Antenatal Anxiety and Dyadic Immune Risk(ADIR Study)

项目摘要 特应性疾病是一个主要的公共卫生问题，影响到世界上20%的人口， 近几十年来的流行。它与致命反应（食物过敏）有关， 对儿童和家庭的心理社会和经济负担。已知环境和子宫内暴露 风险因素，但很少有人知道的机制，通过接触可能带来的风险。其中一 已知的暴露是母亲产前焦虑，这与孕妇产前焦虑的标志物升高有关。 过敏风险（如免疫球蛋白E（IgE）水平）和儿童特应性诊断。产妇 产前焦虑也与母亲和儿童的免疫失调有关， 出生时儿童的先天免疫活性可能是未来过敏风险的关键标志-但没有研究表明 试图将母亲和新生儿的免疫失调与同一母亲-儿童的过敏风险联系起来 对.在这项前瞻性、纵向、观察性研究中，我们计划跟踪200对母子（132对， 临床显著焦虑的风险和68名健康对照），从妊娠中期至 婴儿满12个月。我们假设有临床意义的产前焦虑的妇女 与健康对照相比，显示出增强的免疫活性，刺激细胞和基因表达， 从这些怀孕的脐带血中提取的免疫活性也会同样显示出增强的免疫活性， 母亲和儿童的免疫活动将与儿童过敏风险的标志物相关。我们将 测量母亲和儿童受刺激细胞产生的免疫细胞群和细胞因子; 进行儿童脐带血中免疫相关基因的甲基化分析（重点是已知的 未来过敏风险的生物标志物）;将测量儿童特应性皮炎;并将测量常见的IgE 过敏原和母亲报告的食物过敏反应的儿童。此外，我们将观察母婴 围绕喂养的相互作用，以解释出生后环境的因素， 增加儿童过敏风险。我们全面而严格的实验计划将有助于阐明 有助于母亲产前焦虑和儿童过敏风险之间的联系，并可能导致新的 采取干预措施，改善母亲和儿童的症状和风险。

PROJECT SUMMARY Atopic disease is a major public health problem affecting up to 20% of the world’s population, with rising prevalence in recent decades. It is associated with fatal reactions (food allergy), and with significant psychosocial and financial burden for children and families. Environmental and in utero exposures are known risk factors, but little is known about the mechanisms through which exposures may confer risk. One of these known exposures is maternal antenatal anxiety, which has been associated both with elevated markers of allergy risk (such as levels of Immunoglobluin E (IgE)) and with atopic diagnosis in children. Maternal antenatal anxiety has also been linked to immune dysregulation in both mothers and children, and elevated innate immune activity in children at birth may be a key marker of future allergic risk – yet no study has attempted to link dyadic maternal and neonatal immune dysregulation to allergy risk in the same mother-child pairs. In this prospective, longitudinal, observational study, we propose to follow 200 mother-child pairs (132 at risk for clinically significant anxiety and 68 healthy controls) from the second trimester of pregnancy until infants reach 12 months of age. We hypothesize that women with clinically significant antenatal anxiety will demonstrate elevated immune activity compared to healthy controls, that stimulated cells and gene expression from umbilical cord blood in these pregnancies will similarly show evidence of increased immune activity, and that maternal and child immune activity will be associated with markers of allergy risk in children. We will measure immune cell populations and cytokines produced by stimulated cells in mothers and children; will conduct methylation analyses of immune-related genes in the cord blood of children (focusing on known biomarkers of future allergic risk); will measure atopic dermatitis in children; and will measure IgE to common allergens and maternal report of food allergic reactions in children. In addition, we will observe mother-child interactions surrounding feeding to account for elements of the postnatal environment that may contribute to elevated child allergic risk. Our thorough and rigorous experimental plan will help to illuminate pathways that contribute to the association between maternal antenatal anxiety and child allergy risk, and may lead to novel interventions to ameliorate symptoms and risk in both mother and child.