目的:接触环境化学物质与胎盘形态和功能的改变有关吗?
结论:邻苯二甲酸盐,一类普遍存在的化学物质,显示与胎盘重量改变有关,胎盘血管阻力(PVR),和胎盘效率。
背景:只有少数流行病学研究评估了酚和邻苯二甲酸酯对胎盘健康的影响。他们的结果受到与这些化合物的快速排泄有关的暴露测量误差以及对有限数量的斑点尿液样品进行评估暴露的依赖的影响。
■准母子队列,改进非持久性化学品的暴露评估,2014年至2017年招募的参与者。样本量介于355(出生时测量的胎盘参数:胎盘重量和胎盘与胎儿重量比(PFR):胎盘效率的代表)和426(怀孕期间测量的胎盘参数:胎盘厚度和血管阻力)之间。
方法:酚类(四种对羟基苯甲酸酯,两种双酚,三氯生,和二苯甲酮-3),13邻苯二甲酸酯代谢物,在妊娠第二和第三三个月期间收集的受试者体内重复尿液样本中测量了两种非邻苯二甲酸酯增塑剂代谢物(中位数=21份样本/妊娠月/女性).在怀孕期间测量胎盘厚度和PVR。出生时对胎盘称重并计算PFR。使用调整的线性回归和贝叶斯内核机器回归来评估酚和邻苯二甲酸酯(单独或作为混合物)与胎盘参数之间的关联。还研究了儿童性别的效果改变。
结果:几种邻苯二甲酸盐代谢产物与胎盘结局呈负相关。邻苯二甲酸单苄基酯(MBzP)浓度,在怀孕的第二和第三个三个月,与出生时胎盘重量的减少有关(β=-20.1g[95%CI:-37.8;-2.5]和β=-17.4g[95%CI:-33.2;-1.6],第二和第三个三个月,分别)和PFR(β=-0.5[95%CI:-1,-0.1]和β=-0.5[95%CI:-0.9,-0.1],对于第二和第三个三个月,分别)。此外,妊娠晚期MBzP与PVR呈负相关(β=-0.9[95%CI:-1.8;0.1])。邻苯二甲酸单正丁酯(MnBP),在两个孕期均与PVR呈负相关(β=-1.3,95%CI:[-2.3,-0.2],和β=-1.2,95%CI:[-2.4,-0.03],对于第二和第三个三个月,分别)。儿童性别分层后,Σ邻苯二甲酸二异壬酯(DiNP)(第二或第三三个月暴露,根据所考虑的结果)与妊娠晚期PVR降低相关,以及男性胎盘重量和PFR下降。未观察到苯酚生物标志物的关联。
结论:不能排除误报。因此,与多个结局(MnBP和DiNP)相关或现有文献报道的与胎盘结局(MBzP)相关的化学物质应被视为主要结果.
结论:我们的结果与体外研究一致,表明邻苯二甲酸酯靶向过氧化物酶体增殖物激活受体γ,在涉及关键胎盘发育过程如滋养细胞增殖的核受体家族中,迁移,和入侵。除了出生时的胎盘重量,我们研究了怀孕期间的胎盘参数,这可以更广泛地了解环境化学物质如何在怀孕过程中影响母胎交换。我们的发现有助于越来越多的证据表明邻苯二甲酸酯暴露对胎盘健康的不利影响。
背景:这项工作得到了法国研究机构-ANR(MEMORI项目ANR-21-CE34-0022)的支持。SEPAGES队列得到了欧洲研究理事会(N°311765-E-DOHaD)的支持,欧洲共同体第七框架计划(FP7/2007-206-N°308333-892HELIX),欧盟地平线2020研究与创新计划(N°874583ATHLETE项目,N°825712OBERON项目),法国研究机构-ANR(PAPER项目ANR-12-PDOC-0029-01,SHALCOH项目ANR-14-CE21-0007,ANR-15-IDEX-02和ANR-15-IDEX5,GUMME项目ANR-18-CE36-005,ETAPE项目ANR-18-CE36-0005-EDeN项目ANR-19-01,法国食品局,环境与职业健康与安全ANSES(CNAP项目EST-2016-121,PENDORE项目EST-2016-121,HyPAxE项目EST-2019/1/039,PENDALIRE项目EST-2022-169),癌症计划(加拿大航空项目),法国癌症研究基金会癌症研究协会,法国慢性病捐赠基金AGIR-APMC(项目PRENAPAR,LCI-FOT,DysCard),法国呼吸健康捐赠基金,法国基金会(CLIMATHES-00081169,SEPAGES5-00099903,ELEMENTUM-00124527)。新泽西州得到了格勒诺布尔阿尔卑斯大学博士奖学金的支持。V.M.由SaraBorrell博士后研究合同(CD22/00176)支持,由CarlosIII(西班牙)和NextGenerationEU基金授予。作者声明没有利益冲突。
背景:ClinicalTrials.govNCT02852499。
OBJECTIVE: Is exposure to environmental chemicals associated with modifications of placental morphology and function?
CONCLUSIONS: Phthalates, a class of ubiquitous chemicals, showed an association with altered placental weight, placental vascular resistance (PVR), and placental efficiency.
BACKGROUND: 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.
UNASSIGNED: A prospective mother-child 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).
METHODS: 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 = 21 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.
RESULTS: 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 (β = -20.1 g [95% CI: -37.8; -2.5] and β = -17.4 g [95% CI: -33.2; -1.6], for second and third trimester, respectively) and PFR (β = -0.5 [95% CI: -1, -0.1] and β = -0.5 [95% CI: -0.9, -0.1], for the second and third trimester, respectively). Additionally, MBzP was negatively associated with PVR during the third trimester (β= -0.9 [95% CI: -1.8; 0.1]). Mono-n-butyl phthalate (MnBP), was negatively associated with PVR in both trimesters (β = -1.3, 95% CI: [-2.3, -0.2], and β = -1.2, 95% CI: [-2.4, -0.03], for the second and third trimester, respectively). After stratification for child sex, Σ 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.
CONCLUSIONS: 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.
CONCLUSIONS: Our results are consistent with in vitro studies showing that phthalates target peroxisome proliferator-activated receptor γ, 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-fetal exchanges over the course of pregnancy. Our findings contribute to the increasing evidence indicating adverse impacts of phthalate exposure on placental health.
BACKGROUND: This work was supported by the French Research Agency-ANR (MEMORI project ANR-21-CE34-0022). The SEPAGES cohort was supported by the European Research Council (N°311765-E-DOHaD), the European Community\'s Seventh Framework Programme (FP7/2007-206-N°308333-892 HELIX), the European Union\'s Horizon 2020 research and innovation programme (N° 874583 ATHLETE Project, N°825712 OBERON Project), the French Research Agency-ANR (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-EDeN project ANR-19-CE36-0003-01), the French Agency for Food, Environmental and Occupational Health & Safety-ANSES (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\'Air project), the French Cancer Research Foundation Association de Recherche sur le Cancer-ARC, the French Endowment Fund AGIR for chronic diseases-APMC (projects PRENAPAR, LCI-FOT, DysCard), the French Endowment Fund for Respiratory Health, the French Fund-Fondation de France (CLIMATHES-00081169, SEPAGES 5-00099903, ELEMENTUM-00124527). 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.
BACKGROUND: ClinicalTrials.gov NCT02852499.