Yang Ying, Liu Minghua, Shao Hua, Jiang Hongfang, Yang Lei, Zhang Xixia
Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, PR China.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110000, PR China.
Ecotoxicol Environ Saf. 2025 Sep 15;303:119022. doi: 10.1016/j.ecoenv.2025.119022. Epub 2025 Sep 16.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants with endocrine-disrupting properties. Prenatal exposure to PAHs has been linked to metabolic alterations, but its long-term impact on childhood overweight risk remains unclear. This is the first large-scale study to comprehensively assess the impact of prenatal exposure to urinary polycyclic aromatic hydrocarbons (PAHs) on early childhood overweight and obesity outcomes using advanced mixture modeling approaches. Conducted in Shenyang, China, we enrolled 5600 mother-child pairs with maternal urine samples collected in the third trimester to quantify 11 PAH metabolites using HPLC-MS/MS. Children's weight and height were measured between the ages of 4 and 6 years to calculate BMI and determine overweight status based on the Chinese National Standards. Multivariable linear regression analyses revealed significant positive associations between several individual urinary OH-PAH metabolites and increased weight in children after adjusting for confounders. Notably, 2-hydroxynaphthalene (β = 0.139, 95 % CI: 0.078, 0.201), 3-hydroxyfluorene (β = 1.709, 95 % CI: 0.932, 2.486), 9-hydroxyphenanthrene (β = 3.733, 95 % CI: 1.885, 5.581), 1-hydroxypyrene (β = 0.914, 95 % CI: 0.003, 1.825), and 9-hydroxybenzo[a]pyrene (β = 2.102, 95 % CI: 0.270, 3.934) were significantly linked with higher weight. Total OH-PAHs also showed a robust association (β = 0.110, 95 % CI: 0.066, 0.154). Similar positive associations were observed for BMI, including 2-hydroxynaphthalene (β = 0.090, 95 % CI: 0.027, 0.153), 3-hydroxyfluorene (β = 1.464, 95 % CI: 0.665, 2.263), 9-hydroxyphenanthrene (β = 2.800, 95 % CI: 0.900, 4.701), and total OH-PAHs (β = 0.073, 95 % CI: 0.028, 0.119). Logistic regression indicated that 3-hydroxyfluorene exposure was strongly associated with increased odds of overweight (adjusted OR = 12.66, 95 % CI: 2.94-54.54). Mixture analyses using G-computation (g-comp) and generalized weighted quantile sum (gQWS) regression confirmed the overall positive effect of PAH mixtures on child weight (β = 0.425 and 0.285, respectively; p < 0.01), though associations with BMI were weaker and non-significant. Bayesian kernel machine regression (BKMR) further highlighted dose-response relationships for weight but not BMI. These findings suggest that prenatal PAH exposure may contribute to increased weight and risk of overweight in early childhood, emphasizing the need for public health interventions to reduce maternal exposure to PAHs during pregnancy.
多环芳烃（PAHs）是广泛存在的具有内分泌干扰特性的环境污染物。孕期接触PAHs与代谢改变有关，但其对儿童超重风险的长期影响仍不清楚。这是第一项使用先进的混合模型方法全面评估孕期接触尿多环芳烃（PAHs）对幼儿超重和肥胖结局影响的大规模研究。在中国沈阳进行的这项研究中，我们招募了5600对母婴，收集了孕晚期母亲的尿液样本，采用高效液相色谱-串联质谱法（HPLC-MS/MS）对11种PAH代谢物进行定量分析。在儿童4至6岁时测量其体重和身高，以计算身体质量指数（BMI），并根据中国国家标准确定超重状态。多变量线性回归分析显示，在调整混杂因素后，几种个体尿中OH-PAH代谢物与儿童体重增加之间存在显著的正相关。值得注意的是，2-羟基萘（β = 0.139，95%置信区间：0.078，0.201）、3-羟基芴（β = 1.709，95%置信区间：0.932，2.486）、9-羟基菲（β = 3.733，95%置信区间：1.885，5.581）、1-羟基芘（β = 0.914，95%置信区间：0.003，1.825）和9-羟基苯并[a]芘（β = 2.102，95%置信区间：0.270，3.934）与较高体重显著相关。总OH-PAHs也显示出强烈的相关性（β = 0.110，95%置信区间：0.066，0.154）。在BMI方面也观察到类似的正相关，包括2-羟基萘（β = 0.090，95%置信区间：0.027，0.153）、3-羟基芴（β = 1.464，95%置信区间：0.665，2.263）、9-羟基菲（β = 2.800，95%置信区间：0.9着0，4.701）和总OH-PAHs（β = 0.073，95%置信区间：0.028，0.119）。逻辑回归表明，接触3-羟基芴与超重几率增加密切相关（调整后的比值比=12.66，95%置信区间：2.94 - 54.54）。使用G计算（g-comp）和广义加权分位数和（gQWS）回归进行的混合分析证实了PAH混合物对儿童体重的总体积极影响（β分别为0.425和0.285；p<0.01），尽管与BMI的相关性较弱且无统计学意义。贝叶斯核机器回归（BKMR）进一步突出了体重的剂量反应关系，但未发现BMI的剂量反应关系。这些发现表明，孕期接触PAHs可能导致幼儿体重增加和超重风险上升，强调了采取公共卫生干预措施以减少孕期母亲接触PAHs的必要性。
