Changes in amniotic fluid concentration of thrombin-antithrombin 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 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.

Study design: 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.

Results: (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).

Conclusions: 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.

Figure 1

Amniotic fluid thrombin-antithrombin III complexes concentration in patients in the mid-trimester of pregnancy and women at term not in labor (mid-trimester: median 8.1μg/L, range 2.1–160.0 vs. term no labor: median 66.9 μg/L, range 10.2–154).

Figure 2

Amniotic fluid thrombin-antithrombin III complexes concentration in patients with term pregnancies not in labor, women at term in labor and patients with term labor and intra-amniotic infection/inflammation(term no labor: median 66.9μg/L, range 10.2–154 vs. term in labor: median 50.8 μg/L, range 6.8–150.0).

Figure 3

Amniotic fluid thrombin-antithrombin III complexes concentration in patients with preterm labor who delivered at term, women with preterm labor who delivered preterm without intra-amniotic infection/inflammation, and women with preterm labor and intra-amniotic infection/inflammation (PTL with IAI: median 147.7μg/L, range 15.3–1424.8; PTL without IAI: median 116.0μg/L, range 10.7–2073.9; PTL who delivered at term: median 73.4 μg/L, range 7.6–507.0).

Figure 4

Figure 4a. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on gestational age at delivery in patients with preterm labor. Figure 4b. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on the amniocentesis-to-delivery interval in patients with preterm labor

Figure 4

Figure 4a. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on gestational age at delivery in patients with preterm labor. Figure 4b. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on the amniocentesis-to-delivery interval in patients with preterm labor

Figure 5

Figure 5a. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on gestational age at delivery, among patients with preterm labor without intra-amniotic infection/inflammation. Figure 5b. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on the amniocentesis-to-delivery interval of patients with preterm labor without intra-amniotic infection/inflammation.

Figure 5

Figure 5a. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on gestational age at delivery, among patients with preterm labor without intra-amniotic infection/inflammation. Figure 5b. The effect of an elevated amniotic fluid thrombin-antithrombin III complexes concentration on the amniocentesis-to-delivery interval of patients with preterm labor without intra-amniotic infection/inflammation.