城市室内降尘途径多环芳烃类化学物质暴露对幼儿早期神经发育影响

Exposure of chemicals with neurodevelopmental toxicity through settled house dust is very important for infants and toddlers, who are at highest risk because their brain is undergoing rapid development and they frequently place their hands in their mouth and ingest dust. Our pilot cross-sectional study found that the geometric mean concentrations of polycyclic aromatic compounds (PAHs) in settled house dust were far higher than those reported in other countries and localities, which is consistent with the results reported in 2012 that the urine levels of PAH metabolites in the general population of China are far higher than those reported for other countries thus far. Our results also indicated that dust PAH concentrations were associated with the developmental quotients and neurobehavior scores. Based on the preceding studies, we plan to further go on our study with a longituditional birth cohort study design. Nine urinary hydroxylat- ed- polycyclic aromatic hydrocarbons will be used to assess PAH exposure, together with PAH concentrations in settled house dust and in the air of toddler's breathing zone, to evaluate the contribution of settled house dust PAHs and to explore the possible effects on the neurodevelopment at toddlers. Simultaneously, the influencing factors screened in our pilot study on the settled house dust PAH levels and the polymorphisms in PAH metabolic genes will be studied to expore the possible intervention on and the sensitive biomarkers for the prediction of PAH risk on the toddler's neurodevelopmental health.

手-口途径是幼儿期体内化学物质暴露的主要途径，因此室内降尘中具有神经发育毒性物质对处于大脑快速发育幼儿影响的研究至关重要。我们前期的横断面调查发现多环芳烃类化学物质（PAHs）在室内降尘中的几何均数浓度远高于其他国家和地区，与2012年报道的一般人群尿中PAHs内暴露水平远高于其他国家或地区的结果一致；降尘中PAHs暴露浓度与3-6岁儿童发育与神经行为异常得分相关。在此基础上，本研究拟采用出生队列研究设计，利用尿中多种PAHs的羟基代谢物作为生物标志物评价PAHs的暴露水平，结合室内降尘与幼儿呼吸带空气中PAHs浓度，重点探讨出生后1岁经室内降尘途径暴露对PAHs内暴露水平的贡献及对幼儿早期发育及神经行为的影响。其中，结合我们前期研究筛选的影响室内降尘中PAHs水平的因素及体内PAHs代谢酶基因多态性，进行综合分析和判断可能的干预措施和可供预测的易感性生物标志物。

神经行为异常性疾病已经成为继恶性肿瘤和心脏性疾病之后的第三大类疾病，一些神经毒性化学物质胎儿期暴露能够导致儿童认知能力损害或神经行为改变。出生后2岁以内是人类大脑的第二个发育关键期，而该时期幼儿体内化学物质负荷的主要来源是室内灰尘。我们前期的横断面研究发现灰尘中半挥发性有机化合物以多环芳烃（PAHs）水平为最高，与神经发育异常效应关联也最明显。本次研究，我们通过出生队列研究设计，建立了1904对母亲和新生儿的出生队列人群，前瞻性观察出生后12月龄PAHs暴露对幼儿不同月龄神经发育影响，同时考虑出生前PAHs暴露（脐带血中PAH-DNA加合物）、幼儿遗传因素（PAHs代谢通路关键酶基因多态性）及幼儿基本稳定期的肠道菌群影响。多因素线性回归模型显示，萘能够影响36月龄幼儿的感觉能力及总自闭症行为得分，β及其95%可信区间（CI）分别为0.079 (0.003, 0.155)和0.497(0.038, 0.957)；虽然PAHs代谢物未进入12月龄幼儿发育商（盖泽尔量表，DQ）的模型中，但其关键代谢酶基因CYP1A1（rs2472299） 、CYP1A2（rs762551）和CYP1B1（rs2617266）多态性能够影响到12月龄幼儿的神经发育。PAH-DNA加合物抑制了12月龄幼儿所有能区DQs，并升高36月龄幼儿的自闭症行为中运动能力得分，β及其95% CI为0.659(0.222, 1.096)。PAHs暴露导致肠道菌群中厚壁菌门丰度升高，而拟杆菌门丰度降低，该改变保护幼儿神经发育免受PAHs的影响。居室内自然通风显示了对少环萘和多环䓛相反的影响，β及其95% CI分别为0.258 (0.013, 0.504)和-0.253 (-0.500, -0.007)；楼层越低，PAHs含量越高；居住年限越长居室其PAHs浓度越高。总结本次研究的结果，出生前和出生后PAHs暴露均能影响幼儿早期的神经发育，该影响同时受到遗传因素及成熟肠道菌群的干扰。自然通风、彻底清扫地板灰尘为可供选择的干预措施。此研究将为今后儿童早期神经发育损伤的个体化预防、干预提供理论依据和重要参考，推动人群儿童早期神经发育损伤的一级预防。