Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes

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补充叶酸是否会增加儿童早期哮喘和特应性反应的风险。建议在围孕期补充叶酸，合成叶酸，以防止神经管缺陷（NTD）。对不同人群的研究表明，在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。虽然充足的叶酸摄入对于预防被忽视的热带病至关重要，但重要的是要确定补充叶酸对常见呼吸系统疾病和特应性疾病风险的影响。叶酸在DNA甲基化中起重要作用，是基因表达的调节因子。叶酸补充与儿童呼吸系统预后之间的因果关系尚未确定。然而，这种关系确实有一些生物学上的合理性。在怀孕小鼠模型中，高甲基供体（包括叶酸）的饮食导致后代过敏表型增强，如哮喘所见。机会和影响。目前还没有针对哮喘等特应性疾病的初级预防策略。我们的目的是确定是否较高的母亲叶酸摄入量或这种摄入量的时间增加了儿童喘息，哮喘和其他特应性疾病的风险。这项集体工作将使用客观测量来描述母亲叶酸状况，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。这将是第一次在一个有国家强化计划的国家进行调查，那里的个人可能从饮食中摄取大量叶酸。的方法。这项工作将使用母子对的互补回顾性和前瞻性队列。具体目标#1将调查基于人群的哮喘和哮喘的发病率在生命的前6年，通过在孕期服用叶酸处方的时间，在80,000对来自田纳西州医疗补助人口的母子对中回顾性队列。特定目标#2将确定a)测量的母体血浆叶酸水平或b)报告的叶酸摄入量是否与参加影响幼儿神经认知发育和学习的条件（CANDLE）队列的母婴双体在生命的前5年的哮喘、哮喘和/或特应性反应的预期发展有关。创新和可持续发展。这一创新的、具有成本效益的项目将具有以下优势：1)一个具有良好特征的回顾性队列，包含大量母子对，并根据怀孕月份确定叶酸处方；2)一个前瞻性队列，包括丰富的、现有的CANDLE队列基础设施，包括孕产妇和婴儿生物标本、营养数据，以及使用经过验证的工具和客观措施评估呼吸和特应性结局的前瞻性随访。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。

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.