Prenatal exposure to chemical mixtures and metabolic syndrome risk in children

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• dc.contributor.author Güil Oumrait, Núria
• dc.contributor.author Stratakis, Nikos
• dc.contributor.author Maitre, Léa
• dc.contributor.author Anguita Ruiz, Augusto
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Fabbri, Lorenzo
• dc.contributor.author Basagaña Flores, Xavier
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Vrijheid, Martine
• dc.date.accessioned 2024-07-11T06:07:11Z
• dc.date.available 2024-07-11T06:07:11Z
• dc.date.issued 2024
• dc.description.abstract Importance: Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures. Objective: To investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites. Design, setting, and participants: This population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK. Eligible participants included mother-child pairs with measured prenatal EDC exposures and complete data on childhood MetS risk factors, proteins, and metabolites. Data were analyzed between October 2022 and July 2023. Exposures: Nine metals, 3 organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 5 perfluoroalkyl substances (PFAS), 10 phthalate metabolites, 3 phenols, 4 parabens, and 4 organophosphate pesticide metabolites measured in urine and blood samples collected during pregnancy. Main outcomes and measures: At 6 to 11 years of age, a composite MetS risk score was constructed using z scores of waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Childhood levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were quantified using targeted methods. Associations were assessed using bayesian weighted quantile sum regressions applied to mixtures for each chemical group. Results: The study included 1134 mothers (mean [SD] age at birth, 30.7 [4.9] years) and their children (mean [SD] age, 7.8 [1.5] years; 617 male children [54.4%] and 517 female children [45.6%]; mean [SD] MetS risk score, -0.1 [2.3]). MetS score increased per 1-quartile increase of the mixture for metals (β = 0.44; 95% credible interval [CrI], 0.30 to 0.59), organochlorine pesticides (β = 0.22; 95% CrI, 0.15 to 0.29), PBDEs (β = 0.17; 95% CrI, 0.06 to 0.27), and PFAS (β = 0.19; 95% CrI, 0.14 to 0.24). High-molecular weight phthalate mixtures (β = -0.07; 95% CrI, -0.10 to -0.04) and low-molecular weight phthalate mixtures (β = -0.13; 95% CrI, -0.18 to -0.08) were associated with a decreased MetS score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were associated with increased MetS score. Conclusions and relevance: This cohort study suggests that prenatal exposure to EDC mixtures may be associated with adverse metabolic health in children. Given the pervasive nature of EDCs and the increase in MetS, these findings hold substantial public health implications.
• dc.description.sponsorship This project was supported by the European Union Horizon 2020 research and innovation programme (Grant Agreement No. 874583, Advancing Tools for Human Early Lifecourse Exposome Research and Translation [ATHLETE]). Data collection received support from the European Community Horizon 2020 programme (Grant Agreement No. 825712 [the Oberon project]) and the European Union 7th Framework Programme (Grant Agreement No. 308333 [the Human Early Lifecourse Exposome [HELIX] project]). The study was also supported by the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya (AGAUR; fellowship to Ms Güil-Oumrait), and Fons Social Europeu (FSE; fellowship to Ms Güil-Oumrait), the Strategic Plan for Research and Innovation in Health (PERIS) Catalan program (grant No. SLT017/20/000119 by the Departament de Salut de la Generalitat de Catalunya, Spain to Dr Urquiza), the European Comission (HORIZON-MSCA-2021-PF-01-01 - 2021 LIVER-X 101059245 to Dr Stratakis), and the Spanish Ministry of Science and Innovation (MCIN) and Research State Agency/(AEI; grant No. /10.13039/501100011033 to Dr Maitre).The Institute for Global Health (ISGlobal) acknowledges support from the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 Program (grant No. CEX2018-000806-S) and support from the Generalitat de Catalunya through the Research Centres of Catalonia (CERCA) Program. The Born in Bradford [BiB] study was supported by the Wellcome Trust (grant No. WT101597MA) and the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (grant No. MR/N024397/1). The Infancia y Medio Ambiente [INMA] study was supported by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), and the Generalitat de Catalunya-Catalan National Science Foundation (CIRIT). The Kanaus cohort [KANC] study was supported by the Lithuanian Agency for Science Innovation and Technology (grant No. 6-04-2014_31V-66). The Norwegian Mother, Father, and Child Cohort [MoBa] study was supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea Mother Child cohort [RHEA] study was supported by European Projects (grant Nos. EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. [Project No 211250 Escape], EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. [Proposal No 226285 ENRIECO], and EU- FP7- HEALTH-2012 [Proposal No 308333 HELIX]), and the Greek Ministry of Health, Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece (2011-2014) and the Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health (2012-2015).
• dc.format.mimetype application/pdf
• dc.identifier.citation Güil-Oumrait N, Stratakis N, Maitre L, Anguita-Ruiz A, Urquiza J, Fabbri L, et al. Prenatal exposure to chemical mixtures and metabolic syndrome risk in children. JAMA Netw Open. 2024 May 1;7(5):e2412040. DOI: 10.1001/jamanetworkopen.2024.12040
• dc.identifier.doi http://dx.doi.org/10.1001/jamanetworkopen.2024.12040
• dc.identifier.issn 2574-3805
• dc.identifier.uri http://hdl.handle.net/10230/60721
• dc.language.iso eng
• dc.publisher American Medical Association
• dc.relation.ispartof JAMA Netw Open. 2024 May 1;7(5):e2412040
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825712
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101059245
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.rights © 2024 Güil-Oumrait N et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Síndrome metabòlica
• dc.title Prenatal exposure to chemical mixtures and metabolic syndrome risk in children
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion