Oldenburg Kirsi S, Eaves Lauren A, Smeester Lisa, Santos Hudson P, O'Shea T Michael, Fry Rebecca C
Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Institute for Environmental Health Solutions, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Placenta. 2021 Aug;111:82-90. doi: 10.1016/j.placenta.2021.06.010. Epub 2021 Jun 18.
Placental inflammation is associated with a variety of adverse health outcomes, including poor pregnancy outcomes as well as later in life health. The current clinical methodologies for evaluating placental histology for inflammation are limited in their sensitivity. The objective of this study was to develop a genomic inflammatory index (GII) that can be utilized as a biomarker to effectively quantify and evaluate placental inflammation.
RNA-sequencing of n = 386 placentas from the Extremely Low Gestational Age Newborn (ELGAN) cohort was conducted. Transcriptional data for a biologically-targeted set of 14 genes, selected for their established role in pro-inflammatory signaling pathways, were aggregated to construct the GII. Multiple linear regression models were used to examine relationships between 47 perinatal factors and the GII.
The GII demonstrated a nine-fold difference across subjects and displayed positive trends with other indicators of placental inflammation. Significant differences in the GII were observed for race where women who self-identified as Black displayed higher levels of placental inflammation than those who self-identified as White women (p < 0.001). Additionally, married Black women showed reduced placental inflammation compared to those who were unmarried (beta value: 0.828, p-value: 0.032). Placentas from women who were treated with steroids during the delivery of the infant displayed higher GII levels than those who were not (p = 0.023).
Overall, the GII demonstrated an association between various perinatal factors and placental inflammation. It is anticipated that the GII will provide a novel genomics tool for quantifying placental inflammation, allowing for further investigation of causes, and ultimately the prevention, of inflammation in the placenta.
胎盘炎症与多种不良健康结局相关，包括不良妊娠结局以及日后的健康问题。目前用于评估胎盘组织学炎症的临床方法在敏感性方面存在局限性。本研究的目的是开发一种基因组炎症指数（GII），可作为生物标志物有效量化和评估胎盘炎症。
对极低孕周新生儿（ELGAN）队列中的386份胎盘进行RNA测序。选择了一组14个基因，这些基因在促炎信号通路中具有既定作用，汇总其转录数据以构建GII。使用多元线性回归模型来研究47个围产期因素与GII之间的关系。
GII在不同受试者之间显示出9倍的差异，并与胎盘炎症的其他指标呈正相关趋势。在种族方面观察到GII存在显著差异，自我认定为黑人的女性胎盘炎症水平高于自我认定为白人的女性（p < 0.001）。此外，已婚黑人女性与未婚黑人女性相比，胎盘炎症有所减轻（β值：0.828，p值：0.032）。在婴儿分娩期间接受类固醇治疗的女性的胎盘GII水平高于未接受治疗的女性（p = 0.023）。
总体而言，GII显示出各种围产期因素与胎盘炎症之间的关联。预计GII将提供一种用于量化胎盘炎症的新型基因组学工具，以便进一步研究胎盘炎症原因，并最终预防胎盘炎症。
