McNell Erin E, Stevens Danielle R, Welch Barrett M, Rosen Emma M, Fenton Suzanne, Calafat Antonia M, Botelho Julianne Cook, Sinkovskaya Elena, Przybylska Ann, Saade George, Abuhamad Alfred, Ferguson Kelly K
Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA; Curriculum in Toxicology and Environmental Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Environ Res. 2025 Aug 15;279(Pt 1):121739. doi: 10.1016/j.envres.2025.121739. Epub 2025 Apr 29.
Exposure to endocrine-disrupting chemicals such as phthalates may increase risk of hypertensive disorders of pregnancy (HDP). Prior studies lack investigation of chemical mixtures, phthalate replacements, or key periods of susceptibility including early pregnancy. In the present study, we used a longitudinal approach to evaluate gestational exposure to phthalates and replacements, as both single-pollutants and mixtures, in association with blood pressure and diagnosis of preeclampsia or any HDP. The Human Placenta and Phthalates prospective pregnancy cohort includes 291 participants recruited from two U.S. clinics. Urinary metabolites of ten phthalates and replacements were quantified at up to 8 time points per individual and averaged to create early (12-15 weeks) and overall (12-38 weeks) pregnancy exposure biomarkers. We collected data on gestational blood pressure (mean = 6.2 measures per participant) and diagnosis of preeclampsia (n = 26 cases) or any HDP (n = 44 cases). Linear mixed effects models estimated associations between exposure biomarkers and repeated blood pressure measures. We estimated exposure biomarker associations with preeclampsia and HDP using Cox proportional hazards or logistic regression models, respectively. Quantile g-computation was used to estimate joint effects of a phthalate or replacement mixture with each outcome. Early pregnancy exposure biomarkers demonstrated greater associations with adverse outcomes compared to overall pregnancy. A one-interquartile range increase in early pregnancy di-isononyl phthalate metabolites (ƩDiNP) was associated with a 1.13 mmHg (95 % confidence interval [CI]: 0.25, 2.37) and 0.90 mmHg (CI: 0.16, 1.65) increase in systolic and diastolic blood pressure, respectively. We also found positive but nonsignificant associations of early pregnancy mono-3-carboxypropyl phthalate, di-2-ethylhexyl terephthalate metabolites, and the high molecular weight phthalate mixture with blood pressure. Early pregnancy ƩDiNP was furthermore associated with increased odds of HDP (odds ratio: 1.37, CI: 1.03, 1.82), but not preeclampsia. In sum, early gestational exposure to DiNP and other high molecular weight phthalates may contribute to HDP.
接触邻苯二甲酸盐等内分泌干扰化学物质可能会增加妊娠高血压疾病(HDP)的风险。先前的研究缺乏对化学混合物、邻苯二甲酸盐替代品或包括孕早期在内的关键易感性时期的调查。在本研究中,我们采用纵向研究方法,评估孕期邻苯二甲酸盐及其替代品作为单一污染物和混合物的暴露情况,以及它们与血压和子痫前期或任何HDP诊断之间的关系。人类胎盘与邻苯二甲酸盐前瞻性妊娠队列研究纳入了从美国两家诊所招募的291名参与者。对每位个体最多8个时间点的10种邻苯二甲酸盐及其替代品的尿液代谢物进行定量,并取平均值以创建孕早期(12 - 15周)和整个孕期(12 - 38周)的暴露生物标志物。我们收集了孕期血压数据(每位参与者平均测量6.2次)以及子痫前期(26例)或任何HDP(44例)的诊断信息。线性混合效应模型估计了暴露生物标志物与重复血压测量值之间的关联。我们分别使用Cox比例风险模型或逻辑回归模型估计暴露生物标志物与子痫前期和HDP之间的关联。分位数g计算用于估计邻苯二甲酸盐或替代品混合物与每种结局的联合效应。与整个孕期相比,孕早期暴露生物标志物与不良结局的关联更强。孕早期邻苯二甲酸二异壬酯代谢物(ƩDiNP)增加一个四分位数间距与收缩压升高1.13 mmHg(95%置信区间[CI]:0.25,2.37)和舒张压升高0.90 mmHg(CI:0.16,1.65)相关。我们还发现孕早期邻苯二甲酸单 - 3 - 羧丙酯、邻苯二甲酸二 - 2 - 乙基己酯代谢物以及高分子量邻苯二甲酸盐混合物与血压呈正相关,但无统计学意义。此外,孕早期ƩDiNP与HDP的发生几率增加相关(优势比:1.37,CI:1.03,1.82),但与子痫前期无关。总之,孕早期接触DiNP和其他高分子量邻苯二甲酸盐可能会导致HDP。