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

项目摘要 免疫系统在维持儿童的健康和免疫方面起着至关重要的作用 赤字可能会产生严重的后果，从增加感染的易感性到 过敏和自身免疫性疾病。尽管许多因素对整体免疫健康有贡献， 新出现的数据表明，早年接触环境会干扰免疫力 发展和功能。确定影响儿童健康的可改变的环境因素 免疫，我们的首要目标是降低婴儿发病率和死亡率，长期以来- 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， 邻苯二甲酸酯、杀虫剂和阻燃剂用于消费和个人护理产品， 电子产品、家具和建筑材料。由于它们的广泛使用和环境 持久性，在室内环境中检测到SVOCs的频率很高，而人类 暴露在SVOCs混合物中的情况很普遍。我们建议的研究评估暴露在 SVOC混合物贯穿整个孕期和婴儿期。我们将调查个人特征 与较高水平的暴露相关，并评估不良健康后果的可能性 在受感染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，这些研究扩展到人类群体的程度是 不清楚，特别是因为他们主要考虑接触单一化学品，而不是 反映真实世界的暴露(即，在混合物中发生的暴露)。我们的主要目标是 探讨儿童早期暴露于SVOC混合物对儿童免疫功能的影响 在这样做的过程中，填补了在理解SVOCs影响方面的一个关键空白。这项研究将 第一个通过评估来评估SVOC在改变新生儿保护中的作用 早期免疫功能的两个最关键的方面：1)被动的免疫转移和2) 对一种新的病原体相关抗原的反应能力。我们将充分利用 HOPE 1000的基础设施，这是一项正在进行的队列研究，纵向收集了SVOC 在怀孕的每三个月和儿童早期的暴露监测，以及 生物素需要评估免疫功能和病原菌免疫力。 识别影响免疫的特定SVOCs或SVOCs混合物可能会提供新的 在个人和政策层面进行干预的机会。这样的数据是非常需要的 由于预计未来几年一些SVOCs的使用量将会增加。

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.