Sex-and stage-specific effect of prenatal exposure to organophosphate esters with children's physical growth patterns and adiposity rebound timing: Modification by breastfeeding
产前接触有机磷酸酯对儿童体格生长模式和脂肪重积聚时相的影响：母乳喂养的修饰作用

Authors：Xing Wang, Juan Tong, Han Li, Mengjuan Lu, Yuan Liu, Hong Gan, Yifan Wang, Menglong Geng, Xuejiao Qie, Xiulong Wu, Hui Gao, Beibei Zhu, Shuman Tao, Xingyong Tao, Shuangqin Yan, Guopeng Gao, Xiaoyan Wu, Kun Huang, Yunxia Cao, Fangbiao Tao
Source：Journal of Hazardous Materials
DOI: 10.1016/j.jhazmat.2025.138309

Abstract
Introduction: Exploring the stage-specific effects of prenatal exposure to organophosphate esters (OPEs) on offspring growth and developmental trajectories is critical for early-life health management.
Methods: Based on 2519 mother-child dyads from the Ma'anshan Birth Cohort, we examined the concentrations of OPEs in maternal urine during the three trimesters. Seventeen follow-up visits were made to the children, and physical data were collected. A grouped trajectory model was used to fit the growth trajectories.

Results: First-trimester bis(2-butoxyethyl) phosphate (BBOEP) was inversely associated with the children's adiposity rebound (AR) timing (β = -0.33, 95 % CI: -0.65, -0.01), and the ORs (95 % CIs) for early age at AR for each doubling of BBOEP and dibutyl phosphate (DBP) were 1.07 (1.00, 1.14) and 1.12 (1.03, 1.22), respectively. BBOEP increased the risk of a high-stable BMI-for-age z score (BMIz) group (OR = 1.18, 95 % CI: 1.01, 1.39), whereas tris(2-chloroethyl) phosphate (TCEP) and bis(2-ethylhexyl) phosphate reduced this risk. Diphenyl phosphate (OR = 0.74, 95 % CI: 0.59, 0.94) and aromatic OPEs (OR = 0.70, 95 % CI: 0.54, 0.90) reduced the odds of an extreme-high body fat group. TCEP also reduced the risk of a high body fat percentage group (p < 0.05). There appeared to be sex and ester bond differences in these associations, and breastfeeding could counteract the association between the OPEs and growth trajectories. No mixed effects of OPEs on BMIz trajectories were found.
Conclusions: The present study identified a heterogeneous association between OPE exposure during pregnancy and AR timing and physical growth patterns in offspring. Future studies are needed involving more regions and populations, with consideration of other developmentally toxic compounds, to obtain more reliable and comprehensive results.
Keywords: Adiposity rebound; Breastfeeding; Organophosphate esters; Physical growth pattern; Prenatal exposure; Trajectory.

摘要

背景：探讨产前接触有机磷酸酯（OPEs）对后代持续生长和发育轨迹的阶段特异性影响，对于早期生命健康管理至关重要。

方法：基于马鞍山出生队列中的2519对母婴对，我们分别检测了孕早、中、晚期孕妇尿液中的OPEs浓度。对儿童进行了17次的随访，每次都进行了标准化的体格测量评估。最后采用分组轨迹模型拟合后代的体格生长轨迹。

结果：孕早期磷酸二（2-丁氧基乙基）酯（BBOEP）与子代脂肪反弹（AR）时间呈现负相关（β = -0.33，95% CI：-0.65，-0.01），同时逻辑回归模型中显示BBOEP和磷酸二丁酯浓度每增加一倍，AR时相提前的几率就会增加1.07（95% CI: 1.00, 1.14）和1.12（95% CI: 1.03, 1.22）。BBOEP与高稳定性组BMIz风险增加相关（OR = 1.18，95% CI：1.01，1.39），而磷酸三（2-氯乙基）酯（TCEP）和磷酸二（2-乙基己基）酯 则会降低其发生风险（p < 0.05）。与正常体脂组相比，2-乙基己基-二苯基磷酸酯（DPHP）（OR = 0.74，95% CI：0.59，0.94）和ΣAr-OPEs（OR = 0.70，95% CI：0.54，0.90）与极高体脂率组的几率降低相关。TCEP浓度较高也会降低子代高体脂百分比组的风险（p < 0.05）。这些关联似乎存在一定性别和酯键差异，并且发现母乳喂养可以抵消OPEs对儿童生长轨迹的影响。未发现OPEs对BMIz轨迹的混合效应。

结论：本研究确定了孕期OPE暴露与后代脂肪反弹时间和体格生长模式之间的异质性关联，未来有必要开展涉及更多地区和人群的研究，同时考虑其他的具有发育毒性的化合物，以此进一步获得更可靠、更全面的结果。

关键词：脂肪重积聚；母乳喂养；有机磷酸酯；体格生长模式；产前暴露；轨迹