Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. EMA is a population-based, nested case–control study which linked archived maternal serum samples collected during weeks 15–19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from − 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.

中文翻译：

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孕期母亲的免疫反应和空气污染暴露：自闭症早期标志物 (EMA) 研究的见解


围产期空气污染暴露和免疫系统失调是与自闭症谱系障碍 (ASD) 和其他神经发育结果始终相关的两个因素。然而，人们对空气污染如何影响怀孕期间母亲的免疫功能知之甚少。评估妊娠中期母体细胞因子/趋化因子循环水平与各神经发育组前一个月空气污染暴露之间的关系，并评估细胞因子/趋化因子是否介导空气污染暴露与 ASD 和/或智力障碍风险之间的关系 (ID ）在自闭症早期标记（EMA）研究中。 EMA 是一项基于人群的巢式病例对照研究，它将妊娠 15-19 周期间收集的存档母体血清样本联系起来，用于常规产前筛查、出生记录和发育服务部 (DDS) 记录。接受 DDS 服务的 ASD 无智力障碍儿童（无智力障碍的 ASD；n = 199）、有智力障碍的 ASD（有智力障碍的 ASD；n = 180）、无 ASD 的智力障碍（ID；n = 164）和普通人群的儿童（本分析包括没有 DDS 服务的 GP；n = 414。使用 Luminex 多重分析技术对血清样品中的 22 种细胞因子/趋化因子进行定量。产妇血清采集前一个月的空气污染暴露是根据环境保护局的空气质量系统数据，使用产前筛查访问期间报告的产妇居住地址确定的。上个月的空气污染暴露与妊娠中期母体细胞因子和趋化因子水平显着相关，但幅度较弱（范围为-0.16至0.13）。 在一个儿童神经发育组中，十对妊娠中期免疫标记物和上个月的空气污染物显着相关，并调整了协变量（p < 0.001）。怀孕中期的空气污染与任何神经发育结果无关。即使在调整了空气污染暴露后，IL-6 仍然与患有 ID 的 ASD 相关。这项研究表明，母体免疫激活与神经发育障碍的风险相关。此外，产前空气污染暴露对怀孕期间母体免疫系统功能的影响虽小，但可能具有生物学相关性。如果能够确定易感性升高的窗口，以及这些因素如何影响后代的神经发育，还需要进行更多研究，以更好地评估产前接触空气污染如何影响怀孕期间母体免疫激活的轨迹。