). This paper reports an association between prenatal exposure to some phthalates and child IQ 7 years later.

  64. 64.

    et al. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the HOME study. Environ. Health Perspect. 122, 513–520 (2014).

  65. 65.

    et al. Fetal and childhood exposure to phthalate diesters and cognitive function in children up to 12 years of age: Taiwanese Maternal and Infant Cohort Study. PLoS ONE 10, e0131910 (2015).

  66. 66.

    et al. Prenatal exposure to phthalates and neuropsychological development during childhood. Int. J. Hyg. Environ. Health 218, 550–558 (2015).

  67. 67.

    , , , & Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6–11 years of age: CHMS 2007–2009. Neurotoxicology 54, 89–98 (2016).

  68. 68.

    et al. Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children. Biol. Psychiatry 66, 958–963 (2009).

  69. 69.

    et al. Prenatal phthalate exposure and reduced masculine play in boys. Int. J. Androl. 33, 259–269 (2010).

  70. 70.

    et al. Prenatal phthalate exposure and childhood growth and blood pressure: evidence from the Spanish INMA-Sabadell Birth Cohort Study. Environ. Health Perspect. 123, 1022–1029 (2015).

  71. 71.

    et al. Prenatal exposure to phthalates and childhood body size in an urban cohort. Environ. Health Perspect. 124, 514–520 (2015).

  72. 72.

    et al. Prenatal phthalate exposures and childhood fat mass in a New York City cohort. Environ. Health Perspect. 124, 507–513 (2015). A pooled cohort study examining the association between prenatal phthalate exposure and child adiposity.

  73. 73.

    et al. Food packaging and bisphenol A and bis(2-ethyhexyl) phthalate exposure: findings from a dietary intervention. Environ. Health Perspect. 119, 914–920 (2011).

  74. 74.

    et al. Phthalates in indoor dust and their association with building characteristics. Environ. Health Perspect. 113, 1399–1404 (2005).

  75. 75.

    et al. Phthalate metabolites in urine samples from Danish children and correlations with phthalates in dust samples from their homes and daycare centers. Int. J. Hyg. Environ. Health 217, 78–87 (2013).

  76. 76.

    et al. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic. J. Expo. Sci. Environ. Epidemiol. 24, 459–466 (2014).

  77. 77.

    , & Maternal–fetal transfer of 14C-di-2-ethylhexyl phthalate and 14C-diethyl phthalate in rats. J. Pharm. Sci. 64, 1347–1350 (1975).

  78. 78.

    & Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food Chem. Toxicol. 22, 123–131 (1984).

  79. 79.

    Contemporary issues in exposure assessment using biomonitoring. Curr. Epidemiol. Rep. 3, 145–153 (2016).

  80. 80.

    , , & Within-subject pooling of biological samples to reduce exposure misclassification in biomarker-based studies. Epidemiology 27, 378–388 (2016).

  81. 81.

    et al. Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate and diisononyl phthalate. Toxicol. Sci. 123, 206–216 (2011).

  82. 82.

    et al. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague–Dawley rat in a cumulative, dose-additive manner. Toxicol. Sci. 105, 153–165 (2008).

  83. 83.

    et al. Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns. Chemosphere 157, 42–48 (2016).

  84. 84.

    et al. Childhood exposure to phthalates: associations with thyroid function, insulin-like growth factor I, and growth. Environ. Health Perspect. 118, 1458–1464 (2010).

  85. 85.

    et al. Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis. Reprod. Biol. Endocrinol. 13, 4 (2015).

  86. 86.

    & Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions. Toxicol. Lett. 189, 67–77 (2009).

  87. 87.

    & Characteristics of 3,5,3<0x0374>-triiodothyronine (T3)-uptake system of tadpole red blood cells: effect of endocrine-disrupting chemicals on cellular T3 response. J. Endocrinol. 183, 627–637 (2004).

  88. 88.

    , & The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers. Mol. Cell. Endocrinol. 244, 75–78 (2005).

  89. 89.

    , & Environmental pollutants and hydroxysteroid dehydrogenases. Vitam. Horm. 94, 349–390 (2014).

  90. 90.

    , , , & Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: a repeated measures analysis. Environ. Health Perspect. 123, 210–216 (2015).

  91. 91.

    , , & First-trimester urine concentrations of phthalate metabolites and phenols and placenta miRNA expression in a cohort of U.S. women. Environ. Health Perspect. 124, 380–387 (2015).

  92. 92.

    National Research Council (US) Committee on the Health Risk of Phthalates. Phthalates and Cumulative Risk Assessment: the Tasks Ahead (National Academies Press, 2008).

  93. 93.

    et al. Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6–10 years of age. Environ. Health Perspect. 122, 521–528 (2014).

  94. 94.

    et al. Prenatal exposure to phthalate esters and behavioral syndromes in children at eight years of age: Taiwan Maternal and Infant Cohort Study. Environ. Health Perspect. 123, 95–100 (2014).

  95. 95.

    et al. Prenatal phthalate exposures and body mass index among 4 to 7 year old children: a pooled analysis. Epidemiology 27, 449–458 (2016).

  96. 96.

    et al. Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ. Res. 112, 186–193 (2012).

  97. 97.

    et al. Longitudinal associations of phthalate exposures during childhood and body size measurements in young girls. Epidemiology 27, 492–499 (2016).

  98. 98.

    , , , & Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ. Health Perspect. 121, 501–506 (2013).

  99. 99.

    et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ. Health 7, 27–41 (2008).

  100. 100.

    , , , & Canned soup consumption and urinary bisphenol A: a randomized crossover trial. JAMA 306, 2218–2220 (2011).

  101. 101.

    , , & Bisphenol A: how the most relevant exposure sources contribute to total consumer exposure. Risk Anal. 30, 473–487 (2010).

  102. 102.

    , , , & Handling of thermal receipts as a source of exposure to bisphenol A. JAMA 311, 859–860 (2014).

  103. 103.

    et al. Pharmacokinetics of bisphenol A in humans following a single oral administration. Environ. Int. 83, 107–115 (2015).

  104. 104.

    et al. Early-life bisphenol A exposure and child body mass index: a prospective cohort study. Environ. Health Perspect. 122, 1239–1245 (2014).

  105. 105.

    et al. Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environ. Health Perspect. 121, 514–520 (2013).

  106. 106.

    et al. Association of early life exposure to bisphenol A with obesity and cardiometabolic traits in childhood. Environ. Res. 146, 379–387 (2016). This article describes a cohort study examining prenatal BPA exposure and child obesity and cardiometabolic health.

  107. 107.

    et al. Bisphenol A and adiposity in an inner-city birth cohort. Environ. Health Perspect. 124, 1644–1650 (2016).

  108. 108.

    et al. Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children. Environ. Int. 37, 858–866 (2011).

  109. 109.

    et al. Patterns, variability, and predictors of urinary bisphenol A concentrations during childhood. Environ. Sci. Technol. 50, 5981–5990 (2016).

  110. 110.

    et al. Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children. Environ. Res. 126, 43–50 (2013).

  111. 111.

    et al. Prenatal bisphenol A exposure and early childhood behavior. Environ. Health Perspect. 117, 1945–1952 (2009).

  112. 112.

    et al. Impact of early-life bisphenol A exposure on behavior and executive function in children. Pediatrics 128, 873–882 (2011).

  113. 113.

    et al. Bisphenol A exposure and behavioral problems among inner city children at 7–9 years of age. Environ. Res. 142, 739–745 (2015).

  114. 114.

    et al. Prenatal bisphenol A exposure and child behavior in an inner-city cohort. Environ. Health Perspect. 120, 1190–1194 (2012).

  115. 115.

    et al. Prenatal bisphenol A exposure and maternally reported behavior in boys and girls. Neurotoxicology 45, 91–99 (2014).

  116. 116.

    et al. Exposure to bisphenol A during pregnancy and child neuropsychological development in the INMA–Sabadell cohort. Environ. Res. 142, 671–679 (2015). This paper details one of the only prospective cohort studies examining the association between prenatal BPA exposure and both child behaviour and cognition.

  117. 117.

    et al. Prenatal bisphenol A urine concentrations and early rapid growth and overweight risk in the offspring. Epidemiology 24, 791–799 (2013).

  118. 118.

    et al. Prenatal exposure to phenols and growth in boys. Epidemiology 25, 625–635 (2014).

  119. 119.

    , & Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA 308, 1113–1121 (2012).

  120. 120.

    et al. Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study. Environ. Health 11, 79 (2012).

  121. 121.

    & Synthetic oestrogenic agents without the phenanthrene nucleus. Nature 137, 996 (1936).

  122. 122.

    , & Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay. Environ. Health Perspect. 106, 23–26 (1998).

  123. 123.

    , & Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-α-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells. Environ. Health Perspect. 113, 431–439 (2005).

  124. 124.

    et al. In vitro molecular mechanisms of bisphenol A action. Reprod. Toxicol. 24, 178–198 (2007).

  125. 125.

    et al. Bisphenol A disrupts steroidogenesis in human H295R cells. Toxicol. Sci. 121, 320–327 (2011).

  126. 126.

    et al. Daily bisphenol A excretion and associations with sex hormone concentrations: results from the InCHIANTI Adult Population Study. Environ. Health Perspect. 118, 1603–1608 (2010).

  127. 127.

    , & Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic. Environ. Sci. Technol. 44, 1458–1463 (2010).

  128. 128.

    et al. Are environmental levels of bisphenol A associated with reproductive function in fertile men? Environ. Health Perspect. 118, 1286–1291 (2010).

  129. 129.

    , & Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 146, 607–612 (2005).

  130. 130.

    et al. Bisphenol A interferes with thyroid specific gene expression. Toxicology 304, 21–31 (2013).

  131. 131.

    et al. Maternal urinary bisphenol A during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study. Environ. Health Perspect. 121, 138–144 (2013).

  132. 132.

    & Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008. Environ. Health Perspect. 119, 1396–1402 (2011).

  133. 133.

    et al. Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: the HOME Study. Environ. Res. 138, 453–460 (2015).

  134. 134.

    et al. NTP–CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res. B Dev. Reprod. Toxicol. 83, 157–395 (2008).

  135. 135.

    et al. Association of bisphenol A exposure and attention-deficit/hyperactivity disorder in a national sample of U.S. children. Environ. Res. 150, 112–118 (2016).

  136. 136.

    et al. Exposure to bisphenol A and behavior in school-age children. Neurotoxicology 53, 12–19 (2016).

  137. 137.

    et al. Bisphenol A in relation to behavior and learning of school-age children. J. Child Psychol. Psychiatry 54, 890–899 (2013).

  138. 138.

    , , , & Prenatal exposure to environmental phenols and childhood fat mass in the Mount Sinai Children's Environmental Health Study. Environ. Int. 91, 350–356 (2016).

  139. 139.

    , , , & Triclosan: a critical review of the experimental data and development of margins of safety for consumer products. Crit. Rev. Toxicol. 40, 422–484 (2010).

  140. 140.

    , , & Pharmacokinetics of triclosan following oral ingestion in humans. J. Toxicol. Environ. Health A 69, 1861–1873 (2006).

  141. 141.

    , , , & Urinary concentrations of triclosan in the U.S. population: 2003–2004. Environ. Health Perspect. 116, 303–307 (2008).

  142. 142.

    , & Disruption of LH-induced testosterone biosynthesis in testicular Leydig cells by triclosan: probable mechanism of action. Toxicology 250, 124–131 (2008).

  143. 143.

    & Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 34, 1423–1436 (2009).

  144. 144.

    et al. Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan. Environ. Int. 92–93, 716–728 (2016).

  145. 145.

    , , , & Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors. Toxicol. In Vitro 27, 2049–2060 (2013).

  146. 146.

    , , & Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in NHANES 2007–2008. Sci. Total Environ. 445–446, 299–305 (2013).

  147. 147.

    , , , & Long term use of triclosan toothpaste and thyroid function. Sci. Total Environ. 416, 75–79 (2012).

  148. 148.

    & Is triclosan harming your microbiome? Science 353, 348–349 (2016).

  149. 149.

    et al. Prenatal triclosan exposure and anthropometric measures including anogenital distance in Danish infants. Environ. Health Perspect. 124, 1261–1268 (2016).

  150. 150.

    et al. Prenatal phenol and phthalate exposures and birth outcomes. Environ. Health Perspect. 116, 1092–1097 (2008).

  151. 151.

    , , , & Cognitive ability in adolescents born small for gestational age: associations with fetal growth velocity, head circumference and postnatal growth. Early Hum. Dev. 91, 755–760 (2015).

  152. 152.

    et al. Urinary levels of endocrine-disrupting chemicals, including bisphenols, bisphenol A diglycidyl ethers, benzophenones, parabens, and triclosan in obese and non-obese Indian children. Environ. Res. 137, 120–128 (2015).

  153. 153.

    et al. Urinary triclosan concentrations are inversely associated with body mass index and waist circumference in the US general population: experience in NHANES 2003–2010. Int. J. Hyg. Environ. Health 218, 401–406 (2015).

  154. 154.

    , & Association of urinary phenols with increased body weight measures and obesity in children and adolescents. J. Pediatr. 165, 744–749 (2014).

  155. 155.

    Panel on Contaminants in the Food Chain. Perfluoroctane sulfonate, perfluorooctanoic acid and their salts: scientific opinion of the panel on contaminants in the food chain. EFSA J. 653, 1–131 (2008).

  156. 156.

    et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Integr. Environ. Assess. Manag. 7, 513–541 (2011).

  157. 157.

    et al. The Navigation Guide — evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ. Health Perspect. 122, 1028–1039 (2014). This systematic review and meta-analysis of rodent studies examines early life triclosan exposure and serum thyroxine concentrations.

  158. 158.

    et al. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ. Health Perspect. (2016). This article describes a prospective cohort study examining the association between prenatal perfluoralkyl substance exposures and detailed measures of child adiposity.

  159. 159.

    et al. Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: the HOME study. Obesity (Silver Spring) 24, 231–237 (2016).

  160. 160.

    et al. Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study. Environ. Health Perspect. 120, 668–673 (2012).

  161. 161.

    et al. Anthropometry in 5- to 9-year-old Greenlandic and Ukrainian children in relation to prenatal exposure to perfluorinated alkyl substances. Environ. Health Perspect. 123, 841–846 (2015).

  162. 162.

    et al. Maternal concentrations of polyfluoroalkyl compounds during pregnancy and fetal and postnatal growth in British girls. Environ. Health Perspect. 120, 1432–1437 (2012).

  163. 163.

    et al. Prenatal exposures to perfluorinated chemicals and anthropometry at 7 years of age. Am. J. Epidemiol. 178, 921–927 (2013).

  164. 164.

    , & Perfluorooctanoate and neuropsychological outcomes in children. Epidemiology 24, 590–599 (2013).

  165. 165.

    et al. Prenatal exposure to perfluroalkyl substances and children's IQ: the Taiwan maternal and infant cohort study. Int. J. Hyg. Environ. Health 218, 639–644 (2015).

  166. 166.

    et al. Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study. Environ. Int. 83, 176–182 (2015).

  167. 167.

    & Serum perfluorinated compound concentration and attention deficit/hyperactivity disorder in children 5–18 years of age. Environ. Health Perspect. 119, 1466–1471 (2011).

  168. 168.

    & Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years. Environ. Health Perspect. 119, 573–578 (2011).

  169. 169.

    et al. Prenatal polybrominated diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children. Environ. Res. 147, 556–564 (2016).

  170. 170.

    et al. Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women. Environ. Health 11, 21 (2012).

  171. 171.

    et al. Prenatal exposure to perfluoroalkyl substances and the risk of congenital cerebral palsy in children. Am. J. Epidemiol. 180, 574–581 (2014). A nested case–control study identifying an increased risk of congenital cerebral palsy with increasing perfluoralkyl substance exposure.

  172. 172.

    et al. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ. Health Perspect. 123, 367–373 (2015).

  173. 173.

    et al. Fetal exposure to perfluorinated compounds and attention deficit hyperactivity disorder in childhood. PLoS ONE 9, e95891 (2014).

  174. 174.

    , , , & Exposure to polyfluoroalkyl chemicals and attention deficit/hyperactivity disorder in U.S. children 12–15 years of age. Environ. Health Perspect. 118, 1762–1767 (2010).

  175. 175.

    , & Perfluorooctanoate exposure in a highly exposed community and parent and teacher reports of behaviour in 6–12-year-old children. Paediatr. Perinat. Epidemiol. 28, 146–156 (2014).

  176. 176.

    et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ. Health Perspect. 115, 1298–1305 (2007).

  177. 177.

    & An assessment of the exposure of Americans to perfluorooctane sulfonate: a comparison of estimated intake with values inferred from NHANES data. J. Expo. Sci. Environ. Epidemiol. 21, 150–168 (2011).

  178. 178.

    United States Environmental Protection Agency. Child-specific exposure factors handbook (final report) 2008. EPA (2008).

  179. 179.

    et al. Pre- and postnatal exposure to perfluorinated compounds (PFCs). Environ. Sci. Technol. 44, 7123–7129 (2010).

  180. 180.

    , & Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature. Environ. Res. 116, 93–117 (2012).

  181. 181.

    et al. Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds. Epigenetics 5, 539–546 (2010).

  182. 182.

    et al. Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation. Environ. Int. 63, 71–76 (2014).

  183. 183.

    et al. Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans. Environ. Int. 57–58, 2–10 (2013).

  184. 184.

    , , & Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-α, -β, and -γ, liver X receptor-β, and retinoid X receptor-α. Toxicol. Sci. 92, 476–489 (2006).

  185. 185.

    et al. Differential effects of environmental chemicals and food contaminants on adipogenesis, biomarker release and PPARγ activation. Mol. Cell. Endocrinol. 361, 106–115 (2012).

  186. 186.

    et al. Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicol. In Vitro 27, 1634–1643 (2013).

  187. 187.

    , & Thyroid effects of endocrine disrupting chemicals. Mol. Cell. Endocrinol. 355, 240–248 (2012).

  188. 188.

    , , , & Perfluorinated acids and hypothyroxinemia in pregnant women. Environ. Res. 111, 559–564 (2011).

  189. 189.

    , & Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-γ agonists. Front. Biosci. 13, 1813–1826 (2008).

  190. 190.

    et al. The Navigation Guide — evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ. Health Perspect. 122, 1015–1027 (2014).

  191. 191.

    et al. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study. BMJ 348, g14 (2014).

  192. 192.

    et al. Birth size, early life weight gain, and midchildhood cardiometabolic health. J. Pediatr. 173, 122–130. e1 (2016).

  193. 193.

    , , , & Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure. Environ. Res. 132, 62–69 (2014).

  194. 194.

    & Childhood overweight prevalence in the United States: the impact of parent-reported height and weight. Obesity (Silver Spring) 17, 1574–1580 (2009).

  195. 195.

    & The obesity epidemic and changes in self-report biases in BMI. Obesity (Silver Spring) 21, 856–860 (2013).

  196. 196.

    , & Exposure to polyfluoroalkyl chemicals and cholesterol, body weight, and insulin resistance in the general U.S. population. Environ. Health Perspect. 118, 197–202 (2010).

  197. 197.

    , , , & Longitudinal associations of exposure to perfluoroalkylated substances in childhood and adolescence and indicators of adiposity and glucose metabolism 6 and 12 years later: the European Youth Heart Study. Diabetes Care 39, 1745–1751 (2016).

  198. 198.

    , , & Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants. Environ. Health Perspect. 119, 409–415 (2011). This methods paper describes several techniques that can be used to identify windows of vulnerability to environmental pollutants.

  199. 199.

    National Institute of Environmental Health Sciences. Statistical approaches for assessing health effects of environmental chemical mixtures in epidemiology studies. NIEHS (2015).

  200. 200.

    et al. Statistical approaches for assessing health effects of environmental chemical mixtures in epidemiology: lessons from an innovative workshop. Environ. Health Perspect. (2016).

  201. 201.

    et al. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16, 493–508 (2015).

  202. 202.

    , , & Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting. J. Agric. Biol. Environ. Stat. 20, 100–120 (2014).

  203. 203.

    , , & Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003–2004. Int. J. Hyg. Environ. Health 216, 703–709 (2013).

  204. 204.

    Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ. Health Perspect. 106 (Suppl. 4), 1051–1058 (1998).

  205. 205.

    et al. Male specific association between xenoestrogen levels in placenta and birthweight. Environ. Int. 51, 174–181 (2013).

  206. 206.

    et al. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ. Health Perspect. (2016).

  207. 207.

    , & Spatial measurement error and correction by spatial SIMEX in linear regression models when using predicted air pollution exposures. Biostatistics 17, 377–389 (2016).

  208. 208.

    , , & Methods of covariate selection: directed acyclic graphs and the change-in-estimate procedure. Am. J. Epidemiol. 169, 1182–1190 (2009).

  209. 209.

    , & Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 20, 488–495 (2009).

  210. 210.

    et al. Birth weight and subsequent risk of obesity: a systematic review and meta-analysis. Obes. Rev. 12, 525–542 (2011).

  211. 211.

    , , & Personal care product use predicts urinary concentrations of some phthalate monoesters. Environ. Health Perspect. 113, 1530–1535 (2005).

  212. 212.

    et al. Rate of decline in serum PFOA concentrations after granular activated carbon filtration at two public water systems in Ohio and West Virginia. Environ. Health Perspect. 118, 222–228 (2010).

  213. 213.

    , , , & Perfluorinated compounds — exposure assessment for the general population in Western countries. Int. J. Hyg. Environ. Health 212, 239–270 (2009).

  214. 214.

    The environment and disease: association or causation? Proc. R. Soc. Med. 58, 295–300 (1965).

  215. 215.

    et al. Trends in the prevalence of developmental disabilities in US children, 1997–2008. Pediatrics 127, 1034–1042 (2011).

  216. 216.

    Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators & Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorder among children aged 8 years — Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2010. MMWR Surveill. Summ. 63, 1–21 (2014).

  217. 217.

    et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS ONE 7, e33224 (2012).

  218. 218.

    , , , & Deficient emotional self-regulation in preschoolers with ADHD: identification, comorbidity, and interpersonal functioning. J. Atten. Disord. (2016).

  219. 219.

    et al. A conceptual framework in the study of neuropsychological development in epidemiological studies. Neuroepidemiology 38, 203–208 (2012).

  220. 220.

    et al. Prenatal and childhood traffic-related pollution exposure and childhood cognition in the Project Viva Cohort (Massachusetts, USA). Environ. Health Perspect. 123, 1072–1078 (2015).

  221. 221.

    , , & Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311, 806–814 (2014).

  222. 222.

    World Health Organization. Global status report on noncommunicable diseases 2010. WHO (2010).

  223. 223.

    , & Childhood obesity: public-health crisis, common sense cure. Lancet 360, 473–482 (2002).

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Acknowledgements

The author would like to thank K. L. Hanson and R. Hauser for their helpful comments and edits on an earlier version of this manuscript. The author acknowledges support from the NIH (grants R00 ES020346, R01 ES025214, R01 ES024381 and R01 ES021357).

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  1. Department of Epidemiology, Brown University, Box G-S121(2), Providence, Rhode Island 02912, USA.

    • Joseph M. Braun

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The author declares no competing financial interests.

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https://doi.org/10.1038/nrendo.2016.186

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