Takeda Jun, Fang Xin, Olson David M
Departments of Obstetrics and Gynecology, Pediatrics and Physiology, 220 Heritage Medical Research Center, University of Alberta, Edmonton, T6G 2S2, AB, Canada.
Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
BMC Pregnancy Childbirth. 2017 Jan 10;17(1):16. doi: 10.1186/s12884-016-1204-5.
Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition. Since migration is an early parturitional event our purpose was to study the migration of maternal peripheral blood leukocytes in response to a standard chemotactic signal during several different conditions of late pregnancy.
We used a cross-sectional observational study design. Subjects were (sTL) spontaneous normal labour delivered vaginally at term, (TNL) elective caesarean section at term without labour, (PTL) preterm in labour, (PTNL) preterm not in labour, (TPTL) threatened preterm labour, and (pPROM) preterm with premature rupture of membranes. Leukocytes (100,000) obtained by venipuncture and chemotactic factor isolated from term labour fetal membranes were placed in the upper and lower halves, respectively, of a Boyden chamber separated by a filter with 3μm pores. Migrated leukocytes were assessed by flow cytometry. The number of leukocytes that migrated in 90 min was the primary outcome measure.
Increased numbers of leukocytes from peripheral blood of women in labour (TL or PTL) or soon to go into labour (PPROM) migrated towards a chemotactic signal than did leukocytes from women not in labour (TNL, PTNL, or TPTL) (p < 0.0001). All pPROM delivered within 7d; TPTL delivered >30d. Receiver operating characteristic curve parameters indicated the cut-off point for delivery within 7d to be 37,082 leukocytes with sensitivity 78.1%, specificity 88.9%, positive predictive value 91.4%, negative predictive value 72.7%, and area under the curve 0.83.
Leukocyte migration to a fetal membrane signal varies in a predictable fashion during various clinical situations of late gestation. This principle has the potential to be improved to become a clinical test to predict delivery.
足月分娩和早产的特征是在无感染情况下发生的无菌性炎症过程，在此过程中，外周血白细胞会响应趋化信号浸润妊娠组织。响应归巢信号时，募集到的白细胞会发生穿壁作用，并通过毛细血管渗出，迁移到基质组织中。在那里，它们与驻留的免疫细胞和基质细胞相互作用，产生基质金属蛋白酶、前列腺素和细胞因子的混合物，包括白细胞介素-1β（IL-1β）和IL-6，这些物质进而使子宫从妊娠状态转变为分娩状态。由于迁移是分娩早期的一个事件，我们的目的是研究在妊娠晚期的几种不同情况下，母体外周血白细胞对标准趋化信号的响应迁移情况。
我们采用横断面观察性研究设计。研究对象包括（sTL）足月时经阴道自然分娩的产妇、（TNL）足月时择期剖宫产且未临产的产妇、（PTL）早产临产的产妇、（PTNL）未临产的早产产妇、（TPTL）先兆早产产妇以及（pPROM）胎膜早破的早产产妇。通过静脉穿刺获取的白细胞（100,000个）和从足月分娩胎膜中分离出的趋化因子分别置于由孔径为3μm的滤膜隔开的Boyden小室的上半部分和下半部分。通过流式细胞术评估迁移的白细胞。以90分钟内迁移的白细胞数量作为主要结局指标。
与未临产的女性（TNL、PTNL或TPTL）的白细胞相比，临产（TL或PTL）或即将临产（PPROM）的女性外周血白细胞向趋化信号迁移的数量增加（p < 0.0001）。所有pPROM产妇均在7天内分娩；TPTL产妇分娩时间超过30天。受试者工作特征曲线参数表明，7天内分娩的临界值为37,082个白细胞，敏感性为78.1%，特异性为88.9%，阳性预测值为91.4%，阴性预测值为72.7%，曲线下面积为0.83。
在妊娠晚期的各种临床情况下，白细胞向胎膜信号的迁移以可预测的方式变化。这一原理有潜力得到改进，成为一种预测分娩的临床检测方法。
