Roberto Romero1,2,3, Jezid Miranda1,4, Tinnakorn Chaiworapongsa1,4, Piya Chaemsaithong1,4, Francesca Gotsch1,5, Zhong Dong1,4, Ahmed I Ahmed1,4, Bo Hyun Yoon6, Sonia S Hassan1,4, Chong J Kim1,7, Steven J Korzeniewski1,3,4, Lami Yeo1,4, Yeon Mee Kim1,8. 1. a Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH , Bethesda, MD and Detroit , MI , USA. 2. b Department of Obstetrics and Gynecology , University of Michigan , Ann Arbor , MI , USA. 3. c Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA. 4. d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA. 5. e Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria , Verona , Italy. 6. f Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Korea. 7. g Department of Pathology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea , and. 8. h Department of Pathology , College of Medicine Inje University, Haeundae Paik Hospital , Busan , Democratic People's Republic of Korea.
Abstract
OBJECTIVE: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. METHODS: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations. RESULTS: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD <34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47-98) days, (p < 0.0001)]. CONCLUSION: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD.
OBJECTIVE: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. METHODS: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AFIL-6 concentrations. RESULTS: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AFIL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD <34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47-98) days, (p < 0.0001)]. CONCLUSION: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD.
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