Longitudinal Associations between Prenatal Exposure to Phthalates and Steroid Hormones in Maternal Hair Samples from the SEPAGES Cohort

We assessed phthalate-hormone
associations in 382 pregnant women
of the new-generation SEPAGES cohort (2014–2017, France) using
improved exposure and outcome assessments. Metabolites from seven
phthalate compounds and the replacement di­(isononyl)­cyclohexane-1,2-dicarboxylate
(DINCH) were measured in within-subject pools of repeated urine samples
collected at the second and third pregnancy trimesters (≈21
samples/trimester). Metabolites from five steroid hormones were measured
in maternal hair samples collected at delivery, reflecting cumulative
levels over the previous weeks to months. Adjusted linear regression
and Bayesian weighted quantile sum (BWQS) mixture models were performed.
Each doubling in third-trimester urinary mono-benzyl phthalate (MBzP)
concentrations was associated with an average increase of 13.3% (95%
CI: 2.65, 24.9) for ∑cortisol, 10.0% (95% CI: 0.26, 20.7) for
∑cortisone, 17.3% (95% CI: 1.67, 35.4) for 11-dehydrocorticosterone,
and 16.2% (95% CI: 2.20, 32.1) for testosterone, together with a suggestive
10.5% (95% CI: −1.57, 24.1) increase in progesterone levels.
Each doubling in second-trimester urinary di-isononyl phthalate (DiNP)
concentrations was inversely associated with testosterone levels (−11.6%;
95% CI: −21.6, −0.31). For most hormones, a nonsignificant
trend toward a positive phthalate mixture effect was observed in the
third but not in the second trimester. Our study showed that exposure
to some phthalate metabolites, especially MBzP, may affect adrenal
and reproductive hormone levels during pregnancy.

本研究对新一代SEPAGES队列（2014-2017年，法国）中382名孕妇进行了对酞酸-激素关联的评估，该评估采用了改进的暴露和结局评估方法。在第二和第三孕期的尿液样本（≈每季度21个样本）中，对七种酞酸化合物及其替代品二异壬基环己烷-1,2-二羧酸（DINCH）的代谢物进行了测量。在分娩时收集的母体头发样本中，对五种类固醇激素的代谢物进行了测量，这些样本反映了前几周至几个月的累积水平。本研究采用了调整后的线性回归和贝叶斯加权分位数和（BWQS）混合模型进行分析。第三孕期尿液单苄基酞酸（MBzP）浓度的每翻倍增加，与平均13.3%（95% CI：2.65，24.9）的皮质醇总和、10.0%（95% CI：0.26，20.7）的皮质酮总和、17.3%（95% CI：1.67，35.4）的11-脱氢皮质酮以及16.2%（95% CI：2.20，32.1）的睾酮水平增加相关，同时，孕酮水平也显示出10.5%（95% CI：-1.57，24.1）的潜在增加。第二孕期尿液二异壬基酞酸（DiNP）浓度的每翻倍增加与睾酮水平呈负相关（-11.6%；95% CI：-21.6，-0.31）。对于大多数激素而言，第三期而非第二期观察到一种非显著的正酞酸混合效应趋势。本研究结果表明，某些酞酸代谢物（尤其是MBzP）的暴露可能会影响孕期肾上腺和生殖激素水平。