Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Environ Pollut. 2022 Jan 1;292(Pt B):118476. doi: 10.1016/j.envpol.2021.118476. Epub 2021 Nov 8.
Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of ∑DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean ∑DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation.
孕前和产前接触邻苯二甲酸酯与早产风险增加有关。然而，目前尚不清楚怀孕期间是否存在易感性增加的时期。这项前瞻性队列研究纳入了 386 名接受生育治疗的女性，她们在 2005 年至 2018 年期间生下了一个单胎婴儿。在每个孕期，采集了点尿样，检测了 11 种邻苯二甲酸酯代谢物。在大约 50%的参与者中，还测量了两种 1,2-环己烷二羧酸二异壬酯（DINCH）的代谢物，DINCH 是一种邻苯二甲酸酯替代品。计算了四种二（2-乙基己基）邻苯二甲酸酯代谢物（∑DEHP）的摩尔总和。我们使用修正后的对数二项式模型评估了母体生物标志物浓度平均值与早产风险之间的关系，并利用多信息模型比较了特定孕期的关联。我们使用二次混合模型比较了早产妇女和足月分娩妇女的相对生物标志物浓度，以评估妊娠期间生物标志物浓度的变化。与尿中∑DEHP（孕期平均值）的自然对数转换浓度增加一个单位相关的早产风险比为 1.21（95%置信区间：0.84，1.72）。在多信息模型中，这些关联在孕晚期最强（RR=1.51；95%置信区间：1.17，1.95）。与足月分娩相比，早产妇女的∑DEHP 浓度估计值更高，尤其是在妊娠晚期。每个单独的 DEHP 代谢物也与早产有关。检测环己烷-1,2-二羧酸单羧酸异辛酯（MCOCH），DINCH 的一种代谢物，似乎与早产呈正相关。在这个亚生育夫妇的前瞻性队列中，孕妇孕期的∑DEHP 代谢物浓度与早产风险增加相关，尤其是在妊娠晚期。
