Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Modification of the association by sex between the prenatal exposure to di(2-ethylhexyl) phthalate and fat percentage in a cohort of Mexicans schoolchildren

Abstract

Introduction

Children’s overweight and obesity are global public health problems, children with obesity have grater obesity risk as adults, thus leading to develop cardiometabolic diseases. Previous studies have found positive and significant associations between the exposure to phthalates and body mass index and body composition.

Objective

To evaluate the modification of the association by sex between DEHP exposure during pregnancy and the percentage of body fat in a cohort of Mexican schoolchildren.

Material and methods

The sample was comprised by children which had previously participated in a POSGRAD longitudinal study. A subsample of 190 mother–children binomials were included. Mothers’ DEHP concentrations and its metabolites had been measured in the second trimester of pregnancy: Mono-2-ethylhexyl phthalate (MEHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), Mono-2-ethyl-5-hidroxyhexyl phthalate (MEHHP), and Mono-2-ethyl-5-oxohexyl phthalate (MEOHP). The children’s adipose mass was measured at age 8, 9, and 10. Longitudinal data were analyzed using the mixed effects linear regression model, with intercept and random slope, adjusted by important confounders and stratified by sex.

Results

We found a differentiated effect by sex, the exposure to DEHP during pregnancy significantly increases the adipose mass in boys. The average increase was 0.058% (p = 0.02) for every 1% variation in MECPP; 0.047% (p = 0.04) in MEHHP; 0.051% (p = 0.03) in MEOHP, and 0.066% (p = 0.007) in MECPP.

Conclusions

The results suggest an effect differentiated by sex; with boys being the main ones affected by the prenatal exposure to phthalates. However, we cannot rule out effects in girls.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    National Institute of Public Health. Midway National Health and Nutrition Survey 2016—Final results report. Cuernavaca, Morelos; 2016.

  2. 2.

    Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ. 2005;331:929.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes. 2011;35:891–8.

    CAS  Article  Google Scholar 

  4. 4.

    Harley KG, Berger K, Rauch S, Kogut K, Claus Henn B, Calafat AM, et al. Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatr Res. 2017;82:405–15.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Kim JS, Alderete TL, Chen Z, Lurmann F, Rappaport E, Habre R, et al. Longitudinal associations of in utero and early life near-roadway air pollution with trajectories of childhood body mass index. Environ Health. 2018;17:64.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  6. 6.

    Koch HM, Calafat AM. Human body burdens of chemicals used in plastic manufacture. Philos Trans R Soc Lond B Biol Sci. 2009;364:2063–78.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Biemann R, Navarrete Santos A, Navarrete Santos A, Riemann D, Knelangen J, Blüher M, et al. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows. Biochem Biophys Res Commun. 2012;417:747–52.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Barrandon Y, Green H. Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor. Cell. 1987;50:1131–7.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    DiVall SA. The influence of endocrine disruptors on growth and development of children. Curr Opin Endocrinol Diabetes Obes. 2013;20:50–5.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Goodman M, LaKind JS, Mattison DR. Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature. Crit Rev Toxicol. 2014;44:151–75.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Buckley JP, Engel SM, Mendez MA, Richardson DB, Daniels JL, Calafat AM, et al. Prenatal phthalate exposures and childhood fat mass in a New York city cohort. Environ Health Perspect. 2016;124:507–13.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Vafeiadi M, Myridakis A, Roumeliotaki T, Margetaki K, Chalkiadaki G, Dermitzaki E, et al. Association of early life exposure to phthalates with obesity and cardiometabolic traits in childhood: sex specific associations. Front Public Heal. 2018;6:327.

    Article  Google Scholar 

  13. 13.

    Zhang Q, Chen X-Z, Huang X, Wang M, Wu J. The association between prenatal exposure to phthalates and cognition and neurobehavior of children-evidence from birth cohorts. Neurotoxicology. 2019;73:199–212.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Valvi D, Casas M, Romaguera D, Monfort N, Ventura R, Martinez D, et al. Prenatal phthalate exposure and childhood growth and blood pressure: evidence from the Spanish INMA-Sabadell Birth cohort study. Environ Health Perspect. 2015;123:1022–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Maresca MM, Hoepner LA, Hassoun A, Oberfield SE, Mooney SJ, Calafat AM, et al. Prenatal exposure to phthalates and childhood body size in an urban cohort. Environ Health Perspect. 2016;124:514–20.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Muscogiuri G, Barrea L, Laudisio D, Savastano S, Colao A. Obesogenic endocrine disruptors and obesity: myths and truths. Arch Toxicol. 2017;91:3469–75.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Unüvar T, Büyükgebiz A. Fetal and neonatal endocrine disruptors. J Clin Res Pediatr Endocrinol. 2012;4:51–60.

    PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Blount BC, Milgram KE, Silva MJ, Malek NA, Reidy JA, Needham LL, et al. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem. 2000;72:4127–34.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Croghan CW, Egeghy PP. Methods of dealing with values below the limit of detection using SAS. In: 11th Annual Southeast SAS Users Group (SESUG). St. Pete Beach, Florida; 2003.

  20. 20.

    Sánchez-Jaeger A, Adela BM. Uso de la bioimpedancia eléctrica para la estimación de la composición corporal en niños y adolescentes. An Venez Nutr. 2009;22:105–10.

    Google Scholar 

  21. 21.

    Aguilar-Cordero MJ, Sánchez-López AM, Barrilao G, Rodriguez-Blanque R, Noack-Segovia J, Cano P. Descripción del acelerómetro como método para valorar la actividad física en los diferentes periodos de la vida: revisión sistemática. Nutrición Hospitalaria. 2014;29:1250–61.

    CAS  PubMed  Google Scholar 

  22. 22.

    Lewis RC, Meeker JD, Peterson KE, Lee JM, Pace GG, Cantoral A, et al. Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children. Chemosphere. 2013;93:2390–8.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Guo J, Wu M, Gao X, Chen J, Li S, Chen B, et al. Meconium exposure to phthalates, sex and thyroid hormones, birth size and pregnancy outcomes in 251 mother-infant pairs from Shanghai. Int J Environ Res Public Health. 2020;17:7711.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  24. 24.

    Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2009;48:143–57.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Martínez NA, Mazzucco MB, Kurtz MA. El receptor activado por proliferadores peroxisomales-α y su función reguladora del metabolismo lipídico fetal y placentario. Rev SAEGRE. 2011;XVII:60–4.

    Google Scholar 

  26. 26.

    Hurst CH, Waxman DJ. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci. 2003;74:297–308.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Taxvig C, Dreisig K, Boberg J, Nellemann C, Schelde AB, Pedersen D, et al. Differential effects of environmental chemicals and food contaminants on adipogenesis, biomarker release and PPARγ activation. Mol Cell Endocrinol. 2012;361:106–15.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Lin Y, Wei J, Li Y, Chen J, Zhou Z, Song L, et al. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat. Am J Physiol Endocrinol Metab. 2011;301:E527–38.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Boberg J, Metzdorff S, Wortziger R, Axelstad M, Brokken L, Vinggaard AM, et al. Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats. Toxicology. 2008;250:75–81.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Feige JN, Gerber A, Casals-Casas C, Yang Q, Winkler C, Bedu E, et al. The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms. Environ Health Perspect. 2010;118:234–41.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Gray LE, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 2000;58:350–65.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Meeker JD, Calafat AM, Hauser R. Di(2-ethylhexyl) phthalate metabolites may alter thyroid hormone levels in men. Environ Health Perspect. 2007;115:1029–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Shafei AE-S, Nabih ES, Shehata KA, Abd Elfatah ESM, Sanad A bakr A, Marey MY, et al. Prenatal exposure to endocrine disruptors and reprogramming of adipogenesis: an early-life risk factor for childhood obesity. Child Obes. 2018;14:18–25.

    PubMed  Article  Google Scholar 

  34. 34.

    Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. Biología molecular del gen. 5a. Buenos Aires, Madrid: Editorial Médica Panamericana, S. A.; 2008.

  35. 35.

    Maliqueo M, Echiburú B. Programación fetal de las enfermedades metabólicas. Rev Farmacol Chile. 2014;7:33–46.

    Google Scholar 

  36. 36.

    LaRocca J, Binder AM, McElrath TF, Michels KB. The impact of first trimester phthalate and phenol exposure on IGF2/H19 genomic imprinting and birth outcomes. Environ Res. 2014;133:396–406.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Zhao Y, Shi H, Xie C, Chen J, Laue H, Zhang Y-H. Prenatal phthalate exposure, infant growth, and global DNA methylation of human placenta. Environ Mol Mutagen. 2015;56:286–92.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Solomon O, Yousefi P, Huen K, Gunier RB, Escudero-Fung M, Barcellos LF, et al. Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. Environ Mol Mutagen. 2017;58:398–410.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Zhou Y, Simmons D, Lai D, Hambly BD, McLachlan CS. rs9939609 FTO genotype associations with FTO methylation level influences body mass and telomere length in an Australian rural population. Int J Obes. 2017;41:1427–33.

    CAS  Article  Google Scholar 

  40. 40.

    Vanderwall C, Randall Clark R, Eickhoff J, Carrel AL. BMI is a poor predictor of adiposity in young overweight and obese children. BMC Pediatrics. 2017;17:135.

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Costa-Urritia P, Vizuet-Gámez A, Ramírez-Alcántara M, Guillén-González MA, Medina-Contreras O, Valdes-Moreno M, et al. Obesity measured as percent body fat, relationship with body mass index, and percentile curves for Mexican pediatric population. PLoS ONE. 2019;14:e0212792.

    Article  CAS  Google Scholar 

  42. 42.

    Zeng Q, Dong SY, Sun XN, Xie J, Cui Y. Percent body fat is a better predictor of cardiovascular risk factors than body mass index. Braz J Med Biol Res. 2012;56:591–600.

    Article  Google Scholar 

  43. 43.

    Chuang HH, Li WC, Sheu BF, Liao S, Chen JY, Chang KC, et al. Correlation between body composition and risk factors for cardiovascular disease and metabolic syndrome. Biofactors. 2012;38:284–91.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Kontopantelis E, Springate DA, Parisi R, Reeves D. Simulation-based power calculations for mixed effects modeling: ipdpower in Stata. J Stat Softw. 2016;74:10–28.

    Article  Google Scholar 

  45. 45.

    Hunt BG, Wang Y-L, Chen M-S, Wang S-C, Waltz SE. Maternal diethylhexyl phthalate exposure affects adiposity and insulin tolerance in offspring in a PCNA-dependent manner. Environ Res. 2017;159:588–94.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Heindel JJ, Vom Saal FS, Blumberg B, Bovolin P, Calamandrei G, Ceresini G, et al. Parma consensus statement on metabolic disruptors. Environ Health. 2015;14:54.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  47. 47.

    Perry NC, Davies EK. The use of 3D modelling databases for identifying structure activity relationships. Prog Clin Biol Res. 1989;291:189–93.

    CAS  PubMed  Google Scholar 

  48. 48.

    Yang TC, Peterson KE, Meeker JD, Sánchez BN, Zhang Z, Cantoral A, et al. Bisphenol A and phthalates in utero and in childhood: association with child BMI z-score and adiposity. Environ Res. 2017;156:326–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Funding

Supported by the Consejo Nacional de Ciencia y Tecnología (grant 202062 and 233903) and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01HD058818.

Author information

Affiliations

Authors

Contributions

LHC directed the writing of the manuscript and approved the final version. JOAM prepared the first draft and adjusted the analysis of body composition data and the formal analysis, ABV coordinated the study and with IR organized the original study protocol and obtained funding. DBB acquired data about exposure and interpreted results, KCM data: substantive contributions in the statistical methods, review and edition of the article. All authors participated in the design of the study protocol, helped to draft the manuscript, read and approved the final manuscript.

Corresponding author

Correspondence to Leticia Hernández Cadena.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

Both women and infants signed an agreement letter adjacent to the consent letter from parents or tutors. The protocol was approved by Instituto Nacional de Salud Pública and Instituto Mexicano del Seguro Social Ethical Committee in Cuernavaca, Morelos, Mexico.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Montes, J.O.A., Villarreal, A.B., Romieu, I. et al. Modification of the association by sex between the prenatal exposure to di(2-ethylhexyl) phthalate and fat percentage in a cohort of Mexicans schoolchildren. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00952-w

Download citation

Search

Quick links