Developmental effects of early-life exposure to airborne PAHs.

摘要 需要进一步研究，为新的政策举措提供信息，以减轻发展负担， 对儿童的伤害。我们建议扩展和丰富分子流行病学前瞻性队列研究 2000年启动，旨在评估产前暴露于多环芳烃对儿童神经行为的长期影响。 多环芳烃是城市空气中普遍存在的化石燃料燃烧。研究人群是独特的，包括 超过400名居住在波兰克拉科夫的白人母亲和孩子， 怀孕需要对队列进行随访，因为我们观察到了 产前暴露于多环芳烃对儿童发育的影响。我们还 观察到对相同暴露水平的反应存在明显的个体间差异，表明易感性 由于遗传或营养因素。由于这一队列的留存率一直很高，我们很容易能够 将研究扩展到学龄（9岁），使我们能够诊断神经发育问题， 可能最终影响学习和学术表现。 我们的主要目的是确定产前暴露于空气中的多环芳烃对神经行为的影响， 在控制出生后PAH暴露的影响后，从出生到9岁的发育， 儿童发育的已知决定因素和潜在混杂因素。我们的次要目标是探索 a）代谢活化和解毒基因的遗传多态性和B）脂质- 脐带血和母血中可溶性微量营养素浓度与产前PAH之间的关系 暴露和神经行为发育到9岁。我们还将比较该队列的结果 在我们的平行研究中，在高加索人与非裔美国人和多米尼加人中进行的研究 在纽约市。 很少有这样的全面的队列研究开始于怀孕，可以提供所需的 关于常见城市污染物对神经发育风险的政策相关信息。我们预计， 这项研究不仅将为空气污染暴露，而且还将为易感因素提供可靠证据基础 这可能会导致神经发育障碍的风险。

ABSTRACT Further research is needed to inform new policy initiatives to reduce the burden of developmental impairment in children. We propose to extend and enrich a molecular epidemiologic prospective cohort study launched in 2000 to assess the longer-term neurobehavioral effects of prenatal exposure to PAHs in children. PAHs are ubiquitous in urban air from combustion of fossil fuel. The study population is unique, comprising more than 400 Caucasian mothers and children residing in Krakow, Poland who have been followed since pregnancy. Follow-up of the cohort is required because we have observed significant adverse effects of prenatal exposures to PAHs on child development among children followed through age 5. We have also observed marked inter-individual variation in response to the same levels of exposure, indicating susceptibility due to genetic or nutritional factors. Because the retention rate in this cohort has been high, we are readily able to extend the study through school age (age 9), allowing us to diagnose neurodevelopmental problems that may ultimately impact learning and academic performance. Our primary aim is to determine the effect of prenatal exposures to airborne PAHs on neurobehavioral development from birth through age 9 years of age, after controlling for the effects of postnatal PAH exposure, known determinants of child development, and potential confounders. Our secondary aims will be to explore the modifying roles of a) genetic polymorphisms in metabolic activation and detoxification genes and b) lipid- soluble micronutrient concentrations in cord and maternal blood on the associations between prenatal PAH exposure and neurobehavioral development through age 9 years. We will also compare results from this cohort study in Caucasians with those from African Americans and Dominicans in our parallel study being conducted in New York City. There are few such comprehensive cohort studies beginning in pregnancy that can provide needed policy-relevant information on neurodevelopmental risks from common urban pollutants. We anticipate that this study will provide a sound evidence-base not only on air pollution exposures, but also on susceptibility factors which may contribute to the risk of neurodevelopmental disorders.