Prenatal Fatty Acid Supplementation and Early Childhood Asthma and Atopy in Black American Families

项目摘要 哮喘是一种慢性炎症性肺部疾病，目前在美国估计有8.4%的儿童受到影响， 导致每年超过600,000次急诊科就诊和超过75,000次住院(Moorman等人， 2012年)。几十年来，美国哮喘的负担不成比例地落在了生活在低收入家庭的黑人儿童身上 资源丰富的社区，他们的患病率、发病率和死亡率远远超过白人 孩子们。黑人儿童的住院率和急诊率是其他儿童的2-3倍 随着白人儿童的增加，与哮喘相关的死亡率增加了近5倍(Vollman等人，2019年)。在一些 芝加哥南部的社区年幼黑人儿童的哮喘率超过40%(Gupta et Al.，2008)。黑人儿童哮喘和过敏症的高发病率似乎在一定程度上受到了产前压力的影响 曝光。因此，旨在改善黑人女性产前压力调节的干预措施也可能减少 他们的孩子有患哮喘的风险。营养与怀孕研究(NAPS)(NCT02647723)即将完成 产前补充脂肪酸改善生育的双盲随机对照研究 通过改善产前应激调节的结果和婴儿神经发育。二十二碳六烯酸(DHA)，以及 Omega-3脂肪酸已被证明在受控动物中可以预防哮喘和特应性疾病的发展。 对人类的研究和观察性研究。婴儿配方奶粉补充剂的两项小型随机对照试验结果 为膳食脂肪酸对哮喘的保护作用提供进一步的支持(Birch等人，2010年；Foiles等人 Al.，2016)。NAPS研究提供了一个前所未有的机会来测试产前DHA水平对 儿童哮喘和特应性疾病，并进一步研究产前应激调节模式如何影响 效果。我们建议对130名5-6岁的儿童进行哮喘和其他特应性反应的临床评估。 母亲参加NAPS研究的年龄，并从医疗记录和产妇中收集数据 报告测试两个目标。目的1：测试产前脂肪酸水平是否与哮喘和特应性疾病有关 在孩提时代。我们假设，较高的产前血液DHA水平将与较低的 通过对哮喘和变态反应的实验室评估，在子代中测量哮喘和特应性 5-6岁，以及病历摘要和产妇报告。目标2：测试产前应激是否 调控影响产前脂肪酸水平与早期哮喘和特应性疾病的关系 童年。我们的主要假设是皮质醇和细胞因子水平、心率变异性和感知的压力 妊娠期将部分中介产前DHA水平与儿童哮喘和 特应性疾病。我们还将测试产前DHA水平与儿童早期哮喘之间的关系 特应性疾病是通过产前应激调节在基线水平和在产前期间应激调节的变化来缓解 怀孕了。据我们所知，这将是第一次测试产前脂肪酸水平对哮喘和过敏的黑人 美国生活在资源匮乏环境中的儿童

Project Summary Asthma is a chronic inflammatory lung disease that currently affects an estimated 8.4% of children in the U.S., resulting in over 600,000 emergency department visits and over 75,000 hospitalizations each year (Moorman et al., 2012). For decades the burden of asthma in the U.S. has fallen disproportionately on Black children living in low- resourced communities, for whom the prevalence, morbidity and mortality rates far exceed those for White children. Black children have 2-3 times higher rates of hospitalization and emergency department visits compared with White children, and a nearly 5-fold increase in asthma-related mortality (Volerman, et al., 2019). In some neighborhoods on the South Side of Chicago the rates of asthma among young Black children are over 40% (Gupta et al., 2008). The high rate of asthma and allergy in Black children appears to be in part influenced by prenatal stress exposure. Thus, an intervention designed to improve prenatal stress regulation in Black women may also reduce the risk of asthma in their children. The Nutrition and Pregnancy Study (NAPS) (NCT02647723) is a nearly completed double-blind, randomized controlled study (RCT) of prenatal fatty acid supplementation aiming to improve birth outcomes and infant neurodevelopment via improved prenatal stress regulation. Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been shown to protect against the development of asthma and atopy in controlled animal studies and in observational studies of humans. Results from two small RCTs of infant formula supplementation provide further support for the protective effects of dietary fatty acids against asthma (Birch et al., 2010; Foiles et al., 2016). The NAPS study provides an unprecedented opportunity to test the effects of prenatal DHA levels on childhood asthma and atopic disease, and to further examine how patterns of prenatal stress regulation impact that effect. We propose to conduct clinical assessments of asthma and other atopic outcomes in 130 children at 5-6 years of age whose mothers participated in the NAPS study, and to collect data from medical records and maternal report to test two aims. Aim 1: Test whether prenatal fatty acid levels are associated with asthma and atopic disease in early childhood. We hypothesize that higher prenatal blood levels of DHA will be associated with lower levels of asthma and atopy in the offspring as measured via laboratory assessments of asthma and allergic sensitization at ages 5-6 years, as well as medical record abstraction and maternal report. Aim 2: Test whether prenatal stress regulation impacts the association between prenatal fatty acid levels and asthma and atopic disease in early childhood. Our primary hypothesis is that cortisol and cytokine levels, heart rate variability, and perceived stress during pregnancy will partially mediate the association between prenatal DHA levels and childhood asthma and atopic disease. We will also test whether the association between prenatal DHA levels and early childhood asthma and atopic disease is moderated by prenatal stress regulation at baseline and by changes in stress regulation during pregnancy. To our knowledge, this will be the first test of prenatal fatty acid levels on asthma and allergy in Black children living in low-resourced environments in the U.S.