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Research Letter| Volume 213, ISSUE 3, P435-436, September 2015

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Detection of intraamniotic inflammation in fresh and processed amniotic fluid samples with the interleukin-6 point of care test

      Objective

      Preterm prelabor rupture of membranes (PPROM) is responsible for approximately one-third of all preterm deliveries.
      • Romero R.
      • Dey S.K.
      • Fisher S.J.
      Preterm labor: one syndrome, many causes.
      The most common complication associated with PPROM is intraamniotic inflammation (IAI), either infection related or sterile.
      • Romero R.
      • Miranda J.
      • Chaemsaithong P.
      • et al.
      Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes.
      Among the different potential markers for IAI identification, a traditional amniotic fluid marker, interleukin (IL)-6, appears to be the optimal choice. The availability of the point of care (POC) IL-6 test is very important from a clinical prospective.
      • Kacerovsky M.
      • Musilova I.
      • Hornychova H.
      • et al.
      Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes.
      • Chaemsaithong P.
      • Romero R.
      • Korzeniewski S.J.
      • et al.
      A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10.
      A recent study in which IL-6 was measured by the POC test in the processed amniotic fluid samples from a biobank (a centrifuged sample that underwent a frozen-thawed cycle) suggested a cut-off amniotic fluid IL-6 of 745 pg/mL for the detection of IAI in PPROM.
      • Chaemsaithong P.
      • Romero R.
      • Korzeniewski S.J.
      • et al.
      A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection.
      Clinicians would prefer to use fresh, noncentrifuged amniotic fluid than processed samples for the IL-6 POC test. However, there is a lack of information regarding the comparison between the amniotic fluid IL-6 concentrations measured by the POC test in the fresh and processed samples. The aim of this study was to test whether the amniotic fluid IL-6 POC cut-off of 745 pg/mL could be used for the identification of IAI in fresh, noncentrifuged amniotic fluid from PPROM cases.

      Study Design

      From January 2014 through February 2015, a prospective study was conducted on pregnant women at the gestational ages of 24+0 or 36+6 weeks who were admitted to the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Czech Republic. Pregnant women with singleton pregnancies complicated by PPROM and with a maternal age ≥18 years were invited to participate in the study. In total, 98 women with PPROM were included in the study. Ultrasound-guided transabdominal amniocentesis was performed at admission before the administration of antibiotics, corticosteroids, and tocolytics. Amniotic fluid IL-6 was assessed in fresh, noncentrifuged amniotic fluid. The remaining amniotic fluid was immediately centrifuged for 10 minutes at 2000g at 4°C to remove cells and debris, and then the samples were divided into aliquots and stored at –80°C until analysis (April 2015). IL-6 was assessed with a Milenia QuickLine IL-6 lateral flow immunoassay using a Milenia POCScan reader (Millenia Biotec GmbH, Giessen, Germany) in the fresh and processed amniotic fluid samples. The measurement range was 50–10,000 pg/mL. A correlation between the amniotic fluid IL-6 concentrations in the fresh and processed samples was assessed using Spearman correlation coefficients. A Bland-Altman plot was constructed. A value of P < .05 was considered significant.

      Results

      A strong correlation between the amniotic IL-6 concentrations in the fresh and processed samples was found (Spearman rho 0.86; P < .0001) (Figure). In all, 27 women had IL-6 >745 pg/mL in the processed samples; 26 of these women had IL-6 >745 pg/mL in the fresh samples as well. None of the women with IL-6 ≤745 pg/mL in the processed samples had IL-6 >745 pg/mL in the fresh samples. The amniotic fluid IL-6 cut-off of 745 pg/mL in the fresh samples had a sensitivity of 96%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99% to identify IAI.
      Figure thumbnail gr1
      FigureAmniotic fluid interleukin-6 concentrations
      A, Correlation between amniotic fluid interleukin (IL)-6 concentrations in processed and fresh samples. B, Bland-Altman plot is direct comparison between amniotic fluid IL-6 measurement in processed and fresh samples
      Kacerovsky. Intraamniotic inflammation in amniotic fluid with the IL-6 POC test. Am J Obstet Gynecol 2015.

      Conclusion

      An IL-6 concentration of 745 pg/mL measured by the POC test could be used as the cutoff to identify IAI in cases in which fresh, noncentrifuged amniotic fluid is used. This approach could be very helpful in the clinical setting because it provides a unique opportunity to initiate very early treatment of IAI in pregnancies complicated by PPROM.

      References

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        • Dey S.K.
        • Fisher S.J.
        Preterm labor: one syndrome, many causes.
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        • Romero R.
        • Miranda J.
        • Chaemsaithong P.
        • et al.
        Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes.
        J Matern Fetal Neonatal Med. 2014; 29: 1-16
        • Kacerovsky M.
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        Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes.
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        • et al.
        A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10.
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        A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection.
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