Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes

Am J Reprod Immunol. 2014 Nov;72(5):458-74. doi: 10.1111/aji.12296. Epub 2014 Jul 31.

Abstract

Problem: Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) 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: (i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) 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 (iii) 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).

Conclusion: (i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.

Keywords: Alarmins; danger signal; high mobility group box-1; polymerase chain reaction with electrospray ionization mass spectrometry; pregnancy; preterm delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Amniotic Fluid / immunology*
  • Amniotic Fluid / metabolism
  • Female
  • HMGB1 Protein / immunology*
  • HMGB1 Protein / metabolism
  • Humans
  • Inflammation / epidemiology
  • Inflammation / immunology
  • Inflammation / metabolism
  • Obstetric Labor, Premature / epidemiology*
  • Obstetric Labor, Premature / immunology*
  • Obstetric Labor, Premature / metabolism
  • Placenta / immunology*
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Complications / immunology*
  • Pregnancy Complications / metabolism
  • Prevalence

Substances

  • HMGB1 Protein
  • HMGB1 protein, human