The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?

Abstract

OBJECTIVE The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. METHODS Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). RESULTS 1) Intra-amniotic inflammation was present in 12.1% (16/132); 2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and 3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < .05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. CONCLUSION Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes.

The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6

“…Moreover, even with negative cultures, an elevated IL-6 concentration was associated with a short amniocentesis-to-delivery interval and a significantly higher rate of neonatal adverse outcomes [200]. Subsequently, the value of this cut-off as a marker of intra-amniotic inflammation has been confirmed by others [71,162,252]. …”

“…Subsequently, other methods were used, including the detection of microbial products, such as endotoxin [25,140–142], the acridine orange stain [143], leukocyte esterase [138,139,144] and gas liquid chromatography of microbial metabolites [145,146]. Immunoassays have also been used for the detection of proteins produced in response to microorganisms or during the course of inflammation, such as interleukin 6 (IL-6) [32,127,137,147–162], other cytokines and chemokines [26,27,77,78,163–188], and rapid tests for matrix metalloproteinase-8 (MMP-8) [160,162,189–194]. …”

A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10

“…Subsequently, the AF IL-6 cut-off of 2.6 ng/ml was proposed to diagnose intra-amniotic inflammation that is associated with a shorter amniocentesis-to-delivery interval, and also with significantly higher risks of adverse neonatal outcomes, even among patients with a negative AF culture [57]. The cut-off of 2.6 ng/ml has been extensively used in the literature by other investigators to identify those at risk for adverse pregnancy outcome in patients with preterm labor and intact membranes [129,171-173]. …”

Applying Precision Public Health to Prevent Preterm Birth

“…Animal models and clinical studies demonstrate a causal relationship between infection and PTB, while the immune-pathophysiological pathways responsible for triggering preterm labor in response to infection have been studied, replicated and characterized in a variety of models (86–88). The most common pathway via which bacteria trigger PTB is the so-called ascending infection route: microorganisms residing in cervico-vaginal fluid in pregnancy ascend through the cervical barrier and colonize the fetal membranes, passing through in some cases to colonize the amniotic fluid and from there infect the fetus (86, 89). The severity of the infection and the ensuing inflammatory response determines, to a large part, the obstetric and neonatal outcomes, including the timing and onset of preterm labor, the effectiveness of tocolytic therapy, and the risk of serious neonatal morbidities.…”