Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Environ Int. 2024 May;187:108678. doi: 10.1016/j.envint.2024.108678. Epub 2024 Apr 20.
Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking.
To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP.
Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs).
In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses.
In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.
邻苯二甲酸酯暴露可能导致妊娠高血压疾病（HDP），包括子痫前期/子痫（PE/E），但流行病学研究尚缺乏。
评估妊娠期间邻苯二甲酸酯暴露与 PE/E 和 HDP 发生的关系。
使用来自八项环境影响儿童健康结果（ECHO）计划队列的 3430 名参与者的数据（1999 年至 2019 年期间招募），我们在至少一次妊娠期间收集的尿液样本中定量了 13 种邻苯二甲酸酯代谢物（8 种在所有队列中测量，13 种在四个队列的子集中测量）。我们将结局定义为 PE/E 和复合 HDP（PE/E 和/或妊娠期高血压）。在对尿液稀释后的邻苯二甲酸酯代谢物浓度进行校正后，我们通过广义估计方程评估个体邻苯二甲酸酯与 PE/E 或复合 HDP 的比值比（OR）的协变量调整关联，并用基于分位数的 g 计算法评估邻苯二甲酸混合物的关联。我们还通过分层模型探索了胎儿性别对效应测量的修饰作用。效应估计值以比值比（OR）和 95%置信区间（95%CI）表示。
在调整后的分析中，邻苯二甲酸单苄基酯（MBzP）和邻苯二甲酸单（3-羧丙基）酯（MCPP）浓度加倍与 PE/E 以及复合 HDP 的发生风险较高相关，PE/E 的关联更大。例如，MCPP 浓度加倍与 PE/E 的比值比为 1.12（95%CI 1.00，1.24），与复合 HDP 的比值比为 1.02（95%CI 1.00，1.05）。邻苯二甲酸混合物的四分位距增加与 PE/E 的比值比为 1.27（95%CI 0.94，1.70）。邻苯二甲酸单羧基异壬基酯（MCiNP）和邻苯二甲酸单羧基异辛基酯（MCiOP）浓度加倍与 PE/E 的比值比分别为 1.08（95%CI 1.00，1.17）和 1.11（95%CI 1.03，1.19）。PE/E 的效应估计值在携带女性胎儿的妊娠中通常更大。
在这项研究中，多种邻苯二甲酸酯与 PE/E 和 HDP 的发生风险较高相关。估计值较为准确，且有些估计值的幅度较小。在妊娠期间减少邻苯二甲酸酯暴露的干预措施可能有助于降低这些疾病的风险。
