Amniotic fluid angiopoietin-2 in term and preterm parturition, and intra-amniotic infection/inflammation

Objective: Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design: This cross-sectional study included 486 patients in the following groups: 1) women in the mid-trimester of pregnancy (14-18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n = 52); 2) normal pregnant women at term with (n = 48) and without (n = 45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n = 152); b) PTL without IAI who delivered preterm (<37 weeks gestation; n = 107); and c) PTL with IAI (n = 82). Ang-2 concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analysis. Results: 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P < 0.001); 3) among patients with PTL, the median AF Ang-2 concentration was significantly higher in patients with IAI than in those without IAI (4031.3 pg/mL vs. 2599.4 pg/mL; P < 0.001) and those with PTL without IAI who delivered at term (4031.3 pg/mL vs. 2707.3 pg/mL; P < 0.001); and 4) no significant differences were observed in the median AF Ang-2 concentration between patients with spontaneous labor at term and those at term not in labor (1722.9 pg/mL vs. 1877.4 pg/mL; P = 0.6). Conclusions: 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation.