Craniofacial Microsomia: The Vascular Disruption Hypothesis

描述(申请人提供)：头面部矮小(CFM)是最常见的头面部畸形之一。这种疾病涉及面部骨骼和软组织的不对称发育不足，通常影响到下巴和耳朵。CFM除了美容效果外，通常还会损害基本功能，如听力、言语、呼吸和/或咀嚼。由于呼吸道受损，它可能会危及生命。治疗通常需要多种复杂的手术干预。关于CFM的病因，人们几乎一无所知。动物模型已经证明了CFM的特征与供养发育中的头面部结构的血管破裂之间的关系。CFM的唯一一项大型流行病学研究表明，母亲暴露于影响出血或凝血风险的因素，如怀孕、使用伪麻黄碱和吸烟，与此相关。我们建议利用现有的数据库资源进行两项数据关联病例对照研究，以检验“血管破裂”假说。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学中心的患者数据库识别CFM病例。我们将从华盛顿州的活产中随机选择对照组。使用华盛顿州出生证明和医院出院数据库，我们将确定与婴儿和母亲出血或凝血风险相关的因素信息。我们将比较它们在病例和对照中的分布。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的数据库中确定病例，2)病例将是被诊断为耳朵发育不良的婴儿，这是CFM最温和的表现。使用出生证明数据可以避免在对母亲进行回溯性访谈时可能产生的偏见。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其他不容易通过面谈确定的潜在风险因素。这项研究将是第一批CFM流行病学研究之一，也是第一批使用相关联的出生证明和出院数据的研究。血管破裂被广泛认为是导致CFM的原因，尽管缺乏流行病学数据来解决这一说法或更广泛的CFM。拟议的研究解决了这一知识差距，并可能导致开发减少CFM发病率的干预措施。

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.