Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance

Abstract

Objective: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix.

Methods: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations.

Results: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD <34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47-98) days, (p < 0.0001)].

Conclusion: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD.

Keywords: Broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry; cervical length; infection; pregnancy; premature birth; prematurity; preterm delivery; ureaplasma urealyticim.

Figure 1

Kaplan-Meier survival curves of amniocentesis-to-delivery interval (days) among asymptomatic patients diagnosed with a CL ≤25 mm, according to the presence of microbial-associated or sterile intra-amniotic inflammation. Patients in whom labor was induced were censored and are represented by crosses. The amniocentesis-to-delivery interval among women with sterile intra-amniotic inflammation was significantly shorter than that of: 1) women without intra-amniotic inflammation; and 2) women with MIAC [median 35, (IQR: 10 – 70) vs. median 71, (IQR: 47 – 98) days, and median 79, (IQR: 51 – 99) days (p<0.001 and p=0.02), respectively]. There was no significant difference in the amniocentesis-to-delivery interval between patients with sterile intra-amniotic inflammation and those with microbial-associated intra-amniotic inflammation (p>5).