Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Hum Reprod. 2024 Sep 1;39(9):2104-2114. doi: 10.1093/humrep/deae152.
What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes?
Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes.
Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta.
STUDY DESIGN, SIZE, DURATION: 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.
PARTICIPANTS/MATERIALS, SETTING, 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.
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]).
LIMITATIONS, REASONS FOR CAUTION: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance.
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.
STUDY FUNDING/COMPETING INTEREST(S): 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.
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妊娠期间邻苯二甲酸酯暴露与体内胎盘结局的纵向关联是什么？
邻苯二甲酸盐与胎盘微血管、硬度和钙化的存在呈负相关，不同的代谢物与不同的结果相关。
邻苯二甲酸酯暴露普遍存在，并被认为是导致不良妊娠结局的原因之一，其可能通过对胎盘的影响而产生影响。
研究设计、规模、持续时间：共有 303 名妇女在妊娠早期被招募，并在人类胎盘和邻苯二甲酸盐研究中进行了长达 8 次的妊娠期间前瞻性随访。
参与者/材料、地点、方法：在每次就诊时，女性提供尿液样本并接受胎盘超声检查。对尿液进行了 18 种邻苯二甲酸酯和替代品的代谢物分析。我们取重复测量的几何平均值来反映每个参与者（n=303）的妊娠平均邻苯二甲酸酯或替代品暴露。每次就诊时都从超声中量化了胎盘微血管、硬度和微钙化的存在。对于所有测量值，分数越高表示胎盘功能越差。创建了广义线性混合模型来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 比例风险模型来建模钙化检测时的胎龄。
单羧基异壬基邻苯二甲酸酯和二（2-乙基己基）邻苯二甲酸酯代谢物与受损的微血管发育有关，因此浓度的四分位距增加与微血管比的 0.11 个标准差增加相关，表明血管生成较差（95%CI：0.00，0.22）；0.11[95%CI：-0.01，0.22]，分别。单乙基邻苯二甲酸酯与胎盘硬度增加（0.09[95%CI：-0.01，0.19]）有关，而二异丁基邻苯二甲酸酯代谢物和单苄基邻苯二甲酸酯与钙化检测的危险增加有关（风险比：1.18[95%CI：0.98，1.42]；1.13[95%CI：0.96，1.34]）。
局限性、谨慎的原因：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。
我们发现了一些邻苯二甲酸酯生物标志物与体内胎盘健康的各个方面之间的关联证据，尽管我们没有观察到胎盘结果的一致性。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。
研究资金/利益冲突：本研究部分得到美国国立卫生研究院、国家环境卫生科学研究所（ZIA ES103344）和 NIEHS T32ES007018 的内部研究计划的支持。作者声明他们没有利益冲突需要披露。本报告中的发现和结论是作者的观点，不一定代表疾病预防控制中心的官方立场。使用商品名仅用于识别，并不表示疾病预防控制中心、公共卫生服务或美国卫生与公众服务部的认可。
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