Craniofacial Microsomia: The Vascular Disruption Hypothesis

颅面微小症：血管破坏假说

• 批准号: 7267088
• 负责人: Jacqueline R Starr
• 金额: $ 10.27万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267088
• 关键词: Address; Affect; Animal Model; Birth; Birth Certificates; Blood Vessels; Cardiac; Case-Control Studies; Child; Clinical; Coagulation Process; Code; Complex; Condition; Data; Data Linkages; Data Sources; Databases; Dermoid Cyst; Development; Diagnosis; Disease; Disruption; Ear; Epidemiologic Studies; Esthetics; Etiology; External Ear; Face; Facial asymmetry; Family; Feeds; Hearing; Hemorrhage; Hemostatic function; Hospitalization; Hospitals; ICD-9; Incidence; Infant; Interview; Ischemia; Jaw; Kidney; Knowledge; Labor Complications; Lead; Life; Life Style; Link; Live Birth; Macrostomia; Mastication; Maternal Exposure; Medical; Medical center; Mothers; Operative Surgical Procedures; Patients; Pediatric Hospitals; Phenotype; Placement; Play; Predisposition; Pregnancy; Prevalence; Procedures; Pseudoephedrine; Relative (related person); Research; Resources; Respiration; Risk; Risk Factors; Role; Side; Skeletal bone; Speech; Structure; Testing; Tracheotomy procedure; Washington; case control; cigarette smoking; craniofacial; feeding; patient registry; soft tissue; spine bone structure; therapy development; tube feeding

DESCRIPTION (provided by applicant): Craniofacial microsomia (CFM) is among the most common craniofacial anomalies. The disorder involves the asymmetric underdevelopment of facial skeletal bones and soft tissue, typically affecting the jaw and ear. CFM usually impairs basic functions such as hearing, speech, respiration, and/or chewing, in addition to its aesthetic effects. It can be life-threatening due to airway compromise. Treatment often requires multiple complex surgical interventions. Almost nothing is known about what causes CFM. Animal models have demonstrated a relationship between the features of CFM and disruption of the vessel that feeds the developing craniofacial structures. The only large epidemiologic study of CFM showed associations with maternal exposures that influence the risk of bleeding or clotting, such as pregnancy pseudoephedrine use and cigarette smoking. We propose to test the "vascular disruption" hypothesis by conducting two data- linkage case-control studies using existing database resources. First, lacking an ICD-9 code specific to CFM, we will identify CFM cases through patient databases at Children's Hospital and Regional Medical Center. We will randomly select controls from among live births in Washington State. Using the Washington State birth certificate and hospital discharge databases, we will ascertain information on factors that are associated with infants' and mothers' risk of bleeding or clotting. We will compare their distribution among cases and controls. The second study differs from the first in that 1) we will ascertain cases directly from the Washington State databases, and 2) cases will be infants diagnosised with underdeveloped ears, the mildest expression of CFM. Using birth certificate data may obviate biases potentially arising in retrospectively conducted interviews of mothers. The relative completeness of Washington State birth certificates and the routine linkage to birth hospital discharge data offer unique resources for the conduct of these analyses. They will allow us to evaluate other potential risk factors not easily ascertained through interviews. This research will be among the first epidemiologic studies of CFM and the first to use linked birth certificates and hospital discharge data. Vascular disruption is widely cited as causing CFM, despite the lack of epidemiologic data that address this claim or CFM more generally. The proposed research addresses this gap in knowledge and could lead to the development of interventions that reduce CFM incidence.

描述（由申请人提供）：颅面微小症（CFM）是最常见的颅面异常之一。该疾病涉及面部骨骼和软组织的不对称发育不良，通常影响下巴和耳朵。除了美观效果之外，CFM 通常还会损害听力、言语、呼吸和/或咀嚼等基本功能。由于气道受损，可能会危及生命。治疗通常需要多次复杂的手术干预。对于导致 CFM 的原因几乎一无所知。动物模型已经证明了 CFM 的特征与为发育中的颅面结构提供营养的血管的破坏之间的关系。唯一的 CFM 大型流行病学研究表明，CFM 与影响出血或凝血风险的母体暴露有关，例如怀孕期间使用伪麻黄碱和吸烟。我们建议通过使用现有数据库资源进行两项数据链接病例对照研究来检验“血管破坏”假设。首先，由于缺乏针对 CFM 的 ICD-9 代码，我们将通过儿童医院和地区医疗中心的患者数据库来识别 CFM 病例。我们将从华盛顿州的活产中随机选择对照。使用华盛顿州出生证明和出院数据库，我们将确定与婴儿和母亲出血或凝血风险相关的因素的信息。我们将比较它们在病例和对照之间的分布。第二项研究与第一项研究的不同之处在于：1）我们将直接从华盛顿州数据库确定病例，2）病例将是被诊断为耳朵发育不全的婴儿，这是 CFM 最轻微的表现。使用出生证明数据可以消除对母亲进行回顾性访谈时可能出现的偏见。华盛顿州出生证明的相对完整性以及与出生医院出院数据的常规联系为进行这些分析提供了独特的资源。它们将使我们能够评估通过访谈不易确定的其他潜在风险因素。这项研究将是第一个 CFM 流行病学研究，也是第一个使用关联出生证明和出院数据的研究。尽管缺乏流行病学数据来证明这一说法或更普遍的 CFM，但血管破裂被广泛认为是导致 CFM 的原因。拟议的研究解决了这一知识空白，并可能导致开发减少 CFM 发生率的干预措施。