Gestational exposure to phthalates and gender-related play behaviors in 8-year-old children: an observational study

Zana Percy, Yingying Xu, Heidi Sucharew, Jane C Khoury, Antonia M Calafat, Joseph M Braun, Bruce P Lanphear, Aimin Chen, Kimberly Yolton, Zana Percy, Yingying Xu, Heidi Sucharew, Jane C Khoury, Antonia M Calafat, Joseph M Braun, Bruce P Lanphear, Aimin Chen, Kimberly Yolton

Abstract

Background: Phthalates, used in a variety of consumer products, are a group of chemicals that are ubiquitous in the environment, and their metabolites are detectable in most humans. Some phthalates have anti-androgenic properties; a prior study reported an association between gestational exposure to phthalates and reduced masculine behaviors in preschool boys.

Methods: Concentrations of 9 phthalate metabolites were measured in urine collected at 16 and 26 weeks' gestation from pregnant women enrolled in the HOME Study, a prospective pregnancy and birth cohort. Measures of gender-related play were collected at 8 years of age, including the Gender Identity Questionnaire (GIQ) completed by mothers, and the Playmate and Play Style Preferences Structured Interview (PPPSI) completed by children. We examined these measures as continuous variables using both bivariate and multivariable approaches with adjustment for covariates. Additional analyses included logistic regression of GIQ and PPPSI scores dichotomized by sex at the lower 25th percentile, indicating the least typical behavior.

Results: Mothers' phthalate metabolite concentrations during pregnancy were similar to the reported national average among US women. All children scored within a typical range on both measures of gender-related play behavior. No statistically significant associations were found between averaged maternal phthalate metabolite concentrations and continuous PPPSI scores or any GIQ scores. For the dichotomized PPPSI; higher maternal monoethyl phthalate (MEP) concentrations were associated with more typical play behaviors for females (OR = 0.70, CI = 0.51-0.97). In contrast, higher maternal mono-isobutyl phthalate (MiBP) concentrations were associated with higher odds of membership in the least typical play behaviors group for males (OR = 1.69, CI = 1.00-2.86).

Conclusions: In this sample of typically developing children, higher maternal urinary MEP concentrations during pregnancy were associated with more typical gender-related play behaviors in both males and females, and increased urinary MiBP concentrations were associated with less masculine gender-related play behaviors in males.

Keywords: Children; Gender; Phthalates; Play.

Figures

Fig. 1
Fig. 1
Adjusted Odds Ratio of Low PPPSI Score with Doubling of Maternal Urinary Phthalate Metabolite Concentration

References

    1. Centers for Disease Control and Prevention . Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables. 2015.
    1. Koch HM, Calafat AM. Human body burdens of chemicals used in plastic manufacture. Philos Trans R Soc B. 2009;364:2063–2078. doi: 10.1098/rstb.2008.0208.
    1. Hauser R, Duty S, Godfrey-Bailey L, Calafat AM. Medications as a source of human exposure to phthalates. Environ Health Perspect. 2004;112:751–753. doi: 10.1289/ehp.6804.
    1. Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB. Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect. 1982;45:19–25. doi: 10.1289/ehp.824519.
    1. Silva MJ, Reidy JA, Herbert AR, Preau JL, Jr, Needham LL, Calafat AM. Detection of phthalate metabolites in human amniotic fluid. Bull Environ Contam Toxicol. 2004;72:1226–1231. doi: 10.1007/s00128-004-0374-4.
    1. Wittassek M, Angerer J, Kolossa-Gehring M, Schafer SD, Klockenbusch W, Dobler L, Gunsel AK, Muller A, Wiesmuller GA. Fetal exposure to phthalates-a pilot study. Int J Hyg Environ Health. 2009;212:492–498. doi: 10.1016/j.ijheh.2009.04.001.
    1. Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, Inoue K, Nakazawa H, Tsugane S, Takahashi K. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect. 2006;114:1643–1648.
    1. Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, Gray LE., Jr The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci. 2000;58:339–349. doi: 10.1093/toxsci/58.2.339.
    1. United States Environmental Protection Agency . Phthalates: Toxicity and Exposure Assessment for Children’s Health Summary. 2007.
    1. Howdeshell KL, Wilson VS, Furr J, Lambright CR, Rider CV, Blystone CR, Hotchkiss AK, Gray LE., Jr A mixture of 5 phthalate esters inhibits fetal testicular testosterone production in the Sprague–Dawley rat in a cumulative, dose-additive manner. Toxicol Sci. 2008;105:153–165. doi: 10.1093/toxsci/kfn077.
    1. Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants 3 months of age. Environ Health Perspect. 2006;114:270–276. doi: 10.1289/ehp.8075.
    1. Foster PM. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl. 2006;29:140–147. doi: 10.1111/j.1365-2605.2005.00563.x.
    1. Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology. 2006;17:682–691. doi: 10.1097/01.ede.0000235996.89953.d7.
    1. Moore RW, Rudy TA, Lin TM, Ko K, Peterson RE. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di (2-ethylhexyl) phthalate. Environ Health Perspect. 2001;109:229–237. doi: 10.1289/ehp.01109229.
    1. Lin YC, Yao PL, Richburg JH. FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis. Toxicol Sci. 2010;114:335–345. doi: 10.1093/toxsci/kfq015.
    1. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005;113:1056–1061. doi: 10.1289/ehp.8100.
    1. Li Y, Zhuang M, Li T, Shi N. Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure. J Appl Toxicol. 2009;29:603–611. doi: 10.1002/jat.1447.
    1. American Psychiatric Association . Diagostic and Statistical Manual of Mental Disorders. 5. Washington: American Psychiatric Publishing; 2013.
    1. Weiss B. The intersection of neurotoxicology and endocrine disruption. Neurotoxicology. 2012;33:1410–1419. doi: 10.1016/j.neuro.2012.05.014.
    1. Cohen-Bendahan CC, van de Beek C, Berenbaum SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev. 2005;29:353–384. doi: 10.1016/j.neubiorev.2004.11.004.
    1. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G, Hines M. Fetal testosterone predicts sexually differentiated childhood behavior in girls and in boys. Psychol Sci. 2009;20:144–148. doi: 10.1111/j.1467-9280.2009.02279.x.
    1. Swan SH, Liu F, Hines M, Kruse RL, Wang C, Redmon JB, Sparks A, Weiss B. Prenatal phthalate exposure and reduced masculine play in boys. Int J Androl. 2010;33:259–269. doi: 10.1111/j.1365-2605.2009.01019.x.
    1. Braun JM, Kalloo G, Chen A, Dietrich KN, Liddy-Hicks S, Morgan S, Xu Y, Yolton K, Lanphear BP. Cohort Profile: The Health Outcomes and Measures of the Environment (HOME) study. Int J Epidemiol. 2016:1–10.
    1. Silva MJ, Preau JL, Needham LL, Calafat AM. Cross validation and ruggedness testing of analytical methods used for the quantification of urinary phthalate metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;873:180–186. doi: 10.1016/j.jchromb.2008.08.017.
    1. Elizabeth PH, Green R. Childhood sex-role behaviors: similarities and differences in twins. Acta Genet Med Gemellol. 1984;33:173–179. doi: 10.1017/S0001566000007200.
    1. Johnson LL, Bradley SJ, Birkenfeld-Adams AS, Kuksis MA, Maing DM, Mitchell JN, Zucker KJ. A parent-report gender identity questionnaire for children. Arch Sex Behav. 2004;33:105–116. doi: 10.1023/B:ASEB.0000014325.68094.f3.
    1. Alexander GM, Hines M. Gender labels and play styles: Their relative contribution to children’s selection of playmates. Child Dev. 1994;65:869–879. doi: 10.2307/1131424.
    1. Fridell SR, Owen-Anderson A, Johnson LL, Bradley SJ, Zucker KJ. The playmate and play style preferences structured interview: a comparison of children with gender identity disorder and controls. Arch Sex Behav. 2006;35:729–737. doi: 10.1007/s10508-006-9085-8.
    1. SAS Institute . SAS 9.3. Cary: SAS Institute, Inc; 2011.
    1. Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5:46–51. doi: 10.1080/1047322X.1990.10389587.
    1. Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL. Urinary creatinine concentrations in the US population: Implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005;113:192–200. doi: 10.1289/ehp.7337.
    1. Fisher M, Arbuckle TE, Mallick R, LeBlanc A, Hauser R, Feeley M, Koniecki D, Ramsay T, Provencher G, Berube R, Walker M. Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability. J Expo Sci Environ Epidemiol. 2015;25:231–239. doi: 10.1038/jes.2014.65.
    1. Bigner JJ. Sibling influence on sex-role preference of young children. J Genet Psychol. 1973;122:271–282. doi: 10.1080/00221325.1973.10532667.
    1. Kamphaus RW, Reynolds CR. PRQ: Parenting relationship questionnaire manual. Minneapolis: NCS Pearson; 2006.
    1. Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008;108:177–184. doi: 10.1016/j.envres.2008.08.007.
    1. Werner EF, Braun JM, Yolton K, Khoury JC, Lanphear BP. The association between maternal urinary phthalate concentrations and blood pressure in pregnancy: The HOME Study. Environ Health. 2015;14:1. doi: 10.1186/s12940-015-0062-3.
    1. Braun JM, Froehlich T, Kalkbrenner A, Pfeiffer CM, Fazili Z, Yolton K, Lanphear BP. Brief report: are autistic-behaviors in children related to prenatal vitamin use and maternal whole blood folate concentrations? J Autism Dev Disord. 2014;44:2602–2607. doi: 10.1007/s10803-014-2114-x.
    1. Vuong AM, Yolton K, Webster GM, Sjödin A, Calafat AM, Braun JM, Dietrich KN, Lanphear BP, Chen A. Prenatal polybrominated diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children. Environ Res. 2016;147:556–564. doi: 10.1016/j.envres.2016.01.008.
    1. Collaer ML, Hines M. Human behavioral sex differences: a role for gonadal hormones during early development? Psychol Bull. 1995;118:55–107. doi: 10.1037/0033-2909.118.1.55.
    1. Unger RK, Crawford M. Commentary: Sex and gender: The troubled relationship between terms and concepts. Psychol Sci. 1993;4:122–124. doi: 10.1111/j.1467-9280.1993.tb00473.x.
    1. Levine DA, Committee OA. Office-based care for lesbian, gay, bisexual, transgender, and questioning youth. Pediatrics. 2013;132:e297–e313. doi: 10.1542/peds.2013-1283.
    1. Conard LA. Child Psychiatry Grand Rounds. Cincinnati: Cincinnati Children’s Hospital Medical Center; 2014. The T in LGBT: Last but Not Lost. Child Psychiatry Grand Rounds.
    1. Roy JR, Chakraborty S, Chakraborty TR. Estrogen-like endocrine disrupting chemicals affecting puberty in humans--a review. Med Sci Monit. 2009;15:RA137–RA145.
    1. De Los RA, Kazdin AE. Informant discrepancies in the assessment of childhood psychopathology: a critical review, theoretical framework, and recommendations for further study. Psychol Bull. 2005;131:483. doi: 10.1037/0033-2909.131.4.483.
    1. Hannas BR, Lambright CS, Furr J, Howdeshell KL, Wilson VS, Gray LE., Jr 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. 2011;123:206–216. doi: 10.1093/toxsci/kfr146.
    1. Mankidy R, Wiseman S, Ma H, Giesy JP. Biological impact of phthalates. Toxicol Lett. 2013;217:50–58. doi: 10.1016/j.toxlet.2012.11.025.
    1. Andrade AJ, Grande SW, Talsness CE, Grote K, Chahoud I. A dose–response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose–response and low dose effects on rat brain aromatase activity. Toxicology. 2006;227:185–192. doi: 10.1016/j.tox.2006.07.022.
    1. Braun JM, Smith KW, Williams PL, Calafat AM, Berry K, Ehrlich S, Hauser R. Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy. Environ Health Perspect. 2012;120:739–745. doi: 10.1289/ehp.1104139.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren