Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts

Freire, Carmen; Castiello, Francesca; Babarro, Izaro; Anguita Ruiz, Augusto; Casas Sanahuja, Maribel; Vrijheid, Martine; Sarzo, Blanca; Beneito, Andrea; Kadawathagedara, Manik; Philippat, Claire; Thomsen, Cathrine; Sakhi, Amrit Kaur; López Espinosa, Maria José

Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts

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dc.contributor.author Freire, Carmen
dc.contributor.author Castiello, Francesca
dc.contributor.author Babarro, Izaro
dc.contributor.author Anguita Ruiz, Augusto
dc.contributor.author Casas Sanahuja, Maribel
dc.contributor.author Vrijheid, Martine
dc.contributor.author Sarzo, Blanca
dc.contributor.author Beneito, Andrea
dc.contributor.author Kadawathagedara, Manik
dc.contributor.author Philippat, Claire
dc.contributor.author Thomsen, Cathrine
dc.contributor.author Sakhi, Amrit Kaur
dc.contributor.author López Espinosa, Maria José
dc.date.accessioned 2024-11-15T07:15:21Z
dc.date.available 2024-11-15T07:15:21Z
dc.date.issued 2024
dc.description.abstract Background: There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing. Objective: To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts. Methods: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999-2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7-12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed. Results: Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98-1.30] and 1.20 [1.06-1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85-1.01] and BuPB: 0.95 [0.90-1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77-0.95] and 0.90 [0.84-0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls. Conclusions: Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.
dc.description.sponsorship The HELIX Project has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no 308333. This study was also supported in part by European Union grant agreement number 874583 (ATHLETE) and research grants from the Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) and Instituto de Salud Carlos III (ISCIII) supported by European Development Fund (FEDER) (grant no. PI13/1944, PI14/00891, PI17/01194), and from RecerCaixa (Register number: 2010ACUP 00349) and CIBER-ISCIII (Mobility Actions, 2024), MICIU-FEDER. INMA: This research would not have been achieved without the selfless collaboration of the INMA families who took part in the study. INMA-Gipuzkoa cohort was funded by grants from ISCIII (PI06/0867, PI09/00090, PI13/02187, PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089, and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA-Sabadell cohort was funded by grants from ISCIII (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, grant CEX 2018-000806-S funded by MCIN/AEI/10.13039/501100011033, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF 2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010), and EU Commission (grant no. 261357, 603794, and 634453). INMA-Valencia was funded by grants from ISCIII (PI11/02591, PI13/1944, PI14/00891, P117/00663 and PI17/01526; Miguel Servet-FEDER (CP11/00178, CP15/00025, and CP20/0006) and Generalitat Valenciana (UGP-15-249).
dc.format.mimetype application/pdf
dc.identifier.citation Freire C, Castiello F, Babarro I, Anguita-Ruiz A, Casas M, Vrijheid M, et al. Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts. Int J Hyg Environ Health. 2024 Aug;261:114418. DOI: 10.1016/j.ijheh.2024.114418
dc.identifier.doi http://dx.doi.org/10.1016/j.ijheh.2024.114418
dc.identifier.issn 1438-4639
dc.identifier.uri http://hdl.handle.net/10230/68705
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Int J Hyg Environ Health. 2024 Aug;261:114418
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261357
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/603794
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634453
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-32991
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.keyword Bisphenol a
dc.subject.keyword Endocrine-disrupting chemicals
dc.subject.keyword Phenols
dc.subject.keyword Phthalates
dc.subject.keyword Puberty
dc.title Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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