Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes

怀孕叶酸状况

• 批准号: 8686937
• 负责人: KECIA Nicole CARROLL
• 金额: $ 69.64万
• 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/8686937
• 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母亲在怀孕期间补充叶酸是否会增加儿童早期哮喘和特应性的风险。建议在围孕期补充叶酸（合成叶酸）以预防神经管缺陷 (NTD)。对不同人群的研究表明，报道的怀孕期间补充叶酸与婴儿下呼吸道感染和幼儿哮喘风险增加之间存在关联，但数据有限。虽然摄入足够的叶酸对于预防 NTD 至关重要，但了解补充叶酸对常见呼吸道疾病和特应性疾病风险的影响也很重要。叶酸在 DNA 甲基化（基因表达的调节因子）中发挥着重要作用。叶酸补充与儿童呼吸系统结局之间的因果关系尚未确定。然而，这种关系确实具有一定的生物学合理性。在怀孕小鼠模型中，富含甲基供体（包括叶酸）的饮食会导致后代过敏表型增强，如哮喘中所见。 机会和影响。对于哮喘等特应性疾病，没有一级预防策略。我们的目标是确定母亲叶酸摄入量较高或摄入叶酸的时间是否会增加儿童患喘息、哮喘和其他特应性疾病的风险。这项集体工作将使用客观测量来表征母亲叶酸状况，并将使用经过验证的工具和客观测量来评估儿童喘息、哮喘、过敏性鼻炎和特应性皮炎。这将是在一个拥有国家强化计划的国家进行的首次调查，该计划中的个人可能从饮食中摄入大量叶酸。 方法。这项工作将使用互补的回顾性和前瞻性母子队列。具体目标#1 将通过对来自田纳西州医疗补助人群的 80,000 名母子二人组进行回顾性队列研究，通过怀孕期间服用含叶酸处方的时间来调查生命前 6 年内喘息和哮喘的人群发病率。具体目标#2将确定a)测量的母亲血浆叶酸水平或b)报告的叶酸摄入量是否与参加影响幼儿期神经认知发展和学习的条件(CANDLE)队列的母子二人在生命的前5年出现喘息、哮喘和/或特应性相关。 创新和可持续发展。这个创新的、具有成本效益的项目将具有以下优点：1) 一个特征明确的回顾性队列，包含大量母子二元组，并确定按怀孕月份填写的叶酸处方；2) 一个前瞻性队列，其中包括 CANDLE 队列丰富的现有基础设施，包括母婴生物样本、营养数据和使用经过验证的工具和客观测量的前瞻性随访 评估呼吸和特应性结果。这项研究有可能为产前建议提供信息，并确定哮喘和特应性的可改变危险因素。