Kyung Joon Oh1, JoonHo Lee2, Roberto Romero3, Hyun Soo Park4, Joon-Seok Hong5, Bo Hyun Yoon6. 1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, South Korea. 2. Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Yonsei University Health System, South Korea. 3. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, the Detroit Medical Center, Detroit, MI; Department of Obstetrics and Gynecology, Florida International University, Miami, FL. 4. Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang, South Korea. 5. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, South Korea; Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, South Korea. 6. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, South Korea. Electronic address: yoonbh@snu.ac.kr.
Abstract
BACKGROUND: Microbial invasion of the amniotic cavity, a clinical condition present in approximately 50% of patients with preterm prelabor rupture of membranes, is often associated with intraamniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a transcervical amniotic fluid collector, the device that allows the collection of fluid noninvasively from the cervical canal when membrane rupture occurs. OBJECTIVE: This study was designed to determine whether rapid analysis of an interleukin-8 concentration in fluid obtained noninvasively by the transcervical amniotic fluid collector can be used to assess the risk of intraamniotic inflammation. We also compared the diagnostic performance of this point-of-care test for interleukin-8 in transcervically obtained fluid to that of a white blood cell count determined in amniotic fluid retrieved by transabdominal amniocentesis. STUDY DESIGN: This prospective cohort study was conducted between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and the use of a transcervical amniotic fluid collector within 24 hours of amniocentesis in patients with a singleton pregnancy and preterm prelabor rupture of the membranes (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; a white blood cell count was also measured in amniotic fluid. Intraamniotic infection was diagnosed when microorganisms were identified by the cultivation of amniotic fluid. Intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL) assayed by enzyme-linked immunosorbent assay. Interleukin-8 in cervical fluid obtained by the collector was measured by the point-of-care test that used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the 2 different tests were calculated. RESULTS: First, interleukin-8 concentration ≥9.5 ng/mL in cervical fluid, determined by the point-of-care test, was at the knee of the receiver operating characteristic curve analysis and had a sensitivity of 98% (56/57; 95% confidence interval, 91-99.96%), specificity of 74% (40/54; 95% confidence interval, 60-85%), positive predictive value of 80% (56/70; 95% confidence interval, 72-86%), negative predictive value of 98% (40/41; 95% confidence interval, 85-99.6%), positive likelihood ratio of 3.79 (95% confidence interval, 2.41-5.96), and negative likelihood ratio of 0.02 (95% confidence interval, 0.003-0.17) in the identification of intraamniotic inflammation; a concentration of matrix metalloproteinase-8 >23 ng/mL by enzyme-linked immunosorbent assay had a prevalence of 51% (57/111). Second, a cervical fluid interleukin-8 concentration ≥9.5 ng/mL had significantly higher sensitivity than a transabdominally obtained amniotic fluid white blood cell count (≥19 cells/mm3) in the identification of intraamniotic inflammation (sensitivity: 98% [95% confidence interval, 91-99.96%] vs 84% [95% confidence interval, 72-93%]; P<.05; specificity: 74% [95% confidence interval, 60-85%] vs 76% [95% confidence interval, 62-87%); positive and negative predictive values: 80% [95% confidence interval, 72-86%] and 98% [95% confidence interval, 85-99.6%] vs 79% [95% confidence interval, 69-86%] and 82% [95% confidence interval, 71-89%]) and in the identification of intraamniotic inflammation/infection (gold standard: positive culture for bacteria or a matrix metalloproteinase-8 >23 ng/mL; sensitivity: 91% [95% confidence interval, 82-97%] vs 75% [95% confidence interval, 63-85%]; P<.05). CONCLUSION: The point-of-care test was predictive of intraamniotic inflammation, based on the determination of interleukin-8 in fluid retrieved by a transcervical amniotic fluid collector. Therefore, the analysis of cervically obtained fluid by such point-of-care test may be used to noninvasively monitor intraamniotic inflammation in patients with preterm prelabor rupture of membranes.
BACKGROUND: Microbial invasion of the amniotic cavity, a clinical condition present in approximately 50% of patients with preterm prelabor rupture of membranes, is often associated with intraamniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a transcervical amniotic fluid collector, the device that allows the collection of fluid noninvasively from the cervical canal when membrane rupture occurs. OBJECTIVE: This study was designed to determine whether rapid analysis of an interleukin-8 concentration in fluid obtained noninvasively by the transcervical amniotic fluid collector can be used to assess the risk of intraamniotic inflammation. We also compared the diagnostic performance of this point-of-care test for interleukin-8 in transcervically obtained fluid to that of a white blood cell count determined in amniotic fluid retrieved by transabdominal amniocentesis. STUDY DESIGN: This prospective cohort study was conducted between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and the use of a transcervical amniotic fluid collector within 24 hours of amniocentesis in patients with a singleton pregnancy and preterm prelabor rupture of the membranes (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; a white blood cell count was also measured in amniotic fluid. Intraamniotic infection was diagnosed when microorganisms were identified by the cultivation of amniotic fluid. Intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL) assayed by enzyme-linked immunosorbent assay. Interleukin-8 in cervical fluid obtained by the collector was measured by the point-of-care test that used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the 2 different tests were calculated. RESULTS: First, interleukin-8 concentration ≥9.5 ng/mL in cervical fluid, determined by the point-of-care test, was at the knee of the receiver operating characteristic curve analysis and had a sensitivity of 98% (56/57; 95% confidence interval, 91-99.96%), specificity of 74% (40/54; 95% confidence interval, 60-85%), positive predictive value of 80% (56/70; 95% confidence interval, 72-86%), negative predictive value of 98% (40/41; 95% confidence interval, 85-99.6%), positive likelihood ratio of 3.79 (95% confidence interval, 2.41-5.96), and negative likelihood ratio of 0.02 (95% confidence interval, 0.003-0.17) in the identification of intraamniotic inflammation; a concentration of matrix metalloproteinase-8 >23 ng/mL by enzyme-linked immunosorbent assay had a prevalence of 51% (57/111). Second, a cervical fluid interleukin-8 concentration ≥9.5 ng/mL had significantly higher sensitivity than a transabdominally obtained amniotic fluid white blood cell count (≥19 cells/mm3) in the identification of intraamniotic inflammation (sensitivity: 98% [95% confidence interval, 91-99.96%] vs 84% [95% confidence interval, 72-93%]; P<.05; specificity: 74% [95% confidence interval, 60-85%] vs 76% [95% confidence interval, 62-87%); positive and negative predictive values: 80% [95% confidence interval, 72-86%] and 98% [95% confidence interval, 85-99.6%] vs 79% [95% confidence interval, 69-86%] and 82% [95% confidence interval, 71-89%]) and in the identification of intraamniotic inflammation/infection (gold standard: positive culture for bacteria or a matrix metalloproteinase-8 >23 ng/mL; sensitivity: 91% [95% confidence interval, 82-97%] vs 75% [95% confidence interval, 63-85%]; P<.05). CONCLUSION: The point-of-care test was predictive of intraamniotic inflammation, based on the determination of interleukin-8 in fluid retrieved by a transcervical amniotic fluid collector. Therefore, the analysis of cervically obtained fluid by such point-of-care test may be used to noninvasively monitor intraamniotic inflammation in patients with preterm prelabor rupture of membranes.
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