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: 10410116
• 负责人: Jennifer K Hoffman
• 金额: $ 71.61万
• 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/10410116
• 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; Disease; Electronics; Environmental Exposure; Environmental Impact; Environmental Pollution; Environmental Risk Factor; Esters; Exposure to; Fetus; Flame Retardants; Frequencies; Furniture; General Population; Goals; Health; 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; Pertussis Vaccine; Pesticides; Placenta; Plasticizers; Play; Policies; Population; Population Policies; Predisposition; Pregnancy; Pregnancy Trimesters; Property; Prospective cohort; Public Health; Reporting; Research; Resources; Role; Silicones; Specimen; Systems Development; Testing; Tetanus; Umbilical Cord Blood; Vaccination; Vaccines; Woman; base; 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/mortality; influenza virus vaccine; mortality; multiplex assay; neoantigens; neonate; neutralizing antibody; novel; pathogen; personal care products; phthalates; 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 免疫系统在维持孩子的健康和免疫方面起着至关重要的作用 缺陷可能会产生严重的后果，从增加易感性到感染到 过敏和自身免疫性状况。尽管许多因素导致整体免疫健康，但 新兴数据表明，早期环境暴露于免疫的干扰 发展和功能。确定影响儿童的可修改环境因素 免疫力，我们的总体目标对于降低婴儿的发病率和死亡率至关重要，并且具有长期 对改善健康的术语含义。 半挥发性有机化合物（SVOC），包括有机磷酸酯， 邻苯二甲酸盐，农药和阻燃剂用于消费者和个人护理产品， 电子，家具和建筑材料。由于他们广泛使用和环境 持续存在，在室内环境中以高频检测到SVOC，人类 暴露于SVOC的混合物是广泛的。我们提出的研究评估暴露于 整个怀孕和婴儿期SVOC混合物。我们将调查个人特征 与较高的接触水平相关并评估不良健康结果的潜力 在暴露的妇女及其子女中。 动物研究提供了令人信服的证据，表明暴露于各个SVOC会影响 免疫功能；但是，这些研究扩展到人群的程度是 不清楚，尤其是因为它们在很大程度上考虑接触单一化学物质，这不是 反映现实世界中的暴露（即发生在混合物中的暴露）。我们的主要目标是 研究早期生命暴露于SVOC混合物对儿童免疫功能的影响， 在这样做的过程中，在理解SVOC的影响方面的关键空白。这项研究会 成为第一个评估SVOC通过评估来改变新生儿保护的作用的人 早期生命免疫功能的两个最关键方面：1）免疫的被动转移和2） 对新型病原体相关抗原做出反应的能力。我们将利用 Hope 1000的基础架构，这是一项正在进行的队列研究，纵向收集了SVOC 在怀孕和幼儿期间每个三个月的暴露监测， 评估免疫功能和病原体免疫所需的生物测量。 确定影响免疫力的特定SVOC或SVOC的混合物可能会提供新的 在个人和政策层面上进行干预的机会。这样的数据至关重要 由于预计在未来几年将使用一些SVOC。