Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes

Abstract

Problem Inflammation and infection play a major role in preterm birth. The purpose of this study was to: 1) determine the prevalence and clinical significance of sterile intra-amniotic inflammation; and 2) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis-to-delivery in patients with sterile intra-amniotic inflammation. Method of Study AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). Results 1) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) vs. 11% (15/135); (p=0.005)]; 2) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages, had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation; and 3) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥ 8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (p=0.02). Conclusions 1) sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation; and 2) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.

Damage-Associated Molecular Pattern and Fetal Membrane Vascular Injury and Collagen Disorganization in Lipopolysaccharide-Induced Intra-amniotic Inflammation in Fetal Sheep

“…19 Although the association of increased amniotic fluid HMGB1 with preterm delivery is strong, the source of HMGB1 is not known in cases of IA inflammation. 27 The amniotic fluid concentrations of other DAMPs, soluble RAGE, were increased in patients with clinical chorioamnionitis at term, and HSP70 concentrations were increased in patients with histological chorioamnionitis. 23,28 We use preterm sheep given IA injections of proinflammatory agonists to cause chorioamnionitis and multiple fetal organ injury responses similar to those reported in humans.…”

Myometrial cytokines and their role in the onset of labour

“…It is important to note that sterile inflammation (defined as an inflammatory process without the presence of microorganisms) has also been associated to PTL and is more common in PTL with intact membranes than microbial-associated inflammation (Romero et al 2014b). The aetiology of sterile intra-amniotic inflammation is unknown; however, the inflammation is understood to result from activation of the innate immune system by endogenous danger signals, derived from necrosis or cellular stress, termed damage-associated molecular pattern molecules, or alarmins (Gomez-Lopez et al 2016).…”

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta

“…Intrauterine infection or chorionamnionitis are responsible for up to 40% of all PTD cases worldwide [3-7]. Important components of the pathophysiology of PTD, such as infection and/or inflammation, have been shown to influence the expression of selected ATP-binding cassette (ABC) transporters [8].…”