Maternal Vasoactive Exposures and Risk of Clubfoot

母亲血管活性暴露和马蹄内翻足的风险

• 批准号: 7146799
• 负责人: MARTHA M. WERLER
• 金额: $ 45.89万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146799
• 关键词: behavioral /social science research tag; cardiovascular disorder; clinical research; developmental disease /disorder; disease /disorder proneness /risk; disease /therapy duration; early experience; embryo /fetus toxicology; gestational age; health behavior; human subject; infant human (0-1 year); interview; longitudinal human study; maternal behavior; nasal decongestants; nonsteroidal antiinflammatory agent; pregnancy circulation; smoking; tobacco abuse; vasoactive agent

DESCRIPTION (provided by applicant): Talipes equinovarus or clubfoot occurs in approximately one of every 1000 live births. Although it is one of the most common structural malformations, little is known about its etiology. There are many lines of evidence that suggest vascular disruption in early development plays an etiologic role. Thus, maternal exposure to vasoactive agents during pregnancy may be associated with increased clubfoot risk. Decongestants and non-steroidal anti-inflammatory drugs are vasoactive and use of each has been associated with other malformations that are similarly thought to arise from vascular disruption. Maternal cigarette smoking, which is also vasoactive, has been found to increase clubfoot risk in three previous studies. We propose to examine maternal use of vasoactive medications and cigarette smoking in relation to clubfoot risk, with particular attention to timing of exposure. We will conduct a population-based case-control study of clubfoot in Massachusetts, New York, and North Carolina. Within each state, newly diagnosed cases with clubfoot will be identified from the birth defect registry. A random sample of controls will be identified from birth certificate records in each state. Over a four year period, we will enroll 800 cases and 1600 controls. Mothers of cases and controls will be interviewed by telephone within 12 months after delivery. Detailed questions will be asked about vasoactive exposures in pregnancy, including use of decongestants and non-steroidal anti-inflammatory drugs and cigarette smoking. Medication use will be ascertained with help of a medication identification booklet that includes color pictures of over 350 over-the-counter cough, cold, and analgesic products. Medical record review will be conducted to confirm clubfoot diagnoses. The separate and combined effects of cigarette smoking and maternal use of vasoactive medications will be studied in relation to clubfoot risk, while controlling for potential confounding factors. Findings from this study will be useful in counseling women of childbearing age. In addition, findings will help further understanding of the vascular disruption pathway. Buccal cell swabs will be collected from cases, controls, and their mothers. DNA will be extracted and stored for the purpose of studying genetic risk factors in future studies.

描述（由申请人提供）：大约每 1000 名活产婴儿中就有 1 人患有马蹄内翻足或马蹄内翻足。尽管它是最常见的结构畸形之一，但对其病因知之甚少。有许多证据表明早期发育中的血管破坏起着病因作用。因此，母亲在怀孕期间接触血管活性药物可能与马蹄足风险增加有关。减充血剂和非甾体抗炎药具有血管活性，每种药物的使用都与其他畸形有关，这些畸形同样被认为是由血管破坏引起的。之前的三项研究发现，母亲吸烟对血管有影响，会增加马蹄内翻足的风险。我们建议检查母亲使用血管活性药物和吸烟与马蹄内翻足风险的关系，特别注意暴露的时间。我们将在马萨诸塞州、纽约州和北卡罗来纳州开展一项基于人群的马蹄内翻足病例对照研究。在每个州，新诊断的马蹄内翻足病例将从出生缺陷登记处确定。将从每个州的出生证明记录中随机抽取对照样本。在四年内，我们将招募 800 个病例和 1600 个对照。病例和对照的母亲将在分娩后 12 个月内接受电话采访。将询问有关怀孕期间血管活性暴露的详细问题，包括使用减充血剂和非甾体抗炎药以及吸烟。药物使用情况将通过药物识别手册来确定，其中包括 350 多种非处方止咳、感冒和镇痛产品的彩色图片。将进行医疗记录审查以确认马蹄内翻足的诊断。将研究吸烟和母亲使用血管活性药物的单独和综合影响与马蹄内翻足风险的关系，同时控制潜在的混杂因素。这项研究的结果将有助于为育龄妇女提供咨询。此外，研究结果将有助于进一步了解血管破坏途径。将从病例、对照及其母亲处收集口腔细胞拭子。 DNA将被提取并储存，以便在未来的研究中研究遗传风险因素。