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, 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) vs. 2.2% (5/231); p<0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of spontaneous preterm delivery <34 weeks of gestation [70.8% (17/24) vs. 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) vs. 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 spontaneous preterm delivery (<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 spontaneous preterm delivery.

Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance

“…It is noteworthy that the frequency of acute chorioamnionitis in patients who delivered between 21 to 24 weeks of gestation was 94.4% (17/18) 2 . This is consistent with extensive studies subsequently reported by our group 17, 18 and others 19, 20 , and emphasizes the importance of acute inflammation in early preterm deliveries and midtrimester spontaneous abortions.…”

Chorioamniotic membrane senescence: a signal for parturition?

“…81 Other alarmins including IL-1a, heat shock protein 70, and calcium-binding protein B have been reported to have similar effects in inducing labor. 22 Prevalence and clinical significance of sterile inflammation has been reported recently by Romero et al 23,82,83 in multiple pregnancy-associated conditions. We postulate that inflammatory responses seen at term labor likely result from fetal cell senescence, signaling readiness for parturition.…”

Clinical chorioamnionitis at term III: how well do clinical criteria perform in the identification of proven intra-amniotic infection?

“…Most work in clinical chorioamnionitis has been based on a case definition that relies heavily on clinical signs. The shortcomings of such an approach have become clear, now that sterile inflammation has emerged as an important entity for patients at term (137) as well as for those in preterm labor (83, 86), those with preterm prelabor rupture of the membranes (84), or those with an asymptomatic sonographic short cervix (85). Non-microbial-associated inflammation appears to account for a sizable segment of patients with clinical chorioamnionitis at term (69, 80).…”