Impact of Early-life Exposure to Semi-Volatile Organic Compounds (SVOCs) on Neonatal and Early Childhood Immune Function

生命早期接触半挥发性有机化合物 (SVOC) 对新生儿和幼儿免疫功能的影响

• 批准号: 10612458
• 负责人: Jennifer K Hoffman
• 金额: $ 74.21万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-21 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612458
• 关键词: Active immunity; Affect; Age Months; Allergic; Animals; Antibodies; Antibody Formation; Antibody Response; Antigens; Autoimmune Diseases; Binding; Birth; Blood specimen; Cellular Immunity; Characteristics; Chemicals; Child; Child Health; Childhood; Cohort Studies; Collection; Communicable Diseases; Data; Developed Countries; Development; Diphtheria-Tetanus-acellular Pertussis Vaccines; Disease; Electronics; Environmental Exposure; Environmental Impact; Environmental Pollutants; Environmental Risk Factor; Esters; Exposure to; Fetus; Flame Retardants; Frequencies; Furniture; General Population; Goals; Health; Hospitalization; Human; IgG Receptors; Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Impairment; In Vitro; Incidence; Individual; Indoor environment; Infant; Infection; Infrastructure; Intervention; Life; Maternal antibody; Measurement; Measures; Medical; Modeling; Monitor; Morbidity - disease rate; Mus; Neonatal; Organophosphates; Outcome; Passive Transfer of Immunity; Pesticides; Placenta; Plasticizers; Play; Policies; Population; Predisposition; Pregnancy; Pregnancy Trimesters; Property; Prospective cohort; Public Health; Reporting; Research; Resources; Role; Silicones; Specimen; Systems Development; Technology; Testing; Umbilical Cord Blood; Vaccination; Vaccines; Woman; building materials; cell mediated immune response; cohort; design; early childhood; early life exposure; emerging pathogen; environmental chemical; epidemiology study; experience; exposed human population; follow-up; immune function; immune health; immune system function; immunoregulation; improved; infancy; infant death; infant morbidity; infant morbidity/mortality; influenza virus vaccine; mortality; multiplex assay; neoantigens; neonate; neutralizing antibody; novel; pathogen; personal care products; phthalates; placental transfer; prevent; prospective; response; seasonal influenza; vaccine response; volatile organic compound

Project Summary The immune system plays a critical role in maintaining a child’s health, and immune deficits may have serious consequences ranging from increased susceptibility to infections to allergic and autoimmune conditions. Although many factors contribute to overall immune health, emerging data suggest that early life environmental exposures interfere with immune development and function. Identifying modifiable environmental factors that affect children’s immunity, our overarching goal is critical to reducing infant morbidity and mortality and has long- term implications for improving health. Semi-volatile organic compounds (SVOCs), including organophosphate esters, phthalates, pesticides, and flame retardants, are used in consumer and personal care products, electronics, furniture, and building materials. As a result of their extensive use and environmental persistence, SVOCs are detected with high frequency in indoor environments, and human exposure to mixtures of SVOCs is widespread. Our proposed research assesses exposure to SVOC mixtures throughout pregnancy and in infancy. We will investigate individual characteristics associated with higher levels of exposure and evaluate the potential for adverse health outcomes among exposed women and their children. Animal studies provide compelling evidence that exposure to individual SVOCs impacts immune function; however, the extent to which these studies extend to human populations is unclear, particularly because they largely consider exposure to single chemicals, which does not reflect real-world exposures (i.e., those occurring in mixtures). Our primary objective is to investigate the impacts of early life exposure to SVOC mixtures on children’s immune function, and in doing so, to fill a critical gap in the understanding of the impacts of SVOCs. This study will be the first to evaluate the role of SVOC in altering the protection of the neonate by evaluating the two most critical aspects of early life immune function: 1) passive transfer of immunity and 2) the capacity to respond to a novel pathogen-associated antigen. We will capitalize on the infrastructure of HOPE 1000, an ongoing cohort study with longitudinal collection of SVOC exposure monitors during each trimester of pregnancy and in early childhood, and the biospecimen needed to evaluate immune function and pathogen immunity. Identifying specific SVOCs or mixtures of SVOCs that affect immunity may provide new opportunities for interventions at the individual and policy levels. Such data are critically needed as the use of some SVOCs is predicted to increase in the coming years.

项目摘要 免疫系统在维持儿童健康方面起着至关重要的作用， 缺陷可能会产生严重的后果，从增加感染的易感性， 过敏和自身免疫性疾病。虽然许多因素有助于整体免疫健康， 新出现的数据表明，生命早期的环境暴露会干扰免疫 发展和功能。确定影响儿童健康的可改变的环境因素 免疫，我们的总体目标是降低婴儿发病率和死亡率至关重要， 长期影响改善健康。 半挥发性有机化合物（SVOC），包括有机磷酸酯， 邻苯二甲酸盐、杀虫剂和阻燃剂，用于消费品和个人护理产品， 电子产品、家具和建筑材料。由于其广泛的使用和环境 持久性，SVOCs在室内环境中以高频率检测到， 暴露于SVOC的混合物是普遍的。我们提议的研究评估暴露于 整个孕期和婴儿期的SVOC混合物。我们将调查个体特征 与高水平暴露相关，并评估不良健康后果的可能性 在接触过的妇女和她们的孩子中。 动物研究提供了令人信服的证据，表明暴露于单个SVOCs会影响 免疫功能;然而，这些研究扩展到人群的程度是 不清楚，特别是因为他们主要考虑接触单一化学品，而这些化学品并不 反映真实世界的暴露（即，以混合物的形式存在）。我们的首要目标是 调查生命早期暴露于SVOC混合物对儿童免疫功能的影响， 并在此过程中，填补了对SVOCs影响的理解方面的关键空白。本研究将 通过评估SVOC在改变新生儿保护方面的作用， 生命早期免疫功能的两个最关键的方面：1）免疫的被动转移和2） 对新病原体相关抗原的反应能力。我们将利用 HOPE 1000的基础设施，一项正在进行的队列研究，纵向收集SVOC 在怀孕的每三个月和幼儿期进行接触监测， 评价免疫功能和病原体免疫力所需的生物标本。 识别影响免疫力的特定SVOC或SVOC混合物可以提供新的 在个人和政策层面进行干预的机会。这些数据是非常需要的。 因为预计未来几年一些SVOC的使用将增加。