Air Toxics, Neighborhood Environment and Risk of Oral Clefts

空气毒物、社区环境和唇裂风险

• 批准号: 8243869
• 负责人: Philip Lupo
• 金额: $ 16.73万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-11 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8243869
• 关键词: Accounting; Affect; Air; Air Pollutants; Air Pollution; Animals; Area; Attention; Benzene; Birth; Censuses; Child; Cleft lip with or without cleft palate; Clinical; Cognition; Communities; Complex; Complex Mixtures; Congenital Abnormality; Data; Data Sources; Defect; Development; Embryo; Environment; Epidemiologic Studies; Epidemiologist; Epidemiology; Etiology; Exposure to; Face; Frequencies; Head; Health; Hearing; Human; Individual; Life; Live Birth; Locales; Low Prevalence; Maternal Exposure; Methods; Modeling; Morbidity - disease rate; National Institute of Dental and Craniofacial Research; Neighborhoods; Neural Tube Defects; Occupational; Outcome; Ozone; Particulate Matter; Population; Pregnancy; Prevalence; Principal Investigator; Public Health; Publishing; Registries; Relative (related person); Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Source; Speech; Strategic Planning; Study Subject; Subgroup; System; Texas; Toxic Environmental Substances; United States; United States Environmental Protection Agency; Woman; Work; adverse outcome; base; comparison group; experience; mortality; novel; novel strategies; offspring; oral cleft; pollutant; population based; toxicant

DESCRIPTION (provided by applicant): Over 70% of all birth defects in humans affect the head and face. Cleft lip with or without cleft palate (CL¿P) is one of the most common of these defects, occurring in approximately 1 per 1,000 live births. Children with CL¿P suffer deficits in speech, hearing and cognition and have higher morbidity and mortality throughout life compared to their unaffected contemporaries. Despite its frequency and clinical importance, little is known about the etiology of CL¿P , and there are currently no strategies for reducing its prevalence. Because of this, the identification of risk factors for CL¿P is part of the National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan for 2009-2013. Suspected CL¿P risk factors that have not been fully explored include environmental toxicants. An important group of toxicants, as defined by the U.S. Environmental Protection Agency (EPA), are hazardous air pollutants, or HAPs (e.g., benzene, diesel particulate matter). HAPs are important potential risk factors for several reasons, including: 1) they are known or suspected to cause a range of adverse health outcomes; 2) the potential for exposure is increasing in many communities throughout the U.S.; and 3) there are currently no national air quality standards as there are for other air pollutants (e.g., ozone). Although there is evidence from occupational studies that maternal exposure to certain HAPs is associated with CL¿P, the teratogenic potential of environmental concentrations of HAPs (which are lower than in occupational settings but a more common source of exposure) has not been assessed. It is important to examine the association between maternal exposure HAPs and CL¿P risk, as all women, in varying degrees, are exposed to HAPs during pregnancy. Furthermore, the developing embryo appears to be particularly vulnerable to the effects of HAPs. The investigators will examine the role of on CL¿P risk using a novel application of Bayesian hierarchical modeling, which accounts for census tract-level data, exposure assessment confidence and multiple pollutants. Data on study subjects will be obtained from the Texas Birth Defects Registry; one of the largest population-based, active surveillance systems of birth defects in the world. Exposure to HAPs will be determined using the U.S. EPA National-Scale Air Toxics Assessment. The proposed study builds on 1) the exceptional resources provided by the Texas Birth Defects Registry, which includes data on approximately 2,500 nonsyndromic, isolated CL¿P cases, 2) a large comparison group including all unaffected births in Texas, 3) the extensive HAP exposure assessment conducted by the U.S. EPA, 4) the principal investigator's expertise in birth defects epidemiology and 5) a strong group of research collaborators. This study is expected to identify those HAPs that deserve further exploration in independent populations, while resulting in a novel method for assessing these and other environmental toxicants. Ultimately, the identification of CL¿P risk factors will open the door to new strategies for lowering the prevalence of these significant conditions. PUBLIC HEALTH RELEVANCE: Cleft lip with or without cleft palate ( CL¿P ) is a significant public health problem in the U.S., and because of this, the National Institute of Dental and Craniofacial Research (NIDCR) has made the identification of risk factors part of its Strategic Plan for 2009-2013. Although the causes of CL¿P are complex and poorly understood, questions arise regarding the association between these adverse outcomes and maternal exposure to environmental toxicants, such as hazardous air pollutants (HAPs), due to evidence from occupational and animal studies. This study will provide the first assessment of maternal exposure to environmental concentrations of HAPs and the risk of CL¿P in offspring and will be critical in identifying previously unidentified risk factors for these serious and relatively common conditions.

描述（由申请人提供）：超过70%的人类出生缺陷影响头部和面部。唇裂伴或不伴腭裂（CL¿P）是这些缺陷中最常见的一种，大约每1000个活产婴儿中有1个发生。患有CL - P的儿童在语言、听力和认知方面存在缺陷，与未受影响的同龄人相比，终生发病率和死亡率更高。尽管其发生频率和临床重要性，但对CL¿P的病因知之甚少，目前也没有降低其患病率的策略。正因为如此，识别CL¿P的危险因素是国家牙科和颅面研究所（NIDCR） 2009-2013年战略计划的一部分。尚未充分探索的疑似CL - P风险因素包括环境毒物。根据美国环境保护署（EPA）的定义，一组重要的有毒物质是有害空气污染物，或HAPs（如苯、柴油颗粒物质）。HAPs是重要的潜在风险因素，原因包括：1)已知或怀疑它们会导致一系列不利的健康后果；2)在美国许多社区，暴露的可能性正在增加；3)目前没有像其他空气污染物（如臭氧）那样的国家空气质量标准。尽管有来自职业研究的证据表明，母亲接触某些有害物质与氯磷有关，但环境中有害物质浓度（低于职业环境，但是更常见的接触源）的致畸潜力尚未得到评估。由于所有妇女在怀孕期间都在不同程度上暴露于HAPs，因此检查产妇接触HAPs与CL - P风险之间的关系非常重要。此外，发育中的胚胎似乎特别容易受到HAPs的影响。研究人员将使用贝叶斯分层模型的新应用来研究CL - P风险的作用，该模型考虑了人口普查区域水平的数据、暴露评估置信度和多种污染物。研究对象的数据将从德克萨斯州出生缺陷登记处获得；世界上最大的以人口为基础的出生缺陷主动监测系统之一。接触HAPs将使用美国环保署的全国空气毒性评估来确定。拟议的研究建立在1)德克萨斯州出生缺陷登记处提供的特殊资源，其中包括大约2,500个非综合征，孤立的CL¿P病例的数据，2)一个大型比较组，包括德克萨斯州所有未受影响的新生儿，3)美国环保署进行的广泛的HAP暴露评估，4)首席研究员在出生缺陷流行病学方面的专业知识，5)一个强大的研究合作者群体。这项研究预计将确定那些值得在独立人群中进一步探索的HAPs，同时产生一种评估这些和其他环境毒物的新方法。最终，确定慢性阻塞性肺病风险因素将为制定降低这些重大疾病患病率的新战略打开大门。