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（由适用提供）：超过70％的人类出生缺陷会影响头部和脸部。带有或没有裂口的裂口唇裂（Cl¿p）是这些缺陷中最常见的唇裂之一，每1000只活出生约1个。与未受影响的当代人相比，患有CL？P的儿童在言语，听力和认知中遭受辩护，并在一生中具有更高的发病率和死亡率。尽管其频率和临床重要性，但对Cl课的病因却知之甚少，目前尚无降低其患病率的策略。因此，CL？P的危险因素的识别是2009 - 2013年国家牙科与颅面研究所（NIDCR）战略计划的一部分。尚未充分探索的可疑危险因素包括环境有毒物质。由美国环境保护局（EPA）定义的重要毒物是有害空气污染物或HAPS（例如苯，柴油颗粒物质）。由于几个原因，HAP是重要的潜在危险因素，包括：1）他们已知或怀疑会引起一系列不良健康结果； 2）在美国的许多社区中，暴露的可能性正在增加； 3）目前没有其他国家空气质量标准，而其他空气污染物（例如臭氧）。尽管从职业研究中有证据表明，某些HAP的物质暴露与Cl知识有关，但尚未评估HAP的环境浓度的致畸潜力（在占用环境中低于占用环境，但更常见的暴露来源）尚未评估。重要的是要检查孕产妇的暴露HAP和Cl prisk的风险，因为在怀孕期间，所有妇女在不同程度上都暴露于HAP。此外，发育中的胚胎似乎特别容易受到HAP的影响。研究人员将使用贝叶斯分层建模的新应用来检查Cl¿p风险的作用，该建模的新应用说明了人口普查级别的数据，暴露评估信心和多种污染物。研究对象的数据将从德克萨斯州的出生缺陷注册中获得；世界上最大的基于人群的主动监视系统之一。将使用美国EPA国家规模的空气毒物评估确定接触HAP。 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合作者。预计这项研究将确定那些值得在独立人群中进一步探索的HAP，同时导致一种评估这些和其他环境毒物的新方法。最终，识别Cl`P风险因素将为降低这些重要条件的普遍性的新策略打开大门。 公共卫生相关性：有或没有裂口的裂口（Cl¿p）在美国是一个重大的公共卫生问题，因此，国家牙科与颅面研究所（NIDCR）已确定了其2009 - 2013年战略计划的危险因素部分。尽管CL知识的原因是复杂且理解不足的，但由于职业和动物研究的证据，这些不良结果与孕产妇接触环境有毒物质（例如有害空气污染物（HAP））的关联提出了问题。这项研究将对孕产妇对HAP的环境浓度的暴露和后代的CL级风险进行首次评估，对于确定这些严重和相对常见条件的先前未识别的危险因素至关重要。