Nutrition and Oral Clefts in Asia: Planning Grant

描述（由申请人提供）：唇裂是最常见的出生缺陷之一，在亚洲通常比其他地方更普遍。口裂的负担是巨大的，因为受影响的儿童需要大量的医疗护理，并可能长期生活在残疾中。我们的长期目标是阐明常见的母体营养和代谢因素在口裂中的作用，作为制定预防措施的先决条件。与一碳代谢（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）与口裂风险相关-但在开始公共卫生干预之前，需要澄清几个不一致之处。2型糖尿病是一个全球性的公共卫生威胁，并已与出生缺陷的风险增加，但其在口腔裂的作用是不确定的。亚洲的国际研究是有效的，因为那里的许多人群有很高的唇腭裂风险，而且暴露特征在不同的地理区域是可变的，这增加了检测到有意义的关联的可能性。本研究拟在菲律宾、新加坡、中国台湾及中国大陆进行一项多中心、以人口为基础的病例对照研究，探讨口裂产妇的营养及代谢因素。在全规模研究中，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，各自独立地与唇腭裂风险相关;（2）1-CM生物标志物相互作用以影响唇腭裂风险;（3）葡萄糖耐量受损和糖尿病各自与唇腭裂风险相关;（4）1-CM受损和葡萄糖耐量受损与糖尿病相互作用，增加了口裂的风险。具体目标：1）制定细化的研究设计;（2）制定各研究中心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，并在各研究中心进行中试。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，学习材料，并提交R 01申请的完整研究的规划项目结束。 公共卫生相关性：口裂是最常见的出生缺陷之一，公共卫生负担很大，因为受影响的儿童需要大量的医疗护理，并可能长期生活在残疾状态下。我们研究小组的长期目标是阐明常见的母体营养和代谢因素在口裂中的作用，作为制定预防措施的先决条件。

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.