Antibiotic treatment reduces the intensity of intraamniotic inflammation in pregnancies with idiopathic vaginal bleeding in the second trimester of pregnancy

Abstract

Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intra-amniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intra-amniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intra-amniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intra-amniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin (IL)-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma spp. DNA in amniotic fluid. This retrospective cohort study included singleton gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission and those with intra-amniotic inflammation who received a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. Follow-up amniocentesis was performed in the subset of patients unless abortion or delivery occurred earlier. Concentrations of IL-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intra-amniotic inflammation was defined as an IL-6 concentration ≥3,000 pg/mL in the amniotic fluid samples. Thirty-six patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intra-amniotic inflammation (n=25) were treated using a combination of antibiotics. The patients without intra-amniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intra-amniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the IL-6 concentration in the amniotic fluid at follow-up amniocentesis compared to that at the initial amniocentesis in patients with intra-amniotic inflammation (median [interquartile range]: 3,457 pg/mL [2,493-13,203] vs. 19812 pg/mL [11,973-34,518]; p=0.0001). Amniotic fluid samples with Ureaplasma spp. DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (median [IQR]: 1.5x105 copies DNA/mL [1.3x105-1.7x105] vs. 8.0x107 copies DNA/mL [6.7x106-1.6x108]; p=0.02). Antibiotic therapy was associated with reduced intra-amniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intra-amniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma spp. DNA in the amniotic fluid.