Department of Obstetrics & Gynecology, Perinatal Research Division, the University of Texas Medical Branch at Galveston, Galveston, Texas; and the Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, Pennsylvania.
Obstet Gynecol. 2019 Oct;134(4):765-773. doi: 10.1097/AOG.0000000000003470.
To examine inflammatory mediators in three fetomaternal biological compartments to inform theory related to the fetal and maternal inflammatory contributions to parturition at term and preterm.
We conducted a cross-sectional study of amniotic fluid, cord blood, and maternal plasma from women with singleton pregnancies. Women had one of four conditions: term labor (n=11), term not in labor (n=13), spontaneous preterm birth with intact membranes (preterm birth; n=13), or preterm prelabor rupture of membranes (PROM; n=8). We measured two damage-associated molecular pattern markers (high-mobility group box-1 [HMGB1] and uric acid) and two acute phase response markers (interleukin [IL]-6 and C-reactive protein [CRP]) using enzyme-linked immunosorbent assay. The distribution of each analyte within amniotic fluid, cord blood, and maternal plasma across the four conditions (term not in labor, term labor, preterm birth, and preterm PROM) were calculated. To explore whether there were distributional differences in each analyte across each of the four labor conditions, we used a nonparametric Kruskal-Wallis test. For analytes that differed across groups, we further compared distributions by labor group (term labor vs term not in labor, and preterm PROM vs preterm birth).
Fetal compartments (amniotic fluid and cord blood) showed higher HMGB1 in term labor vs term not in labor and preterm PROM vs preterm birth. Amniotic fluid IL-6, cord blood CRP and cord blood uric acid were higher in term vs term not in labor. Cord blood uric acid was higher in preterm PROM vs preterm birth. Only maternal plasma IL-6 was higher in term labor vs term not in labor.
Accumulation of HMGB1 and an overall increase in inflammation observed on the fetal side, but not the maternal side, may be signals of parturition. Understanding fetal-derived proparturition inflammatory signals at term and preterm, especially in preterm PROM, might provide fetal-specific biomarkers and identify underlying mechanisms and targets for interventions to reduce the risk of preterm birth and preterm PROM.
研究三种胎-母生物学样本中的炎症介质，为与足月和早产时胎儿和母体炎症对分娩的贡献相关的理论提供信息。
我们对单胎妊娠的孕妇的羊水、脐血和母血浆进行了横断面研究。这些女性具有以下四种情况之一：足月产时临产（n=11）、足月产时未临产（n=13）、自发性胎膜完整的早产（早产；n=13）或早产胎膜早破（PROM；n=8）。我们使用酶联免疫吸附试验（ELISA）测量了两种损伤相关分子模式标志物（高迁移率族蛋白 B1 [HMGB1]和尿酸）和两种急性相反应标志物（白细胞介素 [IL]-6 和 C 反应蛋白 [CRP]）。在这四种情况下（未临产、临产、早产和早产 PROM），计算了每种分析物在羊水、脐血和母血浆中的分布。为了探讨每种分析物在四个分娩条件中的分布是否存在差异，我们使用了非参数 Kruskal-Wallis 检验。对于在各组之间存在差异的分析物，我们进一步通过分娩组（临产与未临产，早产 PROM 与早产）比较分布情况。
胎儿区（羊水和脐血）中 HMGB1 在足月产时临产与未临产和早产 PROM 与早产之间存在差异。羊水 IL-6、脐血 CRP 和脐血尿酸在足月产时与未临产之间存在差异。早产 PROM 与早产之间，脐血尿酸较高。只有母血浆 IL-6 在足月产时临产与未临产之间较高。
在足月和早产时，在胎儿侧而不是母体侧观察到 HMGB1 的积累和整体炎症增加，这可能是分娩的信号。了解足月和早产，尤其是早产 PROM 时胎儿来源的促分娩炎症信号，可能为早产和早产 PROM 的风险提供胎儿特异性生物标志物，并确定潜在的机制和干预靶点。
