Expecting Mothers' Study of Consumption or Avoidance of Peanut and Egg (ESCAPE)

项目总结/摘要 而花生（PN）过敏是最常见的原因，致命和近致命的食物过敏反应，在老年人中， 无论是儿童还是成人，鸡蛋和牛奶是婴儿期最常见的过敏性食物。鸡蛋过敏 是最常见的儿童IgE介导的食物过敏，一般患病率为1.3- 1.6 高危婴儿占总人口的20%。鸡蛋致敏是PN过敏的重要风险因素， 空气过敏原致敏，这可能导致“特应性行军”。黑人儿童在 鸡蛋过敏和哮喘的儿童在对鸡蛋过敏的儿童中比其他任何食物都要普遍。只 50%的人在学龄前对鸡蛋产生耐受性; PN过敏很少会消失。有一个关键的“窗口”， 在4-6个月左右引入过敏性固体以降低食物过敏的风险， 在鸡蛋和PN的随机对照试验中显示。然而，36%的婴儿已经对鸡蛋过敏， 在入组时，约9%的婴儿接受PN，将其从早期引入中排除; 20%的婴儿临床过敏， 甚至会过敏。为了更有效，初级预防战略必须 早在致敏形成之前开始，甚至可能在怀孕或哺乳期间。 先前的研究在母体饮食（包括或不包括鸡蛋或PN）对发育的影响方面存在矛盾。 婴儿期食物过敏根据美国儿科学会的说法，“目前的证据不支持 母亲在怀孕或哺乳期间的饮食限制”，但缺乏随机对照试验。 因此，迫切需要向母亲提供基于良好营养的具体喂养建议。 质量证据。本申请的总体目标是确定鸡蛋和PN暴露在 妊娠和通过食物中的母乳致敏，并确定致敏或耐受的生物标志物。 我们将进行一项全国招募、随机对照、四组平行试验。孕妇 打算母乳喂养>3个月的高危婴儿（具有患有特应性疾病的一级亲属）将被 使用社交媒体和转诊招募，并随机分配至食用或避免鸡蛋和PN 在整个妊娠期和哺乳期内，评估对鸡蛋和PN致敏的风险， 几个月后，开始吃固体食物。在目标1中，我们将确定母亲饮食鸡蛋和PN的影响 妊娠期和哺乳期避免对高危婴儿的鸡蛋和PN致敏风险的影响。在目标2中， 我们将评估婴儿口服和环境暴露于鸡蛋和PN的水平。在目标3中，我们将确定 在妊娠和哺乳期间，母亲饮食（包括或不包括鸡蛋和PN）引起的免疫应答。 从这些研究中获得的知识将揭示早期生命敏感化的机制， 预防食物过敏和特应性疾病的母亲饮食指南。 1

PROJECT SUMMARY/ABSTRACT Whereas peanut (PN) allergy is the most common cause of fatal and near-fatal food-allergic reactions in older children and adults, egg and cow’s milk are the most common food triggers of anaphylaxis in infancy. Egg allergy is the most common childhood IgE-mediated food allergy with prevalence rates ranging from 1.3-1.6% in general population up to 20% in high-risk infants. Egg sensitization is a significant risk factor for PN allergy and early aeroallergen sensitization, which can lead to the “atopic march”. Black children are over-represented among children with egg allergy and asthma is more prevalent in children with allergy to egg than any other food. Only 50% develop tolerance to egg by school-age; PN allergy is rarely outgrown. There is a critical “window of opportunity” for the introduction of allergenic solids around 4-6 months in decreasing the risk of food allergy as shown in randomized controlled trials with egg and PN. However, 36% of infants were already sensitized to egg at enrollment and about 9% to PN, excluding them from early introduction; 20% infants were clinically allergic, even anaphylactic, on their first introduction of egg. To be more effective, primary prevention strategies must begin much earlier before sensitization is established, possibly even during pregnancy or breastfeeding. Prior studies are conflicting in the effect of maternal diet including or excluding egg or PN on development of food allergy in infancy. Per the American Academy of Pediatrics, “Current evidence does not support a role for maternal dietary restrictions during pregnancy or lactation”, but randomized controlled trials are lacking. Thus, there is an urgent need to provide mothers with concrete advice on feeding practices based on good quality evidence. The overall objective of this application is to define the role for egg and PN exposure during pregnancy and via human milk in food sensitization and to identify the biomarkers of sensitization or tolerance. We will conduct a nationally-enrolled, randomized controlled, four-arm parallel trial. Mothers pregnant with infants at high risk (with first degree relative with an atopic disease) who intend to breastfeed >3 months will be enrolled utilizing social media and referrals and randomized to either consumption or avoidance of egg and PN containing foods throughout pregnancy and lactation to assess the risk of sensitization to egg and PN at 4 months before introduction of solid foods. In Aim 1, we will determine the effect of maternal dietary egg and PN avoidance during pregnancy and lactation on the risk of egg and PN sensitization in high-risk infants. In Aim 2, we will assess the level of infant oral and environmental exposure to egg and PN. In Aim 3, we will identify the immune responses elicited by maternal diet including or excluding egg and PN during pregnancy and lactation. Knowledge gained from these studies will uncover mechanisms of early-life sensitization necessary to establish maternal dietary guidelines in prevention of food allergy and the atopic march. 1