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Original Article

Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance

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Pages 1343-1359 | Received 21 Jul 2014, Accepted 10 Aug 2014, Published online: 24 Sep 2014

References

  • Romero R, Yeo L, Miranda J, et al. A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix. J Perinat Med 2013;41:27–44
  • Andersen HF, Nugent CE, Wanty SD, et al. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol 1990;163:859–67
  • Andersen HF. Transvaginal and transabdominal ultrasonography of the uterine cervix during pregnancy. J Clin Ultrasound 1991;19:77–83
  • Iams JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med 1996;334:567–72
  • Heath VC, Southall TR, Souka AP, et al. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol 1998;12:312–17
  • Watson WJ, Stevens D, Welter S, et al. Observations on the sonographic measurement of cervical length and the risk of premature birth. J Matern Fetal Med 1999;8:17–9
  • Berghella V, Daly SF, Tolosa JE, et al. Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity? Am J Obstet Gynecol 1999;181:809–15
  • Hassan SS, Romero R, Berry SM, et al. Patients with an ultrasonographic cervical length < or =15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000;182:1458–67
  • Cook CM, Ellwood DA. The cervix as a predictor of preterm delivery in ‘at-risk' women. Ultrasound Obstet Gynecol 2000;15:109–13
  • To MS, Skentou C, Liao AW, et al. Cervical length and funneling at 23 weeks of gestation in the prediction of spontaneous early preterm delivery. Ultrasound Obstet Gynecol 2001;18:200–3
  • Owen J, Yost N, Berghella V, et al. Can shortened midtrimester cervical length predict very early spontaneous preterm birth? Am J Obstet Gynecol 2004;191:298–303
  • Kushnir O, Vigil DA, Izquierdo L, et al. Vaginal ultrasonographic assessment of cervical length changes during normal pregnancy. Am J Obstet Gynecol 1990;162:991–3
  • Okitsu O, Mimura T, Nakayama T, et al. Early prediction of preterm delivery by transvaginal ultrasonography. Ultrasound Obstet Gynecol 1992;2:402–9
  • Iams JD, Paraskos J, Landon MB, et al. Cervical sonography in preterm labor. Obstet Gynecol 1994;84:40–6
  • Tongsong T, Kamprapanth P, Srisomboon J, et al. Single transvaginal sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery. Obstet Gynecol 1995;86:184–7
  • Hasegawa I, Tanaka K, Takahashi K, et al. Transvaginal ultrasonographic cervical assessment for the prediction of preterm delivery. J Matern Fetal Med 1996;5:305–9
  • Tongsong T, Kamprapanth P, Pitaksakorn J. Cervical length in normal pregnancy as measured by transvaginal sonography. Int J Gynaecol Obstet 1997;58:313–15
  • Rozenberg P, Goffinet F, Malagrida L, et al. Evaluating the risk of preterm delivery: a comparison of fetal fibronectin and transvaginal ultrasonographic measurement of cervical length. Am J Obstet Gynecol 1997;176:196–9
  • Guzman ER, Mellon C, Vintzileos AM, et al. Longitudinal assessment of endocervical canal length between 15 and 24 weeks’ gestation in women at risk for pregnancy loss or preterm birth. Obstet Gynecol 1998;92:31–7
  • Taipale P, Hiilesmaa V. Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the risk of preterm delivery. Obstet Gynecol 1998;92:902–7
  • Goldenberg RL, Iams JD, Mercer BM, et al. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network. Am J Public Health 1998;88:233–8
  • Arinami Y, Hasegawa I, Takakuwa K, et al. Prediction of preterm delivery by combined use of simple clinical tests. J Matern Fetal Med 1999;8:70–3
  • Andrews WW, Copper R, Hauth JC, et al. Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery. Obstet Gynecol 2000;95:222–6
  • Hibbard JU, Tart M, Moawad AH. Cervical length at 16–22 weeks' gestation and risk for preterm delivery. Obstet Gynecol 2000;96:972–8
  • Owen J, Yost N, Berghella V, et al. Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth. JAMA 2001;286:1340–8
  • Rozenberg P, Gillet A, Ville Y. Transvaginal sonographic examination of the cervix in asymptomatic pregnant women: review of the literature. Ultrasound Obstet Gynecol 2002;19:302–11
  • Gomez R, Romero R, Medina L, et al. Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes. Am J Obstet Gynecol 2005;192:350–9
  • Durnwald CP, Walker H, Lundy JC, et al. Rates of recurrent preterm birth by obstetrical history and cervical length. Am J Obstet Gynecol 2005;193:1170–4
  • Matijevic R, Grgic O, Vasilj O. Is sonographic assessment of cervical length better than digital examination in screening for preterm delivery in a low-risk population? Acta Obstet Gynecol Scand 2006;85:1342–7
  • Silva SV, Damiao R, Fonseca EB, et al. Reference ranges for cervical length by transvaginal scan in singleton pregnancies. J Matern Fetal Neonatal Med 2010;23:379–82
  • Asnafi N, Basirat Z, Hajian-Tilaki K, et al. Assessment of cervical length by transvaginal ultrasonography to predict preterm delivery in twin pregnancy. J Matern Fetal Neonatal Med 2013;26:1435–8
  • Raiche E, Ouellet A, Berthiaume M, et al. Short and inflamed cervix predicts spontaneous preterm birth (COLIBRI study). J Matern Fetal Neonatal Med 2014;27:1015–19
  • Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011;38:18–31
  • Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012;206:124 e1–19
  • Romero R, Yeo L, Chaemsaithong P, et al. Progesterone to prevent spontaneous preterm birth. Semin Fetal Neonatal Med 2014;19:15–26
  • Berghella V, Mackeen AD. Cervical length screening with ultrasound-indicated cerclage compared with history-indicated cerclage for prevention of preterm birth: a meta-analysis. Obstet Gynecol 2011;118:148–55
  • Berghella V, Rafael TJ, Szychowski JM, et al. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol 2011;117:663–71
  • Conde-Agudelo A, Romero R, Nicolaides K, et al. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol 2013;208:42 e1–18
  • Dharan VB, Ludmir J. Alternative treatment for a short cervix: the cervical pessary. Semin Perinatol 2009;33:338–42
  • Goya M, Pratcorona L, Merced C, et al. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet 2012;379:1800–6
  • Alfirevic Z, Owen J, Carreras Moratonas E, et al. Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix. Ultrasound Obstet Gynecol 2013;41:146–51
  • Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical pessary for preventing preterm birth. Cochrane Database Syst Rev 2013;5:CD007873
  • Hui SY, Chor CM, Lau TK, et al. Cerclage pessary for preventing preterm birth in women with a singleton pregnancy and a short cervix at 20 to 24 weeks: a randomized controlled trial. Am J Perinatol 2013;30:283–8
  • Romero R, Espinoza J, Erez O, et al. The role of cervical cerclage in obstetric practice: can the patient who could benefit from this procedure be identified? Am J Obstet Gynecol 2006;194:1–9
  • Moinian M, Andersch B. Does cervix conization increase the risk of complications in subsequent pregnancies? Acta Obstet Gynecol Scand 1982;61:101–3
  • Kristensen J, Langhoff-Roos J, Wittrup M, et al. Cervical conization and preterm delivery/low birth weight. A systematic review of the literature. Acta Obstet Gynecol Scand 1993;72:640–4
  • Blomfield PI, Buxton J, Dunn J, et al. Pregnancy outcome after large loop excision of the cervical transformation zone. Am J Obstet Gynecol 1993;169:620–5
  • Raio L, Ghezzi F, Di Naro E, et al. Duration of pregnancy after carbon dioxide laser conization of the cervix: influence of cone height. Obstet Gynecol 1997;90:978–82
  • Berghella V, Pereira L, Gariepy A, et al. Prior cone biopsy: prediction of preterm birth by cervical ultrasound. Am J Obstet Gynecol 2004;191:1393–7
  • Bruinsma FJ, Quinn MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG 2011;118:1031–41
  • Cukier J, Batzofin JH, Conner JS, et al. Genital tract reconstruction in a patient with congenital absence of the vagina and hypoplasia of the cervix. Obstet Gynecol 1986;68:32S–6S
  • Lee CL, Wang CJ, Swei LD, et al. Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemivagina. Hum Reprod 1999;14:1741–3
  • Carlomagno G, Di Blasi A, Monica MD. Congenital scoliosis associated with agenesis of the uterine cervix. Case report. BMC Womens Health 2004;4:4
  • Kriplani A, Kachhawa G, Awasthi D, et al. Laparoscopic-assisted uterovaginal anastomosis in congenital atresia of uterine cervix: follow-up study. J Minim Invasive Gynecol 2012;19:477–84
  • Goldstein DP. Incompetent cervix in offspring exposed to diethylstilbestrol in utero. Obstet Gynecol 1978;52:73S–5S
  • Singer MS, Hochman M. Incompetent cervix in a hormone-exposed offspring. Obstet Gynecol 1978;51:625–6
  • Mangan CE, Borow L, Burtnett-Rubin MM, et al. Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings. Obstet Gynecol 1982;59:315–19
  • Ludmir J, Landon MB, Gabbe SG, et al. Management of the diethylstilbestrol-exposed pregnant patient: a prospective study. Am J Obstet Gynecol 1987;157:665–9
  • Michaels WH, Thompson HO, Schreiber FR, et al. Ultrasound surveillance of the cervix during pregnancy in diethylstilbestrol-exposed offspring. Obstet Gynecol 1989;73:230–9
  • Salle B, Sergeant P, Awada A, et al. Transvaginal ultrasound studies of vascular and morphological changes in uteri exposed to diethylstilbestrol in utero. Hum Reprod 1996;11:2531–6
  • Goldberg JM, Falcone T. Effect of diethylstilbestrol on reproductive function. Fertil Steril 1999;72:1–7
  • Ploeckinger B, Ulm MR, Chalubinski K. Ehlers-Danlos syndrome type II in pregnancy. Am J Perinatol 1997;14:99–101
  • Romero R, Gonzalez R, Sepulveda W, et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol 1992;167:1086–91
  • Mays JK, Figueroa R, Shah J, et al. Amniocentesis for selection before rescue cerclage. Obstet Gynecol 2000;95:652–5
  • Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med 2006;34:13–9
  • Kiefer DG, Keeler SM, Rust OA, et al. Is midtrimester short cervix a sign of intraamniotic inflammation? Am J Obstet Gynecol 2009;200:374 e1–5
  • Vaisbuch E, Hassan SS, Mazaki-Tovi S, et al. Patients with an asymptomatic short cervix (<or=15 mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling. Am J Obstet Gynecol 2010;202:433 e1–8
  • Mitani M, Matsuda Y, Ono E, et al. Prognosis in cervical insufficiency at less than 32 weeks of gestation. Eur J Obstet Gynecol Reprod Biol 2006;125:34–7
  • Lee SE, Romero R, Park CW, et al. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol 2008;198:633 e1–8
  • ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. Obstet Gynecol 2014;123:372–9
  • Hegele-Hartung C, Chwalisz K, Beier HM, et al. Ripening of the uterine cervix of the guinea-pig after treatment with the progesterone antagonist onapristone (ZK 98.299): an electron microscopic study. Hum Reprod 1989;4:369–77
  • Liapis A, Hassiakos D, Sarantakou A, et al. The role of steroid hormones in cervical ripening. Clin Exp Obstet Gynecol 1993;20:163–6
  • Chwalisz K. The use of progesterone antagonists for cervical ripening and as an adjunct to labour and delivery. Hum Reprod 1994;9:131–61
  • Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol 1998;92:804–9
  • Fidel PI, Jr Romero R, Maymon E, et al. Bacteria-induced or bacterial product-induced preterm parturition in mice and rabbits is preceded by a significant fall in serum progesterone concentrations. J Matern Fetal Med 1998;7:222–6
  • Stenlund PM, Ekman G, Aedo AR, et al. Induction of labor with mifepristone–a randomized, double-blind study versus placebo. Acta Obstet Gynecol Scand 1999;78:793–8
  • Straach KJ, Shelton JM, Richardson JA, et al. Regulation of hyaluronan expression during cervical ripening. Glycobiology 2005;15:55–65
  • Word RA, Li XH, Hnat M, et al. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med 2007;25:69–79
  • Anderson J, Brown N, Mahendroo MS, et al. Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening. Endocrinology 2006;147:130–40
  • Timmons BC, Mahendroo MS. Timing of neutrophil activation and expression of proinflammatory markers do not support a role for neutrophils in cervical ripening in the mouse. Biol Reprod 2006;74:236–45
  • Hassan SS, Romero R, Haddad R, et al. The transcriptome of the uterine cervix before and after spontaneous term parturition. Am J Obstet Gynecol 2006;195:778–86
  • Hassan SS, Romero R, Tarca AL, et al. Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition. Am J Obstet Gynecol 2007;197:250 e1–7
  • Hassan SS, Romero R, Tarca AL, et al. The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: identification of novel molecular functions involved in this process. J Matern Fetal Neonatal Med 2009;22:1183–93
  • Timmons B, Akins M, Mahendroo M. Cervical remodeling during pregnancy and parturition. Trends Endocrinol Metab 2010;21:353–61
  • Hassan SS, Romero R, Tarca AL, et al. The molecular basis for sonographic cervical shortening at term: identification of differentially expressed genes and the epithelial-mesenchymal transition as a function of cervical length. Am J Obstet Gynecol 2010;203:472 e1–14
  • Hassan SS, Romero R, Pineles B, et al. MicroRNA expression profiling of the human uterine cervix after term labor and delivery. Am J Obstet Gynecol 2010;202:80 e1–8
  • Mahendroo M. Cervical remodeling in term and preterm birth: insights from an animal model. Reproduction 2012;143:429–38
  • Timmons BC, Reese J, Socrate S, et al. Prostaglandins are essential for cervical ripening in LPS-mediated preterm birth but not term or antiprogestin-driven preterm ripening. Endocrinology 2014;155:287–98
  • Romero R, Yoon BH, Kenney JS, et al. Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor. Am J Reprod Immunol 1993;30:167–83
  • Romero R, Galasso M, Gomez R, et al. A comparative study of the value of amniotic fluid interleukin-6, white blood cell count and gram stain in the diagnosis of microbial invasion of the amniotic cavity in patients with spontaneous labor at term. Annual Meeting of the Society of Perinatal Obstetricians; Las Vegas, NV. 1994. p. A250
  • Greci LS, Gilson GJ, Nevils B, et al. Is amniotic fluid analysis the key to preterm labor? A model using interleukin-6 for predicting rapid delivery. Am J Obstet Gynecol 1998;179:172–8
  • Maymon E, Romero R, Chaiworapongsa T, et al. Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes. Am J Obstet Gynecol 2001;185:1149–55
  • Yoon BH, Romero R, Moon JB, et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001;185:1130–6
  • Yoon BH, Romero R, Moon JB, et al. The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibronectin. Am J Obstet Gynecol 2001;185:1137–42
  • Shim SS, Romero R, Hong JS, et al. Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2004;191:1339–45
  • Friel LA, Romero R, Edwin S, et al. The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes. J Perinat Med 2007;35:385–93
  • Lee SE, Romero R, Jung H, et al. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2007;197:294 e1–6
  • Romero R, Espinoza J, Hassan S, et al. Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation. J Perinat Med 2008;36:388–98
  • Chaiworapongsa T, Erez O, Kusanovic JP, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med 2008;21:449–61
  • Lee SE, Park IS, Romero R, et al. Amniotic fluid prostaglandin F2 increases even in sterile amniotic fluid and is an independent predictor of impending delivery in preterm premature rupture of membranes. J Matern Fetal Neonatal Med 2009;22:880–6
  • Romero R, Chaiworapongsa T, Alpay Savasan Z, et al. Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med 2011;24:1444–55
  • Romero R, Chaiworapongsa T, Savasan ZA, et al. Clinical chorioamnionitis is characterized by changes in the expression of the alarmin HMGB1 and one of its receptors, sRAGE. J Matern Fetal Neonatal Med 2012;25:558–67
  • Maymon E, Romero R, Chaiworapongsa T, et al. Value of amniotic fluid neutrophil collagenase concentrations in preterm premature rupture of membranes. Am J Obstet Gynecol 2001;185:1143–8
  • Keeler SM, Kiefer DG, Rust OA, et al. Comprehensive amniotic fluid cytokine profile evaluation in women with a short cervix: which cytokine(s) correlates best with outcome? Am J Obstet Gynecol 2009;201:276 e1–6
  • Kiefer DG, Keeler SM, Rust O, et al. Amniotic fluid inflammatory score is associated with pregnancy outcome in patients with mid trimester short cervix. Am J Obstet Gynecol 2012;206:68 e1–6
  • Ecker DJ, Sampath R, Blyn LB, et al. Rapid identification and strain-typing of respiratory pathogens for epidemic surveillance. Proc Natl Acad Sci U S A 2005;102:8012–7
  • Ecker DJ, Sampath R, Willett P, et al. The Microbial Rosetta Stone Database: a compilation of global and emerging infectious microorganisms and bioterrorist threat agents. BMC Microbiol 2005;5:19
  • Sampath R, Hofstadler SA, Blyn LB, et al. Rapid identification of emerging pathogens: coronavirus. Emerg Infect Dis 2005;11:373–9
  • Hofstadler SA, Sampath R, Blyn LB, et al. TIGER: the universal biosensor. International Journal of Mass Spectrometry 2005;242:23–41
  • Ecker JA, Massire C, Hall TA, et al. Identification of Acinetobacter species and genotyping of Acinetobacter baumannii by multilocus PCR and mass spectrometry. J Clin Microbiol 2006;44:2921–32
  • Sampath R, Hall TA, Massire C, et al. Rapid identification of emerging infectious agents using PCR and electrospray ionization mass spectrometry. Ann N Y Acad Sci 2007;1102:109–20
  • Sampath R, Russell KL, Massire C, et al. Global surveillance of emerging Influenza virus genotypes by mass spectrometry. PLoS One 2007;2:e489
  • Eshoo MW, Whitehouse CA, Zoll ST, et al. Direct broad-range detection of alphaviruses in mosquito extracts. Virology 2007;368:286–95
  • Ecker DJ, Sampath R, Massire C, et al. Ibis T5000: a universal biosensor approach for microbiology. Nat Rev Microbiol 2008;6:553–8
  • Blyn LB, Hall TA, Libby B, et al. Rapid detection and molecular serotyping of adenovirus by use of PCR followed by electrospray ionization mass spectrometry. J Clin Microbiol 2008;46:644–51
  • Hannis JC, Manalili SM, Hall TA, et al. High-resolution genotyping of Campylobacter species by use of PCR and high-throughput mass spectrometry. J Clin Microbiol 2008;46:1220–5
  • Ecker DJ, Massire C, Blyn LB, et al. Molecular Genotyping of Microbes by Multilocus PCR and Mass Spectrometry: a new Tool for Hospital Infection Control and Public Health Surveillance. In: Caugant DA, editor. Molecular epidemiology of Microorganisms, Methods in Molecular Biology: Gumana Press, a part of Springer Science + Business Media; 2009
  • Wolk DM, Blyn LB, Hall TA, et al. Pathogen profiling: rapid molecular characterization of Staphylococcus aureus by PCR/electrospray ionization-mass spectrometry and correlation with phenotype. J Clin Microbiol 2009;47:3129–37
  • Hujer KM, Hujer AM, Endimiani A, et al. Rapid determination of quinolone resistance in Acinetobacter spp. J Clin Microbiol 2009;47:1436–42
  • Ecker DJ, Sampath R, Li H, et al. New technology for rapid molecular diagnosis of bloodstream infections. Expert Rev Mol Diagn 2010;10:399–415
  • Metzgar D, Baynes D, Myers CA, et al. Initial identification and characterization of an emerging zoonotic influenza virus prior to pandemic spread. J Clin Microbiol 2010;48:4228–34
  • Deyde VM, Sampath R, Garten RJ, et al. Genomic signature-based identification of influenza A viruses using RT-PCR/electro-spray ionization mass spectrometry (ESI-MS) technology. PLoS One 2010;5:e13293
  • Eshoo MW, Crowder CD, Li H, et al. Detection and identification of Ehrlichia species in blood by use of PCR and electrospray ionization mass spectrometry. J Clin Microbiol 2010;48:472–8
  • Chen KF, Blyn L, Rothman RE, et al. Reverse transcription polymerase chain reaction and electrospray ionization mass spectrometry for identifying acute viral upper respiratory tract infections. Diagn Microbiol Infect Dis 2011;69:179–86
  • Kaleta EJ, Clark AE, Cherkaoui A, et al. Comparative analysis of PCR-electrospray ionization/mass spectrometry (MS) and MALDI-TOF/MS for the identification of bacteria and yeast from positive blood culture bottles. Clin Chem 2011;57:1057–67
  • Massire C, Ivy CA, Lovari R, et al. Simultaneous identification of mycobacterial isolates to the species level and determination of tuberculosis drug resistance by PCR followed by electrospray ionization mass spectrometry. J Clin Microbiol 2011;49:908–17
  • Gu Z, Hall TA, Frinder M, et al. Evaluation of repetitive sequence PCR and PCR-mass spectrometry for the identification of clinically relevant Candida species. Med Mycol 2012;50:259–65
  • Wolk DM, Kaleta EJ, Wysocki VH. PCR-electrospray ionization mass spectrometry: the potential to change infectious disease diagnostics in clinical and public health laboratories. J Mol Diagn 2012;14:295–304
  • Bhatia NS, Farrell JJ, Sampath R, et al. Identification of Streptococcus intermedius central nervous system infection by use of PCR and electrospray ionization mass spectrometry. J Clin Microbiol 2012;50:4160–2
  • Schuetz AN, Huard RC, Eshoo MW, et al. Identification of a novel Acinetobacter baumannii clone in a US hospital outbreak by multilocus polymerase chain reaction/electrospray-ionization mass spectrometry. Diagn Microbiol Infect Dis 2012;72:14–9
  • Metzgar D, Frinder M, Lovari R, et al. Broad-spectrum biosensor capable of detecting and identifying diverse bacterial and Candida species in blood. J Clin Microbiol 2013;51:2670–8
  • Brinkman CL, Vergidis P, Uhl JR, et al. PCR-Electrospray Ionization Mass Spectrometry for Direct Detection of Pathogens and Antimicrobial Resistance from Heart Valves in Patients with Infective Endocarditis. J Clin Microbiol 2013;51:2040–6
  • Farrell JJ, Sampath R, Ecker DJ, et al. “Salvage Microbiology”: Detection of Bacteria Directly from Clinical Specimens following Initiation of Antimicrobial Treatment. PLoS One 2013;8:e66349
  • Jordana-Lluch E, Carolan HE, Gimenez M, et al. Rapid diagnosis of bloodstream infections with PCR followed by mass spectrometry. PLoS One 2013;8:e62108
  • Romero R, Miranda J, Chaiworapongsa T, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol 2014;71:330–58
  • Rust OA, Atlas RO, Reed J, et al. Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help. Am J Obstet Gynecol 2001;185:1098–105
  • Romero R, Hagay Z, Nores J, et al. Eradication of Ureaplasma urealyticum from the amniotic fluid with transplacental antibiotic treatment. Am J Obstet Gynecol 1992;166:618–20
  • Gibbs RS, Blanco JD, St Clair PJ, et al. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982;145:1–8
  • Kim KW, Romero R, Park HS, et al. A rapid matrix metalloproteinase-8 bedside test for the detection of intraamniotic inflammation in women with preterm premature rupture of membranes. Am J Obstet Gynecol 2007;197:292 e1–5
  • DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One 2008;3:e3056
  • DiGiulio DB, Romero R, Kusanovic JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010;64:38–57
  • DiGiulio DB, Gervasi M, Romero R, et al. Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J Perinat Med 2010;38:503–13
  • DiGiulio DB, Gervasi MT, Romero R, et al. Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses. J Perinat Med 2010;38:495–502
  • Redline RW. Inflammatory responses in the placenta and umbilical cord. Semin Fetal Neonatal Med 2006;11:296–301
  • Pacora P, Chaiworapongsa T, Maymon E, et al. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2002;11:18–25
  • Redline RW, Heller D, Keating S, et al. Placental diagnostic criteria and clinical correlation–a workshop report. Placenta 2005;26 Suppl A:S114–17
  • Eshoo MW, Crowder CC, Rebman AW, et al. Direct molecular detection and genotyping of Borrelia burgdorferi from whole blood of patients with early Lyme disease. PLoS One 2012;7:e36825
  • Shin JH, Ranken R, Sefers SE, et al. Detection, identification, and distribution of fungi in bronchoalveolar lavage specimens by use of multilocus PCR coupled with electrospray ionization/mass spectrometry. J Clin Microbiol 2013;51:136–41
  • Kanneganti TD, Ozoren N, Body-Malapel M, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 2006;440:233–6
  • Legoff J, Feghoul L, Mercier-Delarue S, et al. Broad-range PCR/electrospray ionization mass spectrometry for detection and typing of adenovirus and other opportunistic viruses in stem cell transplant patients. J Clin Microbiol 2013;51:4186–92
  • Romero R, Avila C, Santhanam U, et al. Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest 1990;85:1392–400
  • Santhanam U, Avila C, Romero R, et al. Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection. Cytokine 1991;3:155–63
  • Romero R, Sepulveda W, Kenney JS, et al. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp 1992;167:205–20; discussion 20–3
  • Romero R, Yoon BH, Mazor M, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol 1993;169:805–16
  • Romero R, Yoon BH, Mazor M, et al. A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 1993;169:839–51
  • Gomez R, Romero R, Galasso M, et al. The value of amniotic fluid interleukin-6, white blood cell count, and gram stain in the diagnosis of microbial invasion of the amniotic cavity in patients at term. Am J Reprod Immunol 1994;32:200–10
  • Andrews WW, Hauth JC, Goldenberg RL, et al. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol 1995;173:606–12
  • Yoon BH, Romero R, Kim CJ, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol 1995;172:960–70
  • Yoon BH, Romero R, Jun JK, et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1997;177:825–30
  • Yoon BH, Romero R, Park JS, et al. Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol 1998;179:1254–60
  • Yoon BH, Romero R, Lim JH, et al. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor. Am J Obstet Gynecol 2003;189:919–24
  • Madan I, Romero R, Kusanovic JP, et al. The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation. J Perinat Med 2010;38:275–9
  • Gervasi MT, Romero R, Bracalente G, et al. Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery. J Perinat Med 2012;40:329–43
  • Romero R, Kadar N, Miranda J, et al. 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. J Matern Fetal Neonatal Med 2014;27:757–69
  • Gray DJ, Robinson HB, Malone J, et al. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn 1992;12:111–17
  • Seong HS, Lee SE, Kang JH, et al. The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor. Am J Obstet Gynecol 2008;199:375 e1–5
  • Romero R, Lockwood CJ. Pathogenesis of spontaneous preterm labor. In: Creasy RK, Resnik R, Iams JD, eds. Creasy and Resnik's maternal-fetal medicine: principles and practice. Philadelphia (PA): Elsevier; 2009:521–43
  • Minkoff H. Prematurity: infection as an etiologic factor. Obstet Gynecol 1983;62:137–44
  • Romero R, Kadar N, Hobbins JC, et al. Infection and labor: the detection of endotoxin in amniotic fluid. Am J Obstet Gynecol 1987;157:815–19
  • Romero R, Roslansky P, Oyarzun E, et al. Labor and infection. II. Bacterial endotoxin in amniotic fluid and its relationship to the onset of preterm labor. Am J Obstet Gynecol 1988;158:1044–9
  • Gravett MG, Witkin SS, Haluska GJ, et al. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol 1994;171:1660–7
  • Gomez R, Ghezzi F, Romero R, et al. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol 1995;22:281–342
  • Romero R, Gomez R, Mazor M, et al. The preterm labor syndrome. In: Elder MG, Romero R, Lamont RF, eds. Preterm labor. New York (NY): Churchill Livingstone; 1997:29–49
  • Romero R, Gomez R, Chaiworapongsa T, et al. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 2001;15 Suppl 2:41–56
  • Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG 2006;113 Suppl 3:17–42
  • Romero R, Lockwood CJ. Pathogenesis of spontaneous preterm labor. In: Creasy RK, Resnik R, Iams J, eds. Creasy and Resnik's maternal–fetal medicine: principles and practice. 6th ed. Philadelphia (PA): Elsevier; 2009:521–43
  • Romero R, Brody DT, Oyarzun E, et al. Infection and labor. III. Interleukin-1: a signal for the onset of parturition. Am J Obstet Gynecol 1989;160:1117–23
  • Romero R, Mazor M, Brandt F, et al. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol 1992;27:117–23
  • Greig PC, Ernest JM, Teot L, et al. Amniotic fluid interleukin-6 levels correlate with histologic chorioamnionitis and amniotic fluid cultures in patients in premature labor with intact membranes. Am J Obstet Gynecol 1993;169:1035–44
  • Baggia S, Gravett MG, Witkin SS, et al. Interleukin-1 beta intra-amniotic infusion induces tumor necrosis factor-alpha, prostaglandin production, and preterm contractions in pregnant rhesus monkeys. J Soc Gynecol Investig 1996;3:121–6
  • Romero R, Manogue KR, Mitchell MD, et al. Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor. Am J Obstet Gynecol 1989;161:336–41
  • Romero R, Mazor M, Sepulveda W, et al. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol 1992;166:1576–87
  • Baumann P, Romero R, Berry S, et al. Evidence of participation of the soluble tumor necrosis factor receptor I in the host response to intrauterine infection in preterm labor. Am J Reprod Immunol 1993;30:184–93
  • Arntzen KJ, Kjollesdal AM, Halgunset J, et al. TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J Perinat Med 1998;26:17–26
  • Maymon E, Ghezzi F, Edwin SS, et al. The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition. Am J Obstet Gynecol 1999;181:1142–8
  • Hillier SL, Witkin SS, Krohn MA, et al. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol 1993;81:941–8
  • Fidel PL, Jr Romero R, Wolf N, et al. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice. Am J Obstet Gynecol 1994;170:1467–75
  • Dudley DJ, Hunter C, Varner MW, et al. Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis. Am J Perinatol 1996;13:443–7
  • Pacora P, Romero R, Maymon E, et al. Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection. Am J Obstet Gynecol 2000;183:1138–43
  • Hitti J, Tarczy-Hornoch P, Murphy J, et al. Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less. Obstet Gynecol 2001;98:1080–8
  • Shobokshi A, Shaarawy M. Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection. Int J Gynaecol Obstet 2002;79:209–15
  • Romero R, Erez O, Espinoza J. Intrauterine infection, preterm labor, and cytokines. J Soc Gynecol Investig 2005;12:463–5
  • Figueroa R, Garry D, Elimian A, et al. Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. J Matern Fetal Neonatal Med 2005;18:241–7
  • Romero R, Espinoza J, Goncalves LF, et al. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007;25:21–39
  • Romero R, Gotsch F, Pineles B, et al. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev 2007;65:S194–202
  • Bobitt JR, Ledger WJ. Unrecognized amnionitis and prematurity: a preliminary report. J Reprod Med 1977;19:8–12
  • Bobitt JR, Ledger WJ. Amniotic fluid analysis. Its role in maternal neonatal infection. Obstet Gynecol 1978;51:56–62
  • Miller JM, Jr Pupkin MJ, Hill GB. Bacterial colonization of amniotic fluid from intact fetal membranes. Am J Obstet Gynecol 1980;136:796–804
  • Wallace RL, Herrick CN. Amniocentesis in the evaluation of premature labor. Obstet Gynecol 1981;57:483–6
  • Bobitt JR, Hayslip CC, Damato JD. Amniotic fluid infection as determined by transabdominal amniocentesis in patients with intact membranes in premature labor. Am J Obstet Gynecol 1981;140:947–52
  • Wahbeh CJ, Hill GB, Eden RD, et al. Intra-amniotic bacterial colonization in premature labor. Am J Obstet Gynecol 1984;148:739–43
  • Gravett MG, Hummel D, Eschenbach DA, et al. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986;67:229–37
  • Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol 1988;12:262–79
  • Romero R, Sirtori M, Oyarzun E, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol 1989;161:817–24
  • Skoll MA, Moretti ML, Sibai BM. The incidence of positive amniotic fluid cultures in patients preterm labor with intact membranes. Am J Obstet Gynecol 1989;161:813–16
  • Gibbs RS, Romero R, Hillier SL, et al. A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166:1515–28
  • Watts DH, Krohn MA, Hillier SL, et al. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992;79:351–7
  • Yoon BH, Romero R, Kim M, et al. Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction. Am J Obstet Gynecol 2000;183:1130–7
  • Jacobsson B, Mattsby-Baltzer I, Andersch B, et al. Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor. Acta Obstet Gynecol Scand 2003;82:120–8
  • Garite TJ, Freeman RK, Linzey EM, et al. The use of amniocentesis in patients with premature rupture of membranes. Obstet Gynecol 1979;54:226–30
  • Miller JM, Jr Hill GB, Welt SI, et al. Bacterial colonization of amniotic fluid in the presence of ruptured membranes. Am J Obstet Gynecol 1980;137:451–8
  • Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol 1984;63:38–43
  • Broekhuizen FF, Gilman M, Hamilton PR. Amniocentesis for gram stain and culture in preterm premature rupture of the membranes. Obstet Gynecol 1985;66:316–21
  • Romero R, Quintero R, Oyarzun E, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol 1988;159:661–6
  • Asrat T, Nageotte MP, Garite TJ, et al. Gram stain results from amniocentesis in patients with preterm premature rupture of membranes–comparison of maternal and fetal characteristics. Am J Obstet Gynecol 1990;163:887–9
  • Gomez R, Romero R, Edwin SS, et al. Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection. Infect Dis Clin North Am 1997;11:135–76
  • Jacobsson B, Mattsby-Baltzer I, Andersch B, et al. Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes. Acta Obstet Gynecol Scand 2003;82:423–31
  • Bujold E, Morency AM, Rallu F, et al. Bacteriology of amniotic fluid in women with suspected cervical insufficiency. J Obstet Gynaecol Can 2008;30:882–7
  • Oh KJ, Lee SE, Jung H, et al. Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency. J Perinat Med 2010;38:261–8
  • Gomez R, Romero R, Nien JK, et al. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2005;192:678–89
  • Gomez R, Romero R, Nien JK, et al. Idiopathic vaginal bleeding during pregnancy as the only clinical manifestation of intrauterine infection. J Matern Fetal Neonatal Med 2005;18:31–7
  • Park CW, Moon KC, Park JS, et al. The frequency and clinical significance of intra-uterine infection and inflammation in patients with placenta previa and preterm labor and intact membranes. Placenta 2009;30:613–8
  • Kim SK, Romero R, Kusanovic JP, et al. The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD). J Perinat Med 2010;38:45–53
  • Hein M, Helmig RB, Schonheyder HC, et al. An in vitro study of antibacterial properties of the cervical mucus plug in pregnancy. Am J Obstet Gynecol 2001;185:586–92
  • Hein M, Valore EV, Helmig RB, et al. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol 2002;187:137–44
  • Hein M, Petersen AC, Helmig RB, et al. Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy. Acta Obstet Gynecol Scand 2005;84:734–42
  • Becher N, Adams Waldorf K, Hein M, et al. The cervical mucus plug: structured review of the literature. Acta Obstet Gynecol Scand 2009;88:502–13
  • Lee DC, Hassan SS, Romero R, et al. Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy. J Proteomics 2011;74:817–28
  • Hansen LK, Becher N, Bastholm S, et al. The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy. Acta Obstet Gynecol Scand 2014;93:102–8
  • Fournier PE, Drancourt M, Colson P, et al. Modern clinical microbiology: new challenges and solutions. Nat Rev Microbiol 2013;11:574–85
  • Blanchard A, Hentschel J, Duffy L, et al. Detection of Ureaplasma urealyticum by polymerase chain reaction in the urogenital tract of adults, in amniotic fluid, and in the respiratory tract of newborns. Clin Infect Dis 1993;17 Suppl 1:S148–53
  • Oyarzun E, Yamamoto M, Kato S, et al. Specific detection of 16 micro-organisms in amniotic fluid by polymerase chain reaction and its correlation with preterm delivery occurrence. Am J Obstet Gynecol 1998;179:1115–19
  • Bearfield C, Davenport ES, Sivapathasundaram V, et al. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG 2002;109:527–33
  • Gerber S, Vial Y, Hohlfeld P, et al. Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis 2003;187:518–21
  • Yoon BH, Romero R, Lim JH, et al. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor. American journal of obstetrics and gynecology 2003;189:919–24
  • Perni SC, Vardhana S, Korneeva I, et al. Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: association with amniotic fluid cytokine levels and pregnancy outcome. Am J Obstet Gynecol 2004;191:1382–6
  • Holst RM, Mattsby-Baltzer I, Wennerholm UB, et al. Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery. Acta Obstet Gynecol Scand 2005;84:551–7
  • Yi J, Yoon BH, Kim EC. Detection and biovar discrimination of Ureaplasma urealyticum by real-time PCR. Mol Cell Probes 2005;19:255–60
  • Holst RM, Jacobsson B, Hagberg H, et al. Cervical length in women in preterm labor with intact membranes: relationship to intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm delivery. Ultrasound Obstet Gynecol 2006;28:768–74
  • Leon R, Silva N, Ovalle A, et al. Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J Periodontol 2007;78:1249–55
  • Han YW, Shen T, Chung P, et al. Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol 2009;47:38–47
  • Kacerovsky M, Pliskova L, Bolehovska R, et al. The microbial load with genital mycoplasmas correlates with the degree of histologic chorioamnionitis in preterm PROM. Am J Obstet Gynecol 2011;205:213 e1–7
  • Holst RM, Hagberg H, Wennerholm UB, et al. Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids. BJOG 2011;118:240–9
  • Jalava J, Mantymaa ML, Ekblad U, et al. Bacterial 16S rDNA polymerase chain reaction in the detection of intra-amniotic infection. Br J Obstet Gynaecol 1996;103:664–9
  • Hitti J, Riley DE, Krohn MA, et al. Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor. Clin Infect Dis 1997;24:1228–32
  • Markenson GR, Martin RK, Tillotson-Criss M, et al. The use of the polymerase chain reaction to detect bacteria in amniotic fluid in pregnancies complicated by preterm labor. Am J Obstet Gynecol 1997;177:1471–7
  • Gardella C, Riley DE, Hitti J, et al. Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor. Am J Perinatol 2004;21:319–23
  • Miralles R, Hodge R, McParland PC, et al. Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction. Pediatr Res 2005;57:570–7
  • Marconi C, de Andrade Ramos BR, Peracoli JC, et al. Amniotic fluid interleukin-1 beta and interleukin-6, but not interleukin-8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol 2011;65:549–56
  • Romero R, Yoon BH, Mazor M, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol 1993;169:805–16
  • Cobo T, Palacio M, Martinez-Terron M, et al. Clinical and inflammatory markers in amniotic fluid as predictors of adverse outcomes in preterm premature rupture of membranes. Am J Obstet Gynecol 2011;205:126 e1–8
  • Cobo T, Kacerovsky M, Holst RM, et al. Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture. Acta Obstet Gynecol Scand 2012;91:930–5
  • Cherouny PH, Pankuch GA, Romero R, et al. Neutrophil attractant/activating peptide-1/interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants. Am J Obstet Gynecol 1993;169:1299–303
  • Athayde N, Romero R, Gomez R, et al. Matrix metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med 1999;8:213–19
  • Jacobsson B, Holst RM, Wennerholm UB, et al. Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery. Am J Obstet Gynecol 2003;189:1161–7
  • Esplin MS, Romero R, Chaiworapongsa T, et al. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection. J Matern Fetal Neonatal Med 2005;17:365–73
  • Romero R, Gomez R, Galasso M, et al. Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect of microbial invasion of the amniotic cavity. Am J Reprod Immunol 1994;32:108–13
  • Soto E, Espinoza J, Nien JK, et al. Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med 2007;20:15–22
  • Kim SM, Romero R, Lee J, et al. 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? J Matern Fetal Neonatal Med 2012;25:1212–21
  • Pace NR. A molecular view of microbial diversity and the biosphere. Science 1997;276:734–40
  • Relman DA. The search for unrecognized pathogens. Science 1999;284:1308–10
  • Amann R. Who is out there? Microbial aspects of biodiversity. Syst Appl Microbiol 2000;23:1–8
  • Petrosino JF, Highlander S, Luna RA, et al. Metagenomic pyrosequencing and microbial identification. Clin Chem 2009;55:856–66
  • Flores GE, Henley JB, Fierer N. A direct PCR approach to accelerate analyses of human-associated microbial communities. PLoS One 2012;7:e44563
  • Gotsch F, Romero R, Chaiworapongsa T, et al. Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: a link between the inflammasome and parturition. J Matern Fetal Neonatal Med 2008;21:605–16
  • Mittal P, Romero R, Tarca AL, et al. Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term. J Perinat Med 2010;38:617–43
  • Nhan-Chang CL, Romero R, Tarca AL, et al. Characterization of the transcriptome of chorioamniotic membranes at the site of rupture in spontaneous labor at term. Am J Obstet Gynecol 2010;202:462 e1–41
  • Romero R, Ceska M, Avila C, et al. Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition. Am J Obstet Gynecol 1991;165:813–20
  • Romero R, Parvizi ST, Oyarzun E, et al. Amniotic fluid interleukin-1 in spontaneous labor at term. J Reprod Med 1990;35:235–8
  • Romero R, Sepulveda W, Mazor M, et al. The natural interleukin-1 receptor antagonist in term and preterm parturition. Am J Obstet Gynecol 1992;167:863–72
  • Romero R, Emamian M, Quintero R, et al. The value and limitations of the Gram stain examination in the diagnosis of intraamniotic infection. Am J Obstet Gynecol 1988;159:114–19
  • Gauthier DW, Meyer WJ. Comparison of gram stain, leukocyte esterase activity, and amniotic fluid glucose concentration in predicting amniotic fluid culture results in preterm premature rupture of membranes. Am J Obstet Gynecol 1992;167:1092–5
  • Garry D, Figueroa R, Aguero-Rosenfeld M, et al. A comparison of rapid amniotic fluid markers in the prediction of microbial invasion of the uterine cavity and preterm delivery. Am J Obstet Gynecol 1996;175:1336–41
  • Hussey MJ, Levy ES, Pombar X, et al. Evaluating rapid diagnostic tests of intra-amniotic infection: Gram stain, amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio. Am J Obstet Gynecol 1998;179:650–6
  • Odibo AO, Rodis JF, Sanders MM, et al. Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes. J Perinatol 1999;19:407–12
  • Romero R, Emamian M, Wan M, et al. The value of the leukocyte esterase test in diagnosing intra-amniotic infection. Am J Perinatol 1988;5:64–9
  • Egley CC, Katz VL, Herbert WN. Leukocyte esterase: a simple bedside test for the detection of bacterial colonization of amniotic fluid. Am J Obstet Gynecol 1988;159:120–2
  • Romero R, Jimenez C, Lohda AK, et al. Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol 1990;163:968–74
  • Kiltz RJ, Burke MS, Porreco RP. Amniotic fluid glucose concentration as a marker for intra-amniotic infection. Obstet Gynecol 1991;78:619–22
  • Kirshon B, Rosenfeld B, Mari G, et al. Amniotic fluid glucose and intraamniotic infection. Am J Obstet Gynecol 1991;164:818–20
  • Gonen R. Amniotic fluid glucose and intraamniotic infection: sensitivity, specificity, and predictive values. Am J Obstet Gynecol 1992;166:1863–4
  • Dildy GA, Pearlman MD, Smith LG, et al. Amniotic fluid glucose concentration: a marker for infection in preterm labor and preterm premature rupture of membranes. Infect Dis Obstet Gynecol 1994;1:166–72
  • Greig PC, Ernest JM, Teot L. Low amniotic fluid glucose levels are a specific but not a sensitive marker for subclinical intrauterine infections in patients in preterm labor with intact membranes. Am J Obstet Gynecol 1994;171:365–70; discussion 70–1
  • Gonzalez-Bosquet E, Cerqueira MJ, Dominguez C, et al. Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes. J Matern Fetal Med 1999;8:155–8
  • Romero R, Miranda J, Chaiworapongsa T, et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol 2014. [Epub ahead of print]. doi: 10.1111/aji.12296
  • Nien JK, Yoon BH, Espinoza J, et al. A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery. Am J Obstet Gynecol 2006;195:1025–30
  • Park CW, Lee SM, Park JS, et al. The antenatal identification of funisitis with a rapid MMP-8 bedside test. J Perinat Med 2008;36:497–502
  • Pacheco LD, Ghulmiyyah LM, Snodgrass WR, et al. Pharmacokinetics of corticosteroids during pregnancy. Am J Perinatol 2007;24:79–82
  • Smith LM, Qureshi N, Chao CR. Effects of single and multiple courses of antenatal glucocorticoids in preterm newborns less than 30 weeks' gestation. J Matern Fetal Med 2000;9:131–5
  • Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008;359:895–905
  • Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol 2009;200:595–609
  • Doyle LW, Crowther CA, Middleton P, et al. Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol 2009;113:1327–33
  • Doyle LW. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr 2012;24:154–9
  • Burd I, Breen K, Friedman A, et al. Magnesium sulfate reduces inflammation-associated brain injury in fetal mice. Am J Obstet Gynecol 2010;202:292 e1–9
  • Lee KY, Jun HA, Kim HB, et al. Interleukin-6, but not relaxin, predicts outcome of rescue cerclage in women with cervical incompetence. Am J Obstet Gynecol 2004;191:784–9

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