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--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.

中文翻译：

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在重复尿液收集的队列中分析邻苯二甲酸盐和 DINCH 暴露对胎儿生长的影响

之前大多数研究产前接触邻苯二甲酸盐与胎儿生长之间关系的研究都依赖于单个时间点邻苯二甲酸盐代谢物的测量。他们还关注出生时的体重，而不评估怀孕期间的生长情况，从而无法识别胎儿的潜在脆弱期。我们在怀孕期间和出生时两次测量了怀孕尿邻苯二甲酸酯代谢物与胎儿生长结果之间的关联。对于 484 名孕妇，我们评估了受试者每周收集的最多 21 份尿样（中位值分别为 18 和 34 孕周）中的 13 种邻苯二甲酸盐和两种 1,2-环己烷二甲酸二异壬酯 (DINCH) 代谢物浓度。 。在两次常规妊娠随访超声检查（分别为中位妊娠 22 周和 32 周）期间测量胎儿双顶径、股骨长度、头围和腹围，并计算估计胎儿体重 (EFW)。新生儿出生时测量体重、身长和头围。使用调整的线性回归和贝叶斯核机器回归模型研究邻苯二甲酸盐/DINCH代谢物与生长参数之间的关联。所有邻苯二甲酸盐/DINCH 代谢物的检出率均高于 99%。虽然未观察到与出生测量之间存在关联，但邻苯二甲酸单丁酯 (MiBP) 和邻苯二甲酸单正丁酯 (MnBP) 与妊娠中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，且男性之间的相关性更强。妊娠 MnBP 与妊娠晚期的双顶径和股骨长度呈正相关。邻苯二甲酸盐/DINCH 代谢物的混合物与妊娠中期的 EFW 呈正相关。在这个使用重复尿液样本来评估暴露情况的妊娠队列中，MiBP 和 MnBP 与胎儿生长参数的增加相关。进一步研究邻苯二甲酸盐对儿童健康的影响将有助于扩大目前对其长期影响的了解。