Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes

怀孕叶酸状况

• 批准号: 8164104
• 负责人: KECIA Nicole CARROLL
• 金额: $ 74.23万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-06 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8164104
• 关键词: Affect; Agreement; Allergic; Allergic rhinitis; Area; Asthma; Atopic Dermatitis; Australia; Birth; Child; Childhood; Childhood Asthma; Chronic; Clinical Trials; Country; DNA Methylation; Data; Development; Diet; Dietary intake; Disease; Disease Outcome; Dose; Enrollment; Environmental Exposure; Epidemiologic Studies; Epigenetic Process; Etiology; Folate; Folic Acid; Future; Gene Expression; Genetic Predisposition to Disease; Goals; Incidence; Individual; Infant; Intake; Investigation; Learning; Life; Lower Respiratory Tract Infection; Measures; Medicaid; Modeling; Morbidity - disease rate; Mothers; Neural Tube Defects; Neurocognitive; Norway; Nutritional; Outcome; Pattern; Phenotype; Plasma; Play; Policies; Population; Pregnancy; Pregnancy Trimesters; Prevention; Prevention strategy; Primary Prevention; Questionnaires; Recommendation; Regulator Genes; Reporting; Research; Research Infrastructure; Risk; Risk Factors; Role; Supplementation; Tennessee; Testing; Time; Validation; Wheezing; Woman; Work; atopy; cohort; cost; early childhood; follow-up; fortification; innovation; modifiable risk; mouse model; offspring; population based; pregnant; prenatal; prevent; programs; prospective; respiratory; response; tool

DESCRIPTION (provided by applicant): Research Area. The long-term goal of this project is to determine whether maternal folic acid supplementation during pregnancy increases the risk of early childhood asthma and atopy. Supplementation with folic acid, synthetic folate, is recommended during the periconceptional period to prevent neural tube defects (NTD). Studies in different populations have suggested an association between reported folic acid supplementation during pregnancy and increased risk of infant lower respiratory tract infection and early childhood asthma, but data are limited. While adequate intake of folate is essential for prevention of NTDs, it is important to delineate the impact of supplementation on the risk of common respiratory and atopic diseases. Folate plays an important role in DNA methylation, a regulator of gene expression. A causal relationship between folic acid supplementation and respiratory outcomes in children has not been established. However, this relationship does have some biologic plausibility. In a pregnant mouse model, a diet high in methyl donors, including folate, resulted in an augmented allergic phenotype in the offspring, as seen in asthma. Opportunity and Impact. There is no primary prevention strategy for atopic diseases such as asthma. Our objective is to determine whether higher maternal folate intake or the timing of this intake increases the risk of wheezing, asthma, and other atopic diseases in children. This collective work will characterize maternal folate status using objective measures and will assess childhood wheezing, asthma, allergic rhinitis, and atopic dermatitis using validated tools and objective measures. This will be the first investigation in a country with a national fortification program, where individuals may have high intake of folic acid from the diet. Approach. This work will use complementary retrospective and prospective cohorts of mother-child pairs. Specific aim #1 will investigate the population-based incidence of wheezing and asthma during the first 6 years of life, by the timing of folic acid containing prescriptions filled during pregnancy in a retrospective cohort of 80,000 mother-child dyads from the Tennessee Medicaid population. Specific Aim #2 will determine if a) measured maternal plasma folate levels or b) reported folate intake is associated with prospective development of wheezing, asthma, and/or atopy in the first 5 years of life in mother-child dyads enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort. Innovation and Sustainability. This innovative, cost-efficient project will have the advantages of 1) a well-characterized retrospective cohort with a large number of mother-child dyads and determination of folic acid prescriptions filled by month of pregnancy and 2) a prospective cohort that includes the rich, existing infrastructure of the CANDLE cohort with maternal and infant biospecimens, nutritional data, and prospective follow-up using validated tools and objective measures to assess respiratory and atopic outcomes. This study has potential to inform prenatal recommendations and identify modifiable risk factors for asthma and atopy.

描述（由申请人提供）：研究领域。该项目的长期目标是确定孕妇在怀孕期间的补充是否增加了幼儿哮喘和特纳西州早期的风险。建议在周围的叶酸中补充叶酸，合成叶酸，以防止神经管缺陷（NTD）。在不同人群中的研究表明，在怀孕期间补充叶酸与婴儿下呼吸道感染的风险增加与幼儿哮喘之间存在关联，但数据受到限制。虽然足够的叶酸摄入对于预防NTD是必不可少的，但重要的是描述补充对常见呼吸道和特应性疾病风险的影响。叶酸在基因表达的调节剂DNA甲基化中起重要作用。尚未建立补充叶酸与儿童呼吸结局之间的因果关系。但是，这种关系确实具有一定的生物合理性。在怀孕的小鼠模型中，如在哮喘中所见，甲基供体高的饮食（包括叶酸）导致后代的过敏表型增强。 机会和影响。没有针对特应性疾病（例如哮喘）的主要预防策略。我们的目标是确定较高的母体叶酸摄入量或这种摄入的时间是否会增加儿童喘息，哮喘和其他特应性疾病的风险。这项集体工作将使用客观措施来表征母体叶酸状况，并将使用经过验证的工具和客观措施评估儿童期喘息，哮喘，过敏性鼻炎和特应性皮炎。这将是一个通过国家防御计划的国家进行的首次调查，该国家的饮食中可能会有很高的叶酸摄入量。 方法。这项工作将使用母子对的互补回顾和前瞻性人群。特定的目标＃1将通过在田纳西州医疗补助人群的80,000个母子二元组中，在怀孕期间填充处方的叶酸时机调查了生命的头六年中基于人群的喘息和哮喘的发病率。具体目标＃2将确定a）a）测量的母体血浆叶酸水平或b）据报道的叶酸摄入量与在母子二元组中喘息，哮喘和/或特征的前瞻性发展有关。影响幼儿（蜡烛）队列的神经认知发展和学习。 创新和可持续性。这个创新的，具有成本效益的项目的优点为1）具有良好特征的回顾性队列，并具有大量的母子二元组，并确定按怀孕月份填补的叶酸处方和2）包括富人的前瞻性队列，使用经过验证的工具和客观措施评估呼吸和特征性结果的蜡烛队列现有基础设施，营养数据和前瞻性随访。这项研究有可能为产前建议提供信息，并确定可改变的哮喘和特应特性风险因素。