Erez Offer, Romer Roberto, Vaisbuch Edi, Chaiworapongsa Tinnakorn, Kusanovic Juan Pedro, Mazaki-Tovi Shali, Gotsch Francesca, Gomez Ricardo, Maymon Eli, Pacora Percy, Edwin Samuel S, Kim Chong Jai, Than Nandor Gabor, Mittal Pooja, Yeo Lami, Dong Zhong, Yoon Bo Hyun, Hassan Sonia S, Mazor Moshe
Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, USA.
J Matern Fetal Neonatal Med. 2009 Nov;22(11):971-82. doi: 10.3109/14767050902994762.
Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulating thrombin-antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries.
This cross-sectional study included the following groups: (1) mid-trimester (n = 74); (2) term not in labor (n = 39); (3) term in labor (n = 25); (4) term in labor with IAI (n = 22); (5) spontaneous preterm labor (PTL) who delivered at term (n = 62); (6) PTL without IAI who delivered preterm (n = 59); (7) PTL with IAI (n = 71). The AF TAT III complexes concentration was measured by enzyme linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis.
(1) TAT III complexes were identified in all AF samples; (2) patients with PTL who delivered preterm, with and without IAI, had a higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p < 0.001, p = 0.03, respectively); (3) among patients with PTL without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio, 1.5; 95% CI, 1.07-2.1); (4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p = 0.02); (5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; (6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p < 0.001).
We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. PTL leading to preterm delivery is associated with an increased intra-amniotic thrombin generation regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI.
早产与母体凝血酶生成过多有关，循环中凝血酶 - 抗凝血酶（TAT）Ⅲ复合物浓度升高即证明了这一点。除了其止血功能外，凝血酶还具有宫缩作用，在子宫内出血的情况下，可能参与导致早产的机制。凝血酶还具有促炎作用，且炎症与凝血酶生成增加有关。本研究的目的是确定羊膜腔内感染/炎症（IAI）是否与早产和足月分娩女性的羊水（AF）凝血酶生成增加有关。
这项横断面研究包括以下几组：（1）孕中期（n = 74）；（2）足月未临产（n = 39）；（3）足月临产（n = 25）；（4）足月临产合并IAI（n = 22）；（5）足月分娩的自发性早产（PTL）（n = 62）；（6）未合并IAI的早产PTL（n = 59）；（7）合并IAI的PTL（n = 71）。通过酶联免疫吸附测定（ELISA）测量AF TATⅢ复合物浓度。采用非参数统计进行分析。
（1）在所有AF样本中均检测到TATⅢ复合物；（2）早产的PTL患者，无论有无IAI，其AF TATⅢ复合物浓度中位数均高于足月分娩的PTL患者（分别为p < 0.001，p = 0.03）；（3）在未合并IAI的PTL患者中，AF TATⅢ复合物浓度升高与羊膜腔穿刺至分娩间隔时间缩短独立相关（风险比，1.5；95%可信区间，1.07 - 2.1）；（4）在足月患者中，无论临产与否，合并IAI者的AF TATⅢ复合物浓度中位数均高于未合并IAI者（p = 0.02）；（5）足月临产和未临产患者的AF TATⅢ复合物浓度中位数之间无显著差异；（6）孕中期进行羊膜腔穿刺的患者，其AF TATⅢ复合物浓度中位数低于足月未临产患者（p < 0.001）。
我们在此展示了足月分娩和早产时羊膜腔内凝血酶生成模式的明显差异。导致早产的PTL与羊膜腔内凝血酶生成增加有关，无论是否存在IAI。相比之下，足月分娩仅在合并IAI的患者中与羊膜腔内凝血酶生成增加有关。
