{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:38:17Z","timestamp":1793410697341,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":91,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["N\u00b0311765-E-DOHaD"],"award-info":[{"award-number":["N\u00b0311765-E-DOHaD"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Community\u2019s Seventh Framework Programme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Is exposure to environmental chemicals associated with modifications of placental morphology and function?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Phthalates, a class of ubiquitous chemicals, showed an association with altered placental weight, placental vascular resistance (PVR), and placental efficiency.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>Only a few epidemiological studies have assessed the effects of phenols and phthalates on placental health. Their results were affected by exposure measurement errors linked to the rapid excretion of these compounds and the reliance on a limited number of spot urine samples to assess exposure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>A prospective mother\u2013child cohort, with improved exposure assessment for non-persistent chemicals, recruited participants between 2014 and 2017. Sample size ranged between 355 (placental parameters measured at birth: placental weight and placental-to-fetal weight ratio (PFR): a proxy for placental efficiency) and 426 (placental parameters measured during pregnancy: placental thickness and vascular resistance).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>Phenols (four parabens, two bisphenols, triclosan, and benzophenone-3), 13 phthalate metabolites, and two non-phthalate plasticizer metabolites were measured in within-subject pools of repeated urine samples collected during the second and third trimesters of pregnancy (median\u2009=\u200921 samples\/trimester\/woman). Placental thickness and PVR were measured during pregnancy. The placenta was weighed at birth and the PFR was computed. Both adjusted linear regression and Bayesian Kernel Machine Regression were used to evaluate associations between phenols and phthalates (alone or as a mixture) and placental parameters. Effect modification by child sex was also investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>Several phthalate metabolites were negatively associated with placental outcomes. Monobenzyl phthalate (MBzP) concentrations, during the second and third trimesters of pregnancy, were associated with a decrease in both placental weight at birth (\u03b2 = \u221220.1\u2009g [95% CI: \u221237.8; \u22122.5] and \u03b2 = \u221217.4\u2009g [95% CI: \u221233.2; \u22121.6], for second and third trimester, respectively) and PFR (\u03b2 = \u22120.5 [95% CI: \u22121, \u22120.1] and \u03b2 = \u22120.5 [95% CI: \u22120.9, \u22120.1], for the second and third trimester, respectively). Additionally, MBzP was negatively associated with PVR during the third trimester (\u03b2= \u22120.9 [95% CI: \u22121.8; 0.1]). Mono-n-butyl phthalate (MnBP), was negatively associated with PVR in both trimesters (\u03b2 = \u22121.3, 95% CI: [\u22122.3, \u22120.2], and \u03b2 = \u22121.2, 95% CI: [\u22122.4, \u22120.03], for the second and third trimester, respectively). After stratification for child sex, \u03a3 diisononyl phthalate (DiNP) (either second or third-trimester exposures, depending on the outcomes considered) was associated with decreased PVR in the third trimester, as well as decreased placental weight and PFR in males. No associations were observed for phenol biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>False positives cannot be ruled out. Therefore, chemicals that were associated with multiple outcomes (MnBP and DiNP) or reported in existing literature as associated with placental outcomes (MBzP) should be considered as the main results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>Our results are consistent with in vitro studies showing that phthalates target peroxisome proliferator-activated receptor \u03b3, in the family of nuclear receptors involved in key placental development processes such as trophoblast proliferation, migration, and invasion. In addition to placental weight at birth, we studied placental parameters during pregnancy, which could provide a broader view of how environmental chemicals affect maternal\u2013fetal exchanges over the course of pregnancy. Our findings contribute to the increasing evidence indicating adverse impacts of phthalate exposure on placental health.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This work was supported by the French Research Agency\u2014ANR (MEMORI project ANR-21-CE34-0022). The SEPAGES cohort was supported by the European Research Council (N\u00b0311765-E-DOHaD), the European Community\u2019s Seventh Framework Programme (FP7\/2007-206\u2014N\u00b0308333-892 HELIX), the European Union\u2019s Horizon 2020 research and innovation programme (N\u00b0 874583 ATHLETE Project, N\u00b0825712 OBERON Project), the French Research Agency\u2014ANR (PAPER project ANR-12-PDOC-0029-01, SHALCOH project ANR-14-CE21-0007, ANR-15-IDEX-02 and ANR-15-IDEX5, GUMME project ANR-18-CE36-005, ETAPE project ANR-18-CE36-0005\u2014EDeN project ANR-19-CE36-0003-01), the French Agency for Food, Environmental and Occupational Health &amp; Safety\u2014ANSES (CNAP project EST-2016-121, PENDORE project EST-2016-121, HyPAxE project EST-2019\/1\/039, PENDALIRE project EST-2022-169), the Plan Cancer (Canc\u2019Air project), the French Cancer Research Foundation Association de Recherche sur le Cancer\u2014ARC, the French Endowment Fund AGIR for chronic diseases\u2014APMC (projects PRENAPAR, LCI-FOT, DysCard), the French Endowment Fund for Respiratory Health, the French Fund\u2014Fondation de France (CLIMATHES\u201400081169, SEPAGES 5\u201300099903, ELEMENTUM\u201400124527). N.J. was supported by a doctoral fellowship from the University Grenoble Alpes. V.M. was supported by a Sara Borrell postdoctoral research contract (CD22\/00176), granted by Instituto de Salud Carlos III (Spain) and NextGenerationEU funds. The authors declare no conflict of interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>ClinicalTrials.gov NCT02852499.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/hropen\/hoae018","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:13:55Z","timestamp":1712016835000},"source":"Crossref","is-referenced-by-count":12,"title":["Associations between synthetic phenols, phthalates, and placental growth\/function: a longitudinal cohort with exposure assessment in early pregnancy"],"prefix":"10.1093","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3509-4202","authenticated-orcid":false,"given":"Nicolas","family":"Jovanovic","sequence":"first","affiliation":[{"name":"University Grenoble Alpes, Inserm U1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences , Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Mustieles","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, Inserm U1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences , Grenoble, France"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria (ibs. 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