Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes

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• dc.contributor.author Stevens, Danielle R.
• dc.contributor.author Blaauwendraad, Sophia M.
• dc.contributor.author Bommarito, Paige A.
• dc.contributor.author van den Dries, Michiel
• dc.contributor.author Trasande, Leonardo
• dc.contributor.author Spaan, Suzanne
• dc.contributor.author Pronk, Anjoeka
• dc.contributor.author Tiemeier, Henning
• dc.contributor.author Gaillard, Romy
• dc.contributor.author Jaddoe, Vincent W. V.
• dc.contributor.author Ferguson, Kelly K.
• dc.date.accessioned 2024-11-27T07:02:34Z
• dc.date.available 2024-11-27T07:02:34Z
• dc.date.issued 2024
• dc.description.abstract Introduction: The general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood. Methods: We investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype. Results: Carotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: -0.25, -0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: -0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: -0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively. Conclusions: We observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.
• dc.description.sponsorship This research was supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) (ZIAES101575) and a research and development contract (HHSN273201500003C). The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. DRS received a grant from the NIEHS through award number 1K99ES035107-01. VWVJ received a grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw-VIDI 016.136.361) and a European Research Council Consolidator Grant (ERC-2014-CoG-648916). H.T. was supported by the Netherlands Organization for Scientific Research (NWO) VICI grant (NWO-ZonMW: 016. VICI.170.200). RG received funding from the Dutch Diabetes Foundation (grant number 2017.81.002), the Netherlands Organization for Health Research and Development (NWO, ZonMW, grant number 543003109, NWO, ZonMw 09150172110034) and from the European Union’s Horizon 2020 research and innovation program under the ERA-NET Cofund action (no 727565), EndObesity, ZonMW the Netherlands (no. 529051026). LT was supported by NIEHS grants (R01ES022972 and R01ES029779). This project has additionally received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL), EndObesity, ZonMW Netherlands (No. 529051026). Furthermore, this work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 733,206 (LifeCycle), 874,583 (ATHLETE) and 824,989 (EUCAN-Connect), the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program.
• dc.format.mimetype application/pdf
• dc.identifier.citation Stevens DR, Blaauwendraad SM, Bommarito PA, van den Dries M, Trasande L, Spaan S, et al. Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes. Environ Int. 2024 Nov;193:109082. DOI: 10.1016/j.envint.2024.109082
• dc.identifier.doi http://dx.doi.org/10.1016/j.envint.2024.109082
• dc.identifier.issn 0160-4120
• dc.identifier.uri http://hdl.handle.net/10230/68834
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Environ Int. 2024 Nov;193:109082
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/648916
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/727565
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/824989
• dc.rights Published by Elsevier Ltd. This is an open access article under 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.keyword Cardiovascular diseases
• dc.subject.keyword Endocrine disrupters
• dc.subject.keyword Gene polymorphism
• dc.subject.keyword Organophosphates
• dc.subject.keyword Pesticides
• dc.subject.keyword Pregnancy
• dc.subject.keyword Prospective studies
• dc.title Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion