Li Xiang, Yu Xiaofeng, Lian Xin, Kang Longdan, Yang Lei, Ba Fang
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Ecotoxicol Environ Saf. 2025 Feb;291:117767. doi: 10.1016/j.ecoenv.2025.117767. Epub 2025 Jan 27.
The existing evidence indicating that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with a range of adverse outcomes, including alterations in anthropometric indices, underscores the need for further investigation into the underlying mechanisms. This study aims to examine the effects of prenatal PAH exposure on anthropometric indices and telomere length (TL), as well as to explore whether changes in TL can serve as a predictor of alterations in anthropometric measures. The study was conducted in Shenyang, China, with 2460 pregnant women participating between 2022 and 2023. Maternal urine samples were analyzed for eleven PAH metabolites, and neonatal outcomes, such as birth weight (BW), birth length (BL), and head circumference (HC), were extracted from medical records as anthropometric indices. We employed multiple linear regression (MLR), generalized quantile g-computation (g-comp), Bayesian Kernel Machine Regression (BKMR), and mediation analysis to comprehensively assess the associations between PAH exposure and umbilical TL and neonatal outcomes. Notably, significant negative associations were found between several PAH metabolites and umbilical telomere length (TL). These metabolites included 2-hydroxy naphthalene (2-OH Nap), 1-hydroxy pyrene (1-OH Pyr), 6-hydroxy chrysene (6-OH Chr), 9-hydroxy benzo(a)pyrene (9-OH Bap), and the sum of hydroxylated PAHs (Σ-OH PAHs). Additionally, negative correlations were identified between specific PAH metabolites and HC, although no significant associations were found for BW. Birth weight showed a significant inverse relationship with metabolites such as 1-hydroxy phenanthrene (1-OH Phe), 9-hydroxy phenanthrene (9-OH Phe), and 1-hydroxy naphthalene(1-OH Nap). Results from g-comp analysis and BKMR indicated significant mixture effects of PAHs on umbilical TL and HC, with more heterogeneous effects on BW and BL. Mediation analysis indicated that alterations in umbilical TL partially mediated the associations between PAH exposure and BW and HC. Notably, metabolites such as 2-OH Nap and the Σ-OH PAHs demonstrated substantial mediation effects. Overall, our findings suggest that changes in umbilical TL partially mediate the associations between prenatal PAH exposure and HC and BW, highlighting the complex pathways through which PAH metabolites may influence neonatal development.
现有证据表明,产前暴露于多环芳烃(PAHs)与一系列不良后果相关,包括人体测量指标的改变,这凸显了进一步研究其潜在机制的必要性。本研究旨在探讨产前PAH暴露对人体测量指标和端粒长度(TL)的影响,并探究TL的变化是否可作为人体测量指标改变的预测因子。该研究在中国沈阳进行,2022年至2023年期间有2460名孕妇参与。对孕妇尿液样本进行了11种PAH代谢物分析,并从医疗记录中提取新生儿结局,如出生体重(BW)、出生身长(BL)和头围(HC)作为人体测量指标。我们采用多元线性回归(MLR)、广义分位数g计算(g-comp)、贝叶斯核机器回归(BKMR)和中介分析,全面评估PAH暴露与脐带TL及新生儿结局之间的关联。值得注意的是,发现几种PAH代谢物与脐带端粒长度(TL)之间存在显著负相关。这些代谢物包括2-羟基萘(2-OH Nap)、1-羟基芘(1-OH Pyr)、6-羟基屈(6-OH Chr)、9-羟基苯并(a)芘(9-OH Bap)以及羟基化PAHs总和(Σ-OH PAHs)。此外,虽然未发现特定PAH代谢物与BW之间存在显著关联,但发现其与HC之间存在负相关。出生体重与1-羟基菲(1-OH Phe)、9-羟基菲(9-OH Phe)和1-羟基萘(1-OH Nap)等代谢物呈显著负相关。g-comp分析和BKMR结果表明PAHs对脐带TL和HC有显著的混合效应,对BW和BL的影响更具异质性。中介分析表明,脐带TL改变部分介导了PAH暴露与BW和HC之间的关联。值得注意的是,2-OH Nap和Σ-OH PAHs等代谢物表现出显著的中介效应。总体而言,我们的研究结果表明,脐带TL的变化部分介导了产前PAH暴露与HC和BW之间的关联,突出了PAH代谢物可能影响新生儿发育的复杂途径。