Developmental effects of early-life exposure to airborne PAHs.

描述(由研究人员提供)：需要进一步的研究，以便为减轻儿童发育障碍负担的新政策倡议提供信息。我们建议扩展和丰富一项分子流行病学前瞻性队列研究，该研究始于2000年，旨在评估儿童出生前暴露于多环芳烃对神经行为的长期影响。由于燃烧化石燃料，城市空气中普遍存在多环芳烃。研究人群是独一无二的，包括400多名居住在波兰克拉科夫的高加索母亲和儿童，他们自怀孕以来一直受到跟踪。因为我们观察到产前暴露于多环芳烃对五岁以下儿童的儿童发育有显著的不利影响，所以需要对队列进行跟踪调查。我们还观察到对相同暴露水平的反应存在显著的个体间差异，表明遗传或营养因素导致的易感性。因为在这个队列中的保留率很高，我们能够很容易地将研究延长到学龄(9岁)，使我们能够诊断最终可能影响学习和学业表现的神经发育问题。我们的主要目标是在控制了出生后多环芳烃暴露的影响、已知的儿童发育决定因素和潜在的混杂因素后，确定产前暴露于空气中的多环芳烃对从出生到9岁的神经行为发育的影响。我们的第二个目标将是探索a)代谢激活和解毒基因的遗传多态以及b)脐带血和母血中脂溶微量营养素浓度对产前暴露于PAH与九岁以下神经行为发育之间的关系的调节作用。我们还将在纽约进行的平行研究中，将高加索人队列研究的结果与非裔美国人和多米尼加人的结果进行比较。很少有这样的综合性队列研究从怀孕开始，就常见城市污染物造成的神经发育风险提供必要的政策相关信息。我们预计，这项研究不仅将为空气污染暴露提供可靠的证据基础，还将提供可能导致神经发育障碍风险的易感因素的证据基础。与公共卫生的相关性：在过去十年中，儿童发育障碍率有所增加，产前暴露于环境污染物，如多环芳烃(PAHs)也有牵连。这项队列研究的结果将解决知识方面的一个主要差距。我们正在研究的接触并不是波兰独有的，而是全世界普遍存在的；因此，我们的结果将适用于其他地理和民族人口。

DESCRIPTION (provided by investigator): 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 five. 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 nine), 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 nine 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 nine 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. PUBLIC HEALTH RELEVANCE: Rates of developmental disorders have increased in children over the past decade and prenatal exposure to environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs) has been implicated. The results of this cohort study will address a major gap in knowledge. The exposures we are studying are not unique to Poland but are ubiquitous worldwide; our results will thus be generalizable to other geographic and ethnic populations.