Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes

描述(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疾病的风险。建议在妊娠期补充叶酸，合成叶酸，以防止神经管畸形(NTD)。在不同人群中的研究表明，报告的怀孕期间补充叶酸与婴儿下呼吸道感染和儿童早期哮喘风险增加之间存在关联，但数据有限。虽然足够的叶酸摄入量对于预防NTDS是必不可少的，但重要的是描述补充剂对常见呼吸道和特应性疾病风险的影响。叶酸在DNA甲基化中起着重要作用，DNA甲基化是基因表达的调节因子。补充叶酸与儿童呼吸结局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。在怀孕的小鼠模型中，包括叶酸在内的高甲基供体饮食导致后代过敏表型增加，如哮喘所见。机遇和影响。目前还没有针对哮喘等特应性疾病的主要预防策略。我们的目标是确定母亲叶酸摄入量较高或摄取叶酸的时机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测量方法来表征母亲的叶酸状况，并将使用有效的工具和客观测量方法来评估儿童喘息、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第一次调查，在这个国家，个人可能从饮食中摄入高叶酸。接近。这项工作将使用互补性的母子对回顾和预期队列。具体目标1将通过对田纳西州医疗补助人口中80,000名母子二人组在怀孕期间服用含有叶酸的处方的时间选择，来调查在生命的前6年中基于人群的喘息和哮喘发病率。具体目标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登记在影响儿童早期神经认知发展和学习(蜡烛)队列的条件下的母子二人组在生命的头5年预期发生喘息、哮喘和/或特应性疾病有关。创新和可持续性。这一创新的、具有成本效益的项目将具有以下优势：1)具有良好特征的回顾队列，其中包括大量母子二联体和叶酸处方的确定；以及2)前瞻性队列，其中包括蜡烛队列中丰富的现有基础设施、母婴生物样本、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果的前瞻性后续行动。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疾病的可改变的危险因素。

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.