Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes

Abstract

OBJECTIVE: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI and calprotectin in amniotic fluid were determined by specific and sensitive immunoassays. Placentae of patients in both preterm labor with intact membranes and preterm PROM groups who delivered within 72 h of amniocentesis were examined. Non-parametric statistics, receiver-operating characteristic (ROC) curves and Cox regression models were used for analysis. A p value of < 0.05 was considered statistically significant. RESULTS: Intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin in both women with preterm labor and intact membranes, and women with preterm PROM. Preterm PROM was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Preterm parturition was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin, while parturition at term was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3. Among patients with preterm labor and intact membranes, elevation of amniotic fluid HNP 1-3, BPI and calprotectin concentrations was associated with intra-amniotic inflammation, histological chorioamnionitis and a shorter interval to delivery. CONCLUSION: MIAC, preterm parturition and preterm PROM are associated with increased amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Moreover, elevated amniotic fluid concentrations of BPI, immunoreactive HNP 1-3 and calprotectin are associated with intra-amniotic inflammation, histological chorioamnionitis and shorter amniocentesis-to-delivery interval in patients presenting with preterm labor with intact membranes.