Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women.
Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women.
复制标题
DOI：
10.1093/eep/dvac026
复制
发表时间：
2023
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
硬膜外麻醉是一种有效的镇痛方式，广泛应用于分娩镇痛。儿童哮喘是美国最常见的慢性疾病之一，给医疗保健系统带来了沉重的负担。我们最近证实了硬膜外麻醉持续时间与儿童哮喘的发生之间存在负相关;然而，其潜在的分子机制仍不清楚。在这项来自新生儿表观遗传学研究的127对母子对（包括75名非西班牙裔黑人（NHB）和52名非西班牙裔白色（NHW））的研究中，我们测试了脐带血DNA甲基化介导分娩时硬膜外麻醉持续时间与儿童哮喘发展之间的关联的假设，以及这是否因种族/民族而异。在NHB血统的母子配对中，硬膜外麻醉暴露时间每增加1小时，与哮喘风险略微降低相关（比值比= 0.88，95%置信区间= 0.76-1.01）。在NHB人群中显示出最强中介作用的20个CpG中，50%表现出52%的平均中介比例，直接和间接效应的方向一致性。这些前20个CpG映射到21个基因，这些基因富含参与抗原加工、抗原呈递、蛋白泛素化和与主要组织相容性复合物（MHC）I类复合物和核因子κ B（NF κ B）复合物相关的调控网络的途径。我们的研究结果表明，免疫相关途径中的DNA甲基化有助于影响NHB后代暴露于硬膜外麻醉的持续时间对儿童哮喘风险的影响。
Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother–child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother–child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76–1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.