Abstract：
OBJECTIVE: What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes?
CONCLUSIONS: Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes.
BACKGROUND: Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta.
METHODS: A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study.
METHODS: At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models.
RESULTS: Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: -0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: -0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]).
CONCLUSIONS: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance.
CONCLUSIONS: We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function.
BACKGROUND: This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.
BACKGROUND: N/A.
CONCLUSIONS: Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes.
BACKGROUND: Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta.
METHODS: A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study.
METHODS: At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models.
RESULTS: Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: -0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: -0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]).
CONCLUSIONS: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance.
CONCLUSIONS: We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function.
BACKGROUND: This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.
BACKGROUND: N/A.
摘要：
目的：邻苯二甲酸盐暴露与体内胎盘结局之间的纵向关联是什么？
结论：邻苯二甲酸盐与胎盘微脉管系统呈不利相关，刚度,和钙化的存在，不同的代谢物与不同的结果相关。
背景：邻苯二甲酸盐暴露无处不在，并可能导致不良妊娠结局，可能是通过对胎盘的影响。
方法：在人类胎盘和邻苯二甲酸盐研究中，总共招募了303名早期妊娠妇女，并在整个妊娠期间进行了8次前瞻性随访。
方法：每次就诊时，女性提供尿液样本并接受胎盘超声检查.分析尿液中邻苯二甲酸酯和替代物的18种代谢物。我们采用重复测量的几何平均值来反映每个参与者的妊娠平均邻苯二甲酸盐或替代暴露(n=303)。胎盘微脉管系统，刚度,和微钙化的存在在每次访问时通过超声进行量化。较高的分数反映了所有措施的胎盘功能较差。创建广义线性混合模型以估计妊娠平均暴露生物标志物浓度与微血管和硬度的重复结果测量之间的关联。使用Cox比例风险模型对钙化检测时的妊娠年龄进行建模。
结果：邻苯二甲酸单羧基异壬酯和总的邻苯二甲酸二（2-乙基己基）酯代谢物与微血管发育受损有关，使得浓度的四分位数间距增加与微脉管系统比率的0.11标准偏差增加相关，表明血管形成较差（95％CI：0.00，0.22）；0.11[95％CI：-0.01，0.22]，分别。邻苯二甲酸单乙酯与胎盘硬度增加相关(0.09[95%CI:-0.01,0.19]),而邻苯二甲酸二异丁酯代谢产物和邻苯二甲酸单苄基酯总代谢产物与钙化检测风险增加相关(风险比:1.18[95%CI:0.98,1.42];1.13[95%CI:0.96,1.34])。
结论：本研究中使用的结果是新颖的，需要进一步研究以提供临床背景和相关性。
结论：我们发现了一些邻苯二甲酸盐生物标志物与体内胎盘健康的各个方面之间存在关联的证据，尽管我们没有观察到胎盘结局的一致性。这些发现可以说明邻苯二甲酸酯暴露对胎盘功能的异质性影响。
背景：这项研究部分得到了NIH内部研究计划的支持，国家环境健康科学研究所（ZIAES103344），和NIEHST32ES007018。作者宣称，他们没有竞争利益可披露。本报告中的发现和结论是作者的发现和结论，不一定代表疾病控制和预防中心的官方立场。使用商品名称仅用于识别，并不意味着CDC认可，公共卫生服务，或美国卫生与公众服务部。
背景：不适用。
结论：邻苯二甲酸盐与胎盘微脉管系统呈不利相关，刚度,和钙化的存在，不同的代谢物与不同的结果相关。
背景：邻苯二甲酸盐暴露无处不在，并可能导致不良妊娠结局，可能是通过对胎盘的影响。
方法：在人类胎盘和邻苯二甲酸盐研究中，总共招募了303名早期妊娠妇女，并在整个妊娠期间进行了8次前瞻性随访。
方法：每次就诊时，女性提供尿液样本并接受胎盘超声检查.分析尿液中邻苯二甲酸酯和替代物的18种代谢物。我们采用重复测量的几何平均值来反映每个参与者的妊娠平均邻苯二甲酸盐或替代暴露(n=303)。胎盘微脉管系统，刚度,和微钙化的存在在每次访问时通过超声进行量化。较高的分数反映了所有措施的胎盘功能较差。创建广义线性混合模型以估计妊娠平均暴露生物标志物浓度与微血管和硬度的重复结果测量之间的关联。使用Cox比例风险模型对钙化检测时的妊娠年龄进行建模。
结果：邻苯二甲酸单羧基异壬酯和总的邻苯二甲酸二（2-乙基己基）酯代谢物与微血管发育受损有关，使得浓度的四分位数间距增加与微脉管系统比率的0.11标准偏差增加相关，表明血管形成较差（95％CI：0.00，0.22）；0.11[95％CI：-0.01，0.22]，分别。邻苯二甲酸单乙酯与胎盘硬度增加相关(0.09[95%CI:-0.01,0.19]),而邻苯二甲酸二异丁酯代谢产物和邻苯二甲酸单苄基酯总代谢产物与钙化检测风险增加相关(风险比:1.18[95%CI:0.98,1.42];1.13[95%CI:0.96,1.34])。
结论：本研究中使用的结果是新颖的，需要进一步研究以提供临床背景和相关性。
结论：我们发现了一些邻苯二甲酸盐生物标志物与体内胎盘健康的各个方面之间存在关联的证据，尽管我们没有观察到胎盘结局的一致性。这些发现可以说明邻苯二甲酸酯暴露对胎盘功能的异质性影响。
背景：这项研究部分得到了NIH内部研究计划的支持，国家环境健康科学研究所（ZIAES103344），和NIEHST32ES007018。作者宣称，他们没有竞争利益可披露。本报告中的发现和结论是作者的发现和结论，不一定代表疾病控制和预防中心的官方立场。使用商品名称仅用于识别，并不意味着CDC认可，公共卫生服务，或美国卫生与公众服务部。
背景：不适用。
