围产期双酚暴露与胎龄小的新生儿： 替代品在过去和现在不断演变的影响

Perinatal Bisphenol Exposure and Small-for-Gestational-Age Neonates: The Evolving Effect of Replacements Then and Now

围产期双酚暴露与胎龄小的新生儿： 替代品在过去和现在不断演变的影响

Authors: Lin Luo, Chang Gao, Yi-Jun Fan, Ting Zhuang, Yuanyuan Li, Chang-An Li, Jia Lv, Zhong-Wang Hu, Lin Tao, Robert Gibson, Hua Wang, De-Xiang Xu, Yichao Huang

Source: Environmental Science & Technology

DOI: 10.1021/acs.est.4c13266

Abstract

Bisphenol analogues have been shown to have similar estrogenic activity to that of BPA and may affect fetal development. However, no human studies have examined the effects of perinatal exposure to emerging bisphenol alternatives [bisphenol G, bisphenol M, and bisphenol BP (BPBP)] on small for gestational age (SGA) and how placental function may mediate the relationship. Here, 13 urinary bisphenol analogues were detected in 1054 contemporary pregnant women, and BPA was still the most dominant congener. Logistic regressions identified BPA and its traditional alternatives [bisphenol B (BPB), bisphenol E (BPE), bisphenol Z, and bisphenol AP (BPAP)] as being associated with an elevated risk of SGA (all ORs > 1.80, P < 0.05). In contrast, the emerging substitutes, despite high occurrences, all showed much attenuated risk. Mixture effect models Bayesian kernel machine regression and quantile-based g-computation demonstrated that coexposure to bisphenols was strongly correlated with SGA risk (OR = 2.70, P < 0.001), with BPA and the conventional substitutes (BPB, BPE, and BPAP) as primary effect drivers, outweighing the effect from emerging substitutes. Finally, mediation analysis revealed that the placental function index estriol mediated the relationship between exposure and SGA, dominated by BPBP (25.4%). Our findings provide new epidemiological evidence that early BPA alternatives may pose a higher risk for offspring development than those emerging alternatives, potentially via mediation by compromised placental function. Future toxicity assessments and validation studies in other settings on these emerging bisphenols are needed.

Keywords: bisphenol analogue; emerging alternative; estriol; mixture effect; perinatal exposure; placental function index; small-for-gestational-age neonates.

摘要

研究表明，双酚类似物具有与双酚 A 类似的雌激素活性，可能会影响胎儿发育。然而，还没有人类研究探讨过围产期暴露于新出现的双酚替代品（双酚 G、双酚 M 和双酚 BP (BPBP)）对胎龄小（SGA）的影响，以及胎盘功能可能如何介导这种关系。本研究在 1054 名当代孕妇的尿液中检测到 13 种双酚类似物，其中双酚 A 仍是最主要的同系物。逻辑回归确定双酚 A 及其传统替代品 [双酚 B (BPB)、双酚 E (BPE)、双酚 Z 和双酚 AP (BPAP)]与 SGA 风险升高有关（所有 ORs > 1.80，P < 0.05）。相比之下，新出现的替代品尽管出现率很高，但风险都大大降低。混合效应模型贝叶斯核机器回归和基于量纲的 g 计算表明，共同暴露于双酚与 SGA 风险密切相关（OR = 2.70，P < 0.001），双酚 A 和传统替代品（BPB、BPE 和 BPAP）是主要的效应驱动因素，超过了新兴替代品的效应。最后，中介分析表明，胎盘功能指数雌三醇对暴露与 SGA 之间的关系起中介作用，而 BPBP（25.4%）起主导作用。我们的研究结果提供了新的流行病学证据，表明早期的双酚 A 替代品可能比新出现的替代品对后代的发育构成更高的风险，这可能是通过胎盘功能受损来调节的。未来需要在其他环境中对这些新兴双酚进行毒性评估和验证研究。

关键词：双酚类似物；新兴替代品；雌三醇；混合物效应；围产期暴露；胎盘功能指数；小胎龄新生儿