Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, Netherlands.
The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
Environ Health Perspect. 2021 Nov;129(11):117008. doi: 10.1289/EHP9178. Epub 2021 Nov 24.
Prenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact.
We aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight.
Within the Generation R Study, a population-based cohort in Netherlands (), urinary concentrations of 11 phthalate metabolites, 3 bisphenols, and 5 dialkylphosphate (DAP) metabolites were measured at , 18-25, and of gestation and averaged. Ultrasound measures of head circumference, femur length, and estimated fetal weight (EFW) were taken at 18-25 and of gestation, and measurements of head circumference, length, and weight were performed at delivery. We estimated the difference in each fetal measurement per quartile increase in all exposures within the mixture with quantile g-computation.
The average EFW at 18-25 wk and was 369 and , respectively, and the average birth weight was . Higher exposure was associated with smaller fetal and newborn growth parameters in a nonlinear fashion. At 18-25 wk, fetuses in the second, third, and fourth quartiles of exposure (Q2-Q4) had [, ], (, ), and (, 1) lower EFW compared with those in the first quartile (Q1). A similar dose-response pattern was observed at , but all effect sizes were smaller, and no association was observed comparing Q4 to Q1. At birth, we observed no differences in weight between Q1-Q2 or Q1-Q3. However, fetuses in Q4 had (, 76) lower birth weight in comparison with those in Q1. Results observed at 18-25 and were similar for femur length; however, no differences were observed at birth. No associations were observed for head circumference.
Higher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial. https://doi.org/10.1289/EHP9178.
产前暴露于非持久性化学物质混合物是普遍存在的。大多数研究都集中在单一暴露模型上，研究这些化学物质与胎儿生长的关系，而忽略了它们潜在的累积影响。
我们旨在评估产前暴露于邻苯二甲酸酯、双酚和有机磷酸酯（OP）农药混合物与头围、股骨长和体重等胎儿测量值之间的关联。
在荷兰的 Generation R 研究中，这是一个基于人群的队列研究（），在妊娠 、18-25 周和 25-38 周时测量了 11 种邻苯二甲酸酯代谢物、3 种双酚和 5 种二烷基磷酸酯（DAP）代谢物的尿浓度，并取平均值。在妊娠 18-25 周和 时进行了头围、股骨长和估计胎儿体重（EFW）的超声测量，在分娩时进行了头围、长度和体重的测量。我们使用分位数 g 计算法，估计了混合物中所有暴露物每四分位数增加一个单位时，每个胎儿测量值的差异。
妊娠 18-25 周和 时的平均 EFW 分别为 369 和 ，平均出生体重为 。较高的暴露与胎儿和新生儿生长参数呈非线性下降趋势。在妊娠 18-25 周时，与第 1 四分位数（Q1）相比，第 2、3 和 4 四分位数（Q2-Q4）的胎儿 EFW 分别低 （，）、 （，）和 （，1）。在妊娠 时也观察到了类似的剂量反应模式，但所有的效应大小都较小，并且没有观察到 Q4 与 Q1 之间的关联。在出生时，我们没有观察到 Q1-Q2 或 Q1-Q3 之间的体重差异。然而，与 Q1 相比，Q4 的胎儿出生体重低 （，76）。在 18-25 周和 时，股骨长度的结果相似；然而，在出生时没有观察到差异。在头围方面没有观察到关联。
产前暴露于邻苯二甲酸酯、双酚和 OP 农药混合物与妊娠中期 EFW 较低有关。在妊娠晚期，这些差异相似，但程度较小。在出生时，仅当比较 Q1 和 Q4 的个体时才观察到关联。这一发现表明，即使是低水平的暴露也足以在妊娠早期影响生长，而更高水平的暴露可能会影响出生体重。非持久性化学物质的联合暴露可能对胎儿生长产生不利影响，由于这些暴露广泛存在，这种影响可能是巨大的。https://doi.org/10.1289/EHP9178.
