University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Development and Respiratory Health, Institute for Advanced Biosciences, 38000, Grenoble, France.
University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Development and Respiratory Health, Institute for Advanced Biosciences, 38000, Grenoble, France.
Environ Int. 2024 Apr;186:108584. doi: 10.1016/j.envint.2024.108584. Epub 2024 Mar 16.
Most previous studies investigating the associations between prenatal exposure to phthalates and fetal growth relied on measurements of phthalate metabolites at a single time point. They also focused on weight at birth without assessing growth over pregnancy, preventing the identification of potential periods of fetal vulnerability. We examined the associations between pregnancy urinary phthalate metabolites and fetal growth outcomes measured twice during pregnancy and at birth.
For 484 pregnant women, we assessed 13 phthalate and two 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) metabolite concentrations from two within-subject weekly pools of up to 21 urine samples (median of 18 and 34 gestational weeks, respectively). Fetal biparietal diameter, femur length, head and abdominal circumferences were measured during two routine pregnancy follow-up ultrasonographies (median 22 and 32 gestational weeks, respectively) and estimated fetal weight (EFW) was calculated. Newborn weight, length, and head circumference were measured at birth. Associations between phthalate/DINCH metabolite and growth parameters were investigated using adjusted linear regression and Bayesian kernel machine regression models.
Detection rates were above 99 % for all phthalate/DINCH metabolites. While no association was observed with birth measurements, mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were positively associated with most fetal growth parameters measured at the second trimester. Specifically, MiBP was positively associated with biparietal diameter, head and abdominal circumferences, while MnBP was positively associated with EFW, head and abdominal circumferences, with stronger associations among males. Pregnancy MnBP was positively associated with biparietal diameter and femur length at third trimester. Mixture of phthalate/DINCH metabolites was positively associated with EFW at second trimester.
In this pregnancy cohort using repeated urine samples to assess exposure, MiBP and MnBP were associated with increased fetal growth parameters. Further investigation on the effects of phthalates on child health would be relevant for expanding current knowledge on their long-term effects.
大多数先前研究调查产前暴露于邻苯二甲酸酯与胎儿生长之间的关系都依赖于单个时间点的邻苯二甲酸酯代谢物测量。它们还关注出生时的体重，而不评估整个孕期的生长情况，从而无法确定潜在的胎儿脆弱期。我们检查了在妊娠期间和出生时两次测量的妊娠尿液邻苯二甲酸酯代谢物与胎儿生长结局之间的关联。
对 484 名孕妇，我们评估了来自两个个体每周尿液样本的 21 个尿液样本（中位数分别为 18 和 34 孕周）中 13 种邻苯二甲酸酯和两种 1,2-环己烷二羧酸，二异壬酯（DINCH）代谢物浓度。在两次常规妊娠超声检查期间（中位数分别为 22 和 32 孕周）测量了胎儿双顶径、股骨长、头围和腹围，并计算了胎儿估计体重（EFW）。在出生时测量了新生儿体重、长度和头围。使用调整后的线性回归和贝叶斯核机器回归模型研究了邻苯二甲酸酯/DINCH 代谢物与生长参数之间的关系。
所有邻苯二甲酸酯/DINCH 代谢物的检测率均超过 99%。虽然与出生测量值无关，但邻苯二甲酸单异丁酯（MiBP）和邻苯二甲酸单正丁酯（MnBP）与第二孕期测量的大多数胎儿生长参数呈正相关。具体而言，MiBP 与双顶径、头围和腹围呈正相关，而 MnBP 与 EFW、头围和腹围呈正相关，男性中相关性更强。妊娠 MnBP 与第三孕期的双顶径和股骨长呈正相关。邻苯二甲酸酯/DINCH 代谢物混合物与第二孕期的 EFW 呈正相关。
在本项妊娠队列研究中，使用重复尿液样本评估暴露情况，MiBP 和 MnBP 与胎儿生长参数增加有关。进一步研究邻苯二甲酸酯对儿童健康的影响将有助于扩大人们对其长期影响的认识。
