Changes in amniotic fluid concentration of thrombinantithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Abstract

Objective.Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulatingthrombin–antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin hasuterotonic 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 ofthis 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.Study design.This cross-sectional study included the following groups: (1) mid-trimester (n¼74); (2) term not in labor(n¼39); (3) term in labor (n¼25); (4) term in labor with IAI (n¼22); (5) spontaneous preterm labor (PTL) who delivered atterm (n¼62); (6) PTL without IAI who delivered preterm (n¼59); (7) PTL with IAI (n¼71). The AF TAT III complexesconcentration was measured by enzyme linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis.Results.(1) TAT III complexes were identified in all AF samples; (2) patients with PTL who delivered preterm, with andwithout IAI, had a higher median AF TAT III complexes concentration than those with an episode of PTL who delivered atterm (p50.001,p¼0.03, respectively); (3) among patients with PTL without IAI, elevated AF TAT III complexesconcentration 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 thosewithout IAI, whether in labor or not in labor (p¼0.02); (5) there was no significant difference between the median AF TATIII complexes concentration of patients at term with and without labor; (6) patients who had a mid-trimester amniocentesishad a lower median AF TAT III complexes concentration than that of patients at term not in labor (p50.001).Conclusions.We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term andpreterm parturition. PTL leading to preterm delivery is associated with an increased intra-amniotic thrombin generationregardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombingeneration only in patients with IAI.