Nutrition and Oral Clefts in Asia: Planning Grant

描述（由申请人提供）：唇裂是最常见的先天缺陷之一，在亚洲比在其他地方更为普遍。唇腭裂的负担是巨大的，因为受影响的儿童需要大量的医疗护理，并可能长期残疾。我们的长期目标是阐明常见的产妇营养和代谢因素在唇腭裂中的作用，作为制定预防措施的先决条件。与单碳代谢（1-CM）相关的母体生物标志物，包括叶酸、锌、维生素B-6和同型半胱氨酸，与唇腭裂的风险有关，但在开始公共卫生干预措施之前，需要澄清一些不一致之处。2型糖尿病是一个全球性的公共卫生威胁，与出生缺陷的风险增加有关，尽管其在唇腭裂中的作用尚不确定。在亚洲进行的国际研究是有效的，因为那里的许多人群患唇裂的风险很高，而且不同地理区域的暴露特征是不同的，这增加了发现有意义的关联的可能性。​在全面的研究中，将检验以下假设：(1)与1- cm相关的母体生物标志物，包括叶酸、锌、维生素B6和B12以及同型半胱氨酸，都与唇腭裂的风险独立相关；(2) 1-CM生物标志物相互作用影响唇裂风险；(3)糖耐量受损和糖尿病均与唇裂风险相关；(4) 1-CM受损、糖耐量受损和糖尿病相互作用，增加唇腭裂的风险。具体目标：1)细化研究设计；(2)制定各研究点和协调中心的组织结构和计划；(3)完成详细的研究方案和材料，并在每个站点进行中试。这些具体目标的完成将导致加强国际合作伙伴关系、基础设施、研究材料，并在规划项目结束时提交完整研究的R01申请。

DESCRIPTION (provided by applicant): Oral clefts are among the most common birth defects and are generally more prevalent in Asia than elsewhere. The burden of oral clefts is great because affected children require substantial medical care and may live long lives with disabilities. Our long-term goal is to elucidate the role of common maternal nutritional and metabolic factors in oral clefts as a prerequisite to developing preventive measures. Maternal biomarkers related to one-carbon metabolism (1-CM) including folate, zinc, vitamin B-6, and homocysteine have been associated with risk of oral clefts- but several inconsistencies require clarification before public health interventions are initiated. Type 2 diabetes mellitus is a global public health threat and has been associated with an increased risk of birth defects though its role in oral clefts is uncertain. International studies in Asia are efficient because many populations there have a high risk of oral clefts and exposure characteristics are variable across geographic areas, increasing the probability of detecting meaningful associations. A two-year planning project is proposed to develop a multi-center, population-based, case-control study of maternal nutritional and metabolic factors in oral clefts in the Philippines, Singapore, Taiwan, and China. In the full scale study the following hypotheses will be tested: (1) maternal biomarkers related to 1-CM including folate, zinc, vitamins B6 and B12, and homocysteine are each independently associated with risk of oral clefts; (2) 1-CM biomarkers interact to influence oral cleft risk; (3) impaired glucose tolerance and diabetes are each associated with risk of oral clefts; (4) impaired 1-CM and impaired glucose tolerance and diabetes interact to increase risk of oral clefts. Specific Aims: 1) Develop the refined study design; (2) Develop the organizational structures and plans at each study site and the coordinating center; (3) Complete detailed study protocols and materials and pilot-test at each site. Completion of these specific aims will result in enhanced international collaborative partnerships, infrastructure, study materials, and a submitted R01 application for the full study by the end of the planning project. PUBLIC HEALTH RELEVANCE: Oral clefts are among the most common birth defects and the public health burden is great because affected children require substantial medical care and may live long lives with disabilities. The long-term goal of our research team is to elucidate the role of common maternal nutritional and metabolic factors in oral clefts as a prerequisite to developing preventive measures.